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“Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ” November 15, 2017 Patrick Cronin, DO,FACR Clinical Instructor Cooper Medical School of Rowan University Cooper University Bone & Joint Institute Division of Rheumatology

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Page 1: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

ldquoSystemic Sclerosis Recognition

of Systemic and multisystem

autoimmune Disease rdquo

November 15 2017

Patrick Cronin DOFACR

Clinical Instructor

Cooper Medical School of Rowan University

Cooper University Bone amp Joint Institute

Division of Rheumatology

American College of Rheumatology Systemic Sclerosis (1980) Classification criteria Diagnosis 1 major (or) 2 minor

Major criterion Proximal scleroderma

(proximal to the MCP joints)

Minor criteria Sclerodactyly

Digital pitting or scars or loss substance finger pad

Bibasilar pulmonary fibrosis

Classification Scleroderma

Systemic Sclerosis

Diffuse cutaneous

Progressive Systemic Sclerosis

Limited cutaneous

CREST (calcinosis Raynaudrsquos esophageal dysmotility sclerodactyly atelectasis) Syndrome

Scleroderma sine scleroderma

Scleroderma-Like Syndromes

Scleredema mdash Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk particularly the shoulders and back The face may also be affected In severe cases mobility of the shoulders and chest is markedly impaired Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients and internal organ involvement is rare)

Scleromyxedema mdash Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head neck arms and upper trunk commonly occurring over thickened and indurated skin Middle-aged adults are most commonly affected The presence of a monoclonal protein often IgG lambda detected by immunofixation on samples of serum andor urine supports the diagnosis of scleromyxedema Skin biopsy is valuable Scleromyxedema may be associated with AL amyloidosis and multiple myeloma

Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration Endocrine disorders may also occur in some patients with monoclonal gammopathies for example in the POEMS syndrome (Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy and Skin changes)

Scleromyxedemamyxedema

Epidemiology Scleroderma

Female Male = 31 (Greater in African-American women)

Age Peak 35-65 years

Incidence 19 casesmillionyear

Prevalence 19-75 cases100000

Scleroderma Proposed Pathophysiology

Cytokines

Transforming Growth Factor β (TGF- β)

Platelet Derived Growth Factor (PDGF)

Endothelial damage ndash releases endothelin ndash increase fibroblast function

Collagen I

Fibronectin

Glycosaminoglycans

Endothelial injury

VasoconstrictionFibroblastuarr

Hypoxia -- uarr TGF β

Fibroblast uarr

Scleroderma

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 2: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

American College of Rheumatology Systemic Sclerosis (1980) Classification criteria Diagnosis 1 major (or) 2 minor

Major criterion Proximal scleroderma

(proximal to the MCP joints)

Minor criteria Sclerodactyly

Digital pitting or scars or loss substance finger pad

Bibasilar pulmonary fibrosis

Classification Scleroderma

Systemic Sclerosis

Diffuse cutaneous

Progressive Systemic Sclerosis

Limited cutaneous

CREST (calcinosis Raynaudrsquos esophageal dysmotility sclerodactyly atelectasis) Syndrome

Scleroderma sine scleroderma

Scleroderma-Like Syndromes

Scleredema mdash Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk particularly the shoulders and back The face may also be affected In severe cases mobility of the shoulders and chest is markedly impaired Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients and internal organ involvement is rare)

Scleromyxedema mdash Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head neck arms and upper trunk commonly occurring over thickened and indurated skin Middle-aged adults are most commonly affected The presence of a monoclonal protein often IgG lambda detected by immunofixation on samples of serum andor urine supports the diagnosis of scleromyxedema Skin biopsy is valuable Scleromyxedema may be associated with AL amyloidosis and multiple myeloma

Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration Endocrine disorders may also occur in some patients with monoclonal gammopathies for example in the POEMS syndrome (Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy and Skin changes)

Scleromyxedemamyxedema

Epidemiology Scleroderma

Female Male = 31 (Greater in African-American women)

Age Peak 35-65 years

Incidence 19 casesmillionyear

Prevalence 19-75 cases100000

Scleroderma Proposed Pathophysiology

Cytokines

Transforming Growth Factor β (TGF- β)

Platelet Derived Growth Factor (PDGF)

Endothelial damage ndash releases endothelin ndash increase fibroblast function

Collagen I

Fibronectin

Glycosaminoglycans

Endothelial injury

VasoconstrictionFibroblastuarr

Hypoxia -- uarr TGF β

Fibroblast uarr

Scleroderma

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 3: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Classification Scleroderma

