Clinical characteristics of polymyalgia rheumatica in Japanese patients: evidence of synovitis and extracapsular inflammatory changes by fat suppression magnetic resonance imaging

Abstract

Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by diffuse pain and morning stiffness involving neck, shoulder, and pelvic girdles. To facilitate an understanding of PMR and its proper diagnosis, we evaluated clinical symptoms, laboratory data, and radiographic findings of 32 Japanese patients with it. Distal musculoskeletal manifestations were more frequently observed than had been thought before (81% of the patients), and peripheral arthritis was most common (75%). The joints most often affected were knees and wrists, and most episodes were presented as bilateral oligo- or polyarthritis. A swelling of hands was observed in 34% of the patients. Using contrast-enhanced fat suppression magnetic resonance imaging (MRI) of the shoulder, we found the evidence of subacromial and subdeltoid bursitis (100%), glenohumeral joint synovitis (93%), and biceps tenosynovitis (57%) in the PMR patients examined. Inflammatory changes in soft tissues around the joint capsule were prominent. By knee MRI, suprapatellar bursitis and joint synovitis were visualized in all cases examined, and extracapsular abnormalities were also prominent in 90% of the patients. Serum matrix metalloproteinase-3, a parameter of synovial inflammation, was significantly increased in PMR patients. Anticyclic citrullinated peptide antibody was useful for differential diagnosis between PMR and elderly onset rheumatoid arthritis. In conclusion, joint and periarticular synovitis seems to be commonly and primarily responsible for the proximal and distal musculoskeletal symptoms of PMR. The presence of the extracapsular change, probably a nonspecific extension of synovitis, can explain the severe discomfort that radiates toward the periphery. To avoid making a wrong diagnosis, we should be aware that peripheral synovitis is one of the hallmarks of PMR.     

Clinical characteristics of polymyalgia rheumatica in Japanese patients: evidence of synovitis and extracapsular inflammatory changes by fat suppression magnetic resonance imaging

Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by diffuse pain and morning stiffness involving neck, shoulder, and pelvic girdles. To facilitate an understanding of PMR and its proper diagnosis, we evaluated clinical symptoms, laboratory data, and radiographic findings of 32 Japanese patients with it. Distal musculoskeletal manifestations were more frequently observed than had been thought before (81% of the patients), and peripheral arthritis was most common (75%). The joints most often affected were knees and wrists, and most episodes were presented as bilateral oligo- or polyarthritis. A swelling of hands was observed in 34% of the patients. Using contrast-enhanced fat suppression magnetic resonance imaging (MRI) of the shoulder, we found the evidence of subacromial and subdeltoid bursitis (100%), glenohumeral joint synovitis (93%), and biceps tenosynovitis (57%) in the PMR patients examined. Inflammatory changes in soft tissues around the joint capsule were prominent. By knee MRI, suprapatellar bursitis and joint synovitis were visualized in all cases examined, and extracapsular abnormalities were also prominent in 90% of the patients. Serum matrix metalloproteinase-3, a parameter of synovial inflammation, was significantly increased in PMR patients. Anticyclic citrullinated peptide antibody was useful for differential diagnosis between PMR and elderly onset rheumatoid arthritis. In conclusion, joint and periarticular synovitis seems to be commonly and primarily responsible for the proximal and distal musculoskeletal symptoms of PMR. The presence of the extracapsular change, probably a nonspecific extension of synovitis, can explain the severe discomfort that radiates toward the periphery. To avoid making a wrong diagnosis, we should be aware that peripheral synovitis is one of the hallmarks of PMR.     

