Complications of tumor necrosis factor-α blockade in chronic granulomatous disease-related colitis.
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.
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. guzel@mail.nih.gov
Gulbu
G
Uzel
Jordan S
JS
Orange
Nina
N
Poliak
Beatriz E
BE
Marciano
Theo
T
Heller
Steven M
SM
Holland
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D001424:Bacterial Infections / Q000139:chemically induced / Q000401:mortality; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects*; D000069285:Infliximab; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab