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Vasculitis Board Review: 2019

Asso. Prof. Sumapa Chaiamnuay Rheumatic Disease Unit

Department of Medicine Phramongkutklao Hospital and College of Medicine

Vessel size (Chapel hill consensus 2012)

ARTHRITIS & RHEUMATISM Vol. 65, No. 1, Jan 2013, pp 1–11

Aorta and its branches and analogous veins • Subclavian artery,

carotid artery

Artery and vein that supply

organs (main visceral arteries) and initial branches

renal artery, mesenteric artery

Intraparenchymal arteries, arterioles,

venules and capillaries

2012 Revised international Chapel Hill consensus conference nomenclature

Primary vasculitis Diseases

Large Vessel Vasculitis (LVV) • Takayasu Arteritis (TAK)

• Giant Cell Arteritis (GCA)

Medium Vessel Vasculitis (MVV) • Polyarteritis Nodosa (PAN)

• Kawasaki Disease (KD)

Small Vessel Vasculitis (SVV)

ANCA-Associated Vasculitis

(AAV)

Immune Complex SVV

• Microscopic Polyangiitis (MPA)

• Granulomatosis with Polyangiitis (Wegener’s) (GPA)

• Eosinophilic Granulomatosis with Polyangiitis (Churg

Strauss) (EGPA)

• Anti-GBM Disease

• Cryoglobulinemic Vasculitis

• IgA Vasculitis (Henoch -Schönlein) (IgAV)

• Hypocomplementemic Urticarial Vasculitis (HUV)

Variable Vessel Vasculitis (VVV) • Behçet's Disease (BD)

• Cogan’s Syndrome (CS)

Single Organ Vasculitis (SOV) • Cutaneous leukocytoclastic angiitis

• Cutaneous arteritis

• Primary CNS vasculitis

• Isolated aortitis

Secondary vasculitis Definition Diseases

Vasculitis associated with systemic disease

Vasculitis that is associated with and may be secondary to a systemic disease

• Lupus vasculitis • Rheumatoid vasculitis • Sarcoid vasculitis

Vasculitis associated with probable etiology

Vasculitis that is associated with a probable specific etiology.

• Hepatitis C virus-associated cryoglobulinemic vasculitis

• Hepatitis B virus-associated vasculitis

• Syphilis-associated aortitis • Serum sickness-associated

immune complex vasculitis • Drug-associated immune complex

vasculitis • Drug-associated ANCA-associated

vasculitis • Cancer-associated vasculitis

Rasmussen N. The 2012 revised international Chapel Hill consensus conference nomenclature of the vasculitides. Ann Rheum Dis 2012;71 Suppl 3:16.

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Clinical approach

1. Suspected vasculitis

• Constitutional symptom

• Multiple organ involvement

• Sign& symptom

2. Exclude vasculitis mimics

3. secondary vasculitis

4. Defining primary systemic vasculitis 5. Principal of treatment

Approach to patient with suspected vasculitis

Presentation of patient with suspected vasculitis

Identify common clinical features

and assess extent of vasculitis

Systemic vasculitis

Vasculitis mimics

Primary vasculitis

Secondary vasculitis

Properly categorize to

a specific vasculitis syndrome

Signs and symptoms

Laboratory tests

Tissue biopsy

Angiography

Treat vasculitis

Treat underlying

disease and/or

vasculitis

Yes

Yes

No

No

Look for underlying diseases or

etiologies

Exclude vasculitis-like

syndrome

When to suspect vasculitis : clinical features

• Multisystem disease

• Unexplained constitutional signs and symptoms

• Skin lesions (palpable purpura)

• Ischemic vascular changes (gangrene, claudication, Raynaud’s phenomenon, livedo)

• Myalgia

• Arthralgia/arthritis

• Abdominal (intestinal

angina)

• Testicular pain

When to suspect vasculitis : clinical features

Glomerulonephritis

Mononeuritis multiplex

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Large 1. Stroke 2. Claudication 3. Asym pulse,BP 4. Bruit 5. PHT

Medium 1. Digital gangrene 2. Stroke 3. MNM 4. GI, Renal

microaneurysm

Small 1. DAH 2. Pulm infiltrate 3. RPGN 4. MNM 5. GI bleed

Capillaries

Vessel involved Symptoms and signs Cutaneous post-capillary venules Palpable purpura

Vesiculobullous lesions

Urticaria

Cutaneous extravascular necrotizing

granulomas

Splinter hemorrhages

Glomerular capillaries Haematuria

Red cell casts in urine

Proteinuria

Decline in renal function

Pulmonary capillaries Lung hemorrhage

Eyes Uveitis/episcleritis/scleritis

Small and medium sized arteries

Vessels Signs and symptoms Cutaneous arteries Necrotic lesions and ulcers, nail fold infarcts