Systemic Sclerosis

Diffuse cutaneous

Progressive Systemic Sclerosis

Limited cutaneous

CREST (calcinosis Raynaudrsquos esophageal dysmotility sclerodactyly atelectasis) Syndrome

Scleroderma sine scleroderma

Scleroderma-Like Syndromes

Scleredema mdash Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk particularly the shoulders and back The face may also be affected In severe cases mobility of the shoulders and chest is markedly impaired Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients and internal organ involvement is rare)

Scleromyxedema mdash Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head neck arms and upper trunk commonly occurring over thickened and indurated skin Middle-aged adults are most commonly affected The presence of a monoclonal protein often IgG lambda detected by immunofixation on samples of serum andor urine supports the diagnosis of scleromyxedema Skin biopsy is valuable Scleromyxedema may be associated with AL amyloidosis and multiple myeloma

Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration Endocrine disorders may also occur in some patients with monoclonal gammopathies for example in the POEMS syndrome (Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy and Skin changes)

Scleromyxedemamyxedema

Epidemiology Scleroderma

Female Male = 31 (Greater in African-American women)

Age Peak 35-65 years

Incidence 19 casesmillionyear

Prevalence 19-75 cases100000

Scleroderma Proposed Pathophysiology

Cytokines

Transforming Growth Factor β (TGF- β)

Platelet Derived Growth Factor (PDGF)

Endothelial damage ndash releases endothelin ndash increase fibroblast function

Collagen I

Fibronectin

Glycosaminoglycans

Endothelial injury

VasoconstrictionFibroblastuarr

Hypoxia -- uarr TGF β

Fibroblast uarr

Scleroderma

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 4: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma-Like Syndromes

Scleredema mdash Scleredema is characterized by prominent symmetrical skin thickening predominantly on the trunk particularly the shoulders and back The face may also be affected In severe cases mobility of the shoulders and chest is markedly impaired Patients with insulin-dependent diabetes mellitus may develop a type of scleredema called scleredema of Buschke(Raynaud phenomenon and autoantibodies are not present in these patients and internal organ involvement is rare)

Scleromyxedema mdash Scleromyxedema (papular mucinosis) is characterized by waxy yellow-red papules on the head neck arms and upper trunk commonly occurring over thickened and indurated skin Middle-aged adults are most commonly affected The presence of a monoclonal protein often IgG lambda detected by immunofixation on samples of serum andor urine supports the diagnosis of scleromyxedema Skin biopsy is valuable Scleromyxedema may be associated with AL amyloidosis and multiple myeloma

Diabetes mellitus and myxedema due to hypothyroidism can be accompanied by skin induration Endocrine disorders may also occur in some patients with monoclonal gammopathies for example in the POEMS syndrome (Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy and Skin changes)

Scleromyxedemamyxedema

Epidemiology Scleroderma

Female Male = 31 (Greater in African-American women)

Age Peak 35-65 years

Incidence 19 casesmillionyear

Prevalence 19-75 cases100000

Scleroderma Proposed Pathophysiology

Cytokines

Transforming Growth Factor β (TGF- β)

Platelet Derived Growth Factor (PDGF)

Endothelial damage ndash releases endothelin ndash increase fibroblast function

Collagen I

Fibronectin

Glycosaminoglycans

Endothelial injury

VasoconstrictionFibroblastuarr

Hypoxia -- uarr TGF β

Fibroblast uarr

Scleroderma

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 5: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleromyxedemamyxedema

Epidemiology Scleroderma

Female Male = 31 (Greater in African-American women)

Age Peak 35-65 years

Incidence 19 casesmillionyear

Prevalence 19-75 cases100000

Scleroderma Proposed Pathophysiology

Cytokines

Transforming Growth Factor β (TGF- β)

Platelet Derived Growth Factor (PDGF)

Endothelial damage ndash releases endothelin ndash increase fibroblast function

Collagen I

Fibronectin

Glycosaminoglycans

Endothelial injury

VasoconstrictionFibroblastuarr

Hypoxia -- uarr TGF β

Fibroblast uarr

Scleroderma

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 6: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Epidemiology Scleroderma

Female Male = 31 (Greater in African-American women)

Age Peak 35-65 years

Incidence 19 casesmillionyear

Prevalence 19-75 cases100000

Scleroderma Proposed Pathophysiology

Cytokines

Transforming Growth Factor β (TGF- β)

Platelet Derived Growth Factor (PDGF)

