Sera from Patients with Multiple Drug Allergy Syndrome Contain Circulating Histamine-Releasing Factors

BACKGROUND: A subset of drug-intolerant patients show a marked propensity to react to several chemically unrelated antibacterial drugs. This condition is termed multiple drug allergy syndrome (MDAS). The pathogenesis of MDAS is still unclear. A possible mechanism is that a nonspecific patient-related factor leading to direct histamine release from mast cells and basophils is involved. We investigated whether a patient-related facilitating factor such as the clinically unapparent presence of circulating histamine-releasing factors may represent a nonspecific mechanism underlying drug-induced histamine release in patients with MDAS. METHODS: 38 otherwise healthy adults with a history of acute urticaria following the ingestion of antibacterial drugs 18 subjects with MDAS (patients) and 20 monosensitive subjects (drug-allergic controls) on the basis of both clinical history and single-blind peroral challenges with alternative substances and 20 subjects without a history of drug allergy (normal controls) underwent an autologous serum skin test (ASST). IgE specific for beta-lactams was measured in sera from 25 subjects (11 patients and 14 drug-allergic controls) with a history of amoxicillin intolerance. Sera from 13 patients and 5 drug-allergic controls (all positive on ASST) were used in the in vitro histamine release assay using basophils from 3 normal donors. RESULTS: 17 of 18 patients (94%) versus 8 of 20 drug-allergic controls (40%) showed an unequivocal wheal-and-flare reaction on ASST (p < 0.05). Skin reactions were generally more intense in the patient group. In one MDAS patient, the ASST was not assessable due to dermographism. No normal control was positive on ASST. Sera from 3 of 13 patients (23%) versus 0 of 6 drug-allergic controls (not significant) induced significant histamine release from basophils of normal donors. IgE specific for beta-lactams was detected in sera from 1 of 11 patients (9%) versus 5 of 14 drug-allergic controls (36%) (not significant). CONCLUSION: Most patients with MDAS and more than one third of subjects with a history of hypersensitivity to a single antibacterial drug were characterized by the presence of circulating histamine-releasing factors. Such factors might play a role in drug-induced adverse reactions observed in these patients.