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Anne-Laure de Fonclare, MD; Kiarash Khosrotehrani, MD, PhD; Sélim Aractingi, MD, PhD; Paul Duriez, MD; Jacques Cosnes, MD; Laurent Beaugerie, MD, PhD

Arch Dermatol. 2007;143(6):744-748.

Background  Clinical manifestations of hypersensitivity to azathioprine may mimic symptoms of the initial disease. We report 5 cases of peculiar skin hypersensitivity reactions to azathioprine in patients with inflammatory bowel disease.

Observations  In 5 patients with a recent azathioprine regimen, manifestations appeared between 8 and 18 days after drug introduction. All patients had a high fever. Three patients initially had erythema nodosum; 2 patients had sterile pustules. All had elevated neutrophil counts and serum C-reactive protein levels, whereas eosinophil counts were normal, ruling out drug-induced rash with eosinophilia and systemic symptoms. In 3 patients who were rechallenged with azathioprine or with 6-mercaptopurine, dermatological lesions recurred within hours.

Conclusions  Erythema nodosum and pustules are rarely reported manifestations of azathioprine hypersensitivity. Both skin lesions may be related to the clinical activity of inflammatory bowel disease. Relapse of such lesions shortly after thiopurine rechallenge should raise the hypothesis of hypersensitivity rather than pharmacological manifestations.

Author Affiliations: Department of Dermatology, Hôpital Tenon (Drs de Fonclare, Khosrotehrani, and Aractingi), Université Pierre et Marie Curie (Drs Khosrotehrani, Aractingi, Cosnes, and Beaugerie), and Departments of Pathology (Dr Duriez) and Gastroenterology (Drs Cosnes and Beaugerie), Hôpital Saint-Antoine, Assistance Publique–Hôpitaux de Paris, Paris, France.

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