Fat suppression magnetic resonance imaging in shoulders of patients with polymyalgia rheumatica

OBJECTIVE: To evaluate the sites of inflammatory process in the shoulders of patients with polymyalgia rheumatica (PMR) using fat suppressed magnetic resonance imaging (MRI). METHODS: Six consecutive, untreated new patients with PMR were investigated. Five patients with early rheumatoid arthritis (RA) and 4 patients with early psoriatic arthritis (PsA) with bilateral shoulder symptoms served as a control group. Bilateral shoulder fat-suppressed MRI sequences were performed in all patients and controls. We evaluated the presence of joint synovitis, bursitis, tenosynovitis, and bone and soft tissue edema. RESULTS: Bilateral subacromial/subdeltoid bursitis was found in all patients with PMR, in 1/5 (20%) patients with RA (p < 0.05), and in none with PsA (p < 0.02). Glenohumeral synovitis was present in all case and controls. Biceps tenosynovitis was observed in 4/6 (67%) patients with PMR, in 4/5 (80%) with RA (not significant, NS), and in all 4 patients with PsA (NS). No evidence of bone edema adjacent to the joint capsule and entheseal insertions or in the soft tissues was present in either cases or controls. CONCLUSION: The absence of extracapsular abnormalities in the early shoulder disease of PMR does not confirm the hypothesis of a capsular-based disorder.     

Elderly onset rheumatoid arthritis complicated by polymyalgia rheumatica

We report herein the case of a 70-year-old patient with elderly onset rheumatoid arthritis associated with severe muscle pain in shoulder and pelvic girdle. The patient revealed erosive polyarthritis with high titers of rheumatoid factor. Muscle pain started one month after the onset of rheumatoid arthritis followed by muscle weakness and muscle atrophy. Synovial effusion and edema in the soft tissue outside of the articular capsule in the knee joint were confirmed ultrasonographically. Administration of prednisolone at 20 mg/day dramatically abolished the muscular manifestations. The coexistence of an early stage of elderly onset rheumatoid arthritis and polymyalgia rheumatica was considered due to the presence of seropositive erosive arthritis and severe muscle manifestations at the same time.     

Prednisolone pharmacokinetics in patients with rheumatoid arthritis,polymyalgia rheumatica and asthma

Summary The pharmacokinetic profile of a single 10 mg oral dose of prednisolone was studied in three groups of six patients with rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and bronchial asthma (BA) who were already receiving steroid therapy. A fourth group of age and sex-matched normal controls was also studied. Kinetic parameters (including elimination half-life, area under the plasma concentration curve, apparent volume of distribution and total body clearance) were similar for all four groups but there was considerable intersubject variability. The correlations between these kinetic parameters and age, body weight and serum albumin were poor. The results suggest that any differences in the effects of corticosteroids in these inflammatory diseases are unlikely to be due to pharmacokinetic factors. The duration of steroid therapy and the reduction in patient mobility would appear to be more likely explanations for the reduction in bone mass observed in patients with RA.     

The relation of polymyalgia rheumatica to rheumatoid arthritis

Sixty-four patients with the onset of rheumatoid arthritis (RA) after age 60 were followed for at least three years (mean 6.3 years); 33 patients had rheumatoid factor and 31 did not. Twenty-five of the 31 seronegative patients had an excellent response to low dose prednisone and did not require any additional medication. Six of these patients also had an episode diagnosed as polymyalgia rheumatica (PMR). These findings suggest that the synovitis currently diagnosed as seronegative RA in many older patients may not be the same disease as seropositive RA, but may be more closely related to or identical with PMR.     

Cytidine deaminase in polymyalgia rheumatica and elderly onset rheumatoid arthritis

Serum cytidine deaminase (CD) as a marker of inflammatory disease was assessed in 44 patients and 47 controls to differentiate polymyalgia rheumatica (PMR) from elderly onset rheumatoid arthritis (EORA). The patients were divided into four groups: PMR with and without synovitis and seropositive and seronegative EORA. No statistically significant differences were found when serum CD levels of seropositive EORA patients were compared with serum CD of PMR patients without synovitis, neither when serum CD levels of all PMR patients were compared with a seronegative EORA group, nor when serum CD levels of PMR patients with synovitis were compared with those with EORA. Nevertheless, statistically significant differences were detected between EORAs serum CD levels and the control group (p=0.023). This difference was 10% when comparing CD levels of PMR patients with the control group (p=0.070). We did not demonstrate that serum CD levels could be a useful tool to differentiate PMR from EORA, but these findings could nevertheless reflect the presence of an inflammatory disease.     

