engl nemoci pojiva (le dm scl) pro mediky

Antinuclear autoantibodies in CTD. Autoantibidy Antigen Disease Anti-ss-DNA Single strand DNA SLE, MCTD, RA, SS,

Drug induced LE, morphea

Anti-ds-DNA* Double strand DNA SLE

Anti-Sm* complex of proteins rich on RNA

SLE

Anti Histonové Histones SLE, lékový LE, RA, SSc, morphea

Anti-U1RNP complex of proteins rich on uridineé

RNA

SLE, MCTD, SS

Anti-rRNP ribosomal phosphoproteins

SLE

Antinuclear autoantibodies in CTD.Autoantibody Antigen Disease Anti-Ro/SSA complex protein/RNA SLE, SS, SSc, RA

Anti-La/SSB complex phosphoprotein/ RNA-polymerase III

SLE, SS

Anti-Jo1* histidyl tRNA syntetase PM/DM

Anti-Mi-2* nuclear protein DM

Anti-RNA pol* complex proteins/ RNA polymerase I-III

SSc

Anti-PM-Scl nucleolar proteins SSc/PM

Anti-Scl-70* DNA topoizomerase I SSc

Anti-Centromere* kinetochore proteins SSc

Anti-Fibrilarin* Part of U3RNP SSc

Specific cutaneous lesions of LE (ie. with typical histopahtological picture of LE)

Acute (systemic) LE: erythema, maculopapular localized - diseminated

Subacute LE:

annular

papulosquamous (psoriasis-like)

Chronic LE:

discoid: - localized - disseminated

hypertrophic (verrucous)

LE panniculitis (profundus)

mucous LE

lupus tumidus

lupus pernio

Chronic (discoid, cutaneous, scarring) LE

Chronic (discoid) LE - annular

Chronic (discoid) LE – cicatricial alopecia

Chronic (discoid) LE – cicatricial alopecia

Chronic LE – photosensitivity, inappropriate profession: roofer (tile layer)

Diagnostic criteria of SLE

(American Rheumatology Association = ARA) 1. butterfly erythema2. Cutaneous manifestations of LE (subacute, chronic)3. photosensitivity4. Mucous ulcerations (mouth, nose)5. polyarthritis, arthralgia, joint swelling6. serositis (pleuritis, perikariditis)7. renal (proteinuria > 0,5g/24 h, casts in urine sediment)8. CNS (spasms, neuropsychiatric symptoms)9. hematologic (hemolytic anemia, leukopenia, lymfopenia, thrombocytopenia)10. imunology (anti-ds-DNA, anti-Sm ab., positive BWR)11. Antinuklear autoantibodies

Note. 4 criteria sufficient for diagnosis of SLE

Lupus band test (direct immunofluorescence) – Ig (G)+ C3

SLE - urticaria -vasculitis

more burning and painful than itchy pertaine longer than 24 hleaving pigmentations.

splinter hemorrhagia

Subacute LE – annular+anti-SSA/Ro and/or anti-SSB/La

bullous

Neonatal lupus erythematosus - Mother (may be asymptomatic) positivity of anti-SSA/Ro and/or anti-SSB/La. Congenital heart block in 70% - anti SS-A52 cross react with conduction system - cardiostimulator

Subacute LE – papulosquamous-psoriasiform

THERAPY – cutaneous LE Topical: photoprotection, cortikosteroids (external, intralesional),

retinoids (tazaroten), pime/tacro-limus, lasersSystemic: if necessary First choice: antimalarics (OH-chlorochin, chlorochin,

chlorochin+quinacrine) Second choice: retinoids, dapsone (vasculitis) Third choice: methotrexate, thalidomide, gold, clofazimine, Fourth choice: corticosteroids, azathioprine, cyclosporine, cyclofosfamide, IV imunoglobulins Experimental: alfa-interferon, UVA-1 fototerapy, anti-CD4 ab., topical tacrolimus…

Classification

dermatomyositis/polymyositis (DM/PM)

1. primary idiopathic PM

2. primary idiopathic adult DM

3. paraneoplastic DM (PM)

4. juvenile DM (PM)

5. DM (PM) accompanying other connective tissue diseases – overlap syndrome

6. clinically amyopathic DM

Diagnostic criteria (Bohan a Peter) dermatomyositis (DM) a polymyositis (PM)

1. muscle weekness - symetric proximal (shoulder and hip girdle muscles-combing hairs, climbing stairs), other- dysfagia, ptosis, hoarse voice

2. In serum signs of muscle damage: raised kreatinkinase (MM-izoenzymu), aldolase, transaminases, myoglobin

3. EMG: elektromyografic signs of myopathy 4. biopsy muscle with inflammatory myopathy (sono, MRI)3. Cutaneous typical lesions in dermatomyositis

Note: sure diagnosis = 1.-4. in PM, at least 3 criteria plus 5. criterium in DM, probable diagnosis = 3 criteria in PM, 2 criteria plus 5. Criterium in DM.

