Tuesday, January 17, 2017

Palindromic Rheumatism

There still is quite a lot of uncertainty about palindromic rheumatism, but it’s an accepted diagnosis and is classified in ICD-10 as M12.3. It is a form of episodic inflammatory arthritis. One or even multiple joints swell, may be red, and are painful - and then go back to normal. Unlike other forms of arthritis palindromic rheumatism doesn’t damage the joints permanently. Some scientists say that half the patients develop rheumatoid arthritis, but that’s a rough estimation as we lack longitudinal data to confirm this number. Time intervals between attacks vary a lot.

The term palindromic rheumatism was coined in 1941 by P.S. Hench and E.F. Rosenberg. The description is purely clinical as then rheumatoid factor (RF) or even ACPA [anticitrullinated protein antibody] weren’t known or waited for lab tests to be developed. They used palindromic as the symptoms appear and disappear in a similar way.
The cause is still unknown. It is uncertain, if it is a condition, which might lead to what we call early arthritis nowadays and/or rheumatoid arthritis.
Apart from clinical examination lab tests and X-rays are used to rule out rheumatoid arthritis, but there is no test, which could be used to diagnose palindromic arthritis. If ACPA or RF are present, rheumatoid arthritis might develop later. Sometimes palindromic rheumatism is the first presentation of M. Whipple.  The rheumatologist diagnoses palindromic rheumatism by the patient’s history and his finding of acute arthritis. And he has to rule out other forms of arthritis like gout (or the ones already mentioned).
Therapy should focus on treating acute attacks. The mainstays for this are NSAIDs. Sometimes antimalarials are prescribed, but robust data for this indication doesn’t exist.  

G. Salvador and colleagues asked if palindromic rheumatism could be a an abortive form of rheumatoid arthritis in a study (1). They looked at 63 patients with palindromic rheumatism: 33 were defined as pure or persistent and 30 as associated palindromic rheumatism. They concluded: “AntiCCP [ACPA] and, to a lesser extent, AKA [antikeratin antibodies], were found in a high proportion of patients with PR [palindromic rheumatism], suggesting that this syndrome is an abortive form of RA [rheumatoid arthritis]. The predictive value of these antibodies in PR, as markers of progression to an established RA, remains uncertain.” I think these findings are very valuable, but the conclusion is premature as there might be an admission bias.

S. Cabrera-Villalba and colleagues looked at subclinical synovitis in patients with palindromic rheumatism in the intercritical period (2). The study used ultrasound and clinical examination. The authors concluded: “Some differences emerged in the clinical phenotype of PR [palindromic rheumatism] according to ACPA [anticitrullinated protein antibody] status. Most patients with PR do not have US [ultrasound] subclinical synovitis in the intercritical period, even those who are ACPA-positive.”

Y. Emad and colleagues studies, if hand joint involvement and positive ACPA [anticitrullinated protein antibodies] in palindromic rheumatism predict development of rheumatoid arthritis after one year of follow-up (3). The authors concluded: “Early hand joint involvement and positive anti-CCP at disease onset are good predictors for progression to RA in this domain.” Interestingly they had already treated 43 patients with hydroxychloroquine, and the authors think that this had led to remission. Really? The study can’t tell and it muddies the outcome of the original study. Cabrera-Villalba and colleagues voiced their concerns in a letter to the editor (4). CRP levels were high or measurements were made in mg/l and quoted in mg/dl. I think that CRP levels were high, but that patients rather belong to an early arthritis cohort than to a palindromic rheumatism in intercritical period cohort.

R. Sanmartí and colleagues published: “Palindromic rheumatism with positive anticitrullinated peptide/protein antibodies is not synonymous with rheumatoid arthritis. A longterm followup study.” In results we read: “Seventy-one patients (54 women/17 men) with a PR diagnosis were included. Serum ACPA were positive in 52.1%. After a mean followup of 7.6 ± 4.7 years since the first ACPA measurement, 24 patients (33.8%) progressed to chronic disease: 22% RA, 5.6% systemic lupus erythematosus, and 5.6% other diseases. […] Progression to RA was more frequently seen in ACPA-positive than in ACPA-negative patients (29.7% vs 14.7%), but the difference was not significant. […]”. The authors concluded: “ACPA are frequently found in the sera of patients with PR, and a significant proportion of these patients do not progress to RA in the long term.”

To sum it up, palindromic rheumatism still is a challenging diagnosis. We have to make clear distinctions between palindromic rheumatism and early arthritis. I would like to see these patients regularly to make sure that they don’t progress to rheumatoid arthritis.


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