Temporomandibular joints in patients with rheumatoid arthritis using magnetic resonance imaging

The aim of this study was to determine the relationship between the pathogenic duration of rheumatoid arthritis in joints other than the temporomandibular joint and bone and soft tissue involvement of the temporomandibular joint using magnetic resonance imaging. Twenty-six symptomatic patients diagnosed with rheumatoid arthritis were enrolled in this study. All patients were classified according to the duration of rheumatoid arthritis in joints other than the temporomandibular joint. The relationships between the duration of rheumatoid arthritis in these various joints and magnetic resonance findings in the temporomandibular joint were analyzed using the chi-square test. Bony changes in the mandibular condyle were observed in 43 of 52 (82.7 %) temporomandibular joints, but the frequency of such changes was not significantly correlated with the duration of rheumatoid arthritis in other joints. We found a significant correlation between the duration of rheumatoid arthritis in other joints and the type and number of bony changes in the mandibular condyle (P?<?0.05). Superior disc positions were observed in 27 of 52 (51.9 %) temporomandibular joints. T2-weighted images demonstrated effusion in the joint space in 38 of 52 (73.1 %) temporomandibular joints. A biplanar disc configuration was the most frequent configuration in all groups. The duration of rheumatoid arthritis in other joints was significantly correlated with the mobility of the mandibular condyle (P?<?0.05). The type and number of bony changes and mobility of the mandibular condyle showed significant relationships with the duration of rheumatoid arthritis in other joints in the body (P?<?0.05).     

Comparison of low-field dedicated extremity magnetic resonance imaging with articular ultrasonography in patients with rheumatoid arthritis

To compare magnetic resonance imaging (MRI) and ultrasonography (US) in the detection of joint inflammation of rheumatoid arthritis (RA), 6 patients with RA were examined by US and low-field 0.3-T nonenhanced dedicated extremity MRI (compacTscan). All patients were females, with mean age of 50.2 years, mean disease duration of 13.5 years, and mean disease activity score (DAS)28-CRP of 1.78. Each patient was treated with either infliximab, etanercept, adalimumab, or tocilizumab. Intercarpal joints, radioulnar joints, second through fifth proximal interphalangeal (PIP) joints, and first through fifth metacarpophalangeal (MCP) joints (a total of 132 joints, 22 joints in each patient) were assessed by MRI for presence of joint inflammation. A total of 156 joints (24 first interphalangeal and radiocarpal joints plus the above 132 joints), were assessed by grayscale US (GS-US) and power Doppler US (PD-US) for presence of joint inflammation by two trained ultrasonographers. We assessed correlations between joint inflammations on MRI and GS-US/PD-US, and also interobserver correlation between the two ultrasonographers by calculating intraclass correlation coefficients (ICC). Synovial hypertrophy and/or synovial fluid was detected in 74/156 joints on GS-US, and synovitis was detected in 10/156 joints on PD-US and in 38/132 joints on MRI. Using PD-US as a reference, sensitivity of MRI in detection of synovitis was 80%. Using MRI as a reference, sensitivity of PD-US was 21%. Specificity of PD-US was higher than that of MRI. Overall agreement between GS-US and MRI and between PD-US and MRI was 0.56 and 0.76, respectively, suggesting that results of PD-US are close to those of MRI. ICC was 0.545 for GS-US and 0.807 for PD-US, suggesting specificity of PD-US in detecting joint inflammation. Our results show that findings of PD-US correlated with those of MRI. Low-field MRI and PD-US are useful tools for assessment of patients with RA.     

Comparison of low-field dedicated extremity magnetic resonance imaging with articular ultrasonography in patients with rheumatoid arthritis

