Elderly-onset Rheumatoid Arthritis Research Articles

Análisis del polimorfismo rs20541 (R130Q) del gen de la IL-13 en pacientes con enfermedades inflamatorias crónicas asociadas al envejecimiento

ObjectiveTo investigate whether there is association between the rs20541 (R130Q) polymorphism in the IL-13 gene with disease susceptibility and clinical subsets in patients with elderly-associated inflammatory chronic diseases. Material and methods78 patients with giant cell arteritis (GCA), 174 with polymyalgia rheumatica (PMR), 90 elderly-onset rheumatoid arthritis (EORA), and 465 healthy controls from the same geographic area were studied. The rs20541 (R130Q) polymorphism in the IL-13 gene was evaluated by PCR-RFLP. Circulating levels of IL-13 were measured by ELISA. ResultsA higher frequency of the AA genotype [2.349 (0.994-5.554)], as well as the allele A [1.589 (1.085-2.328] and the A carriers [1.656 (1.021-2.686)] (p<0.05) was observed in the GCA patients. No significant differences were observed in the PMR and EORA patients as compared with the healthy controls. Neither difference was observed among the different disease groups studied. In GCA patients, differences in the genotype were associated with a worse prognosis. In PMR patients, the AA genotype was associated with higher levels of serum IL-13 than the GA one. However, such an association was not detected for controls and the other disease groups. ConclusionsGCA is more frequent in carriers of the rs20541 (R130Q) polymorphism in the IL-13 gene. The utility of this polymorphism to predict the GCA prognosis must be confirmed in studies with a higher number of patients.

Do Patients with Elderly-Onset Rheumatoid Arthritis Have Severe Functional Disability?

To identify the clinical features of elderly-onset rheumatoid arthritis (EORA) and their impact on disease outcome. A total of 3169 rheumatoid arthritis (RA) patients were recruited as part of the Korean Observational Study Network for Arthritis, the nationwide cohort of South Korea. Patients were stratified according to age at disease onset: <40 years (younger age-onset RA, n = 1167), between the ages of 40 and 59 (middle-aged-onset RA, n = 1516), and ≥60 years (EORA, n = 486). To evaluate the significance of differences in clinical features among these 3 groups, we performed analysis of variance (anova) and the χ(2) test. We used multivariable logistic regression analysis to examine the association of onset age with functional disability measured with Health Assessment Questionnaire-Disability Index (HAQDI). EORA patients were associated with high HAQDI (≥1) in bivariable analysis [odds ratio (OR) 1.36, confidence interval (CI) 1.04-1.77]. However, in multivariable analysis, not elderly onset but patients' age, female gender, high disease activity, disease duration over 10 years, and comorbidity with cardiovascular disease were associated with high HAQDI. Only in a predefined subgroup with disease duration <10 years, elderly onset was an independent influencing factor for the functional disability of RA patients (OR 3.04, CI 1.85-5.67: disease duration of <5 years, OR 3.07, CI 1.64-5.74: disease duration of 5 to 10 years). Disease onset in older age was associated independently with functional disability of RA patients who have relatively short disease duration.

Anti-type II collagen antibodies are associated with early radiographic destruction in rheumatoid arthritis

IntroductionWe have previously reported that high levels of antibodies specific for native human type II collagen (anti-CII) at the time of RA diagnosis were associated with concurrent but not later signs of inflammation. This was associated with CII/anti-CII immune complex (IC)-induced production of pro-inflammatory cytokines in vitro. In contrast, anti-cyclic citrullinated peptide antibodies (anti-CCP) were associated both with late inflammation and late radiological destruction in the same RA cohort. We therefore hypothesized that anti-CII are also associated with early erosions.MethodsTwo-hundred-and-fifty-six patients from an early RA cohort were included. Baseline levels of anti-CII, anti-CCP and anti-mutated citrullinated vimentin were analyzed with ELISA, and rheumatoid factor levels were determined by nephelometry. Radiographs of hands and feet at baseline, after one and after two years were quantified using the 32-joints Larsen erosion score.ResultsLevels of anti-CII were bimodally distributed in the RA cohort, with a small (3.1%, 8/256) group of very high outliers with a median level 87 times higher than the median for the healthy control group. Using a cut-off discriminating the outlier group that was associated with anti-CII IC-induced production of proinflammatory cytokines in vitro, baseline anti-CII antibodies were significantly (p = 0.0486) associated with increased radiographic damage at the time of diagnosis. Anti-CII-positive patient had also significantly increased HAQ score (p = 0.0303), CRP (p = 0.0026) and ESR (p = 0.0396) at the time of diagnosis but not during follow-up. The median age among anti-CII-positive subjects was 12 years higher than among the anti-CII-negative patients.ConclusionIn contrary to anti-CCP, anti-CII-positive patients with RA have increased joint destruction and HAQ score at baseline. Anti-CII thus characterizes an early inflammatory/destructive phenotype, in contrast to the late appearance of an inflammatory/destructive phenotype in anti-CCP positive RA patients. The anti-CII phenotype might account for part of the elderly acute onset RA phenotype with rather good prognosis.

