The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Diagnosis of Sulfonamide Hypersensitivity Reactions by In-Vitro "Rechallenge" with Hydroxylamine Metabolites

Michael J. Rieder, MD; Jack Uetrecht, MD, PhD; Neil H. Shear, MD; Marilyn Cannon; Margaret Miller, MSc; and Stephen P. Spielberg, MD, PhD
[+] Article, Author, and Disclosure Information

Grant Support: Partial support by grants MT7489, MA10036, and MA9716 from the Medical Research Council of Canada. Dr. Rieder is a Centennial Fellow of the Medical Research Council of Canada, and Dr. Shear is a Career Scientist of the Ontario Ministry of Health.

Requests for Reprints: Stephen P. Spielberg, MD, Division of Clinical Pharmacology, Department of Paediatrics, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8.

Current Author Address: Dr. Rieder: Division of Clinical Pharmacology, Department of Paediatrics, Children's Hospital of Western Ontario, London, Ontario N6C 2V5.

Drs. Spielberg and Shear and Ms. Miller: Division of Clinical Pharmacology, Hospital for Sick Children, Toronto, Ontario M5G 1X8. Dr. Uetrecht: Faculty of Pharmacy, University of Toronto, Toronto, Ontario.

From the Hospital for Sick Children, Sunnybrook Medical Centre, and University of Toronto, Toronto, Ontario. For current author addresses, see end of text.†Deceased.

© 1989 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1989;110(4):286-289. doi:10.7326/0003-4819-110-4-286
Text Size: A A A

Study Objective: To determine whether differences in in-vitro detoxification of sulfonamide-reactive metabolites can be detected among the lymphocytes from controls, patients with sulfonamide hypersensitivity reactions, and patients with nonhypersensitivity reactions to the sulfonamide agents.

Design: In-vitro toxicity assay on lymphocytes.

Setting: Clinics for adverse drug reactions in an adult and pediatric tertiary care center.

Patients: Peripheral blood lymphocytes were obtained from 46 normal volunteers and 76 patients referred to the clinic for assessment of adverse drug reactions to sulfonamide agents. Thirty-one patients had clinical histories consistent with a diagnosis of hypersensitivity reaction, whereas 45 patients had clinical histories felt to be inconsistent with a diagnosis of hypersensitivity reaction.

Interventions: Lymphocytes were assayed with tetrazolium to determine toxicity from the hydroxylamine of sulfamethazole.

Measurements and Main Results: The lymphocytes from patients with a history of hypersensitivity reactions showed markedly increased toxicity across a tenfold-concentration toxicity-concentration curve compared with those from controls and patients with a history of nonhypersensitivity reactions. These differences were highly significant (P < 0.01). No difference was found between the toxicity shown by the lymphocytes from controls and that shown by the lymphocytes from patients with a history of nonhypersensitivity reactions.

Conclusions: Metabolic differences in the production and detoxification of reactive metabolites of sulfonamide agents are important determinants of hypersensitivity reactions to these agents. These results suggest that the hydroxylamine derivative of sulfamethoxazole may be a reactive metabolite mediating these reactions. Sulfonamide hydroxylamines are useful in the diagnosis and study of the pathogenesis of hypersensitivity reactions to sulfonamide agents.





Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $42.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.