title: Induction of myasthenia gravis, myositis, and insulin-dependent diabetes mellitus by high-dose interleukin-2 in a patient with renal cell cancer.
abstract: Interleukin-2 is an effective agent against renal cell carcinoma and melanoma, but it has been associated with autoimmune sequelae such as hypothyroidism and vitiligo. A 64-year-old man with non-insulin-dependent diabetes and metastatic renal cell carcinoma developed insulin-dependent diabetes after his first cycle of therapy with high-dose (HD) interleukin-2. After additional therapy with interleukin-2, the patient developed generalized myasthenia gravis (MG) and polymyositis, both of which responded to treatment with corticosteroids and plasmapheresis. To investigate the role of IL-2 in the development of these autoimmune complications, autoantibody titers were assayed from serum obtained before and after IL-2 treatment and after treatment with corticosteroids plus plasmapheresis. Before IL-2 treatment, the patient had antibodies directed against insulin, islet cell antigens, and striated muscle. Acetylcholine receptor antibody levels were normal before starting IL-2. After treatment with IL-2, the patient developed acetylcholine receptor binding antibodies and exhibited an increase in the striated muscle antibody titer from 1:40 to 1:160. Recovery from the MG and polymyositis was associated with substantial decreases in the acetylcholine receptor and striated muscle antibody titers. These findings suggest that HD IL-2 accelerated the progression of latent autoimmune diabetes and myositis in this patient whose tolerance to islet cell antigens and striated muscle had already been broken and precipitated a break in tolerance to the acetylcholine receptor resulting in the development of MG. This case demonstrates the importance of prompt recognition of IL-2-induced MG and shows how this complication can be successfully managed with aggressive therapy.
authors.affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Paula G
authors.initials: PG
authors.lastname: Fraenkel
authors.forename: Seward B
authors.initials: SB
authors.lastname: Rutkove
authors.forename: Jean K
authors.initials: JK
authors.lastname: Matheson
authors.forename: Mary
authors.initials: M
authors.lastname: Fowkes
authors.forename: Marie E
authors.initials: ME
authors.lastname: Cannon
authors.forename: Mary-Elizabeth
authors.initials: ME
authors.lastname: Patti
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Jared A
authors.initials: JA
authors.lastname: Gollob
mesh_terms: D002292:Carcinoma, Renal Cell / Q000150:complications* / Q000188:drug therapy; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000150:complications* / Q000188:drug therapy; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000139:chemically induced*; D009220:Myositis / Q000139:chemically induced*
chemical_list: D007376:Interleukin-2