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.     

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.     

Polymyalgia rheumatica in der täglichen Praxis

Definition and epidemiology

Polymyalgia rheumatica (PMR) is a very painful inflammatory disease which regularly affects the shoulder region but in 70 % of cases the pelvic girdle region is also affected. The disease occurs in people over the age of 50 years and reaches a peak at 72 years old. Women are affected twice as often as men. The prevalence is estimated to be 0.3-0.7 % in the Caucasian population over 50 years old.

Diagnostics and classification

Misdiagnosis of PMR is common. The differential diagnosis primarily includes impingement syndrome, osteoarthritis of the shoulders, calcifying tendinitis of the rotator cuff, bursitis, omarthritis or inflammatory rheumatic diseases, such as rheumatoid arthritis. Taking a structured medical history and performing a thorough clinical examination are crucial. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are usually highly elevated and should be investigated particularly in patients who present with new onset bilateral shoulder pain and pronounced general impairment of movement. Imaging shows characteristic inflammatory changes around the shoulders and hip joints. The new European League Against Rheumatism and American College of Rheumatology (EULAR/ACR) classification criteria of PMR including ultrasound imaging are superior to previous classification and diagnostic criteria in terms of positive and negative predictive values.

Therapy

Glucocorticoids are still the mainstay of treatment. Recommended daily prednisolone starting doses are between 15 mg and 25 mg with a weekly dose reduction until 10 mg/day and then further dose reductions of 1 mg per month. Methotrexate can aid reducing prednisolone doses in patients who fail to reach doses below the Cushing threshold quickly enough, which can have major side effects.     

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.     

Shoulder ultrasonography in the diagnosis of polymyalgia rheumatica: a case-control study

OBJECTIVE: Magnetic resonance imaging (MRI) showed that subacromial/subdeltoid bursitis is the most frequent shoulder lesion in polymyalgia rheumatica (PMR). We evaluated whether shoulder ultrasonography (US) was as effective as MRI in the detection of this lesion and assessed the sensitivity and specificity of bilateral subacromial/subdeltoid bursitis in the diagnosis of PMR. METHODS: A case-control study of 57 consecutive case patients with untreated PMR and 114 controls seen over a 6 month period in 3 secondary referral rheumatology centers. Control patients consisted of the next 2 consecutive patients with bilateral shoulder aching and stiffness observed after the case patient. In all case and control patients the glenohumeral joint space, bursae, and long head biceps tendon were assessed by bilateral shoulder US. The first 24 case patients were also examined by bilateral shoulder MRI. RESULTS: US showed subacromial/subdeltoid bursitis in 55/57 (96%) patients with PMR and in 25/114 (22%) controls (p < 0.001). The lesion was bilateral in 53/55 (96%) case patients and in 1/25 (4%) controls (p < 0.001). The frequency of glenohumeral joint synovitis and biceps tenosynovitis did not differ significantly between case patients and controls. In 100% of case patients MRI showed subacromial/subdeltoid bursitis confirming US findings. The sonographic evidence of bilateral bursitis had a sensitivity of 92.9%, specificity of 99. 1%, and positive predictive value of 98. 1% for the diagnosis of PMR. CONCLUSION: US and MRI were equally effective in confirming bilateral subacromial and subdeltoid bursitis in PMR. This finding, in view of its high sensitivity and specificity, could be used as a new diagnostic criterion for PMR.     

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.     

Atypical presentations of polymyalgia rheumatica

Seventy patients with polymyalgia rheumatica (PMR) were seen at a suburban rheumatology practice from July 1983 to December 1987. Six of these patients presented without the typical limb girdle features associated with PMR. Presenting symptoms included peripheral synovitis or unilateral shoulder pain (3 patients), lower leg pain (3 patients), carpal tunnel syndrome (1 patient), and abdominal pain (1 patient). The disease evolved into the recognizable syndrome of PMR over a period of 2-12 months. We suggest that PMR may present in a variety of guises, or have a "stuttering evolution" to the full syndrome. The presenting manifestations of these atypical cases result from peripheral synovitis and thus represent a variant of the more common subclinical proximal synovitis seen in PMR. Increased clinical awareness of atypical presentations may assist earlier diagnosis and effective treatment.     

