Delayed Hypersensitivity Reaction to Insulin: A Case Report

Advances in the purification of animal insulin preparations and the introduction of recombinant human insulin have markedly reduced the frequency of insulin hypersensitivity reactions. However, preservatives such as metacresol and other excipients contained in insulin formulations may still induce hypersensitivity reactions, which may be immediate, corresponding to type I hypersensitivity, or delayed, suggesting type III or, more commonly, type IV hypersensitivity according to the Gell and Coombs classification. We report the case of a 25-year-old woman with a 2-year history of type 1 diabetes mellitus who was initially treated with insulin detemir and insulin glulisine. Fifteen months after the initiation of insulin therapy, she developed delayed erythematous skin lesions associated with mild headaches and abdominal pain. Several alternative insulin preparations were subsequently tried, but all reproduced the same symptoms despite antihistamine therapy. Dose splitting and rotation of injection sites failed to improve the reaction. Specific IgE antibodies to human insulin, porcine insulin, protamine, and latex were negative. Skin prick tests performed with different insulin preparations were negative on immediate reading; however, 12 hours later, the patient developed a diffuse and extensive cutaneous reaction, including facial involvement. Because all tested insulin preparations triggered a reaction, their excipient profiles were reviewed, and metacresol was identified as the only common excipient among them. As no metacresol-free insulin preparation was available in Morocco, tolerance induction with insulin was undertaken in an attempt to induce tolerance despite probable hypersensitivity to metacresol. The procedure was successful and resulted in sustained tolerance to all insulin preparations. Insulin allergy remains a rare yet challenging condition that requires careful diagnostic evaluation. Identification of the causative mechanism, including possible hypersensitivity to excipients such as metacresol, is crucial to guide appropriate management.