Vasculitis Carol A. Langford, MD, MHS
Vasculitis Carol A. Langford, MD, MHS Director, Center for Vasculitis Care and Research Department of Rheumatic and Immunologic Diseases Cleveland Clinic Foundation Harrison’s 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 Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. Vasculitis: Histological and Clinical Correlation Courtesy of Carol A. Langford Disruption of the vessel wall with red blood cell extravasation into tissue Copyright © The McGraw-Hill Companies, Inc. All rights reserved. Palpable Purpura Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 Henoch-Schönlein 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) Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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: Supportive care and close observation Prednisone Cytotoxic therapy (cyclophosphamide) Predominant vessel size: Large, medium, small vessel Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 Harrison’s Lecture Notes 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 Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 Physical examination: • Nodular, tender, temporal artery with diminished or absent pulsation • Scalp ischemia • Absent peripheral pulses, asymmetry of blood pressure in extremities Harrison’s Lecture Notes 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), C-reactive protein Diagnosed by: Temporal artery biopsy (+) 50-80% Courtesy of Carol A. Langford Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. Giant Cell Arteritis Treatment: • Prednisone 40-60 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 • 35-85% 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 Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. Medium Vessel Vasculitis Vessel examples: GI tract, nerve, digits, interlobular renal Mesenteric Arteriogram Copyright © The McGraw-Hill Companies, Inc. All rights reserved. Microaneurysms, stenoses, beading Biopsy Courtesy of Carol A. Langford Vessel supplying sural nerve Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 Harrison’s 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 Diagnosed by: Arteriography, biopsies Treatment: Prednisone + cyclophosphamide Prednisone alone for non-severe disease Antiviral treatment if hepatitis B or C are present Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. Small Vessel Vasculitis Capillary, arteriole, venule Courtesy of Carol A. Langford Copyright © The McGraw-Hill Companies, Inc. All rights reserved. Alveolar hemorrhage Courtesy of Carol A. Langford Glomerulonephritis Courtesy of Carol A. Langford Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 PR3-ANCA MPO-ANCA ANCA (-) 75-90% 10-50% 3-20% 5-20% 50-80% 2-40% up to 20% up to 20% up to 60% Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. 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 Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. Wegener’s Granulomatosis Diagnosed by: Typically biopsy Treatment: Prednisone + cyclophosphamide Prednisone + methotrexate (non-severe disease) Outcome: Survival: Untreated: 5 months Treatment: 80% survival Challenges: Damage from prior disease Treatment related toxicity 50-70% relapse Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. Small Vessel Vasculitis: Cutaneous Vasculitis Copyright © The McGraw-Hill Companies, Inc. All rights reserved. Cutaneous vasculitis represents the most common vasculitic manifestation encountered in clinical practice Harrison’s 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 Harrison’s 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? Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. Recognition of Vasculitis History Exam Skin + + Eye + + ENT + + + Lung +/- +/- + Kidney Labs Imaging + GI + + Neuro + + + Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. + + Assessment of Vasculitis History • Do a complete review of systems • Medications: includes over-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 Harrison’s 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 Harrison’s 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 Harrison’s 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 - 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: Harrison’s Principles of Internal Medicine, 17e Chapter 319: The Vasculitis Syndromes By Carol A. Langford and Anthony S. Fauci Harrison’s Lecture Notes Copyright © The McGraw-Hill Companies. All rights reserved. Terms of Use: Harrison’s Lecture Notes PowerPoint Usage Guidelines AccessMedicine users may display, download, or print out PowerPoint slides and images associated with the site for personal and educational use only. 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