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Palindromic rheumatism as part of the rheumatoid arthritis continuum


Palindromic rheumatism is a distinctive syndrome that has a long-recognized association with rheumatoid arthritis (RA). Palindromic rheumatism is characterized by intermittent flares of pain, erythema and swelling in and around the joints, which are typically severe and unpredictable. The observation that most patients with palindromic rheumatism have RA-related autoantibodies and that many eventually develop RA has led to palindromic rheumatism often being viewed as a relapsing–remitting variant of RA. However, the clinical and imaging phenotypes of palindromic rheumatism suggest important distinctions from RA and imply underlying mechanistic differences between the two conditions. Furthermore, the pattern of inflammation seen in palindromic rheumatism has interesting parallels with that seen in other groups of symptomatic individuals at risk of developing RA. In this Review, we explore the concept of palindromic rheumatism as part of the RA continuum and propose an updated disease paradigm for this unique syndrome.

Key points

  • Palindromic rheumatism has a distinct clinical and imaging phenotype and cannot simply be considered as a relapsing–remitting form of rheumatoid arthritis (RA).

  • Palindromic rheumatism has an immunogenetic link with RA but shares clinical features, genetic associations and therapeutic responses with systemic autoinflammatory diseases and crystal-induced arthritis.

  • Palindromic rheumatism can be considered as an overlap syndrome, with both autoimmune and autoinflammatory characteristics.

  • Palindromic rheumatism shares disease targets with other groups of at-risk individuals and could be a genetically determined manifestation of the prodromal phase of RA.

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Fig. 1: Different patterns of inflammation in RA and palindromic rheumatism.
Fig. 2: Palindromic rheumatism and the RA disease continuum.
Fig. 3: A model of progression from extra-capsular to intra-articular disease in RA.


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K.M. researched data for the article. Both authors made a substantial contribution to discussion of the content, writing the article and the review and/or editing of the manuscript before submission.

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Correspondence to Paul Emery.

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Nature Reviews Rheumatology thanks W. Maksymowych, R. Sanmarti and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Rheumatoid factor

An antibody against the Fc portion of IgG, which is associated with rheumatoid arthritis.

Shared epitope

(SE). A preserved peptide sequence found on HLA antigens, which is the strongest genetic risk factor for rheumatoid arthritis.


Inflammation of the tissues immediately surrounding the joints.


Inflammation of tissues outside and separate from the joints.


Inflammation of synovial tendon sheaths, which can cause pain, swelling and stiffness associated with the tendons.


Inflammation of the bone, which is a frequent finding in the joints in rheumatoid arthritis.

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Mankia, K., Emery, P. Palindromic rheumatism as part of the rheumatoid arthritis continuum. Nat Rev Rheumatol 15, 687–695 (2019).

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