Complications of tumor necrosis factor-α blockade in chronic granulomatous disease-related colitis

Abstract

Background: Chronic granulomatous disease (CGD) is a genetic disorder of the phagocyte NADPH oxidase, which predisposes patients to infections and inflammatory complications, including severe colitis. Management of CGD colitis is a challenge because standard immunosuppressive therapy increases the risk of infection in already immunocompromised hosts.

Methods: We report the use of infliximab in 5 patients with CGD.

Results: Infliximab administration predisposed patients to severe infections with typical CGD pathogens but not mycobacteria, as reported with infliximab in other conditions. In addition to infections, infliximab administration led to successful closure of fistulae, sometimes with other untoward consequences. Infliximab-associated complications were associated with 2 deaths.

Conclusions: Infliximab use in the treatment of CGD inflammatory bowel disease requires aggressive antimicrobial prophylaxis, assiduous surveillance for infection, and vigilance for untoward gastrointestinal complications. This experience suggests that infliximab therapy is effective but has untoward consequences in patients with CGD.

Figure 1

Perianal disease in patient 1. A, Extensive perianal disease showing severe anal inflammation with undermining and formation of small tissue flaps and sinus tracts. B, Improvement after infliximab treatment. C, Burkholderia pneumonia after the eighth dose of infliximab. D, Relapse of perianal disease on interruption of infliximab. E, Improvement after reinitiation of infliximab therapy.

Table 1

Demographic Characteristics of Patients