Vasculitis Flashcards
Vasculitis
Definition
Inflammation of the blood vessels
Can be classified based on pathology, vessel size or organ involvement
Vasculitis
Epidemiology
Most common types:
- Children: Henoch-Schonlein purpura
- Adults > 50 y/o: Giant cell arteritis
- Drug-induced cutaneous vasculitis: unknown prevalence
- Rare diseases, vary by type
Vasculitis
Pathogenesis
Varies w/ vasculitis type
Can have infectious trigger ⇒ pathologic auto-Ab causing immune system activation
Vasculitis
Clinical Presentation
Dependent upon type of vasculitis
-
Systemic symptoms:
- Fever
- Malaise
- Weight loss
- Night sweats
-
Organ-specific manifestations:
Can affect any organ depending on the type of vasculitis- Skin rash: petechiae, purpura
- Musculoskeletal: arthralgias, myalgias, arthritis
- Cardiovascular: hypertension, myocardial infarction
- Renal: glomerulonephritis
- Gastrointestinal: abdominal pain, ischemic colitis or mesenteric ischemia
- Respiratory: sinusitis, hemoptysis, pulmonary hemorrhage, lung nodules or infiltrates
- Nervous system: CNS or peripheral (mononeuritis multiplex)
Vasculitis
Diagnosis
- Lab tests: elevated markers of inflammation (ESR, CRP)
- Blood count: Anemia, thrombocytosis, leukocytosis
- Gold standard for dx: biopsy demonstrating inflammatory infiltrate
- Angiography demonstrating “beading of vessels” or aneurysms ⇒ suggestive, not confirmatory
- Blood tests and imaging studies often not sufficient
Vasculitis
Treatment
- Glucocorticoids
- Immunosuppressive medications: cyclophosphamide, rituximab, azathioprine, Methotrexate
- In some instances, plasmapheresis to remove circulating auto-Ab
Vasculitis
Pathological Classification
- Infectious
- Immunological
- Unknown
Vasculitis
Vessel Classification
-
Large-Vessel Vasculitis
- Temporal arteritis (Giant Cell Arteritis)
- Takayasu Arteritis
-
Medium-Vessel Vasculitis
- Kawasaki Disease
- Polyarteritis Nodosa
-
Small-Vessel Vasculitis
-
ANCA-associated vasculitis
- Granulomatosis w/ polyangiitis (Wegener’s granulomatosis)
- Eosinophilic granulomatosis w/ polyangiitis (Churg-Strauss syndrome)
- Microscopic polyangiitis
-
Immune complex vasculitis
- IgA vasculitis (Henoch-Schonlein purpura)
- Cryoglobulinemic vasculitis
- Anti-glomerular basement membrane disease (anti-GBM disease)
-
ANCA-associated vasculitis
-
Variable-vessel vasculitis
- Behcet’s disease
- Cogan’s syndrome
- Single-organ vasculitis
-
Vasculitis associated w/ systemic disease
- Lupus
- Rheumatoid arthritis
Infectious Vasculitis
Direct invasion of vessel walls by pathogens
(syphilis, rickettsia, aspergillus)
Giant Cell Arteritis
Overview
“Temporal Arteritis”
- Most common systemic vasculitis in adults
- Affects large and medium-sized arteries
- Aorta and its major branches
- Predilection for the extracranial branches of the carotid a., especially the temporal aa.
