Multiple-drug Intolerance Syndrome: Clinical Findings and Usefulness of Challenge Tests

Background: Multiple-drug intolerance syndrome (MDIS) is characterized by adverse reactions to several classes of chemically unrelated drugs.

Objective: To analyze all patients with a history of adverse reactions to at least 3 drugs at the Allergy Unit of Policlinico Gemelli in a 6-year period to better characterize patients with MDIS and to find safe alternative drugs.

Methods: We studied 480 patients (aged >16 years) with a history of adverse reactions to at least 3 unrelated drugs and with negative allergy test results. Patients who had experienced mild adverse reactions that remitted spontaneously underwent challenge tests without any premedication (group A). Patients with a clinical history of moderate reactions received sodium cromolyn, 500 mg, before the challenge (group B). Patients with a clinical history of severe reactions or undergoing parenteral challenges were given an antihistamine 30 minutes before the challenge (group C).

Results: In group A, 491 tolerance challenge tests were performed: 414 had negative results and 77 had positive results. In group B, 1,077 tolerance challenge tests were performed: 956 had negative results and 121 had positive results. In group C, 240 tolerance challenge tests were performed: 214 had negative results and 26 had positive results. Comparing the tolerance of alternative drugs in groups A and B, groups A and C, and groups B and C, no significant results were observed (P = .24, .14, and .44, respectively).

Conclusions: Patients with MDIS can tolerate alternative drugs. Premedication with sodium cromolyn or oral H1-antihistamines may be useful in preventing adverse reactions.