Epineural arteries Mononeuritis multiplex

Mesenteric artery Abdominal pain

Gastrointestinal bleeding

and perforation

Branches of coeliac artery

Infarction of liver, spleen, or

Pancreas

Renal artery Renal infarction

Coronary arteries Myocardial infarction

Coronary

artery aneurysm

Ischaemic cardiomyopathy

Small pulmonary arteries Cavitating necrotic lung nodule

Small arteries in ear, nose and

Throat

Nasal crusting

Epistaxis

Chronic sinusitis

Deafness

Sub-glottic stenosis

Vessels Sign and symptoms Extracranial branches of carotid

Artery

Temporal headache (temporal artery)

Blindness (ophthalmic artery)

Jaw claudication (vessels supplying muscles of

mastication)

Thoracic aorta and its branches Limb claudication

Absent pulses

Unequal blood pressure

Bruits

Thoracic aortic aneurysms

Bruits

Renovascular hypertension

Aorta and its branches (large vessels)

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UV, PP (HSP,CLA)

Venule/cap/arterioles Arterioles/small artery Small-artery

skin ulcer (ANCA) LVR, panniculitis, EN like, nodule, (PAN)

Clinical approach

1. Suspected vasculitis

• Constitutional symptom

• Multiple organ involvement

• Sign& symptom

2. Exclude vasculitis mimics

3. secondary vasculitis

4. Defining primary systemic vasculitis 5. Principal of treatment

Vasculitis: exclude mimics

• Emboli – Crystal

– Endocarditis

• Thrombosis – Anti-phospholipid syndrome

– Thrombocytopenic purpura

• Infection – Gonococcal

– Sepsis

Vasculitis Mimics (1) Diseases

Infectious diseases Bacterial endocarditis

Coccidioidomycosis

Disseminated gonococcal infection

Lyme disease

Rocky Mountain spotted fever

Syphilis

Whipple's disease

Drug-related Amphetamines

Arsenic

Cocaine

Ergot alkaloids

Methysergide

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Vasculitis Mimics (2) Diseases

Coagulopathy / microangiopathy Antiphospholipid syndrome

Cryofibrinogenemia

Thrombotic thrombocytopenic purpura

Neoplasms Atrial myxoma

Paraneoplastic syndrome

Miscellaneous Amyloidosis

Atherosclerosis, calciphylaxis

Cholesterol crystal emboli

Coarctation of aorta

Fibromuscular dysplasia

Migraine

Neurofibromatosis

Sarcoidosis

Sickle cell disease

Clinical approach

1. Suspected vasculitis

• Constitutional symptom

• Multiple organ involvement

• Sign& symptom

2. Exclude vasculitis mimics

3. secondary vasculitis

4. Defining primary systemic vasculitis 5. Principal of treatment

Secondary causes of vasculitis 1. Autoimmune diseases

Systemic lupus erythematosus

Sjögren's syndrome

Behçet disease

Rheumatoid vasculitis

Ulcerative colitis

Crohn's disease

Sarcoidosis

2. Infectious diseases Viruses (HIV, CMV)

Bacteria (spirochaetales, mycobacteria, streptococci, tropheryma

whippeli)

Parasites (e.g. Ascaris etc.)

Fungi (e.g. Aspergillus)

3. Neoplasia Non‐Hodgkin lymphoma

Myeloproliferative diseases

Solid tumours

Atrial myxomas

4. Drug abuse (intoxication) Opioids (cocaine, morphine)

5. Drug‐induced Antihypertensive (hydralazine)

Antithyroid drugs (propylthiouracil, methimazole, carbamizole)

Antibiotics (azithromycin, minocycline)

Antifibrotic (penicillamine)

Leukotriene receptor antagonist (zafirlukast, montelukast, pranlukast)

Infection mimics vasculitis

Vessel size Organism

Large Bacterial

Spirochete

Fungus

Staphylococcus, Salmonella, mycobacteria, Streptococcus

Treponema pallidum

Coccidiomycosis

Medium Bacteria

Virus

Group A Streptoccus, mycobacteria

HBV, HCV, HIV, parvovirus B19

Small and

medium

Bacteria

Virus

Streptococcus

HBV, HCV, HIV, CMV

Small

Bacteria

Virus

Staphylococcus, Salmonella, mycobacteria,

Streptococcus, Yersinia, Neisseria, Rickettsia

HIV, CMV, herpes zoster, parvovirus B19, HBV, HCV

Somer T, et al. Vasculitides associated with infections, immunization, and antimicrobial drugs. Clin Infect Dis 1995;20:1010-36.