Elderly onset rheumatoid arthritis and polymyalgia rheumatica: ultrasonographic study of the glenohumeral joints

The glenohumeral joints of 32 patients (aged 60 or above) were examined using ultrasonography. Thirteen patients were suffering from characteristic polymyalgia rheumatica (PMR) symptoms. In contrast 19 other patients initially had similar complaints, but were diagnosed as having elderly onset rheumatoid arthritis (EORA) upon development of typical symptoms. Ultrasound examination revealed glenohumeral joint inflammation in 61% (8 out of 13) of the patients with PMR and 63.2% (12 out of 19) of the patients with EORA. These findings suggest that a subgroup of patients with PMR and EORA suffers from shoulder joint inflammation and this synovitis/bursitis/intraarticular effusion might play an important role in the understanding of their symptoms. We conclude that overlapping forms of PMR and a predominate rheumatoid factor negative subgroup of EORA might exist and should be further characterized. Received: 25 August 1997 / Accepted 9 January 1998     

Inflamed shoulder structures in polymyalgia rheumatica with normal erythrocyte sedimentation rate

OBJECTIVE: To investigate the inflammatory involvement of shoulder articular and extraarticular structures in polymyalgia rheumatica (PMR) patients with a normal erythrocyte sedimentation rate (ESR) at diagnosis. METHODS: This was a case-control study. All consecutive, untreated new outpatients diagnosed as having PMR with a normal ESR (<40 mm/hour) during a 6-month period were included in the study (case patients). Controls were 12 consecutive, untreated PMR outpatients with an ESR of >40 mm/hour who were observed after the case patients. Before starting corticosteroid therapy, all case patients and controls underwent bilateral shoulder ultrasonography (US) and magnetic resonance imaging (MRI). US and MRI scans were evaluated independently by two radiologists who were blinded to the reciprocal results. RESULTS: Six case patients (4 men and 2 women) and 12 controls (4 men and 8 women) were studied. Both US and MRI demonstrated bilateral subacromial/subdeltoid bursitis in all 6 case patients and in 11 of the 12 (92%) controls (P not significant [NS]). One control had unilateral bursitis. Glenohumeral joint synovitis was found in 4 of 6 case patients (67%) by MRI and in 3 of 6 case patients (50%) by US (P NS), as well as in 8 of 12 controls (67%) by MRI and in 7 of 12 controls (58%) by US (P NS). Both MRI and US detected biceps tenosynovitis in 5 of 6 case patients (83%) and in 8 of 12 controls (67%) (P NS). The severity of bursitis did not differ significantly between the groups. US was as effective as MRI in detecting inflammatory changes of the shoulder. CONCLUSION: MRI and US studies showed that PMR patients with normal or high ESRs have similar inflammatory shoulder lesions. Moreover, bilateral subacromial/subdeltoid bursitis represents the imaging hallmark in PMR patients with a high or normal ESR. MRI or US of the shoulder may facilitate the proper diagnosis in patients with the typical proximal symptoms of PMR who also have normal ESRs.     

Inflammatory changes of hip synovial structures in polymyalgia rheumatica

OBJECTIVE: To investigate the hip inflammatory lesions and to evaluate the accuracy of clinical examination compared to magnetic resonance imaging (MRI) in patients with polymyalgia rheumatica (PMR) with pelvic girdle symptoms. Secondary end-point was to evaluate the sensitivity and specificity of ultrasonography (US) compared to MRI in the assessment of hip lesions. METHODS: Case-control study of 20 consecutive PMR patients and 40 controls with different rheumatic conditions. Both groups were clinically assessed for the presence of hip synovitis, trochanteric, iliopsoas and ischiogluteal bursitis. Hip MRI was performed in all case-patients and in 10 controls. Both groups were examined by US. An additional group of 10 healthy controls was examined by hip US. RESULTS: Both MRI and US detected trochanteric bursitis in 100% of PMR patients, bilateral in 18/20 (90%), and in 12/40 (30%) controls (p < 0.001). Hip synovitis was detected in 17/20 (85%) by MRI and in 9/20 (45%) by US (p < 0.02) in case-patients and in 18/40 (45%) controls. In PMR, MRI and US showed iliopsoas bursitis in 10/20 (50%) and 6/20 (30%) and ischiogluteal bursitis in 5/20 (25%) and 4/20 (20%) with no differences compared to controls. Clinical examination showed a good accuracy for hip synovitis, trochanteric and ischiogluteal bursitis, while it overestimated the presence of iliopsoas bursitis. US was less sensitive than MRI for the detection of hip synovitis and iliopsoas bursitis (53% and 60%). CONCLUSION: Trochanteric bursitis represents the most frequent hip lesion in PMR. A careful physical examination allows to detect all inflammatory lesions excluding iliopsoas bursitis. US is less sensitive than MRI in the assessment of hip synovitis and iliopsoas bursitis.     