Eyelid edema andLivid erythema

„Shawl“ sign

Papules and erythema over finger joints and knuckles

Nailfold teleangiectasia:On capilaroscopy - giant capilaries avascular areas, bushy proliferation

Mechanic´s hands - hyperkeratosis, fissures, ulcers

Muscle atrophy and weakness

Therapy - dermatomyositis Systemic:

cortikosteroids – drug of choice

combination with immunosupresives (mostly

methotrexate), IV imunoglobulins

Of cutaneous lesions: similar to lupus erythematosus

Course and progonosis:

Better with early diagnosis and treatment.

In children in 50% complete remission, in 40 %

prolonged therapy

In adults mostly chronic therapy. Malignancy deteriorate prognosis.

Classification of scleroderma:

Localized scleroderma (morphea)

systemic scleroderma

Overlap syndromes

Undifferentiated connective tissue diseases

Scleroderma-like diseases (pseudoscleroderma)

MORPHEASCLERODERMIA CIRCUMSCRIPTA

LOCALIZED SCLERODERMAClassification

I. Morphea PLAQUE

one(several) plaques

disseminated, generalized

II. Morphea LINEAR

"en coup de sabre"

hemiatrophia progressiva faciei

III. Morphea PROFUNDA – SUBCUTANEOUS

morphea profunda

fasciitis eosinophilica

I. MORPHEA plaque

• Plaque (to few plaques)• Generalized• Large plaque• Guttate• Bullous• Nodular (keloid)• Morphea pansclerotica• Atrophodermia idiopathica progressiva Passini-

Pierini

MorpheaInflammatory phaseOrange peel appereance Livid erythema

Peripheral red-violet erythema („Lilac ring)Central ivory induration

Generalized morphea

Generalized morphea

Linear morphea

Linear morphea

Linear morphea

Linear morphea - flexion contracture

Linear morphea

Linear morphea

Linear morphea

Facial hemiatrophy

Deep morphea –

Eosinophilic fasciitis

Deep morphea

Deep morphea

THERAPY - morphea Topic: corticosteroids, vitamin D analogs emolients fysiotherapySystemic: in extensive involvement, functional defect phototherapy: PUVA therapy,, UVA1 methotrexate Corticosteroids (deep morphea) Others: vitamine E, penicillin, penicillamine,

antimalarics… Surgical: contracturesCourse and prognosis: duration 3-5 years. In deep and

extensive morphea can be longer. Rarely flare (linear in 13 %). Persistent hyperpigmentation, disability,

Classification of scleroderma:

localized scleroderma (morphea)

systemic scleroderma

overlap syndromes

Undifferentiated connective tissue diseases

Scleroderma-like disease

SYSTEMIC SCLERODERMA CLASSIFICATION (acc. skin involvement)

LIMITED

DIFFUSE

Typ I - fingers (acroscleroderma digitalis)

Typ II - fingers, forearms,

arms

(acrosclerodermia proximalis) - intermedial

Typ III - trunk

diffuse

MINIMAL (PRE-) SSc (Raynaud + capilaroscopy and/or ANA+)CREST (calcinosis,oesofagus,Raynaud, sklerodactyly, teleangiectasia)SCLERODERMIA SYSTEMICA SINE SCLERODERMIA

(acrosclerosis)

GIT involvement SYSTEMIC SCLERODERMA

• oropharynx (mikro-stomie-glossie, shortened frenulum, alveolar resorption etc.)

• hypomotility/90%/ • gastroesofageal reflux• esophagitis • Barrett.metaplasia • stricture • gastroparesis • malabsorption

• dysmicrobia• diarrhoea• bleeding • Perforation, volvulus • pneumatosis cystoides

intestinalis • INVESTIGATION • rx barium • manometry • scinti 99m Tc • stools - fats, blood

LUNG INVOLVEMENT systemic scleroderma

- alveolitis

- interstic. Fibrosis /53% rx,

92% functional/

- pulmonary hypertension

- pleura (fluid,fibrosis..)

