ReviewThe cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome
Introduction
Azathioprine (AZA) (Imuran, Azasan), the nitroimidazole of 6-mercaptopurine (6-MP), was first used in 1961 as an immunosuppressant for kidney transplantation. Since then it has become an effective corticosteroid-sparing agent in a variety of autoimmune inflammatory diseases to include rheumatoid arthritis, systemic lupus erythematosus, vasculitis, inflammatory bowel disease (IBD), bullous pemphigoid, pemphigus, and others. Dose-dependent toxic side effects (myelosuppression, gastrointestinal side effects, hepatotoxicity) have been well recognized. Less well-characterized is AZA hypersensitivity syndrome and its cutaneous manifestations.
We present two cases of the skin manifestations of AZA hypersensitivity syndrome and review the literature to better characterize the skin findings in this under-recognized but important entity.
Section snippets
Material and methods
From July 2007 through March 2009, the Department of Dermatology at Wilford Hall Medical Center (Lackland AFB, Texas) was consulted on two cases of a “rash” thought to be caused by AZA. The clinical records and photographs of these cases were reviewed. A thorough review of the English-language literature was performed comparing the results of previous case reports with our two patients. The PubMed database was searched using the following terms: azathioprine, hypersensitivity, allergic
Case 1
A 39-year-old Caucasian woman with Crohn's disease presented with vomiting, diarrhea, fever, and arthralgias 4 weeks after starting AZA therapy. Before she started AZA, her thiopurine methyltransferase (TPMT) levels were in the normal range. Her AZA dose at presentation was 100 mg daily. She was also taking prednisone, 30 mg daily. Her AZA was discontinued, and she was admitted to the hospital for work-up and treatment of sepsis and exacerbation of Crohn's disease. Her white blood cell count on
Discussion
AZA is an effective and well-tolerated immunosuppressive agent. While approved by the Food and Drug Administration in the United States for severe rheumatoid arthritis and prevention of rejection in renal transplantation, it has numerous off-label uses. AZA continues to be a useful steroid-sparing medication in the treatment of many systemic autoimmune conditions such as IBD, systemic lupus erythematosus, myasthenia gravis, and others.38 The most common dermatologic conditions treated with AZA
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2019, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :The high frequency of azathioprine hypersensitivity in this population is given more relevance by our finding that febrile azathioprine hypersensitivity is an independent risk factor of relapse, most likely due to the necessity of a switch to less effective maintenance therapy.2 The interval between the start of azathioprine and onset of symptoms (median 14 days), and the most frequently occurring symptoms (fever, malaise, arthralgia, skin eruption) were similar to those described previously.3 Second, hypersensitive patients had a significantly lower TPMT activity compared with controls, with 20% of hypersensitive patients having reduced TPMT activity (≤52 nmol/gHb/hour) compared with 7% of controls.
Funding sources: None.
Conflicts of interest: None declared.
The opinions expressed in this article are that of the authors and do not represent official policy of the United States government, the Department of Defense, the U.S. Air Force or the U.S. Army.