Endothelial damage ndash releases endothelin ndash increase fibroblast function

Collagen I

Fibronectin

Glycosaminoglycans

Endothelial injury

VasoconstrictionFibroblastuarr

Hypoxia -- uarr TGF β

Fibroblast uarr

Scleroderma

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 7: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Proposed Pathophysiology

Cytokines

Transforming Growth Factor β (TGF- β)

Platelet Derived Growth Factor (PDGF)

Endothelial damage ndash releases endothelin ndash increase fibroblast function

Collagen I

Fibronectin

Glycosaminoglycans

Endothelial injury

VasoconstrictionFibroblastuarr

Hypoxia -- uarr TGF β

Fibroblast uarr

Scleroderma

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 8: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 9: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma ANA

Centromere Homogenous

Speckled Nucleolar

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 10: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Skin

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 11: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

ldquoRaynaudrsquosrdquo

Maurice Raynaud in 1862 stated that local asphyxia of the extremitiesldquo ndash loss of oxygen to the tissue

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 12: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

ldquoRaynaudrsquosrdquo httpwwwnhlbinihgovhealthhealth-topicstopicsraynaud

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 13: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Digital Artery

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 14: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Thermography Raynaudrsquos

Control 1 Raynaudrsquos Scleroderma

15 c

23 c

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 15: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Raynaudrsquos

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 16: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Raynaudrsquos

Episodic

Reversible digital color change

White to blue to red

Well-demarcated

Due to vasospasm

Usually cold-induced

Primary amp secondary

forms

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 17: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Raynaudrsquos

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 18: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Raynaudrsquos Cyanosis

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 19: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Capillary Microscopy

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 20: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Causes of Secondary Raynaudrsquos

Connective tissue diseases

Scleroderma systemic lupus erythematosus MCTD

undifferentiated CTD Sjogrenrsquos syndrome dermatomyositis others

Occlusive arterial disease Atherosclerosis anti-phospholipid antibody syndrome Buergerrsquos disease

Vascular injury Frostbite vibratory trauma

Drugs and toxins Beta blockers vinyl chloride bleomycin ergot amphetamines cocaine

Hyperviscositycold-reacting proteins Paraproteinemia polycythemia cryoglobulinemia cryofibrinogenemia cold agglutinins

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 21: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Raynaudrsquos

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 22: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Edematous Changes Hands

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 23: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Puffy Phase Hand

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 24: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Hands

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 25: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Skin Induration

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 26: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Acrosclerosis

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 27: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Acrolysis

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 28: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Acro-sclerosis amp Terminal Digit Resorption

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 29: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Digital Pitting Scars

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 30: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Limited Systemic Sclerosis Calcinosis

bullCalcinosis

(Hydroxyapatite)

bullColchicine

bullCalcium Channel

Blockers

Arthritis Rheum 1995 Nov38(11)1646-54

Treatment of calcinosis with diltiazem

Palmieri GM Sebes JI Aelion JA Moinuddin M Ray MW Wood GC Leventhal MR

Source

University of Tennessee at Memphis 38163 USA

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 31: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Calcinosis Cutis

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 32: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Calcinosis and Acrolysis

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 33: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Limited Systemic Sclerosis Calcinosis Arm

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 34: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Calcinosis

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 35: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 36: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Facial Changes

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 37: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Facial Changes

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 38: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Watermelon Stomach

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 39: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Dysmotility and Esophagus

Upper GI tract

GERD

Proton Pump Inhibitor

Aspiration Pneumonia

PPI vs Carafate

EsophagitisBarrettrsquos

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 40: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Bowel Dilatation

GI Malabsorption

Vitamin D

Difficult to treat

Bacterial Overgrowth

Metronidazole

Tetracycline

Ciprofloxacin

Weight LossCachexia

TPN

Pseudo-obstruction

Non-surgical

General Measures

Octreotide erythromycin

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 41: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Wide-Mouth Diverticula

Diverticula

Wide mouth

Rare diverticulitis

Pneumatosis Cystoides Intestinalis

Non-Surgical

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 42: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Pulmonary

Pulmonary ILDHTN - Rule out ndash Embolic disease (APL) CHF OSA

6 minute walk

Echocardiogram ndash yrrsquoly PAP

PFT with DLCO ndash yrrsquoly compare DLCO

Cardiac

Contraction band necrosis - arrhythmias

Pericardial effusion ndash large non-tamp

Myocarditis

Scleroderma Pulmonary Cardiac

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 43: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Pulmonary HTN

PHTN ndash Echocardiogram or Right Heart Cath

High mortality ndash 52 at 3 years survival ()

Bosentan (next slide)

