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  • Review Article
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Paraneoplastic syndromes in rheumatology

Nature Reviews Rheumatology volume 10, pages 662–670 (2014)Cite this article

Subjects

Key Points

  • Paraneoplasias are caused by soluble factors produced by tumour cells or are the consequence of an immune reaction against these cells

  • An underlying malignancy should be sought if musculoskeletal symptoms do not show an adequate response to therapy

  • Arthritis, myositis, periostitis, fasciitis and osteomalacia can all be musculoskeletal manifestations of a paraneoplastic disease

  • Due to the properties of soluble factors produced by tumour cells, some paraneoplasias show a characteristic involvement of specific musculoskeletal tissues (e.g. VEGF inducing HOA or FGF23 inducing TIO)

  • Despite their rarity, knowledge of distinct clinical patterns of paraneoplasias is essential for the rheumatologist, because their recognition allows for a timely diagnosis and potentially life-saving therapy

  • The dissection of underlying molecular mechanisms can provide insights in the pathogenesis for rheumatic as well as neoplastic diseases

Abstract

For patients that present with musculoskeletal symptoms, diagnostic procedures carried out by physicians and rheumatologists are primarily aimed at confirming or excluding the occurrence of primary rheumatic diseases. Another important trigger for musculoskeletal disease, however, is the presence of a tumour. Careful clinical investigation and knowledge of the gestalt of musculoskeletal syndromes related to respective tumour entities is of utmost importance for the diagnosis of paraneoplastic rheumatic diseases such as hypertrophic osteoarthropathy, paraneoplastic polyarthritis, RS3PE syndrome, palmar fasciitis and polyarthritis, cancer-associated myositis and tumour-induced osteomalacia. This places great responsibility on rheumatologists in diagnosing malignancies and referring the patient for effective treatment. The selective influence of tumours on musculoskeletal tissue is surprising and indicates that tumours alter tissues such as the periosteum, synovial membrane, subcutaneous connective tissue, fascia, muscles and bones by specific molecular processes. Some of the underlying mechanisms have been unravelled, providing valuable information on the physiologic and pathophysiologic roles of mediators such as vascular endothelial growth factor and fibroblast growth factor 23.

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Figure 1: Acanthosis palmaris or tripe palms in a patient with lung cancer who had also developed marked clubbing of the terminal phalanges of all fingers.
Figure 2: Remitting seronegative symmetrical synovitis with pitting oedema in a patient with non-Hodgkin lymphoma.
Figure 3: Nodular palmar fasciitis and flexion contractures in a patient with metastatic ovarian carcinoma.
Figure 4: Pathophysiology and clinical signs of paraneoplastic rheumatic syndromes.

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  1. Department of Internal Medicine 3, University of Erlangen-Nuremberg, Ulmenweg 18, D-91054, Erlangen, Germany

    Bernhard Manger & Georg Schett

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B.M. researched the data for the article. B.M. and G.S. contributed substantially to discussions of the article content, writing the article and reviewing and/or editing the manuscript before submission.

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Correspondence to Bernhard Manger.

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Manger, B., Schett, G. Paraneoplastic syndromes in rheumatology. Nat Rev Rheumatol 10, 662–670 (2014). https://doi.org/10.1038/nrrheum.2014.138

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