CASE REPORT

A Patient with Severe Palindromic and Frequent Episodes of Pain Shingo Takata, Seishi Harada, Fumihiro Mitsunobu, Takashi Mifune, Yasuhiro Hosaki, Kozo Asida, Hirofumi Tsugeno, Makoto Okamoto, Mitsuhiro Iwahashi* , Masanori Kawashima* , Masahiro Yamamura*, Hirofumi Makino* and Yoshiro Tanizaki

Abstract Case Report A 44-year-old man began to experience episodes of joint A44-year-old man had the chief complaint of recurrent epi- pain with erythema in his knees, elbows, shoulders, and sodes of joint pain with erythema. Although his past medical hands in April 1996. He was diagnosed as having palin- history was unremarkable in his family history, his grandmother dromic rheumatism. Due to the increasing frequency and had rheumatoid . severity of these episodes, he was admitted to our hospital The patient first noticed severe knee pain with erythema in in May1999. Heat therapy to the affected area produced a April 1996. Prior to that time he had generally been in good rapid improvementin symptoms. In addition, the contin- health. The pain was relieved with oral NSAIDtherapy. Sub- ued use of physical therapy during symptom-free periods sequently, the patient had recurrent episodes of pain involving tended to reduce the frequency and severity of pain attacks. the knees, hands, and elbows. The pain occurred every week, Wepresent this case and discuss treatment options in pa- lasted 3 to 7 days, and was generally worse in the late evening tients with palindromic rheumatism. or early morning. The patient was diagnosed with by his (Internal Medicine 40: 140-143, 2001) primary care physician based on an elevated serum uric acid level. However, despite normalization of the serum uric acid Key words: , HLADR-4, spa therapy, with treatment, the patient continued to have episodes of joint warmcompress, vicious cycle pain. The patient was examined at the Ryuso Orthopedic Clinic in November1998. He was then referred to the Third Depart- ment of Internal Medicine at the OkayamaUniversity Hospi- Introduction tal, where laboratory tests for antinuclear antibody, anti-ENA antibody, and were negative. The patient was Palindromic rheumatism is a disorder that was first described diagnosed with palindromic rheumatism, and was hospitalized in 1944 by Hench and Rosenberg at the MayoClinic (1). "Pal- at the Third Department of Internal Medicine at Okayama indromic" refers to a rheumatic disorder characterized by re- University Hospital from 10 April 1999 to 30 April 1999 for current episodes of interspersed with symptom- rest and more detailed evaluation. Chest and bilateral shoul- free intervals ( 1 ). "Rheumatism" refers to inflammation involv- der, hand, elbow, and knee radiographs showed no evidence of ing the joints and periarticular tissues (1). This case concerns a abnormalities. The patient continued to have episodes of pain patient with "palindromic rheumatism"in whomheat therapy while in the hospital, but the use of warmcompresses helped to the affected areas of joint involvement reduced the frequency to relieve his symptoms.The patient was admitted to our hos- and severity of pain attacks. The treatment prescribed for se- pital on May 7 1999 for balneotherapy (spa therapy), includ- vere palindromic rheumatismis often similar to that used dur- ing the use of warmcompresses. On admission, his tempera- ing the early stages of rheumatoid arthritis. Nevertheless, there ture was 36.5°C, height 171.5 cm, weight 72.6 kg, pres- have been no formally established therapeutic guidelines. In sure 140/80, and pulse rate, 56/min and regular. Physical ex- addition to this case, here we discuss other treatment options amination revealed no pallor of the palpebral conjunctivea, no for severe palindromic rheumatism. scleral icterus, and no edemaof the palpebral conjunctivea. The lungs, heart, and abdomenwere normal. There was no From the Division of Medicine, the Misasa Medical Branch, OkayamaUniversity Medical School, Misasa and *the Department of Medicine III, Okayama University Medical School, Okayama Received for publication March 24, 2000; Accepted for publication August 7, 2000 Reprint requests should be addressed to Dr. Shingo Takata, the Division of Medicine, the Misasa Medical Branch, Okayama University Medical School, Misasa, Tottori 682-0192 140 Internal Medicine Vol. 40, No. 2 (February 2001) Palindromic Rheumatism and Episodes of Pain

