Induction of myasthenia gravis, myositis, and insulin-dependent diabetes mellitus by high-dose interleukin-2 in a patient with renal cell cancer.

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.

The impact of babesiosis on transfusion medicine.

Babesiosis is an emerging zoonotic disease that has begun to have a noticeable impact on transfusion medicine. This is reflected in the growing medical literature on the topic. There has been no review to summarize the various ways in which babesiosis influences transfusion medicine. Babesiosis is the most frequently reported tick-borne pathogen to be transmitted by blood transmission. Until recently, it has been an underrecognized complication of blood transfusion. However, the increased use of blood products for an ever-increasing elderly and immunodeficient patient population has heightened awareness about this disease. Fortunately, the risk of acquiring a symptomatic infection through a blood transfusion is surprisingly low. Nevertheless, babesiosis should be included in the differential diagnosis of a febrile hemolytic illness in recipients of blood transfusions. Infected individuals who become chronic carriers and donate blood during asymptomatic periods pose the greatest risk to the blood supply. The exact risk that this parasite poses to our blood supply remains to be accurately assessed. Reported cases of transmission, to date, have involved only the transfusion of red blood cells (RBCs) and, more rarely, platelets. Transmission of these piroplasms through plasma alone has not been documented. Much of our understanding about this organism evoked host responses and its requirements for in vitro survival has come from studies on non-human vertebrates. These studies have shown that antigenic variation may play a significant role in the development of prolonged parasitemia, that complement-induced changes to erythrocytes are pivotal in facilitating protozoan entry into host RBCs, and that autoimmunity contributes to disease. Severe infections may require lifesaving exchange transfusions and even plasmapheresis. Controlled studies to clearly define specific indications, benefits, and objectives of this therapy are still needed. Despite the development of novel and improved diagnostic tests, these tests are not readily available for the mass screening of blood donors. Improved strategies to assess and prevent transfusion-associated babesiosis are required. Current measures cannot be relied on to identify infected donors with a high degree of sensitivity or to protect susceptible recipients from this parasite.