Does Allergic Reaction to a Sulfonamide Preclude Use of All Sulfa Drugs?
Thrombocytopenic purpura developed in my patient after 8 days of treatment with trimethoprim(Drug information on trimethoprim)/sulfamethoxazole (TMP/SMX). Should I advise this patient to avoid sulfa drugs in the future? And would the patient also be precluded from using a sulfonylurea?
—— Isaac Blum, MD
Bronx, NY
Sulfonamides are among the most commonly reported causes of drug-induced thrombocytopenia. 1 Affected patients typically present with purpura and platelet counts of less than 20,000/μL after about 7 days of therapy.1-3 On rechallenge, profound thrombocytopenia develops rapidly within 1 to 2 days.3 The rate of thrombocytopenic purpura (TP) attributed to TMP/SMX was found to be 38 cases per 1 million users per week in one study.4
The mechanism by which the sulfonamides cause thrombocytopenia is known as the quinine(Drug information on quinine)-type reaction. 5 On exposure to the sensitizing drug, antibodies are induced that bind to the glycoprotein IIb/IIIa complex on platelet surfaces. This ultimately leads to platelet destruction. The antibodies induced are highly drugspecific, exhibiting minimal cross-reactivity within the same pharmacological class. Curtis and colleagues6 found that only 1 of 15 sulfonamide-induced antibodies cross-reacted between sulfamethoxazole(Drug information on sulfamethoxazole) and sulfisoxazole. However, advise patients to avoid the causative drug permanently; antibodies likely persist.5
Your patient’s course—the development of TP after about 1 week of therapy—is typical for drug-induced immune thrombocytopenia.5 I would advise him to avoid TMP/SMX but not necessarily all sulfa drugs. As for oral hypoglycemic agents, such as sulfonylureas, TP has been reported at a much lower rate—1.2 cases per 1 million users per week—with these agents.4 Moreover, true cross-allergenicity between sulfonamide antibiotics and sulfonamide non-antibiotics is rare.7 Nonetheless, patients with allergic reactions to antibiotics are at higher risk for allergic reactions to other pharmacological classes as well.8
—— Nathan A. Pinner, PharmD
PGY2 Pharmacy Internal Medicine Resident
University of Tennessee College of Pharmacy
Methodist University Hospital
Memphis
—— Timothy H. Self, PharmD
Professor of Clinical Pharmacy
University of Tennessee Health Science Center
Methodist University Hospital
Memphis
1. George JN, Raskob GE, Shah SR, et al. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med. 1998;129:886-890.
2. Herrington A, Mahmood A, Berger R. Treatment options in sulfamethoxazole- trimethoprim-induced thrombocytopenic purpura. South Med J. 1994;87: 948-950.
3. Hamilton HE, Sheets RF. Sulfisoxazole-induced thrombocytopenic purpura immunologic mechanism as cause. JAMA. 1978;239:2586-2587.
4. Kaufman DW, Kelly JP, Johannes CB, et al. Acute thrombocytopenic purpura in relation to the use of drugs. Blood. 1993;82:2714-2718.
5. Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med. 2007;357:580-587.
6. Curtis BR, McFarland JG, Wu GG, et al. Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa complex. Blood. 1994;84:176-183.
7. Brackett CC, Singh H, Block JH. Likelihood and mechanisms of cross-allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group. Pharmacotherapy. 2004;24:856-870.
8. Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med. 2003;349: 1628-1635.