“What was good enough for Hippocrates ought to be good enough for you.” 1
Why palindromic?
Palindromic is derived from the Greek palin dromein, meaning, “to run back” or simply “returning or recurring”. Hippocrates used it to denote erysipelas and other conditions that tend to repeat (recur) in the same individual.2
Why rheumatism?
The influential 1st century botanist Pedanios Dioscorides, believed that arthritis was caused by, “a defluxion of rheum or a humour, bilious, sanguineous, melancholic, but usually pituitrous and crude.”
Since that time, rheumatism has served as the all-encompassing explanation for everything that ached. 2
What is palindromic rheumatism?
The condition was described in 1928 by Dr Philip Hench when working in the Mayo Clinic, Rochester, USA. He gave it the name Palindromic Rheumatism (PR). Hench and Rosenberg1 reported their findings from 34 cases.
PR is characterised by sudden attacks of joint inflammation, which come and go in much the same way. Attacks can last for hours or up to one to two days. Areas around the joint and the nearby tendons may also be inflamed.
Between attacks the joints are normal.3
It has never been clear whether PR is a separate entity, or the forerunner of rheumatoid arthritis.
Any tests?
There are no specific tests. The ESR and C-reactive protein can be mildly raised during an attack. X-Rays of affected joints are normal, even after repeated attacks.
What is the mechanism of the inflammation?
Disorders such as PR are probably caused by activation of the body’s immune system, of which there are two components, the innate component (which is the first line of defence against invading organisms) and the adaptive (or more specific) component.
In some patients, the finding of mutations of the MEFV (familial Mediterranean fever) gene suggests that abnormal activation of the innate immune system ( a process known as auto-inflammation) has occurred.4
Persistent activation of this system results in immune cells mistakenly targeting healthy tissues. This process causes intense episodes of inflammation, with fever, rash, or joint swelling.
The second component of bodily defence, called adaptive immunity, is a slower but more specific response to infection, in which antibodies to invading organisms are produced.
Autoimmune diseases, such as rheumatoid arthritis are caused by an abnormally functioning adaptive immune system. The presence of the characteristic autoantibodies (i.e., rheumatoid factor or anti-CCP) suggests that PR will evolve into RA.
Both the innate and the adaptive immune responses are usually tightly controlled. However, in both autoinflammatory and autoimmune diseases, the body’s immune system is activated for no apparent reason.
How is PR treated?
As no randomised clinical trials have been carried out, there is no consensus on the best form of treatment.5
There is good evidence that hydroxychloroquine reduces the recurrence of PR flares and help achieve disease remission.6
Other types of treatment that have been reported in the literature as being helpful include: non-steroidal anti-inflammatory drugs, oral corticosteroids, sulphasalazine, gold injections, and methotrexate.6
Because it is thought that autoinflammatory processes may be playing a part in some cases, colchicine has been suggested as a means of preventing attacks.
What is the prognosis of PR?
Most, but not all, cases evolve to chronic disease in the long term, particularly RA.5
Solving the enigma?
One proposal is that PR is a condition in which autoinflammatory and autoimmune disorders overlap.7 In this scenario, autoimmune processes appear to drive the development of rheumatoid arthritis, whereas discrete attacks would appear to be caused by an autoinflammatory mechanism.
Future challenges
The first challenge is to achieve a uniform case definition of PR that is generally accepted. The second challenge is to arrive at an optimum treatment strategy, with the hope of preventing progression of PR to rheumatoid arthritis.
TERMINOLOGY
- Erysipelas: a bacterial skin infection.
- MEFV gene is present on chromosome 16. It provides instructions for making a protein called pyrin, which assists in keeping inflammatory processes under control. Pyrin may direct the migration of white blood cells to sites of inflammation and stop or slow the inflammatory response when it is no longer needed.
- The innate immune system is the body’s first line of defence against infection. When microbes such as bacteria or viruses invade the body, the innate immune system quickly springs into action to help the body fight infection.
By John Quintner, Consultant Physician in Rheumatology and Pain Medicine (retired)
REFERENCES
- Hench P, Rosenberg E. Palindromic rheumatism. A new oft-recurring disease of joints (arthritis, peri-arthritis) apparently producing no articular residues. Report of thirty-four cases (its relationship to “angioneural arthrosis”, allergic rheumatism” and rheumatoid arthritis). Arch Inter Med 1944;73:293–321. doi: 10.1001/archinte.1944.00210160025004.
- Helfgott SM. How rheumatism got its name. The Rheumatologist, Issue March, 2014.
- Cabrera-Villalba S, Ramirez J, Salvador G, et al. Is there subclinical synovitis in patients with palindromic rheumatism in the intercritical period? A clinical and ultrasonographic study according to anticitrullinated protein antibody status. J Rheumatol 2014;41:8. doi: 10.3899/jreum.131545.
- Cañete JD, Arostegui JI, Queiró R, et al. An unexpectedly high frequency of MEFV mutations in patients with anti–citrullinated protein antibody–negative palindromic rheumatism. Arth Rheum 2007;56(8):2784-2788. doi: 10.1002/art.22755.
- Sanmartí R, Frade-Sosa B, Morlà R, Castellanos-Moreira R, Cabrera-Villalba S, Ramirez J, Salvador G, Haro I and Cañete JD. Palindromic Rheumatism: just a pre-rheumatoid stage or something else? Front Med 2021;8:657983. doi: 10.3389/fmed.2021.657983.
- Corradini D, Di Matteo A, Emery P, et al. How should we treat palindromic rheumatism? A systematic literature review. Arth Rheum 2021;51(1):266-277, doi: 10.1016/j.seminarthrit.2020.11.008.
- Mankia K, Emery P. Palindromic rheumatism as part of the rheumatoid arthritis continuum. Nat Rev Rheumatol 2019;15(11):687-695. doi: 10.1038/s41584-019-0308-5.
