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What can palindromic rheumatism tell us?

https://doi.org/10.1016/j.berh.2017.09.014Get rights and content

Abstract

Palindromic rheumatism (PR) is a syndrome characterised by recurrent, self-resolving inflammatory attacks in and around the joints. An association between PR and rheumatoid arthritis (RA) has long been postulated; a significant proportion of PR patients eventually develop RA and the majority also have anti-CCP antibodies. Therefore, PR is often considered a prodrome of RA. However, the clinical and imaging phenotype of PR has several important distinctions from RA. This suggests that despite the similarities, distinct disease mechanisms are at play. Given the paucity of evidence-based therapy in PR, a better understanding of these mechanisms will be important for refined and targeted therapeutic approaches for this important condition.

Introduction

Palindromic rheumatism (PR) is a well-recognised clinical syndrome characterised by recurrent episodes of pain and swelling in and around the joints. Exacerbations or ‘flares’ of PR always resolve spontaneously, often giving patients significant periods without symptoms or signs. This is a key distinguishing feature from rheumatoid arthritis (RA), where joint disease is characteristically persistent and does not remit without therapy. There are other important differences between the PR and RA phenotypes, and the question of whether PR should be considered part of the spectrum of RA or a distinct entity remains unanswered over 70 years since it was first posed by Hench and Rosenberg in their original description of the condition [1]. However, there is an undeniable association with RA; several studies have confirmed that up to 50% of PR patients will go on to develop persistent arthritis, most commonly RA [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. This suggests that for many patients, the natural history of PR is to evolve into RA, the corollary of which is that PR represents a prodrome or forme fruste of RA. If this is true, understanding the pathogenesis of PR is an important goal as it is likely to provide invaluable insights into the earliest phase of RA. In this review, we describe what we can learn from the phenotype of PR and its association with RA. We discuss the factors that may predict progression of PR to RA. Finally, we describe therapeutic options.

Section snippets

Palindromic rheumatism: an ‘at-risk’ phenotype

There is currently considerable interest in characterising individuals with risk factors for the future development of RA. This has been driven, in part, by a better understanding of the aetiopathogenic phases leading up to the development of RA [12]. ‘At-risk’ individuals with genetic, serological or clinical risk factors can now be identified and followed prospectively to better understand the factors that influence progression to clinical arthritis [13], [14]. In this way, first-degree

What can we learn from the clinical phenotype of PR?

The hallmark of PR is its clinical presentation. It is characterised by recurrent inflammatory flares in and around the joints, which resolve spontaneously. Flares can be excruciatingly painful but usually last only a few days, and patients are otherwise free of symptoms. Clinical studies have highlighted similarities with RA. Although PR flares are often mono-articular, they commonly affect the same joints as RA. Guerne and Weisman collated the results of five large surveys of PR patients,

Imaging studies in PR

High-resolution ultrasound (US) and magnetic resonance imaging (MRI) have become essential tools for both RA research and clinical practice. Recent data have shown US and MRI abnormalities are detectable in at-risk individuals prior to the development of clinical arthritis [19], [28], [29], [30]. Furthermore, imaging findings are predictive for the development of arthritis and identify at-risk subjects with imminent disease [19], [28]. Despite these data, there have been very few imaging

Progression to RA

Progression from PR to RA has been demonstrated in several cohorts [2], [3], [4], [5], [8], [10], [37]. In their initial description of PR, Hench and Rosenberg acknowledged that the follow-up of their 34 cases was not sufficiently long to determine whether PR patients would eventually progress to RA [1]; most of their cases were followed up for 3 years or less at the time of publication. Subsequently, Ansell and Bywaters described a UK series of 28 PR cases, 18 of whom developed RA within 8

Genetic studies in PR

Given the well-described association between HLA genes and RA, studies have examined the role of these genes in PR and progression to RA [38], [39], [40], [41]. These early studies, which produced variable results, were done on small numbers of patients and used serological rather than DNA typing for HLA antigens. More recently, Maksymowych et al. used PCR to determine HLA-DR genotype in 147 PR patients from a single centre [42]. They reported an increased prevalence of HLA-DR shared epitope

Treatment of PR

There have been no controlled trials for the treatment of PR. As such, there are no agreed guidelines for drug therapy, and in practice, treatments vary according to the preference and experience of the physician. There are several reasons for the lack of robust trials; PR is an uncommon condition, and timely recruitment of large numbers of patients is challenging. In addition, there are several proposed classification criteria in use [4], [5], [8], [22], none of which have been agreed by

Summary

PR is characterised by episodic inflammatory flares that localise to the joints and peri-articular structures. There are clinical, serological and immunogenetic associations with RA, consistent with observational data confirming that up to half of all PR patients eventually develop persistent arthritis. However, it is probably inaccurate to consider PR as simply an RA prodrome. There are important phenotypic differences between the two conditions, which are evident clinically and on

Conflict of interest statement

Paul Emery has undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly.

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