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Palindromic Rheumatism

Palindromic rheumatism (PR) is a rare medical condition, consisting of sudden, intermittent, multiple attacks of joint pain and swelling. Symptoms are typically localized on hands and feet, with each episode lasting from several hours to days. The frequency of attacks also follows a fluctuating time pattern, patients may suffer from one episode per day to several attacks over the course of a year.


Palindromic rheumatism is characterized by an intermittent mono- or oligoarticular arthritis. Episodes do not last long and peri- and para-articular tissue are also subject to the inflammatory process [14]. After the recession of an attack, patients are symptom-free and exhibit no residual damage or alterations observed radiographically. 

Palindromic rheumatism usually begins in one joint, with the patient experiencing localized swelling, stiffness and pain (monoarticular arthritis). The symptomatology then follows an accelerated expansion to other joints, leading to an oligoarticular arthritis [15].

Other symptoms related to palindromic rheumatism include:

Shoulders, knees, wrists, ankles, and small joints of the hand are the ones most commonly affected in cases or PR, with the hips, elbows, and feet being considerably less often involved. However, this does not imply that the symptomatology of PR is limited to these locations. PR is an extremely variable condition, which can practically affect any joint [16].

With reference to the development of a single attack, it essentially begins with mild pain which gradually deteriorates. Symptoms are expected to recede spontaneously within a period of 48 hours. The frequency of attacks also follows a fluctuating time pattern, patients may suffer from one episode per day to several attacks over the course of a year, thus rendering it impossible to predict the duration of the intervals between attacks.

Pain experienced by patients during a PR attack is usually described as very severe, with joint involvement being primarily asymmetric and migratory. Three clinical criteria have been established in order to facilitate the evaluation of palindromic rheumatism:

  • Clinical remission of attacks
  • Persistence of intermittent attacks
  • Progression to RA (up to 50% of patients)

Patients who develop rheumatoid arthritis on the ground of palindromic rheumatism may exhibit this progression within several weeks (severe cases) or even within more than 10 years (milder cases).

PR and rheumatoid arthritis do exhibit common symptoms and characteristics. The primary distinction lies in the absence of permanent damaged caused by the periodic attacks of PR, in contradistinction to RA. The nodules observed in some patients with palindromic rheumatism, as well as the occasional slight fever, are also observed in RA patients, thus making the distinction between the two conditions more difficult.

Constitutional Symptom
  • Constitutional symptoms and morning stiffness are rare.[hopkinsarthritis.org]
  • "The frequency of acute attacks is variable, ranging from less than one every other month to one every other day, and patients rarely present with constitutional symptoms or fever," he said. In this column, Dr.[mdedge.com]
  • The patient had been asymptomatic until 1 year previously, when oligoarthritis migratory manifestation commenced, without constitutional symptoms.[scielo.br]
  • […] use Arthritis, Juvenile/complications* Arthritis, Juvenile/drug therapy Arthritis, Juvenile/genetics Arthritis, Juvenile/pathology Arthritis, Rheumatoid/drug therapy Arthritis, Rheumatoid/etiology* Arthritis, Rheumatoid/genetics Arthritis, Rheumatoid[ncbi.nlm.nih.gov]
  • Besides crystal arthritis, the most frequent cause of recurrent arthritis, there are several diseases that may present clinically as intermittent mono- or polyarthritis.[ncbi.nlm.nih.gov]
  • Palindromic rheumatism must be distinguished from acute gouty arthritis and an atypical, acute onset of rheumatoid arthritis (RA).[en.wikipedia.org]
  • Palindromic rheumatism (PR) is a rare type of arthritis, is closely related to another common condition, rheumatoid arthritis (RA).[symptoma.com]
  • Felty's syndrome consists of leucopenia (selective neutropenia) and splenomegaly, usually occurring in longstanding classic rheumatoid arthritis.[ncbi.nlm.nih.gov]
  • There are 3 groups of patients where this could be assessed: undifferentiated arthritis — those positive for anticitrullinated protein antibodies (ACPA) with arthralgia but no discernible arthritis — and those with palindromic rheumatism (PR).[jrheum.org]
  • The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia. Ann Rheum Dis. 2011;70:128–33.[arthritis-research.biomedcentral.com]
  • Arthralgia simply means pain in or around a joint. Bursitis is the inflammation of a bursa. Arthritis is the inflammation of a joint.[articles.chicagotribune.com]
Knee Pain
  • Take a look at our past articles for heaps of info on diet and arthritis: 5 Foods To Avoid With Arthritis Eat/Drink This (How to Reduce Knee Pain with your Diet) 6 Essential Diet Tips for Women Over 50 Supplements A way to control your diet and add hard[flexcin.com]
Panic Attacks
  • Whether you are looking to adopt,... 610 Members Agoraphobia & Social Anxiety Agoraphobia is an anxiety disorder, often precipitated by the fear of having a panic attack in a setting from which there is no easy means of escape.... 2,792 Members Albinism[dailystrength.org]


