Pathogenesis
A postulated mechanism for necrotizing vasculitis is the deposition in postcapillary venules of circulating immune complexes. Initial alterations in venular permeability, caused by the release of vasoactive amines from platelets, basophils, and/or mast cells, facilitate the deposition of immune complexes and these may activate the complement system or may interact directly with Fc receptors on endothelial cell membranes. When the complement system is activated, the generation of anaphylatoxins C3a and C5a can degranulate mast cells. Also, C5a can attract neutrophils that release lysosomal enzymes during phagocytosis of complexes and subsequently damage vascular tissue.
A new drug taken during the few weeks before the onset of HV is a likely etiologic agent, as may be an infection, a known vascular/connective tissue disease, or paraproteinemia. Onset and course: Acute (days, as in drug induced or idiopathic), subacute (weeks, especially urticarial types), chronic (recurrent over years). Symptoms are pruritus, burning pain; there may be no symptoms or there may be fever, malaise; symptoms of peripheral neuritis, abdominal pain (bowel ischemia), arthralgia, myalgia, kidney involvement (microhematuria), or CNS involvement.
SKIN LESIONS The hallmark is palpable purpura. This term describes palpable petechiae that present as bright red, well-demarcated macules and papules with a central, dot-like hemorrhage (Fig. 14-51) (petechiae caused by coagulation defects or thrombocytopenia are strictly macular and, therefore, not palpable). Lesions are scattered, discrete or confluent, and are primarily localized to the lower legs and the ankles (Figs. 14-51Aand B) but may spread to the buttocks and arms. Stasis aggravates or precipitates lesions. Purpuric lesions do not blanch (with a glass slide). Red initially, they turn purple and even black in the center (Fig. 14-51B). In the case of massive inflammation, purpuric papules convert to hemorrhagic blisters, become necrotic (Fig. 14-51B), and even ulcerate.
HEMATOLOGY Rule out thrombocytopenic purpura.
ESR Elevated.
SEROLOGY Serum complement is reduced or normal in some patients, depending on associated disorders.
URINALYSIS RBC casts, albuminuria.
OTHERS Depending on underlying disease.
DERMATOPATHOLOGYNecrotizing Venulitis. Deposition of eosinophilic material (fibrinoid) in the walls of postcapillary venules in the upper dermis, and perivenular and intramural inflammatory infiltrate consisting predominantly of neutrophils. Extravasated RBC and fragmented neutrophils ("nuclear dust"). Frank necrosis of vessel walls. Intramural C3 and immunoglobulin deposition is seen with immunofluorescent techniques.
Based on clinical appearance and histopathology.
DIFFERENTIAL DIAGNOSIS Thrombocytopenic purpura, rash such as exanthematous drug eruption in setting of thrombocytopenia, disseminated intravascular coagulation (DIC) with purpura fulminans, septic vasculitis (rickettsial spotted fevers), septic emboli (infective endocarditis), bacteremia (disseminated gonococcal infection, meningococcemia [acute/chronic]), pigmented purpura, and other noninfectious vasculitides.
ANTIBIOTICS Antibiotics for patients in whom vasculitis follows bacterial infection.
PREDNISONE For patients with moderate to severe disease.
CYTOTOXIC IMMUNOSUPPRESSIVESCyclophosphamide, azathioprine usually in combination with prednisone. Cyclosporine and intravenous high-dose immunoglobulin. Infliximab and Rituximab.