Table 1. Hematologic Values on Admission C B C B l o o d C h e m i c a l F i n d i n g s C a 9 . 6 m g / d l W B C 9 , 6 0 0 / u l T . R 7 . 6 g / d l C R P 0 . 2 m g / d l L y 2 4 .7 % B U N 2 2 . 6 m g / d l A S T 1 0 U / / M o n 7. 1 % U . A . 7 . 4 m g / d l A L T 1 7 U / / G r 6 8 . 2 % C r e a 1 . 2 m g / d l A L P 8 9 W l E O O % A l b 3 . 7 g / d l L D H 1 3 5 U / Z B A O % F B S 8 1 m g / d l C P K ¥ 4 6 U / l R B C 4 5 8 x l O 4/u l C H O L 1 7 3 m g /d l G G T 3 1 W l H b 1 4 . 7 g / d l T R I G 1 3 5 m m o l / / E S R 2 9 m m / h H c t 4 2. 1 % C L 1 0 2 . 1 m m o l / / 2 4 h C c r 7 9 . 8 m l / m i n P L T 1 9 .5 x l O 7 u l N A 1 4 2 . 1 m m o l / / K 3 . 9 9 m m o l / /

Table 2. Additional Laboratory Findings on strength. Oral treatment with Keishi-ka-jutsubu-to (a Chinese Admission herbal medicine) was started on July 28, 1999. By the second month of hospitalization, the interval between episodes of joint Rheumatoid factor (-) IgG 1,723 mg/dl pain had increased to the point where attacks only occurred IgA 527 mg/dl about twice per month. Theduration of symptomsalso de- > IgM 1 35 mg/dl creased. Rest and application of warmcompresses usually pro- C3 88.0 mg/dl vided pain relief within 1 to 2 days. Other generalized symp- C4 27.0 mg/dl toms such as during pain attacks also disappeared. anti-nuclear antibodies x40 Treatment with oral NSAIDswas not used at the patient's anti -nRNP (-) request. Other therapy such as colchicine, sodium aurothio- anti-Sm (-) malate, and D-penicillamine (reported to be effective in the anti-S S -A (-) anti-S S -B (-) medical literature) also was not used. Monthly tests for rheu- HLA-DR4 (-) matoid factor remained negative. HLAtyping for DR4was also negative. HLA-DR4has been associated with a transition from palindromic rheumatism to rheumatoid arthritis. The pa- tient was discharged from the hospital on October 5, 1999. evidence of joint tenderness or swelling, skin rash, superficial lymphadenopathy, morning stiffness, or Raynaud's phenom- Discussion enon. The laboratory findings on admission are shown in Table 1. The patient's BUNwas 22.6 mg/dl. The serum uric acid was Palindromic rheumatism is a disorder characterized by re- initially elevated at 7.4 mg/dl, but repeat testing during hospi- current episodes of acute inflammation of the joints and peri- talization showednormal levels. The erythrocyte sedimenta- articular tissues. The hands, fingers, knees, and shoulders are tion rate at 1 hour was slightly elevated at 29 mm.However, commonlyaffected, and symptoms typically last from a few this was measured immediately after an episode of joint pain. hours to 2 or 3 days. These attacks are interspersed by com- The CRP was normal. Immunologic studies (Table 2) showed pletely symptom-free periods. Hence, the name "palindromic", an elevated IgA of 527 mg/dl. Antinuclear antibody, rheuma- which is of Greek origin, means "to run back" (1). Palindrom- toid factor, and anti-Sm antibody were negative. ic rheumatismoccurs equally amongmenand womenand gen- The episodes of joint pain (with erythema) in the knees, el- erally affects patients in their 20s to 50s (1). Most laboratory bows, and hands that were present on hospital admission con- test findings, including serum uric acid, are normal. The eryth- tinued to recur at weekly intervals. These symptoms lasted as rocyte sedimentation rate and other acute reactive products may long as 7 days and were accompanied by fever (38°C range). be elevated after a pain attack. Radiographic findings remain After the onset of nocturnal pain attacks, the affected areas normal regardless of the number of joint pain episodes (1). were heated by application of warmcompresses, followed by Gonzalez-Lopez et al reported that approximately 30%of pa- the use of hot packs in the morning. This local heat application tients diagnosed with palindromic rheumatism eventually de- helped to relieve the pain. Cool compresses were not used be- velop rheumatoid arthritis (2). Manyof these patients are al- cause this only further intensified the patient's symptoms. Physi- ready positive for serum rheumatoid factor and HLADR-4(3). cal therapy, consisting primarily of heat therapy, to the affected Other patients maybecomepositive for rheumatoid factor at joints (especially the knees and hands) was continued even the time that rheumatoid arthritis actually develops (4, 5). In during symptom-free periods. The patient also performed addition, some reports have described patients with palin- stretching exercises in a warmwater pool to enhance muscle dromic rheumatism whohave developed other collagen vas-