New-onset Polymyalgia Rheumatica Following the Administration of the Pfizer-BioNTech COVID-19 Vaccine

We herein report the case of an 80-year-old Japanese woman who presented to our hospital with bilateral pain in the shoulders and hips lasting for a month since 2 days after the second dose of the BNT162b2 COVID-19 vaccine. Her physical findings, laboratory data, and ultrasonographic findings of bilateral biceps tenosynovitis and lateral subacromial bursitis were consistent with a diagnosis of polymyalgia rheumatica (PMR). She was successfully treated with oral prednisolone 15 mg/day. Although a causal relationship could not be definitively confirmed, PMR should be considered as a differential diagnosis in cases of persistent myalgia after administration of the BNT162b2 vaccine.     

Sites of inflammation in painful rheumatoid shoulder assessed by musculoskeletal ultrasound and power Doppler sonography

Ultrasonography (US) and power Doppler sonography (PDS) was used to investigate causes of new onset of shoulder pain and sites of shoulder inflammation in 157 shoulders of 99 patients with rheumatoid arthritis (RA). US detected effusion and/or synovitis in 92/157 glenohumeral joints, subdeltoid bursitis in 56/157 shoulders and tenosynovitis of biceps tendon in 55/157 shoulders. Bursitis and/or tenosynovitis were accompanied by glenohumeral synovitis in 68/90 shoulders. 68% of serologically active and 12% of serologically inactive patients had glenohumeral synovitis. PDS showed increased microvascular blood flow in 33 of the 44 investigated shoulders. Glenohumeral synovitis was correlated to elevated C-reactive protein levels (p = 0.0001) and microvascular blood flow assessed by PDS (p = 0.02). This study shows that rheumatoid shoulder pain is not caused by glenohumeral synovitis in 32% of patients, despite serologically active RA. US and PDS are mandatory to elucidate the origin of inflammatory and noninflammatory shoulder pain.     

Synovial expression of vasoactive intestinal peptide in polymyalgia rheumatica

OBJECTIVE: Polymyalgia rheumatica (PMR) is an inflammatory disease that typically affects elderly people. Its clinical hallmark is the severity of pain in the shoulder and pelvic girdle. Mild to moderate synovitis and/or bursitis of the joints involved has been described. Neuropeptides are involved in nociception and modulation of inflammatory reaction. To evaluate whether neuropeptides have a role in PMR pathophysiology, we studied the expression of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in shoulder synovial tissues of PMR patients. METHODS: Synovial expression of neuropeptides was investigated by immunohistochemical analysis, in two groups of PMR patients: the first one at the onset of disease and the second one after corticosteroid treatment, and in other joint diseases, rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: The only significant expression of VIP was found in PMR and, to a lesser extent, in RA synovial tissue. In PMR, we observed VIP immunostaining both in the lining layer and in the sublining area. In patients on corticosteroid treatment VIP lining layer expression was not significantly different while VIP positive cells in the sublining area were almost absent. CONCLUSION: Local VIP production in PMR synovial tissue might contribute to the typical musculoskeletal discomfort and it may have a role in the immunomodulation of synovial inflammation.     

Polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a common chronic inflammatory rheumatic disease with unknown aetiology, affecting predominately people of middle age and older. Besides clinical symptoms and diagnostics, imaging techniques including sonography and magnetic resonance imaging may provide evidence of typical inflammatory lesions with bilateral bursitis subdeltoidea or subacromialis, tenosynovitis of the biceps tendon sheath and/or synovitis of the shoulder joints and thus may support the diagnosis of this disease in difficult cases. Corticosteroids are the cornerstone of treatment of PMR, but adverse events because of chronic corticosteroid use are observed in more than 50% of treated patients. Whether immunosuppressants, such as methotrexate and tumour necrosis factor-α inhibitors are effective in the therapy of PMR has still not yet been clarified.     

Joint involvement in polymyalgia rheumatica/temporal arteritis

The coincidence of arthritis with polymyalgia rheumatica (PMR) or temporal arteritis (TA) is not well established. After reviewing the literature we found that 22% of patients suffering from PMR/TA present with additional signs of inflammatory joint involvement. Joints predominantly affected are the sternal junctions, knee and shoulder joints, and the wrists, involvement of the latter frequently resulting in carpal tunnel syndrome. With the exception of sternal junctions, bony erosions are rarely seen. In most cases, synovitis is mild, pauciarticular, asymmetrical, transient and not destructive. Little evidence for inflammatory involvement of spine or sacroiliac joints was found, thus, back pain in these patients should be considered as caused by osteoporosis of the spinal column, mostly due to prolonged corticosteroid treatment.     

