ALLERGY 1999:54:1224^1232 . COPYRIGHT G MUNKSGAARD 1999 . ISSN 0105-4538 . ALL RIGHTS RESERVED Desensitization after fever induced by mesalazine M.A. Gonzalo*, M.M. Alcalde, J.M. Garcõ Âa, M.I. Alvarado, L. Ferna  ndez Key words: 5-aminosalicylic acid; desensitization; drug fever; mesalazine. . Mesalazine is the 5-amino derivative of salicylic acid (5-ASA), an anti-in¯ammatory agent structurally related to the salicylates which is effective in in¯ammatory bowel diseases. It is considered to be the active component of sulfasalazine (sulfapyridine and 5-ASA). We report a case of successful desensitization to mesalazine in a patient who had had fever on two previous occasions when mesalazine had been administered. The patient was a 29-year-old man with a history of Crohn's disease from 1987. He remained asymptomatic without treatment from 1991, but he suffered a slight recurrence in September 1997, con®rmed by colonoscopy and biopsy, and started mesalazine (Claversal 1 , SB SmithKline Beecham) as maintenance treatment (1 g/8 h). Five days after beginning the treatment, he developed fever (up to 408C), tiredness, headache, thoracic pain, myalgias, and arthralgias. The patient improved without treatment by 3±4 days after mesalazine was stopped. Two weeks later, mesalazine was readministered, and similar symptoms occurred, but earlier (within 3 days). He was admitted to the hospital. Physical examination did not reveal abnormalities. His axillar temperature was 38.58C. Analyses (complete blood count, eosinophil count, blood chemistries, liver enzymes, coagulation studies, complement levels, serum protein electrophoresis, immunoglobulin levels, and urinalysis), chest radiography, and electrocardiogram were normal, excepting erythrocyte sedimentation rate (45 mm in the ®rst hour). Blood, urine, and feces cultures were negative. Abdominal echography showed a thickened bowel wall in the right lower quadrant. Mesalazine was discontinued, and treatment with prednisone (30 mg/day orally) was initiated. The patient recovered and was discharged 6 days later. Prednisone was subsequently tapered. He had not been treated with mesalazine or sulfasalazine previously. There was no past history of drug allergy, atopy, or ASA intolerance. The patient was referred to us 6 weeks after the last episode. He had ®nished the prednisone treatment 2 weeks before, and he was asymptomatic. After obtaining written, informed consent, we performed single-blind, placebo-controlled oral challenge tests in the hospital. Pure mesalazine powder was provided by the manufacturer. Placebo and mesalazine were administered to the patient in white opaque capsules on different days, with an interval of 2 weeks between each challenge test. The same protocol of administration was used for placebo and mesalazine: the ®rst day, progressive doses of 50, 100, 150, and 200 mg with an interval of 1 h in the hospital; then, 500 mg/8 h at home for 7 days. Placebo challenge was negative, but 24 h after starting mesalazine, the patient developed symptoms as described previously; 12 h later, he presented with 38.58C fever. He was treated with paracetamol and methylprednisolone, improving 12±24 h later. Because of the several fever episodes caused by mesalazine and the lack of better Table 1. Mesalazine desensitization protocol Solution 10 mg/ml Solution 100 mg/ml Day Dose Day Dose 1 0.1 ml=1 mg 17 3 ml=300 mg 2 0.2 ml=2 mg 18 4 ml=400 mg 3 0.4 ml=4 mg 19 5 ml=500 mg 4 0.8 ml=8 mg 20 6 ml=600 mg 5 1.5 ml=15 mg 21 7 ml=700 mg 6 2 ml=20 mg 22 8 ml=800 mg 7 3 ml=30 mg 23 9 ml=900 mg 8 4 ml=40 mg 24 10 ml=1000 mg 9 5 ml=50 mg 25 12 ml=1200 mg 1 10 6 ml=60 mg 26 14 ml=1400 mg 1 11 7 ml=70 mg 27 16 ml=1600 mg 1 12 8 ml=80 mg 28 18 ml=1800 mg 1 13 9 ml=90 mg 29 20 ml=2000 mg 1 14 10 ml=100 mg 30 22 ml=2200 mg 2 15 15 ml=150 mg 31 26 ml=2600 mg 2 16 20 ml=200 mg 32 30 ml=3000 mg 2 1 Divided into two doses. 2 Divided into three doses. Desensitization to mesalazine in patient with fever caused by this drug. 1224