Abstract

To compare magnetic resonance imaging (MRI) and ultrasonography (US) in the detection of joint inflammation of rheumatoid arthritis (RA), 6 patients with RA were examined by US and low-field 0.3-T nonenhanced dedicated extremity MRI (compacTscan). All patients were females, with mean age of 50.2 years, mean disease duration of 13.5 years, and mean disease activity score (DAS)28-CRP of 1.78. Each patient was treated with either infliximab, etanercept, adalimumab, or tocilizumab. Intercarpal joints, radioulnar joints, second through fifth proximal interphalangeal (PIP) joints, and first through fifth metacarpophalangeal (MCP) joints (a total of 132 joints, 22 joints in each patient) were assessed by MRI for presence of joint inflammation. A total of 156 joints (24 first interphalangeal and radiocarpal joints plus the above 132 joints), were assessed by grayscale US (GS-US) and power Doppler US (PD-US) for presence of joint inflammation by two trained ultrasonographers. We assessed correlations between joint inflammations on MRI and GS-US/PD-US, and also interobserver correlation between the two ultrasonographers by calculating intraclass correlation coefficients (ICC). Synovial hypertrophy and/or synovial fluid was detected in 74/156 joints on GS-US, and synovitis was detected in 10/156 joints on PD-US and in 38/132 joints on MRI. Using PD-US as a reference, sensitivity of MRI in detection of synovitis was 80%. Using MRI as a reference, sensitivity of PD-US was 21%. Specificity of PD-US was higher than that of MRI. Overall agreement between GS-US and MRI and between PD-US and MRI was 0.56 and 0.76, respectively, suggesting that results of PD-US are close to those of MRI. ICC was 0.545 for GS-US and 0.807 for PD-US, suggesting specificity of PD-US in detecting joint inflammation. Our results show that findings of PD-US correlated with those of MRI. Low-field MRI and PD-US are useful tools for assessment of patients with RA.     

Coexistence of temporal arteritis/polymyalgia rheumatica and rheumatoid arthritis

Summary A patient with biopsy proven temporal arteritis/polymyalgia rheumatica and erosive rheumatoid arthritis is presented. Only 15 such patients have previously been documented in the literature. The coexistence has been thought to be extremely infrequent, but could merely by chance appear in far more patients than previously reported.     

Detection of joint pathology by magnetic resonance imaging in patients with early rheumatoid arthritis

Magnetic resonance imaging (MRI) permits the visualization of anatomical structures not appreciated by conventional radiographic imaging, and may assess inflammatory disease and its progression with greater sensitivity than conventional radiography. In this study of 30 patients with early rheumatoid arthritis (RA), which could be considered as a pilot study because of the relatively small number of patients, we compare MRI of the knee and the fifth metatarsophalangeal joint with clinical and radiographic findings. A parallel study of 10 healthy individuals served as a reference group. In all but one of the 30 patients, MRI revealed some kind of joint abnormality, whereas conventional radiography was normal in 14 patients. The present study thus suggests that MRI may detect inflammatory and/or destructive joint changes in patients with early RA, and that these changes may occur in the absence of clinical symptoms or signs and/or radiographic signs in the examined joint. If these data prove to be confirmed in further controlled studies, MRI may be of importance both for the assessment of prognosis and for the decision to treat in the early critical stages of RA.      

Ultrasound assessment of new onset bilateral painful shoulder in patients with polymyalgia rheumatica and rheumatoid arthritis

The aim of our study was to investigate by ultrasound (US) the anatomical structures affected during a new episode of bilateral painful shoulder in patients with polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA) and to compare the findings between these two conditions. PMR and RA patients complaining of new onset bilateral painful shoulder were included. Subjects without any known rheumatic condition with a new onset unilateral painful shoulder were assessed as a control group. US evaluation includes the depiction subacromial–subdeltoid (SAD) bursitis, long head biceps (LHB) tenosynovitis and/or gleno-humeral (GH) synovitis. Thirty patients with PMR, 30 with RA, and 60 controls were included for a total of 60 shoulders per group. Unilateral SAD bursitis and LHB tenosynovitis were significantly more frequent in patients with PMR when compared to those with RA (p?<?0.0001 and p?<?0.01, respectively) and controls (p?<?0.001 and p?<?0.01, respectively). Unilateral GH synovitis was more common in RA than in PMR and controls (p?<?0.05 and p?<?0.01, respectively). Bilateral SAD bursitis was significantly more frequent in patients with PMR than in those with RA (p?<?0.01) as was bilateral LHB tenosynovitis (p?<?0.01). No significant differences were found in bilateral GH synovitis. US-detected periarticular inflammatory involvement more frequently in PMR both unilaterally and bilaterally and intra-articular inflammatory involvement was commonly in RA but only unilaterally.     

