Background: Multiple drug hypersensitivity syndrome (MDH) is defined as confirmed drug hypersensitivity reactions (DHRs) to at least 2 chemically and pharmacologically unrelated drugs. Reports of MDH are scarce and poorly specified and studies which diagnose MDH on the basis of positive allergy tests are lacking.

Objective: To evaluate retrospectively the frequency and characteristics of MDH patients in a large database.

Methods: All the patients who consulted and were tested in our Allergy Unit between September 1996 and February 2018, with confirmed MDH will be included. Clinical history and allergy work-up results will be extracted from our Drug Allergy and Hypersensitivity Database (DAHD). The frequency of MDH will be calculated, MDH patients will be described, the most frequent associations of DHRs will be identified and analysed.

Inclusion criteria:

• Patients who consulted at our allergy clinic (University Hospital of Montpellier, France)
• Between September 1996 and February 2018 with a clinical history suggestive of DHR
• Who completed a tailored drug allergy work-up, (including a drug allergy questionnaire, skin tests (STs) and drug provocation tests (DPTs)) and were diagnosed with MDH.

Exclusion criteria:

• the DHR was due to a single component contained in 2 different drug formulations
• in composed drugs;
• there was possible cross-reactivity between the responsible drugs; (iv) the patient had positive but non standardized nor validated (i.e. possibly irritant)
• these STs were followed by a negative DPT;
• DPTs with placebo were positive; (vii) doubtful tests were repeated and eventually considered negative;
• a single DHR was associated with one or more non-drug related contact allergies;
• DPTs elicited subjective manifestations (i.e., isolated pruritus, headache, isolated abdominal pain);
• non-specific histamine release was suspected (e.g., chronic spontaneous - desensitization, rather than a diagnostic work-up was preferred in order to meet the urgent therapeutic needs of individual patients (HIV infected patients, cardiac patients).

Patient consulting in our allergy unit for a suspicion of drug hypersensitivity and who underwent diagnostic drug allergy testing