Transcript 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
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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
Harrison’s Lecture Notes
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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
Harrison’s Lecture Notes
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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
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)
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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:
Supportive care and close observation
Prednisone
Cytotoxic therapy (cyclophosphamide)
Predominant vessel size:
Large, medium, small vessel
Harrison’s Lecture Notes
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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
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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
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
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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
Diagnosed by:
Temporal artery biopsy
(+) 50-80%
Courtesy of Carol A. Langford
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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
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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
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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
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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
Harrison’s Lecture Notes
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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
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%
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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
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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
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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
Harrison’s Lecture Notes
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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
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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
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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 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
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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
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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
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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
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