A 32-year-old man is started on infliximab for treatment of refractory Crohn disease. Ten days later, he develops joint pain and a pruritic skin rash. Skin biopsy shows scattered areas of fibrinoid necrosis and neutrophil infiltration involving his small blood vessels. Which of the following findings is most likely to accompany this patient's condition?

Question

A 32-year-old man is started on infliximab for treatment of refractory Crohn disease.  Ten days later, he develops joint pain and a pruritic skin rash.  Skin biopsy shows scattered areas of fibrinoid necrosis and neutrophil infiltration involving his small blood vessels.  Which of the following findings is most likely to accompany this patient's condition?

Quizplus · Accepted Answer

11ec160b_3a72_18da_9249_99363e4b0551_MD0001_00 This patient's symptoms and biopsy findings are suggestive of acute serum sickness, a condition caused by tissue deposition of circulating immune complexes (type III hypersensitivity). The most common manifestations include fever, pruritic skin rash, and arthralgias that begin 7-14 days after exposure to an antigen. Lymphadenopathy and proteinuria may also occur in some patients. Histologic examination of affected tissues typically shows small vessel vasculitis with fibrinoid necrosis and intense neutrophil infiltration. Deposition of IgG and/or IgM complement-fixing antibodies results in localized complement consumption and hypocomplementemia (decreased serum C3 levels). Serum sickness can occur following administration of antigenic heterologous proteins such as chimeric monoclonal antibodies (eg, rituximab and infliximab) or nonhuman immunoglobulins (eg, venom antitoxins). A serum sickness-like reaction is also associated with the use of certain nonprotein drugs (eg, penicillin, cefaclor, and trimethoprim-sulfamethoxazole). (Choice A) Anergy to cutaneously applied Candida antigens would be indicative of depressed cell-mediated immunity. Cell-mediated immunity is involved in the pathogenesis of type IV (delayed) hypersensitivity. (Choice C) Increased serum IgE levels are typically found in atopic individuals prone to IgE-mediated (type I) hypersensitivity reactions. Type I reactions cause vasodilation and tissue edema and inflammatory infiltration; they do not cause vasculitis with fibrinoid necrosis. (Choice D) Deposition of IgA-containing immune complexes is involved in the pathogenesis of Henoch-Schönlein purpura in pediatric patients. IgA does not play an important role in type III hypersensitivity. (Choice E) Serum sickness causes release of the C5a complement fragment (a neutrophil chemoattractant) at sites of immune complex deposition. This leads to neutropenia (not neutrophilia) due to extensive neutrophilic marginalization and tissue infiltration. In addition, infliximab and other TNF-alpha inhibitors can also cause neutropenia. (Choice F) Mild thrombocytopenia has been associated with serum sickness due to platelet consumption at the site of active vascular inflammation. However, severe thrombocytopenia is unlikely to occur. Educational objective: Serum sickness is a type III hypersensitivity reaction to nonhuman proteins characterized by vasculitis resulting from tissue deposition of circulating immune complexes. Clinical findings include fever, pruritic skin rash, arthralgias, and low serum C3 and C4 complement levels.

A 32-Year-Old Man Is Started on Infliximab for Treatment of Refractory