Altered T-cell subtypes in spondyloarthritis, rheumatoid arthritis and polymyalgia rheumatica

The objective of the present study was to assess the prevalences of naive, memory, memory/effector, regulatory and activated T-cells in peripheral blood (PB) and synovial fluid (SF) of patients with spondyloarthritis (SpA), rheumatoid arthritis (RA), polymyalgia rheumatica/giant cell arteritis (PMR/GCA) and healthy controls (HC). Twenty-two patients with SpA, 15 patients with RA, 38 patients with PMR/GCA and 17 HC were prospectively enrolled. The expression of differentiation and activation markers (CD3, CD4, CD8, CD25, CD28, CD45RA, CD45RO) characterizing T-cell subsets were analyzed by flow cytometry. The frequency of CD3⁺CD4⁺CD28⁻ memory/effector T-cells was increased in PB of patients with SpA (median 1.1%, range 0.1–69.6), RA (2.5%, 0–42.9) and PMR/GCA (2.7%, 0–49.5) when compared with HC (0.7%, 0–38.0) and tended to be higher in SF of SpA patients (4.5%, 0.2–7.2, P = 0.084). CD28⁺CD45RA⁺CD4⁺ (9.6%, 4.1–10.3) and CD28⁺CD45RA⁺CD8⁺ naive T-cells (15.0%, 12.9–26.2) were reduced and CD28⁺CD45RO⁺CD4⁺ (93.5%, 51.0–99.0), CD28⁺CD45RO⁺CD8⁺ memory (81.2%, 38.9–83.5), CD8⁺CD25⁺ activated T-cells (10.9%, 2.7–13.8) and CD4⁺CD25^hi TREGs (10.2%, 7.0–13.3) were increased in SF compared to PB (P < 0.05 each). These findings demonstrate altered T-cell subsets in patients with immune-mediated disease, particularly at sites of inflammation.     

Late-onset rheumatoid arthritis vs polymyalgia rheumatica: making the diagnosis

Differentiating polymyalgia rheumatica from the onset of rheumatoid arthritis in the elderly has been the cause of much unnecessary confusion. Differential diagnosis of these disorders can be straightforward. A strategy is outlined, comprising a complete history, attention to clinical signs, and appropriate use of laboratory diagnostics. The clinical picture of each disorder is discussed, as are common obstacles to diagnosis.     

Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly-onset rheumatoid arthritis

BACKGROUND: Polymyalgia rheumatica (PMR) may create some difficulties in the differential diagnosis of elderly-onset rheumatoid arthritis (EORA) and of EORA with PMR-like onset (EORA/PMR). AIM: To investigate possible differences between three groups of patients, with regard to serum levels of inflammatory cytokines and steroidal hormones at baseline and after 1 month of treatment with glucocorticoids (prednisone 7.5-12.5 mg/day). PATIENTS AND METHODS: 14 patients with PMR, 15 with EORA and 14 with EORA/PMR, as well as 15 healthy, matched controls were analysed. Tumour necrosis factor alpha (TNFalpha), interleukin (IL)6, IL1 receptor antagonist (IL1Ra), cortisol, dehydroepiandrosterone sulphate (DHEAS) and 17-hydroxy-progesterone (PRG) were evaluated. RESULTS: Serum levels of both TNFalpha and IL6 were significantly higher in all three groups of patients than in controls (p<0.01). Serum IL6 levels were significantly higher in patients with both PMR and EORA/PMR than in patients with EORA (p<0.05). IL1Ra serum levels were significantly higher in patients with EORA than in controls (p<0.001) and in patients with PMR and EORA/PMR (p<0.05). DHEAS was significantly lower in patients with EORA/PMR than in those with EORA (p<0.05). PRG was significantly higher in all patient groups (p<0.05). After glucocorticoid treatment, serum TNFalpha and IL6 levels significantly decreased in all patient groups; IL1Ra significantly increased in patients with PMR and in those with EORA/PMR; cortisol, DHEAS, and PRG significantly decreased in patients with PMR and in those with EORA/PMR (p<0.05). CONCLUSIONS: Different cytokine and steroidal hormone patterns suggest that patients with PMR and those with EORA/PMR seem to be have a more intensive inflammatory reaction and are more efficient responders to glucocorticoid treatment than patients with EORA.