Internal Medicine Vol. 40, No. 2 (February 2001) 141 Takata et al cular disorders such as systemic lupus erythematosus (2, 5). cur on a moreregular basis. Joint effusions can develop over a Someinvestigators believe that palindromic rheumatism may period of 12 to 24 hours and are associated with mild discom- itself be a clinically distinct rheumatic disorder (2, 5). fort or other inflammatory signs. Laboratory findings, includ- In their original description of palindromic rheumatism, ing the erythrocyte sedimentation rate, are usually normaleven Hench and Rosenberg did not report the presence of fever (1). during attacks. In our patient, the absence of joint effusions However, the present patient did have fever in association with ruled out a diagnosis of intermittent hydrarthrosis. Post-strep- severe pain. Thus, our patient was diagnosed with "severe" tococcal is an aseptic arthritis that mayoccur palindromic rheumatism. This patient initially reported symp- after streptococcal infections (7). However, our patient had no toms of kneepain. Other disease entities that must be consid- clinical findings suggestive of streptococcal infection such as ered in patients with knee pain include rheumatoid arthritis, a sore throat, thus excluding a diagnosis of post-streptococcal connective tissue diseases, gout, and pseudogout. reactive arthritis. The patient did not present typical clinical manifestations This patient complained of recurrent episodes of severe joint of rheumatoid arthritis, which is diagnosed on the basis of well- pain. Hemet all 6 of the diagnostic evaluation criteria pro- defined clinical criteria such as the presence of morningstiff- posed by Pasero and Barbieri for palindromic rheumatism (8), ness, rheumatoid nodules, a positive test for serum rheumatoid and was thus diagnosed as having palindromic rheumatism. factor, and involvement of 3 or more joints. Three years had Therapy similar to that prescribed for patients with early elapsed since the onset of symptoms,yet radiographic studies stage rheumatoidarthritis is sometimesalso recommendedfor showedno evidence of bony erosions or joint space narrowing patients with palindromic rheumatism, but no definitive guide- in this case. Joint symptomsin typical cases of palindromic lines for therapy have been established. Gold therapy and D- rheumatism are of short duration, generally lasting from a few penicillamine have been used in patients with a high frequency hours to a few days, and only 1 or 2 joints are affected during of recurrent attacks (4), but no formal clinical trials with con- each attack. Unlike rheumatoid arthritis, palindromic rheuma- trol groups have investigated the efficacy of such treatment. In tism is not associated with joint and radiographic palindromic rheumatism radiographic abnormalities are absent, findings are negative for bone destruction. The X-ray studies episodes of joint pain generally occur irregularly, and accurate in our patient showedno findings suggestive of rheumatoid evaluation of the effectiveness of therapy maybe difficult. These arthritis. In addition, physical examination revealed no joint factors and potential adverse effects meansthat antirheumatic changes or deformities typical of rheumatoid arthritis. drugs should be prescribed with caution. Given the relatively The negative laboratory test results for antinuclear antibody, high rate of transition from palindromic rheumatismto rheu- anti-Sm antibody, and serum rheumatoid factor ruled out a di- matoid arthritis, the use of antirheumatic drugs should also be agnosis of arthritis due to connective tissue disease. Thepres- considered in patients whodevelop other findings suggestive ence of hyperuricemia when the patient originally developed of early rheumatoid arthritis. Chloroquine has been reported to knee pain initially suggested a diagnosis of gout. The presence be effective for treatment of palindromic rheumatism (4, 9), of hyperuricemia whenthe patient originally developed knee but the production of this drug has been discontinued in Japan. pain initially suggested a diagnosis of gout. However, the sub- Therapy with colchicine has been evaluated in patients who sequent serumurine acid levels werenormalduring symptom failed to respond adequately to heat therapy. Grattan et al treated attacks and remissions. Serum uric acid maybe normal or low 38 patients with nonsteroidal antiinflammatory drugs (NSAIDs) in patients with gout. Nevertheless, we ruled out a diagnosis of and found that treatment was effective in 68%of cases (10). gout in our patient based on: 1) the frequency of recurrent at- Such therapy may be temporarily effective after the onset of a tacks and remission of symptoms after a few days, 2) the lack pain attack, but is ineffective in preventing recurrent episodes of joint pain involvement of the feet or ankles, and 3) the re- of joint pain. The use of oral NSAIDsmay also be associated current episodes of joint pain despite the normalization of se- with renal dysfunction. The occasional serious side effects of rum uric acid levels. NSAIDsmaketheir