9What can palindromic rheumatism tell us?
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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2022, Egyptian RheumatologistCitation Excerpt :The causes and the pathogenesis of PR were not yet clarified. The laboratory and X-ray findings are almost normal in PR [2,26,27]. Therefore, clinical symptoms and signs are of utmost importance in the diagnosis of PR [18–20].
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2021, Joint Bone SpineCitation Excerpt :Palindromic rheumatism may evolve with different courses, mainly rheumatoid arthritis (RA), in the long-term. Therefore, some authors consider PR as a continuum on the spectrum of RA [1–3]. In more than 50% of patients with PR, the characteristic autoantibodies present in RA (rheumatoid factor (RF) or anticitrullinated peptide/protein antibodies (ACPA)) are found [4] and they are a biomarker for RA progression [5].
How should we treat palindromic rheumatism? A systematic literature review
2021, Seminars in Arthritis and RheumatismCitation Excerpt :However, over the last 75 years, several therapeutic strategies for the treatment of PR have been described in the literature. These include non-steroidal anti-inflammatory drugs (NSDAIDs), colchicine, corticosteroids, conventional disease modifying anti-rheumatic drugs (DMARDs) and, to a lesser extent, biological DMARDs [15]. By conducting a systematic literature review (SLR), we aimed to comprehensively examine all studies that have investigated pharmacological treatments for PR.
Is Palindromic Rheumatism a Pre-rheumatoid Arthritis Condition? Low Incidence of Rheumatoid Arthritis in Palindromic Rheumatism Patients Treated with Tight Control Strategy
2021, Reumatologia ClinicaCitation Excerpt :Despite the relatively high frequency of this disease and significant risk of developing RA, no controlled clinical trials have been performed and no consensus exists on the best therapeutic strategy for PR.12,13 Patients may be treated with non-steroidal anti-inflammatory drugs (NSAIDs) or steroids during attacks.12,13 Disease-modifying anti-rheumatic drugs (DMARDs) like hydroxychloroquine (HCQ), D-penicillamine, gold salts and sulfasalazine (SSZ) have been used for prophylaxis of attacks and prevention of disease evolution to RA but have not been evaluated systematically.12
Identification of Distinct Genetic Profiles of Palindromic Rheumatism Using Whole-Exome Sequencing
2023, Arthritis and Rheumatology