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Vasculitis

Carol A. Langford, MD, MHS


Director, Center for Vasculitis Care and Research Department of Rheumatic and Immunologic Diseases Cleveland Clinic Foundation

Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

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 Attenuation of vessel wall

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

Tissue or organ ischemia

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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 Takayasus arteritis Kawasaki disease Polyarteritis nodosa Wegeners granulomatosis Microscopic polyangiitis ChurgChurg-Strauss syndrome Henoch-Sch Henoch-Schnlein 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: Clinical Manifestations:


Age, sex, ethnicity, frequency Symptoms, signs Patterns of organ involvement Clinical and laboratory features Biopsy (granulomas, eosinophils) Arteriography Supportive care and close observation Prednisone Cytotoxic therapy (cyclophosphamide) Large, medium, small vessel

Diagnosis:

Treatment and Outcome:

Predominant vessel size:

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Aorta

Capillary

Vein

Large Vessel
Giant cell arteritis Takayasus arteritis

Medium Vessel
Polyarteritis nodosa Kawasaki disease

Small Vessel
Wegeners granulomatosis Microscopic polyangiitis Churg-Strauss syndrome Henoch-Schnlein purpura Isolated cutaneous vasculitis

Vessel size plays a role in:


Symptoms and signs Methods of diagnostic evaluation

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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


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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 nonnon-cranial large vessel disease

Physical examination:
Nodular, tender, temporal artery with diminished or absent pulsation Scalp ischemia Absent peripheral pulses, asymmetry of blood pressure in extremities
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Giant Cell Arteritis


Laboratories:
Reflective of an inflammatory process: CBC: anemia, thrombocytosis, leukocytosis Elevated erythrocyte sedimentation rate (ESR), C-reactive protein C-

Diagnosed by:
Temporal artery biopsy

(+) 50-80% 50-

Courtesy of Carol A. Langford

Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

Giant Cell Arteritis


Treatment:
Prednisone 40-60 mg daily 40- 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 35-85% have prednisone side effects 35 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
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Medium Vessel Vasculitis


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

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Courtesy of Carol A. Langford

Microaneurysms, stenoses, beading

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 Nerve Renal GI tract Digital infarction Fever, weight loss, arthralgias, night sweats Mononeuritis multiplex (ie: foot drop, wrist drop) Hypertension, infarction Pain, infarction, perforation, bleeding Ischemic finger / toe
Harrisons Lecture Notes 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 PAN-like vasculitis can occur with hepatitis B or C PAN-

Diagnosed by:

Arteriography, biopsies

Treatment:

Prednisone + cyclophosphamide Prednisone alone for non-severe disease nonAntiviral treatment if hepatitis B or C are present
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Small Vessel Vasculitis


Capillary, arteriole, venule

Courtesy of Carol A. Langford

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Alveolar hemorrhage

Glomerulonephritis

Courtesy of Carol A. Langford

Courtesy of Carol A. Langford

Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

Small Vessel Vasculitis: Wegeners Granulomatosis

Sinus (>95%)

Lung (85%)

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

Courtesy of Carol A. Langford

Can be rapidly progressive Typically asymptomatic May lead to renal failure

Courtesy of Carol A. Langford

Detected by urinalysis: Proteinuria, Hematuria Red blood cell casts


Courtesy of Carol A. Langford

Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

Antineutrophil Cytoplasmic Antibodies (ANCA)

cANCA cytoplasmic staining

pANCA perinuclear staining

Courtesy of Carol A. Langford

Target Antigens In Vasculitis

Courtesy of Carol A. Langford

Proteinase 3 (PR3)

Myeloperoxidase (MPO)

PR3PR3-ANCA
Wegeners granulomatosis Microscopic polyangiitis ChurgChurg-Strauss syndrome 7575-90% 1010-50% 3-20%

MPO-ANCA MPO5-20% 550-80% 502-40%

ANCA (-) (up to 20% up to 20% up to 60%

Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

Key Clinical Issues Regarding ANCA


Can ANCA be used to diagnose Wegeners 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
Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

Wegeners Granulomatosis
Diagnosed by:
Typically biopsy

Treatment:

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

Outcome:

Survival:
Untreated: 5 months Treatment: 80% survival

Challenges:
Damage from prior disease Treatment related toxicity 5050-70% relapse
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Small Vessel Vasculitis: Cutaneous Vasculitis

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Cutaneous vasculitis represents the most common vasculitic manifestation encountered in clinical practice
Harrisons Lecture Notes 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
Harrisons Lecture Notes 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?


Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

Recognition of Vasculitis History


Skin Eye ENT Lung Kidney GI Neuro + + + + + + + +/-

Exam
+ + + +/-

Labs

Imaging

+ + + + + +

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Assessment of Vasculitis
History
Do a complete review of systems

Medications: includes over-the-counter, supplements, recreational drugs over-thePhysical 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
Harrisons Lecture Notes 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
Harrisons Lecture Notes 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

Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

What to do if a Vasculitis is Suspected


Rule out potentially organ- or life-threatening disease organ- life- Remember 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:
Harrisons Principles of Internal Medicine, 17e Chapter 319: The Vasculitis Syndromes By Carol A. Langford and Anthony S. Fauci
Harrisons Lecture Notes Copyright The McGraw-Hill Companies. All rights reserved.

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