Diagnostik und Therapie der Polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is the most common autoimmune inflammatory disease in older persons with an average age of onset of 73 years. Typical symptoms include acute or subacute bilateral shoulder pain with severe stiffness and often neck and bilateral hip pain. Giant cell arteritis (GCA) occurs in approximately 20?% of cases and up to two thirds of patients with GCA have symptoms of PMR. There are many disease which mimic PMR, elderly onset rheumatoid arthritis is frequently misdiagnosed as PMR. Although there are no specific laboratory tests, C?reactive protein and erythrocyte sedimentation rates are elevated in over 90?% of patients. The diagnosis may be aided by imaging, especially ultrasonography and magnetic resonance imaging (MRI). Treatment currently consists of glucocorticoids at an initial dose of 12.5–25 mg prednisone equivalent daily. Treatment duration is typically 2?3 years but may be longer. Under certain conditions low-dose methotrexate can be used as adjuvant therapy.     

Polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder and in the pelvic girdles and neck. In the past, PMR was considered a manifestation of giant cell arteritis (GCA) or a variant of elderly-onset rheumatoid arthritis (EORA). The current diagnostic criteria for PMR were empirically formulated by clinical experts who had studied the disease extensively. Arthroscopic, radioisotopic and magnetic resonance imaging studies all have indicated the presence of a synovitis in proximal joints and periarticular structures. The synovitis is probably responsible for the musculoskeletal symptoms in PMR. The prominence assigned to the proximal symptoms has probably overshadowed the less well recognized and more variable distal musculoskeletal manifestations which are present in about half of the cases. A normal erythrocyte sedimentation rate does not exclude a diagnosis of PMR. C-reactive protein and interleukin-6 seem to be more sensitive indicators of disease activity both at diagnosis and during relapse/recurrence. Corticosteroids are the drugs of choice for treating PMR. A course of treatment of 1-2 years is often required. However, some patients have a chronic, relapsing course and require low doses of corticosteroids for several years. Large, multicenter, double-blind, placebo-controlled studies are required to define the role of methotrexate and anti-TNF-alpha agents as corticosteroid-sparing drugs in PMR.     

A patient with polymyalgia rheumatica who exhibited fever as the main symptom for a long period]

We encountered a patient with polymyalgia rheumatica (PMR) who exhibited fever as the main symptom for a long period without muscular pain. As an etiological factor, the condition may have been associated with nonsteroidal anti-inflammatory drugs (NSAIDs). A 71-year-old man consulted our Department of Orthopedics for fever and lumbar pain, which initially developed in early September 2000. Administration of NSAIDs resulted in the disappearance of lumbar pain. However, fever persisted. The C-reactive protein (CRP) level was persistently high. Therefore, on October 5, 2000, the patient was referred to our department. At the outpatient clinic, a detailed examination was performed. However, the etiology could not be determined. Repeated administration of NSAIDs resulted in pyretolysis, and the dose of NSAIDs was decreased from January 31, 2001. Severe fever appeared again, and inflammatory reaction also exacerbated. On March 11, 2001, muscular pain involving the bilateral shoulders and forearms suddenly developed. For diagnostic treatment, administration of prednisolone (PSL) at 10 mg/day was started. Muscular pain rapidly disappeared. According to Bird's criteria, PMR was diagnosed. After the dose of PSL was decreased to 7.5 mg/day, the course is good. PMR should be considered as the etiology of idiopathic fever in elderly patients.     

Internistische und serologische Befunde der Riesenzellarteriitis

Giant cell arteritis (GCA) frequently appears as cranial arteritis (eg. temporal arteritis) with headache, pain on chewing and visual disturbances. In addition, extracranial manifestations are often observed leading to aneurysmatic dilatations and dissections of the aorta as well as stenoses of large thoracic, abdominal or limb arteries. The vascular signs are accompanied by general disease symptoms, e.g. malaise, elevated temperatures, weight loss and depression. Polymyalgia rheumatica (PMR) is the most frequent rheumatic manifestation of GCA but also occurs independently from GCA. The structural correlate for the PMR symptoms is first and foremost extra-articular inflammation (tenosynovitis, bursitis) of large joints and the vertebral column (interspinal bursitis). In addition, vasculitis of large arteries in PMR must be considered particularly in the presence of high inflammatory activity. While specific laboratory markers for GCA and PMR are lacking elevated values for the erythrocyte sedimentation rate and C-reactive protein are present in almost all patients at disease onset. Besides the clinical evaluation, the serological acute phase reaction represents the main parameter for the course during therapy of this relatively frequent disease in elderly people.