Israel Medical Association Journal

Background: Multiple drug allergy syndrome is a rarely reported clinical condition characterized by an adverse reaction to more than one different class of pharmacologically and structurally unrelated drugs. The pathogenesis may involve immediate-type or delayed-type hypersensitivity.

Objectives: To further characterize patients with MDA[1] in terms of the type of CADR, drug intake and clinical drug suspicion.

Methods: The study group comprised 12 patients (6 males, 6 females) with CADRs[2] showing in vitro drug-induced IFNγ[3] release for multiple drugs, suggesting the presence of MDA. The diagnostic role of in vitro IFNγ release in identifying the culprit drugs was evaluated in terms of clinical data and the results of in vivo tests (withdrawal and/or challenge tests) with the offending drugs.

Results: Clinical relevance was attributed to in vitro drug-induced IFNγ release towards multiple drugs in this series of 12 patients with a variety of CADRs, implying MDA. The results of in vivo tests for the offending drugs confirmed the diagnosis. The main causative agents responsible were antibiotics and non-steroidal anti-inflammatory drugs.

Conclusions: The study further supports the role of a T cell-mediated mechanism in the pathogenesis of MDA. The in vitro drug-induced IFNγ release test may serve as a laboratory tool to identify the culprit drugs associated with this allergy.  

Background: Acute generalized exanthematous pustulosis is a rare pustular severe cutaneous adverse reaction characterized by a rapid clinical course and unique histological findings. It is usually attributed to drugs, although other factors have also been implicated.

Objectives: To analyze demographic, clinical and laboratory data of AGEP[1] cases in Israel, based on the RegisCAR study, a multinational European study.

Methods: Patients included in the present study were actively recruited by the Israeli RegiSCAR network, which comprised 10 dermatology departments and units. The cases were validated by a multinational expert committee of dermatologists based on a standardized scoring system.

Results: Overall, 11 potential cases of AGEP were collected in Israel: 9 (81.8%) definite and 2 (19.2%) possible. The adjusted annual incidence of AGEP in Israel was 0.35/million/year. The nine definite cases that entered the analyses showed a male/female ratio of 0.28 with an age range of 10–60 years. Most cases were reported during the summer months. The clinical course and laboratory findings in most of our patients were in accordance with previous reports. A drug etiology was suspected in the majority of cases and consisted of analgesics (66.7%), antibiotics (22.2%) and non-steroidal anti-inflammatory drugs (11.1%) as the main culprit drugs.

Conclusions: Whereas the clinical and laboratory findings of AGEP in Israel corresponded to the reported features of AGEP in the literature, unique findings consisting of marked female predominance, seasonality and a profile of culprit drugs were noted.

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