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Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases, are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Systemic inflammatory rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma or dermatomyositis, may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. Immunosuppressive drugs and biological agents may also be carcinogenic. However, sustained inflammatory activity seems to be the primary risk factor for malignancies in autoimmune diseases. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in rheumatoid arthritis and other autoimmune diseases.

As a result of increasing life expectancy of lupus patients, malignant disorders have become major determinants of morbidity and mortality. The objectives of this study were to analyze cancer-associated morbidity and mortality, the type of malignancies in Hungarian lupus patients, and to analyze association with immune-suppressive therapy, disease duration, and age of the patients. Data from 860 systemic lupus erythematosus (SLE) patients were retrospectively analyzed in a study period between 1970 and 2004. Results were compared to data from age- and sex-matched population obtained from the Health for All database, and also to literature data. A total of 37 patients presented with cancer, reflecting 4.3% cancer-associated morbidity. Patients were 47 (20-73) years old at the onset of malignancy, which appeared 13 (1-45) years later than SLE. Cancer prevalence was the highest in the first 5-10 years of lupus. Breast cancer was the most common malignancy (n = 11) followed by gastrointestinal tumors (n = 9), cervix cancer and hematologic malignancies (n = 5 for both), bronchial cancer (n = 4), bladder, skin, and ovarian cancer (n = 1 for each). Standardized incidence ratio was the highest for non-Hodgkin lymphoma (standardized incidence ratio [SIR] 3.5, 95% CI 0.4-12.5) and cervix cancer (SIR 1.7, 95% CI 0.6-4.1). Although 76% of patients with cancer received immune-suppressive therapy besides corticosteroids, no direct correlation could be confirmed between therapy and malignancy. Out of the 164 patients that expired during the study period, 18 were cancer-related. As such the cancer-associated mortality was 11% (18/164). This peaked during the last 4 years of the study period (8/24, 33%). Lupus patients are at high risk for particular types of malignant disorders, highlighting the importance of screening measures and focused patient examination.

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