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Musculoskeletal Syndromes Associated With Malignancy (Excluding Hypertrophic Osteoarthropathy)

Authors: Jochanan E. Naschitz, MD ; Itzhak Rosner, MDFaculty and Disclosures


Abstract and Introduction


Purpose of review: To examine recent data about the association between rheumatic disorders and cancer. This article focuses on paraneoplastic rheumatic disorders, which usually precede by a short period of time the diagnosis of malignancy, and on malignant transformation, which occurs late in the course of rheumatic disorders. Evidence of causality between malignancies and rheumatic disorders was reviewed based on statistical indicators (standardized incidence ratios and odds ratios) and by applying Bradford Hill's criteria of causality.
Recent findings: Firm epidemiological evidence was found attesting that dermatomyositis and polymyostis may present as paraneoplastic syndromes. Several other musculoskeletal disorders may be present akin to paraneoplastic syndrome, based on clinicians' impressions, but with scarce epidemiological evidence supporting a causal determinism. In contrast, robust evidence has accumulated on the role of longstanding rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis as premalignant conditions. Evidence that systemic lupus erythematosus may evolve into lymphoma is equivocal.
Summary: The link between malignancies and rheumatic disorders may impact on clinical practice. First, paraneoplastic rheumatic syndromes can provide the clinician with hints for earlier diagnosis of occult cancer. Second, the risk of malignant transformation during the course of rheumatic disorders may motivate the search for strategies aimed at prevention.

Introduction: Cancer-associated/Paraneoplastic Disorders

Musculoskeletal disorders associated with malignancy may be classified according to the following categories: musculoskeletal disorders due to direct involvement by tumor of bones, joints, muscles; paraneoplastic syndromes; altered immune surveillance causing both the musculoskeletal and the neoplastic diseases; and adverse reactions to anticancer therapy. Paraneoplastic rheumatic disorders are those cancer-associated rheumatic syndromes that occur at a distance from the primary tumor or metastases and are induced by the malignancy through hormones, peptides, autocrine and paracrine mediators, antibodies, and cytotoxic lymphoctes. All are characterized by the relatively short interval between the appearance of the rheumatic disorder and diagnosis of its associated neoplasm, which in general does not exceed 2 years. In contrast to paraneoplastic syndromes, malignant transformation in the course of certain rheumatic disorders is the result of immune dysregulation; the time interval between the onset of the rheumatic disorder and diagnosis of the secondary malignancy may be as long as 20 years.[1,2•]

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