Immune Complex-Mediated Vasculitis

Development of antibody-antigen (immune) complexes (IC) is called the Arthus reaction; deposition of these complexes in blood vessel walls initiates complement activation, an influx of inflammatory cells, thrombus formation, and hemorrhagic infarction. In the skin, palpable purpura, the most common cutaneous finding in IC-mediated vasculitis, results from extravasation of erythrocytes through damaged vessel walls (Plate 82). These nonblanching lesions are distributed symmetrically in dependent areas of the body, where tissue hydrostatic pressure is increased (eg, lower extremities, buttocks). On light microscopy, cellular infiltrates consisting predominantly of neutrophils within and around vessel walls are seen, along with endothelial swelling and proliferation and neutrophil degranulation; hence, the term leukocytoclastic vasculitis.

Cutaneous Leukocytoclastic Angiitis (Hypersensitivity Vasculitis)

This disease is defined by exposure to an offending agent, usually a medication or infectious agent, and is characterized by palpable purpura and/or maculopapular rash. No systemic involvement is noted. Biopsy shows neutrophilic infiltration around a blood vessel. Therapy involves discontinuation of the medication, with systemic glucocorticoids used only when disease is extensive.

IgA Vasculitis (Henoch-Schönlein Purpura)

Henoch-Schönlein (HSP) usually presents in children younger than 5 years. It presents less frequently in adults. It is usually associated with an upper respiratory tract infection followed by rash, abdominal pain, arthralgias and glomerulonephritis. Biopsy shows a predominance of IgA deposition on immunofluorescence. The disease can be self-limited when mild. In adults, a more prolonged disease course is likely. When kidney involvement is present, aggressive immunosuppressive therapy including systemic glucocorticoids and cyclophosphamide is prescribed.

Cryoglobulinemic Vasculitis

Cryoglobulins are immunoglobulins (IgG or IgM), so called because of their tendency to precipitate from serum below body temperature conditions. Type I cryoglobulinemia is associated with an isolated monoclonal immunoglobulin, typically Waldenström macroglobulinemia (IgM) or multiple myeloma (usually IgG). Such patients most commonly present with hyperviscosity and thrombosis, but vasculitic symptoms can occur. In type II cryoglobulinemia, monoclonal IgM and polyclonal IgG (mixed cryoglobulinemia) are present, and about 90% are associated with hepatitis C infection. When type II cryoglobulinemia is not associated with hepatitis C, the disease is called essential mixed cryoglobulinemia. Type III cryoglobulinemia is characterized by the presence of polyclonal IgG and polyclonal IgM and is frequently seen in patients with chronic infections, Sjögren syndrome, and systemic lupus erythematosus. Vasculitis manifests in types II and III cryoglobulinemic patients with a triad of arthralgias, myalgias, and palpable purpura. Involvement of medium-sized vessels results in cutaneous ulcers, digital ischemia, and fixed livedo reticularis. Severe involvement leads to membranoproliferative glomerulonephritis and mononeuritis multiplex. Laboratory abnormalities include high titers of rheumatoid factor, a low serum complement C4 level (out of proportion to the decreased C3 level), and the detection of serum cryoglobulins.

In patients with hepatitis C-associated cryoglobulinemic vasculitis, treatment is based on suppression of viral replication (see Hepatitis). Patients with severe involvement, such as mononeuritis and glomerulonephritis, require immunosuppressive therapy (glucocorticoids and rituximab) and plasma exchange to reduce circulating cryoglobulins.

Anti-Glomerular Basement Membrane (Goodpasture) Disease

Anti-glomerular basement membrane (GBM) disease is a vasculitis caused by the deposition of autoantibodies reactive against type IV collagen found in basement membranes of the glomerular and pulmonary capillaries. Necrotizing glomerulonephritis or pulmonary hemorrhage are devastating manifestations. The diagnosis is established by the detection of circulating anti-GBM antibodies in serum or detection of linear IgG deposits to GBM on kidney biopsy. Treatment involves plasma exchange and use of immunosuppressants.