- Presents at mean age of 72 y (> 50y)
- May cause blindness if not treated quickly
- Etiology is unknown
Giant Cell Arteritis
Clinical Presentation
- Headache
- Pain and/or pulselessness of temporal artery
- Jaw claudication
- 50% have ocular symptoms
Giant Cell Arteritis
Associations
- Associated w/ polymyalgia rheumatic: morning stiffness, pain in proximal muscles of arms and legs
-
Can be associated w/ aortitis
- Ophthalmic arteries, retinal arteries, and ciliary arteries: medium vessels
- Branches of the above: small vessels
Giant Cell Arteritis
Microscopic Appearance
- Lymphocytes, macrophages and multinucleated giant cells (66%) in media
- Fragmentation of internal elastic lamina
- Affects short segments of the vessel
(⊖ biopsy in up to 50%)
Giant Cell Arteritis
Gross Appearance
- Thrombosis may be present
- Vessel is often left w/ scarring
- Aortic root may be dilated
Giant Cell Arteritis
Clinical Features
- See ↑ ESR
-
Diagnosed by temporal artery biopsy
- Biopsy shows multinucleated giant cells, granulomatous inflammation
- Responsive to anti-inflammatory meds
- If there is a question of temporal arteritis, treatment (glucocorticoids) should precede biopsy
Takayasu Arteritis
Overview
- Affects large to medium-sized arteries
- Aorta and its main branches are most affected
- Young/middle-aged women of Asian descent (< 40 y/o)
- Etiology is unknown
Takayasu Arteritis
DDx
Early-Onset Granulomatous Aortitis
Affects arteries of aortic arch: pulseless disease
Biopsy similar to temporal arteritis but different demographics
Takayasu Arteritis
Clinical Manifestations
Symptoms may include:
- Fever
- Fatigue
- Arthralgias
- Ocular Disturbances
- Claudication
Takayasu Arteritis
Histology
- Arteries become thickened and distorted sometimes leading to occlusion
- Marked intimal thickening
-
Variable inflammatory infiltrate:
- Mononuclear infiltrate of adventitia
- Granulomatous inflammation involving the media
Takayasu Arteritis
Diagnosis
Clinical signs include weak pulses (“pulseless disease”) and lower BP in the upper extremities
Dx is difficult and based on clinical findings in conjunction w/ radiologic evidence (angiogram or MRI)
Kawasaki Disease
Overview
-
Predominantly a medium-sized vessel vasculitis
- May affect large and small arteries as well
- Often involves the coronary arteries (20%)
- Aorta and veins may also be involved
- A disease of infants and children < 4 y/o
- Leading cause of acquired heart disease in children of Japan and North America
- Associated w/ mucocutaneous lymph node syndrome
- Rash, enlarged lymph nodes, “strawberry tongue”
Kawasaki Disease
Clinical Manifestations
Symptoms include:
- Fever
- Conjunctivitis
- Oral erosions
- Palmar and plantar erythema
- Desquamating skin rash
- Lymphadenopathy
Polyarteritis Nodosa
Overview
-
Necrotizing arteritis affecting medium and small arteries of the renal, cardiac and visceral circulation
- Pulmonary vasculature is spared
- Seen most often in young adults but may occur at any age
- Disease course is variable and episodic
- Associated w/ hepatitis B
- Commonly causes aneurysms
- ⊖ ANCA’s
Polyarteritis Nodosa
Clinical Manifestations
Symptoms include:
- Malaise
- Fever of unknown origin (FUO)
- Weight Loss
- HTN
- GI bleeding
- Renal involvement is responsible for most fatalities
Polyarteritis Nodosa
Pathogenesis
- Most prominent at branch points
- May affect only part of the circumference of a vessel
- Acute phase reveals transmural inflammation rich in neutrophils w/ fibrinoid necrosis
- Inflammation is replaced by fibrous thickening
- Lesions of different ages may be seen in the same vessel
ANCA-associated Vasculitis
“Pulmonary-Renal Syndromes”
-
Anti-neutrophil cytoplasmic Ab (ANCA) ⇒ variably associated w/ the disorders
- Proteinase 3-ANCA (PR3) ⇒ cANCA
- Myeloperoxidase-ANCA (MPO) ⇒ pANCA
- Can be ANCA-⊖
-
Includes:
- Granulomatosis w/ polyangiitis (formerly Wegener’s granulomatosis)
- Eosinophilic granulomatosis w/ polyangiitis (formerly Churg-Strauss syndrome)
- Microscopic polyangiitis
- Immune complex vasculitis
- IgA vasculitis (Henoch-Schonlein purpura)
- Cryoglobulinemic vasculitis
- Anti-glomerular basement membrane disease (anti-GBM disease)
Granulomatosis w/ Polyangiitis
(Formerly Wegener’s)
Overview
- Immunologic / hypersensitivity reaction
- Affects young / middle-aged adults
- Slight male predominance
- 95% are c-ANCA ⊕ (proteinase3)
- 80% fatal if untreated
Granulomatosis w/ Polyangiitis