Abnormal laboratory findings in cases of PR include raised ESR and CRP levels, whereas white blood cell counts and ANA are most often negative. Imaging exhibits no observable alterations. This leads to the diagnosis of PR being established with clinical criteria: Typical PR joint manifestations and involvement, normal blood tests and radiographic depiction suggest the existence of palindromic rheumatism, after other types of arthritides have been excluded.

At this point, it is also vital to refer to the complexity of a PR diagnosis. The absence of a specific test to diagnose PR, alongside the potential overlapping of multiple autoimmune diseases usually renders it difficult to reach a decisive conclusion from the very beginning of the attacks. The diagnosis usually follows the process of elimination, where the existence of multiple conditions is assessed and, upon exclusion, a PR diagnosis is safely established.

Joint Space Narrowing
  • With palindromic rheumatism, joint space narrowing and joint damage are not evident, unlike rheumatoid arthritis.[arthritis.about.com]
  • Erosions, joint space narrowing, and periarticular osteopenia are absent.[hopkinsarthritis.org]
Tropheryma Whipplei
  • whipplei (formerly T. whippelii ). [ citation needed ] Anti-citrullinated protein antibody is frequently associated. [2] Diagnosis [ edit ] Due to the symptoms of palindromic arthritis and the nature of the attacks, diagnosis can be difficult or take[en.wikipedia.org]
  • Those of the PR patients who however, developed RA during followup, carried HLA-DR4. The patients with PR, NERA and RA who had familial RA demonstrated increased frequency of HLA-DR4.[ncbi.nlm.nih.gov]
  • It is likely that these two manifestations are linked with the patient's possession of HLA-DR4 and that they are prodromata of the patient's eventual development of rheumatoid arthritis.[ncbi.nlm.nih.gov]
  • The HLA-DR antigens did not reveal any differences between patients' and controls' values, either 40% of patients who developed RA carried the HLA DR4 antigen.[ncbi.nlm.nih.gov]
  • At this point, the best conclusion one can draw is that there is an absence of a striking association with HLA-DR4, which suggests that palindromic rheumatism is not simply a variant of rheumatoid arthritis, and perhaps not in the same spectrum of disease[hopkinsarthritis.org]
  • HLA DR5 has previously been found to be associated with juvenile rheumatoid arthritis, while DR1 in Jews is significantly associated with adult-onset rheumatoid arthritis. DR5 was shared by the mother and her 3 children.[ncbi.nlm.nih.gov]
  • The HLA genotype of the mother was HLA A2, Cw4, Bw41, Bw6, DR5, MT2/Aw32, CX, Bw44, Bw4, DR1, MT1.[ncbi.nlm.nih.gov]


Treatment of palindromic rheumatism includes nonsteroidal anti-inflammatory drugs (NSAIDs) to alleviate severe pain during attacks, as well as antimalarials. The latter has proven effective both in the means of symptom management [19] and to the downscaling of the frequency and duration of the attacks. Antimalarials are also believed to play a crucial role in the prevention of the progression to rheumatoid arthritis or other connective tissue diseases [4] [20].