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Secondary vasculitis/mimicker Vessel size Secondary vasculitis Mimicker

Large Syphilis ,TB, RA FMD, radiation fibrosis, NF, coarctation of aorta, APS

Medium RA, SLE, SS, drug Cholesterol emboli, atrial myxoma, thromboembolic disease, ergotism, APS,MPD, ED IV

Small SLE, SS, RA, DM, drug GC, meningococemia, pseudomonase, HIV,HBV,HCV,CMV, EBV Lymphomatoid granulomatosis

IE, mycotic aneurysm, cholesterol emboli, APS, TTP calciphylaxis

Drug : penicillin, sulfonamide, pill, allopurinol, PTU, Hydralazine

Clinical approach

1. Suspected vasculitis

• Constitutional symptom

• Multiple organ involvement

• Sign& symptom

2. Exclude vasculitis mimics

3. secondary vasculitis

4. Defining primary systemic vasculitis 5. Principal of treatment

Common symptoms of vasculitis Small vessels

Eosinophilic granulomatosis with

polyangiitis

Allergic rhinitis, asthma, eosinophilia, pulmonary infiltrates,

coronary arteritis, intestinal ischemia

Cryoglobulinemic vasculitis Arthritis, Raynaud's phenomenon, glomerulonephritis,

palpable purpura

Cutaneous leukocytoclastic

vasculitis

Palpable purpura, cutaneous infarcts, necrotic papules,

urticarial

Henoch-Schönlein purpura Palpable purpura, arthritis, glomerulonephritis, intestinal

ischemia

Microscopic polyangiitis Palpable purpura, pulmonary hemorrhage,

glomerulonephritis

Granulomatosis with polyangiitis Recurrent epistaxis or sinusitis, pulmonary infiltrates and/or

nodules, glomerulonephritis, ocular involvement

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Medium vessels

Polyarteritis nodosa Fever, weight loss, hypertension, mononeuritis multiplex, intestinal

ischemia, renal ischemia, testicular pain

Kawasaki disease Fever, conjunctivitis, lymphadenopathy, desquamating rash, mucositis,

arthritis, coronary artery aneurysms

Large vessels

Giant cellarteritis Headache, polymyalgia rheumatica, jaw or tongue claudication, scalp

tenderness, fever, vision disturbances

Takayasu's arteritis Extremity claudication, hypertension, constitutional symptoms, renal

ischemia

Mixed sized vessels

Behcet Disease Recurrent uro-genital ulceration, erythema nodosum, folliculitis, pan-

uveitis

Cogan syndrome Interstitial keratitis, tinnitus, deafness, aortitis

Common symptoms of vasculitis Investigation

• To confirm diagnosis

– Serology

– Pathology

• To assess extent of disease involvement

– General laboratory

– Radiographic assessment

Treatment principles: vasculitis • Glucocorticoids alone

– Limited form of GPA, EGPA

• Glucocorticoids and cytotoxic drugs

– MTX/AZA: limited form of GPA, Takayasu, Giant cell arteritis

– Cyclophosphamide: ANCA associated vasculitis, PAN

• Antiviral therapy if indicated

– HCV associated cryoglobulinemic vasculitis

• Plasma exchange and IVIG + aspirin

– Kawasaki diseases

• Surgical correction and angioplasty

– Takayasu arteritis

Quiz!!

29

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Q62 MKSAP18

A 26 years old woman is evaluated for a 4 weeks history of progressive dyspnea on exertion. She has malaise myalgia and arms ache with activity for the past 6 months.

No rash, jaw claudication, GI or neuro symptoms

PE: Rt arm 120/60 Lt arm 95/50

↓Radial pulse Lt arm

Heart: grade 2/6 diastolic murmur at LPSB

Lab: Hct 30% WBC 11,000 Plt 439k ESR 90 Cr 1.1

What is the following is the most likely diagnosis?

A. Takayasu arteritis

B. Polyarteritis nodosa

C. Giant cell arteritis

D. Kawasaki disease

MKSAP18 Q77

A 28 years old woman presented with 3 weeks history of progressive

worsening pain in the left arm which was worsen with the use of it.

Fatigue, malaise, low-grade fever, inability to walk long distance.

BT 38.1 BP right 166/95 left 115/60 PR 72/min

↓left radial and both dorsalis pedis pulses

+ abdominal bruit

No rash

LAB:

ESR 115 Cr 1.4 mg/dL Hct 32% WBC 10,500 PMK 70% Plt 510k

Which of the following is the most appropriate next diagnostic test?

A. Anti-phospholipid antibodies B. Anti-myeloperoxidase antibody

C. Temporal artery biopsy D. Aortic arteriography

Takayasu arteritis

• Japan, Asia > Western countries

• Female > male , 8:1

• Japan : HLA-B52, HLA-Bw52 allele, IL-12B

• Onset : young age

Investigation:

• CBC : inflammatory response

• Increase in acute phase reactants (ESR and/or CRP) : 70%

Imaging

– Aneurysm/ rupture

– Stenosis

– Thickening of vessel wall

Biopsy: granulomatous aortitis

Vaideeswar P, Deshpande JR. Pathology of Takayasu arteritis: A brief review. Ann Pediatr Card 2013;6:52-8

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E17 Q17 GCA

An 82 years old woman is evaluated for a 2-wk history of left-sided headaches with pain on chewing, shoulders and hip achiness.

U/D: HTN, dyslipid

PE: BP 130/80 BT 38.1c

Tenderness and swelling over left temporal area

Limit ROM of shoulders and hips due to pain

Lab: CBC, cr, LFT -normal. ESR 85

What is the most helpful investigation to establish diagnosis?

