Harrison’s Manual of Medicine
Definition and Pathogenesis
Definition and Pathogenesis
A clinicopathologic process characterized by inflammation of and damage to blood vessels, compromise of vessel lumen, and resulting ischemia. Clinical manifestations depend on size and location of affected vessel. Most vasculitic syndromes appear to be mediated in whole or in part by immune mechanisms. May be primary or sole manifestation of a disease or secondary to another disease process. Unique vasculitic syndromes can be identified that can differ greatly with regards to clinical features, disease severity, histology, and treatment.
CLASSIC POLYARTERITIS NODOSA (PAN) Medium-sized muscular arteries involved; frequently associated with arteriographic aneurysms; commonly affects renal arteries, liver, GI tract, peripheral nerves, skin, heart; can be associated with hepatitis B.
MICROSCOPIC POLYANGIITIS Small-vessel vasculitis that can affect the glomerulus and lungs; medium-sized vessels may also be affected.
WEGENER’S GRANULOMATOSIS Granulomatous vasculitis of upper and lower respiratory tracts together with glomerulonephritis; upper airway lesions affecting the nose and sinuses can cause purulent or bloody nasal discharge, mucosal ulceration, septal perforation, and cartilaginous destruction (saddlenose deformity). Lung involvement may be asymptomatic or cause cough, hemoptysis, dyspnea; eye involvement may occur; renal involvement accounts for most deaths.
ALLERGIC ANGIITIS AND GRANULOMATOSIS (CHURG-STRAUSS DISEASE) Granulomatous vasculitis of multiple organ systems, particularly the lung; characterized by asthma, peripheral eosinophilia, eosinophilic tissue infiltration; glomerulonephritis can occur.
POLYANGIITIS OVERLAP SYNDROME Primary systemic vasculitis that does not precisely fit into a single diagnostic category.
GIANT CELL (OR TEMPORAL) ARTERITIS Inflammation of medium- and large-sized arteries; primarily involves temporal artery but systemic involvement may occur; symptoms include headache, jaw/tongue claudication, scalp tenderness, fever, musculoskeletal symptoms (polymyalgia rheumatica); sudden blindness from involvement of optic vessels is a dreaded complication.
TAKAYASU’S ARTERITIS Vasculitis of the large arteries with strong predilection for aortic arch and its branches; most common in young women; presents with inflammatory or ischemic symptoms in arms and neck, systemic inflammatory symptoms, aortic regurgitation.
HENOCH-SCHÖNLEIN PURPURA Characterized by involvement of skin, GI tract, kidneys; more common in children; may recur after initial remission.
PREDOMINANTLY CUTANEOUS VASCULITIS (HYPERSENSITIVITY VASCULITIS) Heterogeneous group of disorders; common feature is small-vessel involvement; skin disease usually predominates.
Exogenous Stimuli Proved or Suspected
Serum sickness and serum sickness–like reactions
Vasculitis associated with infectious diseases
Endogenous Antigens Likely Involved
Vasculitis associated with neoplasms
Vasculitis associated with connective tissue disorders
Vasculitis associated with other underlying diseases
Vasculitis associated with congenital deficiencies of complement system.
MISCELLANEOUS VASCULITIC SYNDROMES
Mucocutaneous lymph node syndrome (Kawasaki disease)
Isolated vasculitis of the central nervous system
Thromboangiitis obliterans (Buerger’s disease)
Erythema elevatum diutinum
Evaluation (See Fig. 160-1)
FIGURE 160-1. Algorithm for the approach to a pt with suspected diagnosis of vasculitis.
Thorough Hx and physical exam—special reference to ischemic manifestations and systemic inflammatory signs/symptoms.
Laboratories—important in assessing organ involvement: CBC with differential, ESR, renal function tests, UA. Should also be obtained to rule out other diseases: ANA, rheumatoid factor, anti-GBM, hepatitis B/C serologies, HIV.
Antineutrophil cytoplasmic autoantibodies (ANCA)—cytoplasmic pattern associated with Wegener’s granulomatosis; presence of ANCA is adjunctive and should not be used in place of biopsy as a means of diagnosis.
Radiographs—CXR should be performed even in the absence of symptoms.
Diagnosis—can only be made by arteriogram or biopsy of affected organ(s).
Guided by organ manifestations. In many instances includes infections and neoplasms, which must be ruled out prior to beginning immunosuppressive therapy.
Therapy is based on the specific vasculitic syndrome and its manifestations. Immunosuppressive therapy should be avoided in disease that rarely results in irreversible organ system dysfunction or that usually does not respond to such agents (e.g., predominantly cutaneous vasculitis). Glucocorticoids alone may control temporal arteritis and Takayasu’s arteritis. Cytotoxic agents are particularly important in syndromes with life-threatening organ system involvement, especially active glomerulonephritis. Frequently used agents:
Prednisone 1 (mg/kg)/d initially, then tapered; convert to alternate-day regimen and discontinue.
Cyclophosphamide 2 (mg/kg)/d, adjusted to avoid severe leukopenia. Morning administration with a large amount of fluid is important in minimizing bladder toxicity. Pulsed intravenous cyclophosphamide (1 g/m2 per month) is less effective but may be considered in selected pts who cannot tolerate daily dosing.
Methotrexate in weekly doses up to 25 mg/week may be used to induce remission in Wegener’s granulomatosis pts who do not have immediately life-threatening disease or cannot tolerate cyclophosphamide. It may also be considered for maintaining remission after induction with cyclophosphamide.
Azathioprine 2 (mg/kg)/d. Less effective in treating active disease but may be useful in maintaining remission in pts who become cyclophosphamide intolerant.
Plasmapheresis may have an adjunctive role in management if manifestations not controlled by above measures.
For a more detailed discussion, see Fauci AS: The Vasculitis Syndromes, Chap. 317, p. 1956, in HPIM-15.