Apart from medication, outbreaks of palindromic rheumatism also need conservative treatment. Healthy nutrition and balance between activity and rest are fundamental factors in the attempt to control a PR crisis. Patients who are affected by it, and in fact by many other autoimmune diseases, need to redirect their everyday routine to a more healthy regime, making responsible choices which will help them deal with a condition that cannot be fully understood or radically addressed.    


The progression of palindromic rheumatism is impossible to foresee, since the condition follows an extremely fluctuating and unpredictable pattern that has yet to be determined with certainty. However, it has been observed that the disorder exhibits a complete resolution in 15% of the patients. 50% of the affected patients experience episodic attacks and 40% of them face a chronic symptomatology. Palindromic rheumatism may develop into rheumatoid arthritis in a 50% of the patients, leading to the permanent damage of joints.

The determination of a positive rheumatoid factor (RF), the involvement of small joints in the early stages of the disease and an ACPA-positive laboratory test are considered indications of a future progression to rheumatoid arthritis [12] [13]. Although data is currently limited to small studies, these potential predictive criteria have been effective in the means of patient management and follow-up.


Palindromic rheumatism is a rare condition of the autoimmune spectrum and its etiology is unknown. Suggestions have proposed an allergic origin and a potential connection with antiphospholipid syndrome. [4].

Patients with palindromic rheumatism and chronic, persistent rheumatoid arthritis also exhibit similar HLA alleles. It is believed that both have common genetic predisposing factors [1].

A study conducted in 2003 indicated that a considerable majority of palindromic rheumatism patients also exhibited a high prevalence of anti-citrullinated peptide/protein antibodies (ACPA), a finding of clinical significance that is common in RA [5].


Studies of 1986 calculated the prevalence of PR as amounting to 5% [6]; nevertheless, more recent studies revealed a nearly 10 times greater prevalence of just under 50%, as diagnosed by rheumatologists [7]. PR tends to affect men and women almost equally, the female to male ratio fluctuates in the range of 1.7:1 to 0.55:1 [8]. The average age of onset is 45 years [8].

The existence of ACPA and the progression to rheumatoid arthritis has also been a subject of clinical observation. Given the hazard ratio (2.46, 95% CI 0.77−7.86), ACPA-positive patients whose condition progressed to RA (29.7%) and ACPA-negative patients with the same progression (14.7%), in reality exhibit a non-significant discrepancy.

Sex distribution
Age distribution


There has yet to be a definitive conclusion towards the etiology and pathogenesis or palindromic rheumatism, although Hench and Rosenberg did suggest a certain association with an allergic cause during their first attempts to describe the condition [2]. Researchers have, at times, proposed food allergies as the trigger for PR, but the causes remains unknown [9] [10]. Other suggestions indicate a potential connection between antiphospholipid syndrome and PR [11].


As mentioned in the previous paragraph, a level of symptom prevention can be achieved with the use of antimalarials. The importance of a balanced diet should also not be underestimated. It is strongly suggested that patients refrain from prostaglandins and arachidonic acid and opt for choices like fruit, vegetables, soy products, nuts and cold water fish instead. A further dietary suggestion is to avoid fatty foods and oils containing omega-6 fatty acids (sesame oil, sunflower oil, corn oil, wheat germ oil soybean oil).


Acute, periodic symptomatology of inflammatory mono- or polyarthritis are the key characteristics of palindromic rheumatism (PR). Symptoms recede spontaneously and may be followed by intense pain and erythema, similar to the symptoms experienced by patients suffering from gout. While palindromic rheumatism attacks resolve spontaneously and completely within a period of 1-3 days, these phenomena may constitute an indication for a developing rheumatoid arthritis (RA), thus requiring a further evaluation of rheumatoid factor (RF) via laboratory tests. 50% of PR patients are RF positive.