A. Temporal artery biopsy B. Lumbar puncture C. MRI brain with gadolinium D. hs-CRP E. Rheumatoid factor

Clinical manifestations of GCA

• Onset: gradual >> abrupt

• Systemic symptoms

– Fever (50%), usually low grade

– Fatigue

– Weight loss

• Headache (60-70%): new onset

– Pain over the temporal areas (may be frontal, occipital or generalise)

– Variable course

– Tender temporal or occipital arteries (30%)

• Jaw claudication (50%)

– Most specific sign of GCA

– Occur with repeated swallowing and in the tongue with eating

Clinical manifestations of GCA • Polymyalgia rheumatica

– Aching and morning stiffness in the shoulder and hip girdles, in the neck, and in the torso.

– PMR occurs in about 40 – 50% of GCA patients

– GCA occurs in about 15 % of PMR patients

• Joint pain and arthritis

• Arm claudication 3 – 15%

– Subclavian and axillary arteries involvement

– Gradual tapering

• Central nervous system involvement

– Documented involvement of intracranial vessels in GCA is rare

– When transient ischemic attacks, vertigo, hearing loss, and stroke occur in GCA, they are most often due to vertebral artery involvement or to internal carotid lesions that are extradural in location

Polymyalgia rheumatica

• Age > 50 years

• Constitutional symptoms

• Aching and stiffness of shoulder, axial musculature and tendinous attachments, often bilaterally

• Elevated ESR/CRP

• 10-15% have positive of temporal arteries biopsy

• PMR itself does not appear to cause vision loss

• Responds to low doses of GC (pred 20-30 mg/day)

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ACR criteria for diagnosis of GCA

Need 3 / 5 items (sen 94 spec 91) 1. Age greater than or equal to 50 years at time of disease onset 2. Localized headache of new onset 3. Tenderness or decreased pulse of the temporal artery 4. Erythrocyte sedimentation rate (ESR) greater than 50 mm/hour 5. Biopsy revealing a necrotizing arteritis with a predominance of mononuclear cells or a granulomatous process with multinucleated giant cells

Hunder et al, 1990

“Halo sign” Ultrasound doppler of temoporal artery

Lymphocytic infiltration of the artery wall

Multinucleated giant cells

Large vessel vasculitis Giant cell VS Takayasu’s

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What is the most appropriate immediate next step management?

A. Initiate prednisolone 15 mg/day

B. Initiate prednisolone 60 mg/day

C. Obtain MRI brain

D. Obtain temporal artery biopsy

E. Lumbar puncture

What is the most appropriate treatment?

A. Prednisolone 15 mg/day

B. Prednisolone 60 mg/day

C. Pulse methylprednisolone 1 gm iv x 3 day

D. Aspirin 81 mg/day

E. B + D

Treatment of GCA • Induction

– High dose steroid

• Pred 1 mkd (avoid alternate dosing)

• Pulse methylprednisolone 500-1000 mg iv x 3 d for patients with visual loss or a history of amaurosis fugax

– Give until complete resolution of symptoms and inflammatory markers

• Maintenance

– ↓ 10 mg of pred q 2 wk to 20 mg then

– ↓2.5 mg q 2-4 wk to 10 mg then

– ↓1 mg q 1-2 mo

• Early methotrexate or other alternative immunosuppressant

therapy following a relapse

• Add aspirin + bone protection + GI protection

Ponte C 2015 Current management of giant cell arteritis

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A 69 years old woman with severe headache and right eye blindness

CC: Sudden visual loss in her left eye 1 hour

HPI:

She had several episodes of transient loss of vision in her left eye in the previous weeks which resolved spontaneously. Eye examination as normal.

ROS: She had temporal headaches and jaw claudication for a few weeks. She did not show weight loss or systemic fever

PE:

Left scalp tenderness with nodular and pulseless temporal artery was noted.

Visual acuity was no light perception

Fundoscopy: a pale and edematous optic disk and ischemia of the papillomacular bundle area which was also noticed on fluorescein angiography

What is the most appropriate treatment?

A. Prednisolone 15 mg/day

B. Prednisolone 60 mg/day

C. Pulse methylprednisolone 1 gm iv x 3 day

D. Aspirin 81 mg/day

E. C + D

A 41 years old man with acute severe abdominal pain

The pain was excruciating and sudden in onset, originating in his right lower quadrant and radiating to his right groin and flank

Two weeks PTA:

A less severe episode of similar pain but in his left lower quadrant, with radiation to his left flank, which subsequently resolved

Fatigue for several months preceding these episodes

BP 180/100

Abdomen: soft, generalized tender, no guarding or rebound tenderness, normal BS, bilateral CVA tenderness

Laboratory test:

WBC 14,280 78% PMN. Hb12.6 g/dL, plt 215,000

BUN 8 mg/dL, Cr 1.5 mg/dL

CRP 181 mg/dL (normal < 3)

PT, INR, PTT, electrolyte, LFT, amylase, lipase-normal

UA: 1+ protein, rbc 10-20, no cast

Echocardiogram: normal

N Engl J Med 2014;370:70-5

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CT abdomen: infarcts in both kidneys, with focal volume loss in the left kidney that was suggestive of scarring

N Engl J Med 2014;370:70-5

Problem lists

1. HTN

2. Bilateral renal infarcts

3. Fatigue

What is the most likely diagnosis?

