Lectures Vasculitis 2zi2y

x Carol A. Langford, MD, MHS Director, Center for Vasculitis Care and Research Department of Rheumatic and Immunologic Diseases Cleveland Clinic Foundation

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Lecture Rationale and Objectives Lecture Rationale: £ The vasculitic diseases are uncommon entities that often present first to internists and family medicine physicians £ Suspicion is essential because certain forms of vasculitis are organ and life threatening £ Recognition and early diagnosis of vasculitis plays an important role in preventing morbidity and even mortality

Lecture Objectives: £ Identify the spectrum of the vasculitic diseases £ Recognize the clinical manifestations of vasculitis £ Develop a diagnostic approach to vasculitis

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Vasculitis = Inflammation of the Blood Vessel

Blood vessel damage Thickening of vessel wall Luminal narrowing or occlusion

Tissue or organ ischemia

Attenuation of vessel wall

Vessel wall thinning Aneurysm formation or Disruption of the vessel wall with hemorrhage into tissue

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Vasculitis: Histological and Clinical Correlation

Courtesy of Carol A. Langford

Disruption of the vessel wall with red blood cell extravasation into tissue

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Palpable Purpura

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Vasculitis Is Not One Specific Disease Blood vessel inflammation can be seen in a variety of settings

Primary Vasculitides Unique disease entities without a currently identified underlying cause where vasculitis forms the pathological basis of tissue injury Giant cell arteritis Takayasu¶s arteritis Kawasaki disease Polyarteritis nodosa Wegener¶s granulomatosis Microscopic polyangiitis Churg--Strauss syndrome Churg Henoch--Sch Henoch Schö önlein purpura

Secondary Vasculitides Vasculitis occurring secondary to an underlying disease or exposure

Medications Infection Malignancy Transplant Cryoglobulinemia Connective tissue disease (Rheumatoid arthritis, SLE Inflammatory myositis)

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How Do Forms of Primary Vasculitis Differ? Epidemiology:

Age, sex, ethnicity, frequency

Clinical Manifestations:

Symptoms, signs Patterns of organ involvement

Diagnosis:

Clinical and laboratory features Biopsy (granulomas, eosinophils) Arteriography

Treatment and Outcome:

ive care and close observation Prednisone Cytotoxic therapy (cyclophosphamide)

Predominant vessel size:

Large, medium, small vessel

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Aorta

Capillary

Large Vessel

Medium Vessel

Giant cell arteritis Takayasu¶s arteritis

Polyarteritis nodosa Kawasaki disease

Vessel size plays a role in: Symptoms and signs Methods of diagnostic evaluation

Vein

Small Vessel Wegener¶s granulomatosis Microscopic polyangiitis Churg-Strauss syndrome Henoch-Schönlein purpura Isolated cutaneous vasculitis

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Large Vessel Vasculitis Aorta, main branches of the aorta, pulmonary arteries

Courtesy of Carol A. Langford Courtesy of Carol A. Langford

Aortic aneurysm

Subclavian artery stenosis | Copyright © The McGraw-Hill Companies. All rights reserved.

Large Vessel Vasculitis: Giant Cell Arteritis

(Historically also called temporal arteritis) £ The most common form of primary systemic vasculitis £ Granulomatous large vessel vasculitis £ Occurs in people over the age of 50 (mean age 74) £ 2:1 women:men £ Preferentially involves extracranial branches of the carotid artery

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Giant Cell Arteritis Clinical Features: £ Headache, Scalp tenderness, jaw / tongue claudication £ Visual loss due to optic nerve ischemia from arteritis of ocular vessels £ Fever, fatigue, weight loss £ Polymyalgia rheumatica: pain along shoulder and hip girdle £ Extremity claudication £ Aortic aneurysm

27% of patients with GCA will have non--cranial large vessel disease non

Physical examination: £ Nodular, tender, temporal artery with diminished or absent pulsation £ Scalp ischemia £ Absent peripheral pulses, asymmetry of blood pressure in extremities | Copyright © The McGraw-Hill Companies. All rights reserved.

