Acute generalized exanthematous pustulosis caused by dihydrocodeine or codeine: A case-based review

Dihydrocodeine is an effective antitussive agent that inhibits the cough reflex by interacting with opioid receptors in the brain. It is easily available in pharmacies without a prescription, which may contribute to a lack of awareness about potential drug hypersensitivity reactions. In the first reported case in Korea, a 29-year-old man developed acute generalized exanthematous pustulosis (AGEP) after consuming an over-the-counter cold medicine containing dihydrocodeine. He was admitted to the Emergency Department with high fever and full-body skin rashes that appeared 3 hours after taking the medicine. His EuroSCAR AGEP score was 9, with symptoms improving upon discontinuation of dihydrocodeine and the application of topical steroids. AGEP caused by dihydrocodeine, including codeine, is very rare, with 3 cases reported worldwide. By analyzing AGEP cases due to dihydrocodeine or codeine, we identified that risk factors for the development of AGEP from dihydrocodeine include a history of psoriasis and the presence of an IL36RN mutation, which result in the activation ofTh17 in the blood or the skin. In cases of AGEP caused by dihydrocodeine, it is also recommended to discontinue codeine due to cross-reactivity with dihydrocodeine. Additionally, patients with AGEP due to dihydrocodeine may be able to use other opioid classes, such as morphine or tramadol, due to low cross-reactivity. ( Allergy Asthma Respir Dis 2024;12:177-183)