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Drug‐induced hypersensitivity syndrome complicated with concurrent fulminant type 1 diabetes mellitus and Hashimoto’s thyroiditis

Drug-induced hypersensitivity syndrome (DIHS), or drug rash with eosinophilia and systemic symptoms, is a severe adverse drug reaction. Diagnostic criteria for DIHS include rash, fever, lymphadenopathy, hematological abnormality, history of causative drug administration, internal organ involvement, and activation of human herpes virus 6 (HHV-6). A 71-year-old female had been treated with mexiletine for arrhythmia 24 days prior to the occurrence of skin rash. She was referred to our hospital with a generalized maculopapular rash and periorbital/facial edema studded with pinhead-sized pustules (Fig. 1a) for 17 days, and intermittent fever, edema, and general fatigue for 10 days. Physical examinations revealed erosion on oral mucosa and axillary lymphadenopathy. Laboratory findings showed hyperglycemia (466 mg/dl), normal glycosylated hemoglobin A1c (6.0%), low serum C-peptide levels (<0.05 ng/ml), and negative diabetes-related antibody titers for islet cell, insulinoma-associated protein-2, and glutamic acid decarboxylase. Both antinuclear antibody (47.1; normal, <9.9) and anti-Sjögren’s syndrome A antibody (104.4; normal, <19.9) indexes were elevated. The titer of anti-cytomegalovirus (CMV) IgM index was elevated (1.79; normal, <0.8; Table 1). Skin biopsy on the trunk demonstrated infiltrations of lymphocytic cells in the epidermis with dyskeratotic cells, liquefaction, and perivascular infiltrations of lymphocytic cells in the dermis (Fig. 1b). Accordingly, we diagnosed the patient with DIHS in conjunction with fulminant type 1 diabetes mellitus. We discontinued medication and initiated systemic corticosteroid administration (prednisolone, 60 mg daily) and subcutaneous insulin injection therapy, which controlled DIHS and diabetes. Twenty-eight days after the onset of skin eruption, the patient exhibited elevated levels of anti-thyroglobulin (5.1 U/ml; normal, <0.299) and antimicrosomal antibodies (44.3 U/ml; normal, <0.299), and decreased levels of free triiodothyronine (1.23 pg/ml; normal, 2.97–4.51) and free thyroxine (0.72 ng/dl; normal, 0.81–1.58). These findings suggested a diagnosis of Hashimoto’s thyroiditis; accordingly, daily administration of 25 mg sodium levothyroxine was initiated. On the 72nd day after onset of skin rash, an elevated titer of anti-HHV-6-IgG (1 : 160) compared with that measured 355