Regression of acanthosis nigricans correlates with disappearance of anti–insulin receptor autoantibodies and achievement of euglycemia in type B insulin resistance syndrome

Autoantibodies directed against specific epitopes in the insulin receptor are rarely the cause of either recurrent hypoglycemia or a severe form of insulin resistance (type B insulin resistance). Type B insulin resistance occurs more commonly in women of African heritage and is frequently associated with a history of other autoimmune diseases. We present the unusual case of a 61-year-old African American woman with a background of autoimmune hypothyroidism and autoimmune hepatitis who developed type 2 diabetes mellitus and marked facial acanthosis nigricans (AN) over a period of weeks. Despite treatment with multiple oral antidiabetic agents, she rapidly developed severe, recalcitrant hyperglycemia and ketoacidosis, requiring hospitalization and intravenous insulin administration for 4 weeks at rates of up to 180 U/h. Immunologic testing revealed a high titer of anti–insulin receptor autoantibodies of both immunoglobulin G and immunoglobulin A classes. After a recurrence of diabetic ketoacidosis despite aggressive management, the patient was treated with a short course of cyclophosphamide; within 10 weeks, she experienced striking improvement of her hyperglycemia as well as marked regression of the AN lesions. Subsequently, the patient also experienced episodes of fasting hypoglycemia, which resolved with a brief course of glucocorticoids. She has since remained euglycemic with no therapy for 5 years. We have documented, for the first time, regression of AN in temporal association with disappearance of circulating anti–insulin receptor autoantibodies and achievement of euglycemia in a patient with type B insulin resistance.