D2.45 - Fixed Drug Eruption Due to Fenofibrate Hypersensitivity

Fixed drug eruption (FDE) is a type IV hypersensitivity reaction mediated by CD8+ T lymphocytes and characterized by recurrent lesions at the same sites upon re-exposure to the culprit drug typically resolving with residual hyperpigmentation. Fenofibrate, widely used for dyslipidemia and hypertriglyceridemia, is primarily linked to muscular adverse effects. Although different drugs have been implicated, fibrates are rarely associated with FDE.

We present a 38-year-old male with pollen allergy, dyslipidemia, morbid obesity, migraine and gout, treated with pravastatin/fenofibrate 40/160 mg, enalapril 5 mg, metformin 850 mg, allopurinol 300 mg, febuxostat 80 mg and topiramate 50 mg. After 15 days of therapy, he developed erythematous-violaceous macules evolving into pruritic papules and vesicles on the elbows, inframammary region, lower back, and genital area without mucosal involvement. Lesions resolved after discontinuation of all medications leaving residual hyperpigmentation. Upon reintroduction of treatment, identical lesions recurred at the same sites. The patient later tolerated enalapril but not the other drugs. Patch tests (30% in petrolatum) were performed on healthy and affected skin with all suspected drugs. Given the positive response to fenofibrate, additional tests were conducted with other fibrates (gemfibrozil, bezafibrate) and ketoprofen to evaluate potential cross-reactivity, considering their similar photosensitizing capacity attributed to the photoexcited chemical structure containing a benzophenone moiety, as observed in fenofibrate.

Patch testing revealed a strong positive reaction to fenofibrate at 48 and 96 hours readings, confirming its role as the causative agent. Tests with other fibrates and ketoprofen were negative suggesting no cross-reactivity. The patient tolerated metformin, dexketoprofen, ibuprofen and paracetamol after the allergy study.

This case highlights a rare presentation of FDE induced with high probability by fenofibrate without showing cross-reactivity with other fibrates or ketoprofen. Accurate identification of the responsible drug through patch testing is essential to prevent recurrence and guide safe therapeutic alternatives in patients requiring lipid-lowering therapy.