Giant Cell Arteritis Laboratories: Reflective of an inflammatory process: £ CBC: anemia, thrombocytosis, leukocytosis £ Elevated erythrocyte sedimentation rate (ESR), CC-reactive protein

Diagnosed by: Temporal artery biopsy

(+) 5050-80%

Courtesy of Carol A. Langford

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Giant Cell Arteritis Treatment: £ Prednisone 4040-60 mg daily - Reduces symptoms and prevents visual loss - Begin immediately while biopsy is being arranged

£ Aspirin 81 mg daily - May reduce cranial ischemic complications - Use in all patients without contraindications Courtesy of Carol A. Langford

Outcome: £ 70% relapse require increased prednisone £ 35 35--85% have prednisone side effects £ Overall no difference in survival £ 18x higher rate of thoracic aortic aneurysms - May occur as a late complication of disease - Associated with a high mortality rate | Copyright © The McGraw-Hill Companies. All rights reserved.

Medium Vessel Vasculitis Vessel examples: GI tract, nerve, digits, interlobular renal Mesenteric Arteriogram

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Microaneurysms, stenoses, beading

Biopsy

Courtesy of Carol A. Langford

Vessel supplying sural nerve

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Medium Vessel Vasculitis: Polyarteritis Nodosa £ First form of vasculitis described

Clinical Features: Often presents with acute severe disease ± Systemic features

Fever, weight loss, arthralgias, night sweats

± Nerve

Mononeuritis multiplex (ie: foot drop, wrist drop)

± Renal

Hypertension, infarction

± GI tract

Pain, infarction, perforation, bleeding

± Digital infarction

Ischemic finger / toe | Copyright © The McGraw-Hill Companies. All rights reserved.

Polyarteritis Nodosa Laboratories:

Elevated ESR Anemia, mild elevations in WBC and platelets May see LFT abnormalities, microscopic hematuria A PANPAN-like vasculitis can occur with hepatitis B or C

Diagnosed by:

Arteriography, biopsies

Treatment:

Prednisone + cyclophosphamide Prednisone alone for nonnon-severe disease Antiviral treatment if hepatitis B or C are present | Copyright © The McGraw-Hill Companies. All rights reserved.

Small Vessel Vasculitis Capillary, arteriole, venule

Courtesy of Carol A. Langford

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Alveolar hemorrhage

Courtesy of Carol A. Langford

Glomerulonephritis

Courtesy of Carol A. Langford

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Small Vessel Vasculitis: Wegener¶s Granulomatosis

Sinus (>95%)

Lung (85%)

Kidney (80%) 20% at diagnosis 80% during course

Courtesy of Carol A. Langford

Courtesy of Carol A. Langford

Can be rapidly progressive Typically asymptomatic May lead to renal failure

Detected by urinalysis: Proteinuria, Hematuria Red blood cell casts Courtesy of Carol A. Langford

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Antineutrophil Cytoplasmic Antibodies (ANCA)

cANCA cytoplasmic staining

Courtesy of Carol A. Langford

pANCA perinuclear staining

Target Antigens In Vasculitis

Proteinase 3 (PR3)

Courtesy of Carol A. Langford

Myeloperoxidase (MPO)

Wegener¶s granulomatosis Microscopic polyangiitis Churg--Strauss syndrome Churg

PR3--ANCA PR3

MPO MPO--ANCA

ANCA ((-)

75-90% 7510--50% 10 3-20%

5 5--20% 50 50--80% 2-40%

up to 20% up to 20% up to 60%

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Key Clinical Issues Regarding ANCA £ Can ANCA be used to diagnose Wegener¶s granulomatosis? Usually no ± because of the toxicity of therapy and the need for diagnostic precision biopsy still required in most people ANCA can be helpful but is not necessary for diagnosis

£ Do high ANCA levels indicate active vasculitis? No - In large cohorts, ANCA levels are higher overall in active disease but«.. In individual patients ANCA does not correlate with disease activity and should not be used alone to guide treatment | Copyright © The McGraw-Hill Companies. All rights reserved.

