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: “Anti‐CCP [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.

Links:

http://www.arthritis.org/about-arthritis/types/palindromic-rheumatism/

https://en.wikipedia.org/wiki/Palindromic_rheumatism

(1) http://rheumatology.oxfordjournals.org/content/42/8/972.long

(2) https://www.ncbi.nlm.nih.gov/pubmed/22898224

(3) https://www.ncbi.nlm.nih.gov/pubmed/24623460

(4) https://www.ncbi.nlm.nih.gov/pubmed/24797773

Rheumatoid Factor

Lately we have been discussing usefulness and misuse of the rheumatoid factor (RF). Patients without RF fear that their complaints are’nt taken earnestly as for their GP no RF means no rheumatic disease. Rheumatologists see lots of patients with osteoarthritis plus RF, who don’t have a rheumatic disease; occasionally patients are referred without any joint complaints ore other hints to a rheumatic disease safe for the RF, which the GP had tested for obscure reasons.


The rheumatoid factor (RF) is an autoantibody that is relevant historically in rheumatoid arthritis, as it defined the disease. But with all autoimmune findings, scrutiny is necessary. Negative results don’t rule out arthritis, not even rheumatoid arthritis. A positive result, however, doesn’t equal having rheumatoid arthritis as the result may be due to other causes. RF is still part of the combined EULAR and ACR classification criteria of rheumatoid arthritis though another biomarker ACPA (Anti Citrullinated Peptide Antibody) has made it’s way into these criteria. Let’s have a closer look at these criteria. The criteria are applied by scoring for joint involvement, serology, duration of synovitis, and acute phase reactants (ESR and CRP). The criteria might be positive for rheumatoid arthritis without RF nor ACPA. On the other hand most people with rheumatoid arthritis test positive for RF. It is much like with ankylosing spondylitis, where most of the patients test positive for HLA B27, but not all – positive for HLA B27 doesn’t mean having the disease, but a negative result doesn’t rule ankylosing spondylitis out (sounds familiar?!).


Which dieases also go along with an elevated RF? Quite a lot. In the field of rheumatic diseases we have: adult onset Still's disease (AOSD), dermatomyositis Sarcoidosis, scleroderma, Sjogren’s syndrome, systemic lupus erythematosus. Other conditions include infectious diseases (viral and bacterial infections, tuberculosis, parasites), leukemia and other cancers, as well as chrinc lung and chronic liver disease. This isn’t an exhausting list.


To go deeper into this look up rheumatoid factor and rheumatoid arthritis on Wikipedia or have a look at my colleague and friend’s, Dr. Shashank Akerker’s page at: http://www.arthritissupportboard.com/rheumatoid_factor.aspx  and http://www.arthritissupportboard.com/Rheumatoid_Arthritis_Diagnosis.aspx.


We have to talk about a tedious topic: classification after the International Statistical Classification of Diseases and related Health Problems: ICD-10. The positive thing about this classification is the world wide distribution. You can compare statistical data, that’s what it has been made for. As we use it to generate DRGs (Diagnose Related Groups) it has become daily practise to put complex diagnosis into a couple of letters and numbers. Rheumatoid factor positive rheumatoid arthritis is classified M05.80, without RF you classify the disease as M6.00. Rheumatoid nodules are classified M6.3x; I haven’t seen one patient without RF having rheumatoid arthritis; has anyone else? This classification reflects an older state of knowledge. It’s arbitrary and idiosyncratic. At this point it seems that RF is tested to distinguish between RF+ and RF- rheumatoid arthritis. As there might be some small differences, I’d like to let it stand like this. But why doe stress RF so much, as we aren’t differentiating between RA of large joints, of small joints, only wrists, only fingers, only feet, with and without cervical spine involvement, with and without involvement of inner organs, with and without other auto antibodies?

Mrs. R.H. is 67 years old and RA was diagnosed in the early 90ies. I’m treating her since the mid-90ies. Until 2006 fluctuations of RF also meant new flares. 2001-2002 we tried an immune absorption therapy; you can see a drop and then a steady state in 2003-2004. The therapy had to be escalated during the low phase. RF was rising and she went into remission (TNF-alpha inhibitor). With Mrs. R.H. any fluctuations of RF have no meaning concerning disease activity


Rheumatoid factor is the oldest antibody we use and we still don’t know its use.