The follFigure.owing observations were made in 5 patients (3 men and 2 women) between January 23, 2004, and May 21, 2006 (Table 1 and Table 2). Four patients had Crohn disease, and 1 patient had ulcerative colitis. All patients had levels of thiopurine methyltransferase activity within the normal range. Azathioprine treatment was introduced in all patients as a corticosteroid-sparing agent. The clinical symptoms occurred, on average, 8 to 18 days after the initiation of azathioprine treatment. All patients had high fever (temperature, 39°C) and skin eruption that was localized initially to the lower limbs. Patient 2 and patient 5 had secondary extension of the disease to other body parts. In 3 patients (patients 1, 4, and 5), the skin eruptions comprised painful erythematous nodules scattered on the legs that were suggestive of erythema nodosum (Figure, A). In 2 patients (patients 2 and 3), erythematous plaques with superficial pustules or isolated pustules were observed on the legs (Figure, C and D). Other manifestations included joint, abdominal, and muscular pain, with worsening of digestive symptoms in 1 patient (patient 2). Biologically, there was a constant increase in neutrophil counts in all patients, with acute inflammation and high levels of serum C-reactive protein. None of the patients initially had hypereosinophilia. Results of microbiological analyses were negative: cultures of blood, urine, and pustules were devoid of bacteria and fungi. Histological examination of skin biopsy specimens of nodules revealed predominantly septal inflammation of the hypodermis with normal aspects of the epidermis and dermis. In addition, the infiltrate comprised lymphocytes and macrophages with few neutrophils (Figure, B). There was no sign of vasculitis. Analysis demonstrated intraepidermic spongiotic pustules containing neutrophils; the surrounding epidermis was also infiltrated with neutrophils (Figure, E and F). No sign of vasculitis was observed in the dermis. In 1 patient (patient 3), hepatitis and pancreatitis were diagnosed (Table 2). The initial suspected diagnoses were infectious disease in 3 patients (patients 1, 3, and 4), digestive disease relapse in 1 patient (patient 2), and hypersensitivity in 1 patient (patient 5). After interruption of azathioprine therapy and initiation of corticosteroid therapy in 2 patients (patients 3 and 1), complete regression of all clinical and biological abnormalities, including neutrophilia, was noted within 2 weeks and persisted afterward. Three patients were rechallenged with azathioprine, the metabolic equivalent 6-mercaptopurine, or both. The rechallenge was scheduled at least 1 month after resolution of the initial symptoms. In all patients, relapse of the initial symptoms occurred within hours. In 1 patient (patient 4), this relapse was complicated by a sharp decrease in blood pressure. Symptoms again resolved within hours after drug withdrawal.