Echocardiogram: normal Hypercoagulable: neg

N Engl J Med 2014;370:70-5

↑CRP vasculitis

Drug screening: neg

A. Atrial myxoma

B. Antiphospholipid syndrome with renal vein thrombosis

C. Fibromuscular dysplasia

D. Polyarteritis nodosa

E. Ergot induced vasospasm

Vasculitis • Renal infarcts small VS medium vessel

• Urine: no sediments, HTN renal artery medium vessel

• ANCA, C3, C4 normal

• Angiograms

Left Renal angiogram Superior mesenteric artery angiogram

A 52 years old man is evaluated for fever, malaise, arthralgia, left foot drop,

abdominal pain that is worse after eating, weight loss 2 kgs over 2 mo.

PE: BT 38.4c BP 154/92

Sinus and lung: normal

Abdominal bruit +

Testicles are tender to palpitation.

Joints are tender, but no swelling.

Weakness of left foot dorsiflexion.

Lab: ESR 72 C3, C4-normal Cr 2.2

UA: rbc 3-5, no proteinuria, no red cell cast

ANCA-negative, HBsAg +

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What is the most likely diagnosis?

A. Granulomatosis with polyangiitis

B. Microscopic polyangiitis

C. Polyarteritis nodosa

D. Henoch-Schonlein purpura

Diagnosis: polyarteritis nodosa

• Systemic necrotizing vasculitis

• Affects medium-sized muscular arteries

• Occasional involvement of small muscular

arteries

• NOT typically associated with ANCA

Pathology

• Transmural necrotizing inflammation with fibrinoid necrosis

• Lesions are segmental and may involve partial circumference only

• Weakening of the arterial wall aneurysmal dilatation and localized rupture

• Impaired perfusion ulceration, infarct, or ischemic atrophy

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Clinical manifestations: PAN

Constitutional symptoms • Fever

• Malaise

• myalgia

• Weight loss, Anorexia

Musculoskeletal • Arthralgia

• Episodic, nondeforming, asymmetrical polyarthritis

• Predominant: large joints , especially the lower extremities

• Myalgia

Clinical manifestations: PAN

Cutaneous manifestations • Livedo reticularis, skin ulcers, bullous or vesicular

eruption, subcutaneous nodule

• Palpable petechial or purpuric lesions

• Frequent sites : fingers, ankles around the malleoli, and pretibial area, often marked over the lower extremities

• Digital gangrene

• Splinter hemorrhage

Clinical manifestations: PAN Palpable purpura Livedo reticularis

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Subcutaneous nodules

Reddish, painful, tender, subcutaneous nodule

Nervous system (Peripheral disease) • Mononeuritis multiplex :frequently affected

peroneal, median, ulnar, sural nerve.

• Distal sensorimotor polyneuropathy

• Cranial nerve palsy less common

• Noted early in 50-70% of patients

• Direct result of occlusion of the vasa vasorum

Clinical manifestations: PAN

Polyarteritis nodosa: wrist drop

This neuropathy is due to ischemia of the vasa nervorum.

Nervous system (Central disease) • Rare

• occur late

• Ischemic stroke, intracerebral hemorrhage small vessel strokes

• Diffuse encephalopathy

• Seizure

Clinical manifestations: PAN

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Renal involvement • Vascular nephropathy common manifestation

• HTN renal artery involvement

• Renal failure Multiple infarcts

• Intrarenal, perirenal, or retroperitoneal hemorrhage rupture of microaneurysm

• Urinalysis :normal or near normal

• No glomerulonephritis

Clinical manifestations: PAN Clinical manifestations

Gastrointestinal involvement • Abdominal pain :mesenteric arteritis

– dull and constant, worse by eating, rapid wt loss

• GI bleeding and bowel perforation • Malabsorption , pancreatitis ,or vasculitis of appendix or gall

bladder

• Liver frequently involved at autopsy; but clinical involvement uncommon

: infarct or hematoma

: hepatomegaly with or without jaundice

Clinical manifestations: PAN

Genitourinary involvement

• Testicular pain : Orchitis

• Prostatitis

Cardiac involvement

• Coronary artery involvement myocardial ischemia

• Heart failure

• Pericarditis

Clinical manifestations Clinical manifestations: PAN * PAN key points

• General confinement to medium sized vessels

• Exclusive involvement of arteries, with sparing of veins except by contiguous spread

• Lack of granuloma formation

• Tendency to form microaneurysm

• Absence of lung involvement

• Absence of renal glomerular involvement

• Absence of associated autoantibodies(ANCA, anti GBM)

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ACR 1990 criteria of PAN (3/10)

Criteria Remarks

1.Unexplained wt. loss > 4 kg at the onset

2.Livedo reticularis Mottled reticulate pattern

3.Testicular pain Exclude infection and trauma

4.Myalgia, weakness or leg tenderness Exclude shoulder and hip girdle

5.Mono-polyneuropathy

6.DBP > 90 mmHg

7.Elevated BUN or Cr BUN > 40 mg/dl or Cr>1.5 mg/dl (exclude dehydration or postrenal)

8.Hepatitis B virus HBs Ag+ or anti-HBs +

9.Arteriographic abnormality Aneurysms or occlusion at visceral a.

