Neoplastic associations of rheumatic diseases and rheumatic manifestations of cancer.

Associations between rheumatic diseases and malignant neoplasms are still inferential and based largely on epidemiologic data. Rheumatoid arthritis predisposes weakly to the occurrence of lymphoreticular neoplasms. This is more clearly true of Sjögren's disease, whether or not it is associated with RA. A subset of DM/PM which becomes manifest in close temporal proximity to a neoplasm may be a paraneoplastic reaction, but DM/PM, in general, does not predispose to neoplasia. Scleroderma in its early phase is associated with the development of breast cancer in women, and after a decade or longer, if pulmonary fibrosis has developed, with lung cancer. Of the drugs that have been used to treat these diseases, cyclophosphamide is most strongly implicated as a carcinogenic agent, particularly inducing lymphoreticular neoplasms and carcinoma of the bladder. Musculoskeletal symptoms that may be clues to the existence of cancer may either be caused by invasion of the neoplasm or be mediated by unidentified neurohumoral mechanisms. Except for multiple myeloma, primary neoplasms of skeletal tissues tend to occur under the age of 50 years. Metastatic disease occurs congruently with the age incidence of the primary neoplasm. Metastases may mimic mono- or oligoarticular arthritis if they happen to be periarticular or synovial. These metastases result most often from carcinoma of the lung or, in women, carcinoma of the breast. Hypertrophic pulmonary osteoarthropathy usually is due to carcinomas of the lung other than the small cell variety, and infrequently from other intrathoracic primary or secondary neoplasms. RA may be mimicked. Both skeletal metastases and HPOA are detected with greater sensitivity, but not specificity, by isotopic scanning techniques than by radiography. Of the other paraneoplastic musculoskeletal syndromes, neuromyopathy is the most frequent. It must be distinguished from cachexia, polymyositis, polymyalgia rheumatica, and the myasthenic syndrome. Both neuromyopathy and Eaton-Lambert (myasthenic) syndrome are predominantly associated with small cell carcinoma of the lung and both are best diagnosed by electromyography. Carcinomatous polyarthritis and the palmar fasciitis-arthritis syndrome occur with various neoplasms, although the latter appears to be particularly associated with ovarian carcinomas. The paraneoplastic arthritides test negatively for the rheumatoid factor, but no reliable positive immunochemical clues have as yet been identified.