- spontaneous pneumothorax

- coincidence with pneumoconiosis

- carcinoma

- drug pneumonitis (CF, PNCA)

-aspiration pneumonia

INVESTIGATION- rx

- spirometry-restriction

- DLCO

- blood gas

- BAL

- HRCT

- scinti (67GA,99mTc-DTPA)

- biopsy

HEART INVOLVEMENT systemic scleroderma

(in 50% on non-invasive investigation)

- pericarditis – (autopsy 71%, symptomatic 7- 20%)

- focal fibrosis of heart muscle – (autopsy 89%)

- fibrosis of conduction system - arythmias /ECG 50%/

- myocarditis

- concentric intimal hypertrophy of coronary a.

INVESTIGATION:

ecg, echokardio, Holter, scintigraphy thalium 201, catetrization

KIDNEY INVOLVEMENT systemic scleroderma

mild : 15 – 45% pacients

- proteinuria 500mg/24h- hypertension 140/90- azotemia 9 mmol/1

serious : 3 – 10%

- chronic renal insufficiency - sklerodermic hypertensive renal crisis (8%)

ANTICENTROMERIC antibodies (in 12-46% SSc)

(Antigenem jsou centromerové nehistonové proteiny:

CENP-A 14-19kD, B 80, C 140, D 47)• HLA-DR 1, 4, 5, DRw8, DQB1• Milder, chronic course• no renal involvement• Less lung, heart and skin• May be serious pulmonary hypertension

a GIT• previous Raynaud phenomena • Role in chromosamal breaks ?

SCL-70 antibodies (in 18-83%)

antigen: DNA topoizomerase I (non-histone protein 70-100kD)

HLA-DR 2, 5, DQB1

• more serious, shorter course• more extensive skin involvement• more frequent lung, heart, renal involvement

Systemic sclerodermaclassification criteria (ARA)

MAIN: (one is sufficient)

proximal scleroderma

OTHER: ( 2 of 3)

sklerodactyly

Pitting scars on fingers

Bilateral interstitial lung fibrosis

(rx) Masi AT, et al., Arthritis Rheum, 1980, 23, 581

THERAPY- systemic scleroderma:

no causal drug - symptomatic, organ directed therapy

Vasoactive drugs: rheological (pentoxiphyllin), vasodilatation (calcium chanel blocators, prostaglandins), antihypertensives (ACE).

Antiinflammatory: NSA, glukokortikosteroids, imunosupresives (cyclophosphamide, azamune, methotrexate).

Antifibrotic: penicillamine, interferons, penicilin, extrakorporal phtopheresis.

General care of pacient: positive approach to disesase, stop smoking, warm enviroment, massage, exercise, prevention of řed trauma and cold.

Course and prognosis: limeted SSc 5 years survival from diagnosis 75-84%, diffuse SSc 34-50%.

Klasifikace sklerodermie:

lokalizovaná sklerodermie (morphea)

systémová sklerodermie

překryvné syndromy

nediferencovaná onemocnění pojiva

pseudosklerodermie

SYSTÉMOVÁ SKLERODERMIE

• je difuzní onemocnění pojiva a drobných cév

charakterizované vznikem fibrózy a vaskulární

obliterace postihující především kůži,

gastrointestinální trakt, plíce, srdce a ledviny.

Tuhá kůže je přitom jeho hlavním klinickým

příznakem, orgánové postižení nejdůležitějším

prognostickým ukazatelem.

Limitovaná systémová sklerodermie

(acrosclerosis)

Raynaudův fenomén trvající roky a desetiletí, tužší kůže aker (ruce, nohy, předloktí, bérce,

hlava, krk) – může i chybět pozdní výskyt plicní hypertenze (s či bez

intersticiální plicní fibrózy), kožní kalcifikace, teleangiektazie, GIT postižení,

kapilaroskopie - ektazie kapilár bez výrazné redukce počtu

anticentromerové protilátky

Štork J: Sklerodermie, Galén, 1996

Difúzní systémová sklerodermie

Raynaudův fenomén – trvá krátce do 1 roku

tuhá kůže - trupu, paží a aker, krepitace šlach orgány - časná a výrazná intersticiální plicní fibróza,

GIT, ev. ledvin, srdce kapilaroskopie - výrazné ektazie, redukce počtu,

avaskulární zóny anti Scl-70 protilátky

Štork J: Sklerodermie, Galén, 1996

Subacute LE – annular+anti-SSA/Ro and/or anti-SSB/La