Evaluation and management of a patient with multiple drug allergies

Multiple drug allergy syndrome (MDAS) is a clinical diagnosis made in patients with adverse reactions to two or more structurally unrelated drugs with an underlying immune-mediated mechanism causing the reaction. The evaluation of a patient with MDAS begins with a comprehensive drug allergy history and consideration of the underlying immune mechanism for each reaction. Skin testing is a useful diagnostic tool; however, the only validated immediate hypersensitivity skin testing is for penicillin where the antigenic determinants have been identified. Skin testing to most other drugs, although not validated, can be considered using a nonirritating concentration (NIC). In general, skin test positivity using an NIC suggests that the drug should be avoided, but a negative result does not rule out an IgE-mediated allergy. A test dose, also called a drug provocation test, graded oral challenge, or incremental challenge, should be performed when there is a low likelihood of an IgE-mediated mechanism for the reaction. In patients with a recent IgE-mediated hypersensitivity reaction or positive skin testing with no reasonable alternative treatment options, desensitization protocols can be used to allow the patient to safely receive a necessary drug. The evaluation of patients with MDAS is both challenging and time-consuming for the practicing allergist, who must systematically evaluate each reaction to help determine which drugs can be safely used again in the future. The molecular mechanisms and risk factors for this condition remain poorly understood, but research to further understand this condition is ongoing.