Genetic predisposition has proven to play a role in the onset of palindromic rheumatism, with PR patients carrying specific HLA alleles in the same dose effect pattern as those exhibiting the standard type of rheumatoid arthritis [1].

With reference to the differential diagnosis of PR, the first step involves distinguishing this particular medical entity from rheumatoid arthritis. To achieve this, a physician must bear in mind the distinctive characteristics of palindromic rheumatism which separate it from RA, ephemeral, non-symmetrical arthritis, episodes followed by swelling of adjoining tissues, symptomatology devoid of other essential RA-related characteristics and lastly, lack of progression and radiographic alterations [2]. Other possible causes of symptomatology resembling a PR attack involve Behcet disease, Whipple disease, sarcoidosis, crystal arthropathiesintermittent hydrarthrosis (HI), relapsing polychondritis, reactive arthritis and other seronegative spondyloarthropathies [3].

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used with variable effectiveness in the treatment of an acute PR attack, alongside RA medication like antimalarials, gold salts, penicillamine, sulfasalazine, methotrexate, and TNF- α inhibitors.

Patient Information

The term palindromic rheumatism is derived from the greek root "palindromos", which essentially means "keep coming over and over again". The name accurately describes the course of the condition, it arises suddenly, and also recedes suddenly.

Palindromic rheumatism (PR) is a rare type of arthritis, is closely related to another common condition, rheumatoid arthritis (RA). PR causes no residual damage in-between attacks, whereas RA, through continual joint inflammation and swelling, can lead to progressive bone and joint damage that is unfortunately permanent.

The sudden outbreaks of joint pain and swelling are characteristic of PR, with the periodic attacks usually occurring in the hands or feet, although any joint can be affected. When you’re not experiencing a PR episode, you will be entirely symptom-free and joints will appear normal on an X-ray or other type of imaging technique.

Symptoms that patients describe during a PR attack include:

  • Sudden, deteriorating sensation of joint pain and swelling
  • Redness of skin over the affected joints
  • Transient impairment if the function of affected joint/joints 
  • Recurring attacks

Attacks of PR vary in duration, they can last from a couple of hours to several days and these particular characteristics are individualized. Some patients may experience symptoms on a predictable basis, whereas others may be completely unable to predict when the next episode is going to occur.

The condition has no known causes; nevertheless it is believed by researchers to be connected to rheumatoid arthritis, since patients from both groups tend to have the same antibodies. At any case, PR is an autoimmune disorder, which means that the body itself forms antibodies against normal substances of the organism. It has also been suggested that PR is connected to antiphospholipid syndrome.

There is no definitive way to determine whether a person will at some point suffer from PR. However, it is believed that the following groups do tend to be affected by it more often than others:

  • Age between 20 and 70
  • Both men and women are affected equally.
  • Specific proteins: people with a positive rheumatoid factor. 

Palindromic rheumatism is a condition which is difficult to diagnose. Joints are not permanently damaged and therefore, no imaging technique can detect what is really happening to a joint. Additionally, there is no other specific test that can establish the diagnosis of PR. A doctor will ask for an extensive medical history and observe the symptoms a patient describes. After carrying out laboratory tests and excluding other possible conditions and given that the symptoms match those pf PR, the diagnosis of the condition is put.

In some cases, PR will gradually develop into rheumatoid arthritis. This is not the case for every PR patient and no one can tell who will develop it and who won't; it is for these reasons that it is extremely important for patients to keep track of their symptoms and visit their doctor when a change arises or when the symptoms get considerably worse.

As for the treatment of the condition, its unknown causes and accurate mechanism makes it impossible to cure. However, drugs used to treat malaria have been often used to treat PR. Strange? Researches have shown that antimalarial drugs can make the attacks last less and also reduce the possibility that a patient will develop rheumatoid arthritis. Other medication prescribed to PR patients are nonsteroidal anti-inflammatory drugs (NSAIDS). They target the pain and inflammation, at the same time reducing the likelihood of developing RA as a complication of palindromic rheumatism.



