Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease in elderly people. It is a common indication for a long term treatment with steroid in patients based in the community. Although the cause of PMR is largely unknown, the presence of articular synovitis in PMR has been proven by synovial biopsy.¹ Recently, we have reported that symmetrical gallium-67 uptake in the shoulders and elevated serum matrix metal-loproteinase-3 (MMP-3) and vascular endothelial growth factor (VEGF) levels as the markers for synovitis in patients with PMR.² Although bilateral aching and stiffness of shoulders and pelvic girdle of acute or subacute onset are very characteristic for PMR, several other diseases can be present with similar symptoms. Here, we studied a gallium scintigraphic findings, and serum C-reactive protein (CRP), MMP-3 and VEGF levels in patients with diseases that mimic PMR. Further, we discuss clues to differentiate between PMR and other diseases that mimic PMR.

We studied Japanese patients with PMR (n = 7), pseudogout (n = 1), remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome (n = 1), and post-infectious polyarthritis (n = 1). Diagnosis for PMR had been done using the Hunder’s criteria.³ The distribution of inflammation in patients was evaluated using a gallium-67 scintigraphy whole body scan before the treatment. We measured serum CRP, MMP-3, and VEGF levels as the markers for a synovial inflammation before and after the treatment.⁴,⁵ Serum CRP and MMP-3 concentrations were measured by polyclonal antibody-based (Dade Behring, Marburg, Germany) and monoclonal antibody-based (Daiichi Fine Chemical, Co., Ltd., Toyama, Japan) latex agglutination method, respectively. Serum concentrations of VEGF₁₆₅ (major form of VEGF) were analyzed by enzyme linked immunosorbent assay (ELISA; VEGF₁₆₅, R&D Systems, Inc, Minneapolis, MN, USA).

PMR is a common disease in the elderly. In the United Kingdom, age-adjusted incidence of diagnosed PMR was reported to have increased by 35% between 1990 and 2001.⁶ However, it is not clear whether this suggests a true increase, increased recognition, or overdiagnosis of PMR. There is considerable uncertainty related to diagnosis in patients with PMR.⁷

Recently, developing classification criteria for PMR has been reported.⁸ Most survey respondents agreed on the importance of seven core criteria. These were 1) age ≥ 50 years, 2) duration ≥2 weeks, 3) bilateral shoulder and/or pelvic girdle aching, 4) duration of morning stiffness >45 min, 5) elevated erythrocyte sedimentation rate, 6) elevated CRP, and 7) rapid steroid response. All other core criteria except rapid steroid response were observed in patients with pseudogout and post-infectious polyarthritis, and all core criteria were observed in a patient with RS3PE syndrome, suggesting that this newly developed classification cannot distinguish pseudogout, post-infectious polyarthritis, and RS3PE syndrome from PMR.

Clinical and biochemical characteristics for PMR that we newly found were shown in Table 3. Patients with pseudogout, RS3PE syndrome, post-infectious polyarthritis manifested similar changes in scintigraphic findings and serum CRP, MMP-3, and VEGF to PMR. A good response to NSAIDs is an effective clue to differentiate pseudogout and post-infectious polyarthritis from PMR.⁹,¹⁰ An abnormality (chondrocalcinosis) in the radiographs of joints is also effective to differentiate pseudogout from PMR. Serum CRP level (24.3 mg/dl) in our patient (Case A) with pseudogout was quite high. A Korean female patient of calcium pyrophosphate dihydrate crystal deposition disease (CPDD) presenting as an acute polyarthritis also showed significantly elevated serum CRP levels (18.8 mg/dl).¹¹ However, it is too difficult to differentiate CPDD and CPDD + PMR from PMR, especially in elderly patients.¹² Therefore, we cannot completely deny a possible existence of an additional inflammatory condition including PMR in Case A.

A significant difference in gallium scintigraphic findings in RS3PE syndrome as compared with PMR was the presence of gallium uptake in both MCP joints. However, symmetrical gallium uptake was observed in shoulders and pelvic girdle, showing the similar scintigraphic findings to PMR. RS3PE syndrome is a very rare inflammatory arthritis.¹³ The features of this syndrome are bilateral pitting edema of both hands, sudden onset of polyarthritis, age > 50 years old, seronegative for RF.¹⁴ Mild to moderate synovitis of the joints and an association of VEGF with the pathogenesis have been observed in RS3PE syndrome as well as PMR.⁵,¹⁵,¹⁶ Elevated serum CRP, MMP-3 and VEGF levels, a bad response to NSAIDs, and rapid steroid response, were observed in our patient with RS3PE syndrome as well as patients with PMR. Pitting edema of the back of hands and symmetric gallium uptake in MCP joints are characteristic for RS3PE syndrome. As neoplasm are common in RS3PE syndrome, but not in PMR. Follow-up evaluation has been suggested to be necessary to observe for the possible occurrence of associated neoplasms.¹⁷

In conclusion, pseudogout, RS3PE syndrome, post-infectious polyarthritis should be included in the spectrum of diseases mimicking PMR. A good response to NSAIDs is a good clue to differentiate pseudogout and post-infectious polyarthritis from PMR. Pitting edema of the back of hands and symmetric gallium uptake in MCP joints are characteristic for RS3PE syndrome.

Disclosures

The authors report no conflicts of interest in this work.