Carbamazepine-Induced Drug-Induced Hypersensitivity Syndrome With Primary Adrenal Insufficiency: A Case Report

Drug-induced hypersensitivity syndrome (DIHS), also known as drug reaction with eosinophilia and systemic symptoms, is a severe adverse reaction involving multiple organs. We describe a case of carbamazepine (CBZ)-induced DIHS with rare primary endocrine complications. A 71-year-old Japanese man developed generalized erythroderma with systemic symptoms 6 weeks after the initiation of CBZ at 200 mg/day for trigeminal neuralgia. Clinical evaluation revealed HLA-A*31:01 positivity, marked eosinophilia, elevated inflammatory markers, and multiorgan involvement, including acute interstitial nephritis and primary hypothyroidism. Primary adrenal insufficiency became clinically evident after levothyroxine administration. Chest computed tomography revealed enlarged cervical and axillary lymph nodes, an abscess in the right upper lobe, and emphysema in both lungs. Although HHV-6 reactivation was not detected, the patient's clinical course was consistent with that of atypical DIHS. The patient was treated by immediate discontinuation of CBZ and initiation of systemic corticosteroids after thyroid hormone replacement therapy, which resulted in clinical improvement. To our knowledge, this is the first report of primary adrenal insufficiency as a manifestation of CBZ-induced DIHS in Japan. Carriers of HLA-A*31:01 require comprehensive endocrine and systemic monitoring because DIHS can precipitate rare primary endocrine gland failure. Pre-prescription HLA genotyping remains an essential preventive strategy for this high-risk population.