frequent use in somepatients inadvisable. Another condition associated with joint pain is pseudogout. Thepatient in this case requested that NSAIDsand other anti- Themost commonsite of calcium pyrophosphate dihydrate rheumatic drugs not be used. Our search of the medical litera- crystal deposition seen in pseudogout is the knees. Character- ture found no studies where the effects of physical modalities istic radiographic findings include calcification of hyaline car- such as heat therapy were evaluated in a control group of pa- tilage and fibrocartilage. Nevertheless, the X-ray findings in tients with palindromic rheumatism. However, Mansel-Jones our patient revealed no evidence of cartilage calcification. The reported that a combination of rest, heat therapy, and NSAIDs absence of these findings ruled out a diagnosis of pseudogout. did relieve symptomsin some patients (1 1). Therefore, physi- Intermittent hydrarthrosis and post-streptococcal reactive cal therapy was the mainstay of his treatment. arthritis are also associated with intermittent and recurrent joint Noxiousstimuli cause pain, which in turn cause muscle symptoms. Intermittent hydrarthrosis, as the nameimplies, is spasmsand vasoconstriction, thus creating a "vicious cycle" associated with recurrent joint effusions of unknownetiology. of pain. The therapeutic application of heat can help to break This condition occurs with a similar incidence in males and this vicious cycle by alleviating muscle spasms and producing females and usually begins at age 20 to 40 (6). Unlike palin- vasodilation. Heat relieves pain by reducing inflammation, al- dromic rheumatism, attacks of intermittent hydrarthrosis oc- leviating muscle spasm, and diminishing vasoconstriction. Heat 142 Internal Medicine Vol. 40, No. 2 (February 2001) Palindromic Rheumatism and Episodes of Pain also relieves pain by improving tissue oxygenation and elimi- nating pain-producing substances such as bradykinin, seroto- References nin, and prostaglandin E2. Heat therapy in our patient helped to relieve pain by virtue of these effects (ie, by reducing inflam- 1) Hench PS, Rosenberg EF. Palindromic rheumatism -a new oft recurring mation, alleviating muscle spasm, and diminishing vasocon- disease of joints (arthritis, periarthritis, para-arthritis) apparently produc- striction). ing no articular residues, report of thirty-four cases; its relation to "angio- neural arthrosis", "allergic rheumatism" and rheumatoid arthritis-. Arch Intern Med 73: 293-321, 1944. Conclusion 2) Gonzalez-Lopez L, Gamez-Nava JI, Jhangri GS, Ramos-Remus C, Russell AS, Suarez-Almazor ME. Prognostic factors for the development of rheu- matoid arthritis and other connective tissue diseases in patients with pal- Werecently hospitalized and treated a patient diagnosed with indromic rheumatism. J Rheumatol 26: 540-545, 1999. severe palindromic rheumatism who had been having recur- 3) Fisher LR, Kirk A, AwadJ, et al. HLAantigens in palindromic rheuma- rent episodes of joint pain over a period of 3 years. tism and palindromic onset rheumatoid arthritis. Br J Rheumatol 25: 345- Heat therapy to the affected areas provided rapid relief of 348, 1986. the patient's pain. The continued use of heat therapy during 4) Hannonen P, Mottonen T, Oka M. Palindromic rheumatism. A clinical survey of sixty patients. Scand J Rheumatol 16: 413^20, 1987. symptom-free periods also decreased the frequency and sever- 5) Guerne P-A, WeismanMH.Palindromic rheumatism: Part of or apart ity of subsequent episodes of joint pain. The patient improved from the spectrum of rheumatoid arthritis. AmJ Med 93: 45 1-460, 1992. to the point where these symptomsno longer caused problems 6) Weiner AD, Ghormley RK. Periodic benign synovitis: idiopathic inter- with his daily activities. mittent hydrarthrosis. J Bone Joint Surg 38A: 1039-1055, 1956. No formal guidelines have yet been established for the treat- 7) Fink CW.The role of the Streptococcus in poststreptococcal reactive ar- ment of palindromic rheumatism. Webelieve that heat therapy thritis and childhood polyarteritis nodosa. J Rheumatol (suppl 29) 18: should be considered as the first-line treatment in patients with 8) Pasero 14-20,G, Barbieri P. Palindromic rheumatism1991.-you just have to think this disorder. about it!-. Clin Exp Rheumatol 4: 197-199, 1986. 9) YoussefW, Yan A, Russell AS. Palindromic rheumatism: a response to chloroquine. J Rheumatol 18: 35-37, 1991. 10) Grattan CEH, Kennedy TD, Yates DB. Prognostic factors in palindromic rheumatism. Bristol Med Chir J 99: 51-54, 1984. 1 1) Mansel-Jones D. Palindromic rheumatism: a case history. Ann Rheum Dis 49: 648, 1990.

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