(Formerly Wegener’s)
Clinical Manifestions
-
Classic triad:
- Necrotizing vasculitis of small to medium vessels ⇒ granuloma w/ upper respiratory tract disease (sinusitis)
- Necrotizing granulomas of the upper and/or lower respiratory tract ⇒ pulmonary nodules/infiltrates
- Necrotizing glomerulonephritis (often crescentic)
- “Limited” WG affects only the respiratory tract
- Systemic WG also affects the eyes, skin (palpable purpura), joints, nerves and occasionally the heart
Churg-Strauss Syndrome
Overview
“Allergic Granulomatosis or Eosinophilic granulomatosis w/ polyangiitis”
- Systemic vasculitis of small vessels
- Usually presents in middle-aged adults w/ new onset or worsening asthma
- Asthma may begin years before vasculitis
- Eosinophilia heralds the second stage
- Vasculitis (3rd stage) typically affects the skin, lungs, nerves and kidneys
- Usu. ⊕ p-ANCA
Churg-Strauss Syndrome
Clinical Manifestations
Signs and symptoms include:
- Sinusitis and nasal polyps
- Pulmonary infiltrates
- Rashes, palpable purpura and nodules
- Glomerulonephritis
- Mononeuritis multiplex
Microscopic Polyangiitis
Overview
-
Necrotizing vasculitis centered on arterioles, capillaries and venules
- Involves the skin, mucous membranes, lungs, brain, heart, GI tract, kidneys and muscle
- Necrotizing glomerulonephritis (GN) and pulmonary capillaritis are common
- No granulomas
- Affects all age groups and ethnic backgrounds
Microscopic Polyangiitis
Clinical Manifestations
- Glomerulonephritis (80%)
- Weight loss (>70%)
- Skin lesions (>60%)
- Palpable purpura favoring dependent areas
- Neuropathy and fever
- Hemoptysis
- Arthralgias and myalgias
Microscopic Polyangiitis
Pathogenesis
- Histology is similar to PAN
- Lesions are consistent in age
- ⊕ p-ANCA in 70% of cases
- Specific for myeloperoxidase
Immune Complex Vasculitis
- Deposition of immunoglobulin or complement components
- Often w/ glomerulonephritis
- Includes:
- IgA Vasculitis (Henoch-Schonlein Purpura)
- Cryoglobulinemic Vasculitis
- Anti-Glomerular Basement Membrane Disease (Anti-GBM Disease)
IgA Vasculitis
“Henoch-Schonlein Purpura”
- Triad of purpura, skin rash, abdominal pain
- Can also cause kidney involvement (glomerulonephritis)
- IgA deposition in small vessels
Cryoglobulinemic Vasculitis
- Associated w/ hepatitis C and lymphoproliferative diseases
- Caused by precipitation of a cryoglobulin
- Protein that is insoluble in reduced temperatures
- Type I: monoclonal paraproteinemia (usually IgM)
- Type II: immune complexes w/ monoclonal IgM (Rheumatoid Factor) and polyclonal IgG
- Type III: immune complexes w/ polyclonal IgM (Rheumatoid Factor) and polyclonal IgG
Anti-Glomerular Basement Membrane Disease
(Anti-GBM Disease)
Pulmonary-renal syndrome w/ deposition of anti-GBM Ab
Hypocomplementemic Urticarial Vasculitis
Glomerulonephritis, arthritis, ocular inflammation, urticaria
Behcet’s Disease
- Recurrent oral/genital ulcers
- Uveitis, arthritis, GI effects, CNS disease
- Small vessel vasculitis and thrombosis (Variable-Vessel Vasculitis)
Cogan’s Syndrome
- Ocular inflammation (keratitis, uveitis, episcleritis)
- Inner ear disease (sensorineural hearing loss and vestibular dysfunction)
- Arteritis of varying sized vessels, valvulitis (Variable-Vessel Vasculitis)
Single-Organ Vasculitis
May be an initial manifestation that later evolves into systemic disease
Cutaneous vasculitis, CNS vasculitis, Testicular vasculitis
Vasculitis Associated w/ Systemic Disease
Lupus: commonly glomerulonephritis (30%) but can have vasculitis affecting the skin and central nervous system
Rheumatoid arthritis: medium vessel vasculitis, often affecting the kidneys, mutaneous ulcers, mononeuritis multiplex
Vasculitis
Differential Dx
Many mimics of vasculitis
Generally mimics cause vascular occlusion/thromboembolism
- Malignancy: elevated ESR, hypercoagulable state causing thrombosis
- Infection: TB, endocarditis (causes a vasculitic-appearing rash, septic emboli)
- Atrial myxoma
- Cholesterol emboli
- Buerger’s disease (Thromboangiitis obliterans)
Thromboangiitis Obliterans
Overview
“Buerger’s Disease”
- Acute and chronic vasculitis of medium and small arteries
- Tibial and radial arteries are most often affected
- May spread secondarily to veins and nerves
- Typically affects young (20–40 y/o) male smokers
Thromboangiitis Obliterans
Clinical Manifestations
Symptoms include:
- Claudication
- Numbness
- Raynaud’s phenomenon
- Gangrene