10. Abnormality of small or medium sized a. PMN or Mononuclear cell infiltrate at the vessel wall

Treatment

• Non-hepatitis associated PAN

• PAN with hepatitis B infection

Clin Exp Rheumatol 2011; 29 (Suppl. 64):S110-S116.

FFS ≥ 1

Prognosis Revisited 2009 Five-factor scores

Presence of each = +1 point

1. Age >65 years

2. Cardiac symptoms

3. Gastrointestinal involvement

4. Renal insufficiency (stabilized peak creatinine ≥ 1.7 mg/dL)

Presence of each = -1 point

1. Ear, nose, and throat (ENT) symptoms

• FFS : 0,1,>2

• 5 yr mortality rate: 9, 21, 40%

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MKSAP18 Q/2

A 55 years old man previously healthy is hospitalized for acute

respiratory failure. He noted leg swelling and non-healing skin ulcers

and joint pain in wrists, MCPs and PIPs 4 weeks ago.

+ tobacco 20 pack-year

PE: BP 150/95 BT 37.2c on mechanical ventilator

CXR: diffuse bilateral infiltrates

Skin bx: non-granulomatous, small vss vasculitis, no immune cpx

deposits by immune fluorescence.

Which of the following is the most likely diagnosis?

A. Systemic lupus erythematosus

B. Microscopic polyangiitis

C. Granulomatous polyangiitis

D. Polyarteritis nodosa

E. Thromboangiitis obliterans

Which of the following is likely to found in this patient?

A. Anti-myeloperoxidase antibody

B. Anti-PR3 antibody

C. Anti-nuclear antibody

D. Low C3 C4 levels

E. Abnormal angiogram: cockscrew collaterol vss.

MKSAP17 Q27

A 32 years old woman admitted for 2 weeks of progressive SOB and 48 hours of hemoptysis.

She also noted rash and weakness of left foot.

Previously healthy except for mild asthma (as needed albuterol MDI)

PE: BT 37.5c RR 26/min BP 146/87

Lab:

ESR 98 Hct 26% WBC 16,000 eo 42% Plt 450k Cr 0.8

ANCA and ANA: neg

UA: negative

What is the most likely diagnosis?

A. Microscopic polyangiitis

B. Eosinophilic granulomatosis with polyangiitis

C. Granulomatosis with polyangiitis

D. Goodpasture's syndrome

E. Systemic lupus erythematosus

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MKSAP 17 Q31

A 65 years old woman referred from her opthalmologist for refractory right eye scleritis evaluation. She also noted weight loss, progressive fatigue and sinus congestion for 5 weeks.

PE: Vital sign: normal

Rt eye: scleral injection.

Mild redness and crusting of nasal mucosa.

PE:

ESR 55 Hct 35% WBC 5200 Plt 550k

UA: prot 3+, rbc cast-present

Cr 0.8 LFT: normal

What is the most likely diagnosis?

A. Behcet syndrome

B. Granulomatosis with polyangiitis

C. Sarcoidosis

D. Systemic lupus erythematosus

Scleritis

ANCA-associated vasculitis (AAV)

• Granulomatosis with polyangiitis (GPA)

(Wegener’s granulomatosis)

• Microscopic polyangiitis (MPA)

• Eosinophilic granulomatosis with

polyangiitis (EGPA: Churg-Strauss

syndrome)

Clinical features Granulomatous polyangiitis

• Inflammatory destructive lesions often affects the eyes, ears, nose, trachea, bronchi and lungs.

• Pulmonary infiltrates and/or nodules

• ENT: sinus, trachea, recurrent epistaxis, mucosal ulcerations, nasal septal perforation or nasal deformity

• Eye disease: non specific

– Proptosis, loss of conjugate gaze and diplopia

– Retro-orbital pseudotumor, loss of vision due to optic nerve ischemia

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Clinical features Granulomatous polyangiitis

• Pauci-immune glomerulonephritis

• Musculoskeletal features are common (arthralgia not frank arthritis)

• 25 % neuro involvement: peripheral or CNS

Biopsy

– Lung : highest diagnostic yield

– Upper airway tissue : may not show vasculitis

– Renal : pauci-immune glomerulonephritis

•Necrotizing

granulomanous vasculitis

•Neutrophilic infiltrates

Kidney

• Glomerulonephritis

• NO GRANULOMA

• PAUCI-IMMUNE = NO IMMUNE COMPLEX DEPOSITION

– Acute renal failure, RPGN

– Active urinary sediment

Definition of disease stages according to EULAR

Rheum Dis Clin N Am 36 (2010) 507–526

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MICROSCOPIC POLYANGIITIS

Clinical manifestation : – Common cause of pulmonary-renal

syndrome

– Constitutional symptom

– Pulmonary : Cough , Dyspnea, Pulmonary hemorrhage

– Kidney : Glomerulonephritis

– Joint : Arthalgia , Arthritis

– Skin : rash, palpable purpura, livido reticularis

– Neuro: mononeuritis multiplex

Microscopic Polyangiitis

• Age of onset 40-50 yrs

• Necrotizing vasculitis

• No granuloma !!!!