  1. Maksymowych WP, Suarez-Almazor ME, Buenviaje H, et al. HLA and cytokine gene polymorphisms in relation to occurrence of palindromic rheumatism and its progression to rheumatoid arthritis. J Rheumatol 2002; 29:2319.
  2. Hench PS, Rosenberg EF. Palindromic rheumatism. "new" oft-recurring disease of joints (arthritis, periarthritis, para-arthritis) apparently producing no articular residues. Report of thirty-four cases; its relation to "angio-neural arthrososis," "allergic rheumatism" and rheumatoid arthritis. Arch Intern Med 1944;73:293–321.
  3. Sanmarti R, Cañete JD, Salvador G. Palindromic rheumatism and other relapsing arthritis. Best Pract Res Clin Rheumatol 2004;18:647–661.
  4. Iyer VR, Cohen GL. Palindromic Rheumatism. South Med J. 2011South Med J. 2011. Feb;104(2):147-9. 
  5. Salvador G, Gomez A, Vinas O, et al. Prevalence and clinical significance of anti-cyclic citrullinated peptide and antikeratin antibodies in palindromic rheumatism. An abortive form of rheumatoid arthritis? Rheumatology (Oxford) 2003; 42:972.
  6. Pasero G, Barbieri P. Palindromic rheumatism: you just have to think about it. Clin Exp Rheumatol 1986;4:197–199.
  7. Powell A, Davis P, Jones N, et al. Palindromic rheumatism is a common disease: comparison of new-onset palindromic rheumatism compared to new-onset rheumatoid arthritis in a 2-year cohort of patients. J Rheumatol2008;35:992–994.
  8. Guerne PA, Weisman MH. Palindromic rheumatism: part of or apart from the spectrum of rheumatoid arthritis. Am J Med 1992;93:451–460.
  9. Panush RS. Food induced ("allergic") arthritis: clinical and serologic studies. J Rheumatol 1990;17:291–294.
  10. Nesher G, Mates M. Palindromic rheumatism: effect of dietary manipulation. Clin Exp Rheumatol 2000;18:375–378.
  11. Reitblat T, Litinsky I, Caspi D, et al. Antiphospholipid syndrome and palindromic rheumatism: a new possible association. Rheumatol Int 2005;25:595–598.
  12. Gonzalez-Lopez L, Gamez-Nava JI, Jhangri GS, et al. Prognostic factors for the development of rheumatoid arthritis and other connective tissue diseases in patients with palindromic rheumatism. J Rheumatol 1999;26:540–545.
  13. Russell AS, Devani A, Maksymowych WP. The role of anti-cyclic citrullinated peptide antibodies in predicting progression of palindromic rheumatism to rheumatoid arthritis. J Rheumatol 2006;33:1240–1242.
  14. Hench PS, Rosenberg EF. Palindromic Rheumatism. Arch Intern Med. 1944;73:293-321.
  15. Palindromic rheumatism. Iyer VR1, Cohen GL. South Med J. 2011 Feb;104(2):147-9. doi: 10.1097/SMJ.0b013e318200c4cc.
  16. Mattingly S. Palindromic rheumatism. Ann Rheum Dis 1966;25:307–317.
  17. Sanmarti R, Cañete JD, Salvador G. Palindromic rheumatism and other relapsing arthritis. Best Pract Res Clin Rheumatol 2004;18:647–661.
  18. Mattingly S. Palindromic rheumatism. Ann Rheum Dis 1966;25:307–317.
  19. Gonzales-Lopes L, Gamez-Nava JI, Jhangri G, Russell AS, Suarez-Almazor ME. Decreased progression to rheumatoid arthritis or other connective tissue diseases in patients with palindromic rheumatism treated with antimalarials. J Rheumatol. 2000;278:41-6.
  20. Youssef W, Yan A, Russell AS. Palindromic rheumatism: a response to chloroquine. J. Rheumatol. 1991;18:35-7.

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Last updated: 2019-07-11 20:49