Rheumatic disorders as paraneoplastic syndromes (2022)


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Autoimmunity Reviews

Volume 7, Issue 5,

May 2008

, Pages 352-358


The long-established observation that some rheumatologic disorders (RDs) are associated with – or precede – the clinical manifestations of a variety of solid and hematological tumors represents an important clue for the early diagnosis and effective treatment of the cancers. Inflammatory myopathies, seronegative rheumatoid arthritis and some atypical vasculitides are the most frequently reported paraneoplastic RDs, although paraneoplastic scleroderma- and lupus-like syndromes, erythema nodosum, and Raynaud's syndrome have also been observed. Generally, the clinical course of a paraneoplastic RD parallels that of the cancer, and surgical removal of the tumor or its medical treatment usually results in a marked regression of the clinical manifestations of the RD. Most paraneoplastic RDs are difficultly distinguishable from idiopathic RDs. Even so, some atypical features of the clinical presentation raise the suspicion of an underlying tumor. This review summarizes current hypotheses for the pathogenesis that leads a tumor to present as an RD and discusses the clinical features that help distinguish paraneoplastic from idiopathic RDs.


The association between cancer and rheumatic disorders (RDs) is a matter of discussion in view of their intriguing relations [1], [2], [3]. Patients with both cancer and an RD are distinguished into three main classes. In the first class, an RD is directly triggered by a tumor or its metastases. An example of this first group is arthritis due to synovial infiltration by leukemic cells. The second class refers to patients with an established idiopathic RD who develop cancer within a temporal interval of up to 20years. Sjögren's syndrome can be such a tumor-associated RD, because it places patients at high risk of developing lymphoma. It is currently unknown whether the higher incidence of cancer in patients with idiopathic RDs is due to the disease itself, the long-term immunosuppressive treatment these patients receive, or both [3]. The third group includes patients with clinical manifestations of an RD, which is actually the expression of an occult cancer that becomes clinically evident within months or years. These apparently idiopathic RDs that precede cancer are called paraneoplastic RDs.

This review focuses on the third group of patients, i.e. those with paraneoplastic RDs. It summarizes current hypotheses for the pathogenetic mechanisms that lead a tumor to present as an RD and discusses the clinical features that help distinguish paraneoplastic from idiopathic RDs.

Section snippets

Pathogenetic hypotheses

The main distinguishing feature between tumor-associated and paraneoplastic RDs is the fact that surgical removal or pharmacological treatment of the cancer in the first case has no influence on rheumatic symptoms, whereas it almost always results in the disappearance of symptoms in paraneoplastic diseases (reviewed in [4]). These observations have prompted oncologists and rheumatologists to investigate the pathogenetic mechanisms of the rheumatic manifestations of cancer, leading to three

(Video) Miscellaneous Rheumatic Disorders -- ep. 11 of 32

Clinical features

That an apparently idiopathic RD can be an early manifestation of cancer has been known since the first case report published in 1916 (reviewed in [10]). Since then, several different types of paraneoplastic RDs have been described. Clinical presentations may resemble, for example, connective tissue disease, polymyalgia rheumatica or vasculitis. These diseases are almost indistinguishable from idiopathic RDs. Even so, certain clinical and laboratory findings can raise the suspicion of an


There is increasing recognition that tumors may be associated with a wide range of rheumatic disorders (RDs). The etiology of paraneoplastic RDs is often unknown and the pathogenesis of this association remains to be determined. Paraneoplastic RDs generally precede the diagnosis of cancer, and thus are predictive of malignant disease. The clinical course usually parallels that of the primary tumor, and in most cases treatment of the tumor resolves the paraneoplastic symptoms.

It is important to


The authors are grateful to Mrs. Maria Daniele and Mr. Vito Iacovizzi for their excellent secretarial assistance. Valerie Matarese provided scientific editing.

Take home messages

Several apparently idiopathic rheumatic diseases can be early manifestations of hidden cancer.

Atypical clinical and laboratory features of these rheumatic diseases aid in the diagnosis.

Recognition of a paraneoplastic rheumatic disease may permit early diagnosis and more effective treatment of the cancer.

Current evidence

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