• Over 80% positive for ANCA, mostly P-ANCA

• Anti-MPO antibodies

• P-ANCA, anti MPO

• Frequent pulmonary and renal inv

• Negative Hep B serology

DDx from WG

DDx from PAN

Eosinophilic granulomatosis with polyangiitis (EGPA)

• M = F , mean age 50 years

• Asthma (esp. late onset, refractory)

• Eosinophilia > 10%

• Mono/polyneuropathy

• Migratory/transient pulmonary opacities on radiography

• Paranasal abnormality: sinusitis, nasal polyp, rhinitis

• Biopsy containing a blood vessel show eosinophils in extravascular area

• Skin : purpura, nodule, urticaria, ulcer

• ANCA : pANCA > cANCA

Clinical features: EGPA

• Prodromal phase – Characterized by atopic disease, allergic rhinitis,

and asthma

• Eosinophilic phase – eosinophilia and eosinophilic infiltration of multiple

organs, esp the lung and gastrointestinal tract

• Vasculitic phase

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Churg-Strauss syndrome

• Compared with WG and MPA

– CSS involves much less frequent and less severe renal disease

– more frequent neuropathy and cardiac disease

A 52 years old man is admitted for several episodes of hemoptysis for 2 days.

3 weeks ago: myalgia, arthralgia, low-grade fever, nasal fullness, ↓hearing in left ear, rash both legs and weakness of right hand

PE: 150/90 BT 38c – Tender bilateral maxillary sinus

– Chest: diffuse rhonchi

– Palpable purpura

– Right wrist drop

CBC: Hct 35% WBC 12,300 PMN 70% L23% eo2% Plt 580K

UA: prot 3+, RBC cast +

Which of the following is most likely to establish the diagnosis?

A. Anti-ds-DNA antibody B. Anti-myeloperoxidase antibody

C. Anti-proteinase 3 antibody D. Serum cryoglobuline

Cytoplasmic ANCA

Diffuse granular

cytoplasmic staining

pattern

Anti-preteinase-3

Perinuclear ANCA

Perinuclear or nuclear

staining pattern

Anti-myeloperoxidase

0

20

40

60

80

100

WG MPA idiopathic

RPGN

CSS

p-ANCA

c-ANCA

Frequency of ANCA reactivity

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ANCA in other diseases

• Non-specific esp P-ANCA

• Autoimmune disease

• Systemic vasculitis : HSP, Kawasaki’s disease

• Other rheumatic disease: RA, SLE, Sjögren syndrome

• Inflammatory bowel disease

• Infections

• Endocarditis, respiratory tract infection, cystic fibrosis, chromomycosis, HIV, amoebiasis

• Drugs

• Propylthiouracil, hydralazine, minocycline

Sign and symptoms GPA (%) MPA (%) EGPA (%)

Upper airways disease 95 - 50-60

Pulmonary disease

Asthma - - 90-100

Radiographic

nodule/infiltrates

70-85 15-70 40-70

Alveolar hemorrhage 5-15 10-50 < 5

Glomerulonephritis 70-80 75-90 10-40

Gastrointestinal system < 5 30 30-50

Nervous system

Peripheral 40-50 60-70 70-80

Central 5-10 10-15 5-30

Cardiac 10-25 10-15 10-40

Ocular 50-60 < 5 < 5

Arthralgia/arthritis 60-70 40-60 40-50

Genitourinary system < 2 < 5 < 2

Skin 40-50 50-65 50-55

ANCA

PR3-cANCA 75-90 10-50 3-35

MPO-pANCA 5-20 50-80 2-50

Pathology Granulomatous

necrotizing vasculitis

Necrotizing vasculitis

without granuloma

Granulomatous

necrotizing vasculitis

with abundant of

eosinophils J ALLERGY CLIN IMMUNOL Feb 2010

Treatment ANCA-associated vasculitis

Induction

• Limited form: methotrexate + pred 1 mkd

• Generalised form:

– Pulse cyclophosphamide iv monthly

– Oral daily cyclophosphomide

– Rituximab 375 mg/m2 x 4 doses

– Pulse methylpred 500 -1000 mg iv x 3 days

– Prednisolone 1 mkd

• Severe generalised form: add plasmapheresis in

– DAH

– Severe renal disease

– Concurrent anti-GBM disease

• PCP prophylaxis: trimethoprim-sulfamethoxazole

– 1 single strength (80 mg/400 mg) daily

– 1 double strength (160 mg/800 mg) 3 times per week

Oral: more leukopenia, less relapse

RTX=CYC Only more remission in relapse pt

ANCA vasculitis. EULAR 2016 guideline

Maintenance after achieved remission: 24 months

– Glucocorticoid can be discontinued

– Methotrexate = Azathioprine (WEGENT)