Sildenafil ndash SUPER-1 trial (1)

() Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension a systematic review

and meta-analysis

Lefegravevre G Dauchet L Hachulla E Montani D Sobanski V Lambert M Hatron PY Humbert M Launay D Arthritis Rheum

201365(9)2412

(1)Sildenafil citrate therapy for pulmonary arterial hypertension

Galiegrave N Ghofrani HA Torbicki A Barst RJ Rubin LJ Badesch D Fleming T Parpia T Burgess G Branzi A Grimminger F

Kurzyna M Simonneau G Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group

N Engl J Med 2005 Nov 17353(20)2148-57

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 44: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Kidney

Scleroderma Renal Crisis

High Renin State

Microangiopathic Hemolytic Anemia

HTN and active urine sediment

Prednisone may play a role () anti-RNA polymerase III autoantibody was detected in 52 percent of SRC or fine speckled immunofluorescence pattern

Treatment

ACE inhibitor ndash Calcium Channel Blocker

Minimize steroids

()Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis

Steen VD Medsger TA Jr

Arthritis Rheum 1998 Sep41(9)1613-9

Reversal of Vascular and Renal Crises of Scleroderma by Oral Angiotensin-Converting-Enzyme Blockade

Jorge A Lopez-Ovejero MD Stuart D Saal MD William A DAngelo MD Jhoong S Cheigh MD Kurt H Stenzel MD and John H Laragh MD

N Engl J Med 1979 3001417-1419

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 45: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Kidney

Scleroderma Renal Crisis renal biopsy with fibrinoid

deposition ldquoonion-ringrdquo muscular hyperplasia

Outcome of renal crisis in systemic sclerosis relation to availability of angiotensin converting enzyme (ACE)

inhibitors

Steen VD Costantino JP Shapiro AP Medsger TA Jr

Ann Intern Med 1990113(5)352

One year survival 15 without and 76 with ACE inhibitors (P lt 0001)

Courtesy of Carol Black MD Graphic 78330 Version 60

Courtesy of Helmut Rennke MD Graphic 70213 Version 20

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 46: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Raynaudrsquos Hands

Raynaudrsquos

Longer term use

Aspirin or pentoxifylline

Calcium Channel Blockers

Bosentan (PAH)

Short term use

Topical NTG

Prostacyclin IV

Phosphodiesterase Inhibitor

Others ndash SSRI ARBACE ect

Arthritis Rheum 2004 Dec50(12)3985-93

Digital ulcers in systemic sclerosis prevention by treatment with bosentan an oral endothelin receptor

antagonist

Korn JH Mayes M Matucci Cerinic M Rainisio M Pope J Hachulla E Rich E Carpentier P Molitor J Seibold JR Hsu

V Guillevin L Chatterjee S Peter HH Coppock J Herrick A Merkel PA Simms R Denton CP Furst D Nguyen N

Gaitonde M Black C

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 47: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Raynaudrsquos HomeostasisPrevention

Life-Style Changes Dry hands and feet

Avoid convection currents Wool socks and mittens

Layer chest wall for heat trapping

Quit tobacco limit caffeine and alcohol

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 48: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Queen Elisa Raynaudrsquos patient and spokesperson

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 49: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Scleroderma Treatment

Immunosuppression (Diffuse Disease only)

Traditional immunotherapy and antifibrotics

Methotrexate

D-penicillamine

Cyclophosphamide

Current clinical immunotherapy treatments

Mycophenolate mofatil

Abatacept

Tocilizumab

Rituximab

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II) a randomised controlled double-blind

parallel group trial

Tashkin DP Roth MD Clements PJ Furst DE Khanna D Kleerup EC Goldin J Arriola E Volkmann ER Kafaja S Silver R Steen V Strange C

Wise R Wigley F Mayes M Riley DJ Hussain S Assassi S Hsu VM Patel B Phillips K Martinez F Golden J Connolly MK Varga J Dematte J

Hinchcliff ME Fischer A Swigris J Meehan R Theodore A Simms R Volkov S Schraufnagel DE Scholand MB Frech T Molitor JA Highland K

Read CA Fritzler MJ Kim GH Tseng CH Elashoff RM Sclerodema Lung Study II Investigators

Lancet Respir Med 20164(9)708 Epub 2016 Jul 25

Thank You Questions

Page 50: Systemic Sclerosis: Recognition of Systemic and ... CME/Handout-Cronin-Rheum...Nov 15, 2017  · “Systemic Sclerosis: Recognition of Systemic and multisystem autoimmune Disease ”

Thank You Questions