D2.84 - Avoiding Mislabeling of Drug Allergy in Patients with Recurrent Cutaneous Symptoms

Background: Recurrent cutaneous reactions attributed to multiple drugs frequently lead to extensive allergy investigations. In some patients, psychological factors may contribute to symptom development, complicating diagnostic interpretation.

Case Description: We present the case of a 50-year-old female followed in our hospital between 2007 and 2009, and re-referred in 2023 due to new suspected drug allergies. She had a long-standing history of cutaneous reactions with urticaria and pruritus, as well as respiratory symptoms, temporally associated with drug intake, which prompted extensive allergological investigation.

In 2007, due to a previous history of suspected nonsteroidal anti-inflammatory drug hypersensitivity, oral provocation test with nimesulide (100 mg) was performed, during which the patient developed bronchospasm. In 2011, she experienced urticaria and bronchospasm approximately 12 hours after the first dose of a beta-lactam antibiotic. Over the years, she reported multiple similar episodes, mainly involving cutaneous manifestations after different medications.

Due to this history, several oral provocation tests (OPT) were performed.  During paracetamol OPT, she developed pruritus and flexural eczema 30 minutes after 250 mg, resolving after intravenous methylprednisolone and intramuscular clemastine. OPT with ebastine (10 mg) induced generalized pruritus and eczema. Celecoxib (200 mg) provocation caused mild pruritus after 30 minutes, resolving spontaneously.

After tetanus vaccination, she developed rash, pruritus, and urticaria one hour later, resolving with cetirizine and intravenous methylprednisolone.

In December 2024, cetirizine OPT was performed. The patient developed generalized pruritus and scratching after placebo intake, associated with marked anxiety. After being informed that she had received placebo, cutaneous symptoms resolved spontaneously. An open provocation with cumulative 8 mg cetirizine was subsequently conducted without immediate or delayed reactions.

During analytical investigation, a monoclonal IgG kappa protein was identified and confirmed by immunofixation, consistent with monoclonal gammopathy of undetermined significance.

Conclusion:This case illustrates how recurrent drug-related cutaneous symptoms may be influenced by psychological factors. The occurrence of symptoms after placebo administration and their resolution following reassurance support a non-immunological mechanism. Recognition of stress-related components, appropriate patient counseling, and careful interpretation of provocation tests are essential to prevent misdiagnosis, unnecessary drug avoidance, and inappropriate labeling of drug allergy.