– Methotrexate 0.3 mkw 20-25 mkw (NORAM)

– Azathioprine 2 mkd (CYCAZAREM)

– Rituximab* 500 mg D1, 14 at months 6, 12, and 18 (better than aza)

Treatment ANCA-associated vasculitis

ANCA vasculitis. EULAR 2016 guideline

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A 39 year old woman is

evaluated for a lower

extremities rash and joint

pain for 8 weeks. She takes

no medication.

PE: BT 37.4c

• Wrist drop on the right

• Joint tenderness with mild

synovitis at MCPs, PIPs,

wrists

• Rash: as shown

Small vascular infarction on the ears Scatter palpable purpuric lesions

Lab: ESR 66 C3: normal, C4:↓, Cr 2.1 RF +, anti-HCV + UA: prot 3+, RBC 5-10, RBC cast +

Which of the following is most likely to establish diagnosis?

A. Anti-CCP antibodies

B. Anti-dsDNA antibody

C. Cryoglobulin

D. Anti-myeloperoxidase antibody

Clinical manifestations of HCV associated mixed cryoglobulinemia

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Investigation Cryoglobunemic vasculitis

• Low early complement C1, C2, C4 but normal C3

– Often seen in mixed cryoglobulinemia

– Not correlate with disease activity

• RF is detected in 2/3 of patients (50% having levels of 3-4x UNL)

– Negative anti-CCP antibody

• Other nonspecific features:↑ESR, ↑CRP, and anemia of inflammation

– ↑↑ESR in type I cryoglobulinemia because of the presence of large concentrations of paraproteins

– CBC

• Pseudothrombocytosis

• Formation of erythrocyte rouleaux

How to detect cryoglobulin??

Warm collecting tube at 37c

No anti-coagulant

Draw 10 cc of blood

Blood transport at 37C

Blood clot at 37C > 1 hr

Centrifuge at 2500 RPM for 10 mins

Incubate serum at 4C for 3-7 days

Centrifuged to measure at 4C

Washing

Rewarm at 37C for resolubility

Characterization of immuno-precipitate by immunofixation

Collected, stored, and centrifuged at 37 ⁰C

Lancet 2012

Arthralgia/arthritis Non-inflammatory musculoskeletal pain General features (malaise, fever)

MKSAP17 Q40

A 32 years old woman presented with new rash on both legs for 4 days. She has had cystitis and was given a 7 day-plan of trimethoprim-sulfamethoxazole.

PMH: Hashimoto thyroiditis

Med: levothyroxine

Which of the following is the most appropriate next step in management?

A. Discontinue trimethoprim-sulfamethoxazole

B. Discontinue levothyroxine

C. Initiate prednisolone

D. Measure anti-histone antibody

E. Obtain skin biopsy

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Hypersensitivity vasculitis

• Hypersensitivity reaction to antigens ex medication or infection

• Resolve after removing offending agents

• Immune complex deposition

• Small vss: capillaries, venules, arterioles

E18 Q65

A 35 years old woman presented with severe abdominal pain, palpable purpura rash both legs, arthralgia and myalgia for 2 days.

Lab: CBC, UA, Cr, LFT: normal

ANA, ANCA: neg

Stool exam: occult blood +

CT abdomen: short segment of small bowel thickening and edema.

Which of the following is the most appropriate test to establish the diagnosis?

A. Kidney biopsy

B. Mesenteric angiography

C. Skin biopsy with immunogfluoresence

D. Complement level

IgA vasculitis (IgAV) Henoch-Scholein Purpura

• Common in children

• Occur after URI 10-14 days

– 90 % purpura

– 75 % arthralgias

– 60 % colicky abdominal pain

– 50 % renal, < ESRD 5%

• Patho: vascular IgA-dominant immune complexes

• Rx: supportive, unless nephritis is present

1. Allergic rhinitis, asthma, eosinophilia, pulmonary infiltrates, coronary arteritis, intestinal ischemia, mononeuritis multiplex

2. Arthritis, Raynaud's phenomenon, glomerulonephritis, palpable purpura, mononeuritis multiplex ,↓C3, C4

3. Recurrent epistaxis or sinusitis, pulmonary infiltrates and/or nodules, glomerulonephritis, ocular involvement, granulomatous necrotizing vasculitis

QUIZ

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4. Fever, weight loss, hypertension, mononeuritis multiplex, intestinal ischemia, renal ischemia, testicular pain, ANCA-negative

5. Headache, polymyalgia rheumatica, jaw or tongue claudication, scalp tenderness, fever, vision disturbances

6. Extremity claudication, hypertension in the young, constitutional symptoms, renal ischemia

QUIZ

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