Autoimmune Conditions In Malignant Diseases

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Numerous autoimmune phenomena have been reported in malignancies. The autoimmune conditions reported in malignancies may be regarded as paraneoplastic syndromes or syndromes that cannot be explained by the local effects of the tumor or its metastases.

2.1. Autoimmune Hemolytic Anemia [1-9]

Autoimmune hemolytic anemia is the most common autoimmune syndrome associated with cancer and is characterized by an increased destruction of red blood cells by autoantibodies. In one series, a malignant disease was found in 14% of 175 patients with autoimmune hemolytic anemia [2]. Usually, autoimmune hemolytic anemia is associated with lymphomas and leukemias [4], However, autoimmune hemolytic anemia has been described in solid tumors including cancer of the lung, breast, colon, cervix [5], hypernephroma and melanoma. In most patients with paraneoplastic autoimmune hemolytic anemia, the tumor had already metastasized. Moreover, steroid treatment has been found to be much less effective in paraneoplastic autoimmune hemolytic anemias than in idiopathic autoimmune hemolytic anemias [9]. In most cases of malignancy related autoimmune hemolytic anemia, the autoantibodies are of the warm auto-natibody type, however, there are reports of cancer patients with cold agglutinins [10-12]. The mechanism of autoimmune hemolytic anemia secondary to neoplasia is unknown, and several hypotheses have been proposed including release of tumor-associated antigens mimicking to red blood cell antigens, production of autoantibodies by the tumor itself in case of B-cell lymphomas, and adsorption of immune complexes, formed as a result of the immune reaction to the tumor, on the erythrocyte membrane [9].

2.2. Autoimmune Thrombocytopenia [13-19]

An autoimmune thrombocytopenia similar to idiopathic thrombocytopenic purpura (ITP) has been reported in neoplastic diseases. In different series a ma lignant disease was found in 4—19% of patients with thrombocytopenia and purpura [13]. In most cases, paraneoplastic autoimmune thrombocytopenia was associated with lymphoproliferative diseases, especially Hodgkin's disease, however, it was also described in epithelial cancers [18-19], Corticosteroid treatment of paraneoplasitc autoimmune thrombocytopenic is less effective than in ITP, but splenectomy may induce long remissions [14], As in the case of paraneoplastic autoimmune hemolytic anemia, several mechanisms have been proposed to explain the development of thrombocytopenia in malignancies and these include cross-reaction between a tumor-associated and thrombocyte antigens, or adhesion of immune complexes to the thrombocyte membrane [18],

2.3. Autoimmune Neutropenia

Autoimmune neutropenia is a rare disorder described in a few patients with Hodgkin's and non-Hodgkin's lymphomas. In these patients the neutropenia was attributed to IgG autoantibodies directed against leukocytes and white blood cell precursors in the bonemar-row [20-22],

2.4. Myasthenia Gravis [23-24]

Myasthenia gravis is a neuromuscular disease characterized by weakness and fatigability of skeletal muscles. The disease is caused by the production of antiacetylcholine receptor antibodies which block and destroy the acetylcholine receptors. The association between myasthenia gravis and thymomas is a well known one. The incidence of myasthenia gravis in patients with thymoma is approximately 35%. In some patients with thymoma only antiacetylcholine receptor antibodies were described without apparent myasthenia gravis. The mechanisms for this association are still unknown.

2.5. Eaton-Lambert Syndrome [25]

This syndrome which clinically resembles myasthenia gravis is caused by antibodies that react with voltage-gated calcium channels on the presynaptic neuromuscular junction. The binding of these antibodies to the calcium channels prevents release of acetylcholine which induces the clinical manifestations of the syndrome. Eaton-Lambert syndrome has been described in patients with small cell carcinoma of the lung, sometimes appearing long before the tumor becomes apparent.

2.6. Dermatomyositis [26-31]

Dermatomyositis and polymyositis are conditions believed to be of autoimmune etiology in which the skeletal muscle is damaged by an inflammatory process consisting mainly of lymphocytic infiltration. In polymyositis there are no skin lesions, but in dermatomyositis there is a characteristic skin rash. As early as 1916, an increased incidence of cancer was noted in patients with polymyositis [26], and since then this association has been reported in many other studies. Recently, the risk of cancer was estimated in a cohort of 788 patients with dermatomyositis or polymyositis in Sweden [31]. Among the 396 patients with polymyositis, cancer was diagnosed in 9% of the patients and the relative risk of cancer was 1.7-1.8. Among the 392 patients with dermatomyositis, cancer was diagnosed in 15% of the patients and the relative risk of cancer was 2.4 in male and 3.4 in female patients. These results demonstrated a moderate but significant increase in the incidence of cancer in patients with polymyositis and a significant increase in the incidence of cancer in patients with dermatomyositis, especially in females.

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