LAUSR

Dear Editor, A 60-year-old man presented to our hospital's Emergency Department with multiple erythematous lesions, blisters on the trunk and limbs, and mucosal erosion. He had started taking methazolamide (100 mg/day) 3 weeks earlier for ocular lymphedema; however, after 2 weeks of this therapy his eyelid and conjunctiva had become congested and swollen. Two days later, he had a fever of 38.5 C and had developed multiple itchy, iris-like, erythematous lesions on his chest, abdomen, and back that extended to involve his limbs, palms, and soles and was accompanied by erosion of oral and penile mucosa. He had taken cetirizine (10 mg/day orally) for 2 days before presenting to our emergency department, with no improvement. He had a history of hypertension for 6 years and no history of drug allergy. Physical examination revealed multiple various-sized, target-like, red macules, papules, erythema, and blisters and bulla. The Nikolsky sign was positive over the face, scalp, trunk, proximal limbs, palms, and soles. He had severe stomatitis with erosion and hemorrhagic crusting on his lips, swollen eyelids, congested conjunctiva, and mucosal erosion of the penis. No lymphadenopathy was detected. There was skin detachment on over 30% of his body surface area (Figure 1). The results of viral serology were negative. A diagnosis of toxic epidermal necrolysis (TEN) was made. Intravenous methylprednisolone (80 mg/day) and intravenous immunoglobulin (30 g/day) were administered for 7 days. He was also given one subcutaneous injection of etanercept (50 mg) on the fourth day of this therapy for ongoing epidermolysis. His skin and mucosal lesions improved significantly, and the dosage of methylprednisolone was gradually tapered and stopped (Figure 2). No flares occurred in the first 3 weeks after stopping medication. Methazolamide, a carbonic anhydrase inhibitor, the chemical structure of which resembles that of sulfonamides. However, it carries a high risk of inducing delayed-type hypersensitivity. Methazolamideinduced Stevens-Johnson syndrome (SJS)/TEN reportedly occurs frequently in Asian individuals (Table 1). A relationship between human leukocyte antigen (HLA) type and drug reactions has been identified. For example, HLA-B*15:02 is reportedly associated with hypersensitivity to aromatic anticonvulsant drugs in Chinese individuals. HLA testing by polymerase chain reaction sequencing of specific oligonucleotides revealed HLA-B*59:01 and HLA-Cw*01:02 alleles in our patient; however, HLA-A*24:02 alleles were not detected. Methazolamide-induced reactions in individuals with HLAA*24:02 and HLA-Cw*01:02 alleles have been reported only in a few Korean patients. To the best of our knowledge, this is the first report of coexistence of HLA-B*59:01 and HLA-Cw*01:02 alleles in a Han Chinese patient with methazolamide-induced TEN. Our patient's HLA test results indicate that HLA-B*59:01 and HLA-Cw*01:02 alleles may be potential predictors of severe reactions to drugs. Screening for HLA before prescribing methazolamide to Asian individuals may be indicated. Tumor necrosis factor alpha (TNF-α) is considered to participate in the pathophysiological process of epithelial cell death in drug eruptions. Though glucocorticoids and immunoglobulin are commonly