Erythema Nodosum–like Eruption as a Manifestation of Azathioprine Hypersensitivity in Patients With Inflammatory Bowel Disease

Abstract

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 druginduced rash with eosinophilia and systemic symp-toms. 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.

Azathioprine Hypersensitivity Presenting as Cardiogenic Shock and Sweet's Syndrome in a Patient with Microscopic Polyangiitis

“…The present case has all of the features (except for a documented fever) consistent with the criteria for drug-induced Sweet's syndrome as proposed by de Fonclare and co-authors (18).…”

The cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome

“…Unlike dose-dependent side effects, these reactions occur regardless of TPMT levels. Abnormal metabolism of AZA does not appear to predict erythema nodosum, 9 Sweet's syndrome, 6 or other manifestations of disease. All cases reviewed showed either a normal TPMT level, as in our cases, or did not report the TPMT level (see Table I).…”

“…Most of the cases reported as neutrophilic dermatoses were from recent case reports in which a biopsy had been performed. [1][2][3][4][5][6]9,14 Several earlier case reports had more detailed descriptions of skin findings suggestive of neutrophilic dermatoses, but were not biopsy confirmed. [15][16][17] If the clinical cases suggestive of neutrophilic dermatoses were included with confirmed cases, then 88% (29/33) of patients presenting with cutaneous findings would have a neutrophilic dermatosis.…”

Skin Side Effects of Inflammatory Bowel Disease Therapy

“…1,2 Exposure to thiopurines might as well increase the risk of developing viral infections, 3 some of which may have cutaneous manifestations, such as herpes simplex virus or varicella zoster virus infections. Furthermore, these infections, which for most of the times are quite trivial, may behave more aggressively in immunocompromised patients.…”