Wegener¶s Granulomatosis Diagnosed by:

Typically biopsy

Treatment:

Prednisone + cyclophosphamide Prednisone + methotrexate (non(non-severe disease)

Outcome:

Survival: Untreated: 5 months Treatment: 80% survival

Challenges: Damage from prior disease Treatment related toxicity 50--70% relapse 50 | Copyright © The McGraw-Hill Companies. All rights reserved.

Small Vessel Vasculitis: Cutaneous Vasculitis

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Cutaneous vasculitis represents the most common vasculitic manifestation encountered in clinical practice | Copyright © The McGraw-Hill Companies. All rights reserved.

Small Vessel Vasculitis: Cutaneous Vasculitis

< 30% no identified cause or disease outside of the skin Treatment of isolated cutaneous vasculitis: £ Do not overtreat: recognize that this is not threatening £ Avoid the use of toxic immunosuppressive agents

> 70% occur in the setting of an underlying process: £ Medication £ Infection £ Malignancy £ Connective tissue disease £ Heralding feature of a primary systemic vasculitis | Copyright © The McGraw-Hill Companies. All rights reserved.

You see a patient with a possible cutaneous vasculitis

What do you need to do? 1. Recognize if a patient is in a potentially threatening situation 2. Confirm that this is vasculitis 3. Determine if there is an underlying cause for the vasculitis

How do you do this? | Copyright © The McGraw-Hill Companies. All rights reserved.

Recognition of Vasculitis History

Exam

Skin

+

+

Eye

+

+

ENT

+

+

+

Lung

+/-

+/-

+

Kidney

Labs

Imaging

+

GI

+

+

Neuro

+

+

+

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+ +

Assessment of Vasculitis History £ Do a complete review of systems

£ Medications: includes overover-the the--counter, supplements, recreational drugs Physical Examination £ Provides clues of organ involvement, features of an underlying disease Laboratories Urinalysis (if (+) blood, check their creatinine immediately) Always Chemistries (to include creatinine and hepatic) Perform CBC with differential ESR, CRP Systemic vasculitis Connective tissue disease Pursue additional lab testing if Infection there are features that point towards: Neoplasm | Copyright © The McGraw-Hill Companies. All rights reserved.

Assessment of Vasculitis Imaging Chest imaging (CXR, CT) ‡ Perform in all patients with pulmonary symptoms ‡ No pulmonary symptoms: obtain imaging if there are other features that suggest a systemic small vessel vasculitis Pursue CT, MRI, arteriography of other sites as clinically indicated

Biopsy £ Lesions that looks like vasculitis may not be £ If disease is outside of the skin, these are usually better locations for biopsy to confirm a systemic vasculitis | Copyright © The McGraw-Hill Companies. All rights reserved.

Recognizing Vasculitis: Suspicion is the Key Any instance of: £ Palpable purpura £ Pulmonary hemorrhage £ Glomerulonephritis £ Ischemic digits £ Mononeuritis multiplex (wrist or foot drop)

Consider also in the setting of: £ Worsening sinus symptoms not responsive to treatment £ Unexplained multisystem disease £ Unexplained pulmonary infiltrates £ Rapidly progressive major organ dysfunction

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What to do if a Vasculitis is Suspected £ Rule out potentially organorgan- or life life--threatening disease - asymptomatic kidney and lung disease £ Categorize where possible to a specific disease entity - Consider pattern of features £ Pursue means of a definitive diagnosis £ Select treatment based upon diagnosis and its severity £ Seek out consultation early as directed by clinical features Further information on vasculitis can be found in: | Chapter 319: The Vasculitis Syndromes By Carol A. Langford and Anthony S. Fauci | Copyright © The McGraw-Hill Companies. All rights reserved.

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