Arthritic disease is more severe in older rats in a kaolin/carrageenan-induced arthritis model

This study examined in an arthritis animal model whether elderly onset rheumatoid arthritis (EORA) is a more severe disease than younger onset rheumatoid arthritis. Arthritis was induced by injecting 5% kaolin/carrageenan into the left tibiotarsal ankles of 18-month-old and 4-week-old rats. Various parameters were measured to evaluate the arthritic progression of kaolin/carrageenan-induced arthritis in the rats. Immunohistochemical staining of arthritic joints was performed to determine the degree of inflammation in old and young rats. Measurements of ankle volume and thickness, arthritic index, number of squeaks, and the paw pressure test showed the 18-month-old rats had more severe disease than the young rats in a kaolin/carrageenan-induced arthritis model. The degree of inflammation and MMP-1 expression of arthritic joints in old rats was significantly higher than that of young rats based on histological evaluation with hematoxylin and eosin (H&E) staining and immunochemistry. More severe disease symptoms were found in old rats with EORA, but the molecular mechanisms still remain to be elucidated. Understanding the molecular mechanisms will be helpful to develop clinical protocols to efficiently treat patients with EORA, which is difficult to control with current protocols.

Tratamiento de la artritis reumatoide del anciano

In the international literature, rheumatoid arthritis (RA) of the elderly is considered to be that affecting persons aged over 65 years. Currently, this population comprises most series of patients with RA and includes both persons with disease onset after this age and those with chronic RA developing years previously. RA with onset after the age of 65 is called elderly onset rheumatoid arthritis (EORA) and shows slightly different clinical manifestations from RA developing in younger individuals. However, both the therapeutic arsenal used and the objectives proposed for the treatment of RA of the elderly differ little from those employed in younger patients. The same therapies are employed but are adapted to the particular characteristics of this population, such as pharmacokinetic changes, comorbidities, and an increased susceptibility to infection. The aim of treatment —disease remission— is the same as in younger patients. Excessive caution in the use of drugs may lead to suboptimal treatment, especially in the initial stages when the disease is more active, and leave irreversible sequelae. Treatment should be individually tailored to the patient's characteristics, with adequate monitoring. Traditionally, elderly patients more frequently received glucocorticoids and were rarely treated with disease-modifying antirheumatic drugs (DMARDs) or biological agents. People over 65 years are underrepresented in clinical trials but there seem to be no particular contraindications to the use of methotrexate or anti-tumor-necrosis factor (anti-TNF) agents in this population. Data from national registries in several countries have confirmed the similar safety and efficacy of DMARDs and anti-TNF agents in elderly patients. Data on the administration of other biological agents in the elderly are limited. Rheumatologists should be aware of the higher risk of adverse events in this population, especially when using non-steroidal anti-inflammatory drugs, and should recognize the need to adjust treatment to the individual characteristics and comorbidities of each patient.

Clinical Characteristics of Elderly Onset Rheumatoid Arthritis

Clinical Characteristics of Elderly Onset Rheumatoid Arthritis

Clinical and Radiographic Observation of Elderly-Onset Rheumatoid Arthritis

Clinical and Radiographic Observation of Elderly-Onset Rheumatoid Arthritis

Ultrasonography in early assessment of elderly patients with polymyalgic symptoms: a role in predicting diagnostic outcome?

Objective: To study the usefulness of ultrasonography (US) in predicting the diagnostic outcome in patients with polymyalgic symptoms.Methods: Sixty-one elderly patients with polymyalgic syndrome were recruited in a secondary care setting and followed up in a prospective way. Clinical, laboratory, and US data obtained at onset were re-evaluated after 1 year when diagnostic outcome was defined.Results: A diagnostic shift was observed in 32 polymyalgic patients (52%). Calcium pyrophosphate deposition disease (CPDD) was diagnosed in nine patients, elderly-onset rheumatoid arthritis (EORA) in 18, and elderly-onset spondyloarthritis (EOSpA) in five. In polymyalgia rheumatica (PMR) patients US demonstrated synovitis in 90% of cases, in both proximal (90%) and peripheral joints (41%). The best predictive US model for the definitive diagnosis of PMR comprised: the presence of subacromial-subdeltoid bursitis [odds ratio (OR) 5.603, p = 0.003], low frequency of wrist (OR 0.074, p < 0.001), metacarpophalangeal (OR 0.052, p < 0.001), and metatarsophalangeal effusion/synovitis (OR 0.107, p < 0.027), low frequency of knee menisci chondrocalcinosis (OR 0.091, p = 0.013), tendinous calcaneal calcifications (OR 0.078, p = 0.006), and Achilles enthesitis (OR 0.107, p = 0.027), and low power Doppler US (PDUS) scores at wrist (OR 0.052, p < 0.001).Conclusions: US and PDUS can be useful in distinguishing, at onset of disease, pure PMR from other diseases mimicking this condition.

Elderly-onset rheumatoid arthritis

The treatment of elderly-onset rheumatoid arthritis pursues the same objectives as in younger patients: to control the clinical manifestations, to prevent structural damage, to preserve function, and to decrease excess mortality. In the elderly, the presence of co-morbidities and increased rate of drug-related adverse effects raise specific therapeutic challenges. Nonsteroidal anti-inflammatory drugs are associated with cardiovascular, gastrointestinal, and renal adverse events. The role for corticosteroid therapy remains controversial. Although glucocorticoids provide a short-term decrease in clinical activity and probably a medium-term decrease in structural damage, these benefits are offset by numerous adverse effects. Methotrexate was effective in clinical trials and observational studies and did not produce a higher adverse event rate compared to younger patients, provided renal function was normal. Data on the efficacy of TNFα antagonists in therapeutic trials are available only for etanercept. Disease activity decreased and function improved. The adverse event rate was higher in older patients, but this was also true of the conventional drugs used as comparators. Registry data confirm that TNFα antagonist therapy is effective in RA. An increased rate of infections was found only in some registries. To combat the 2-fold cardiovascular risk increase associated with RA, disease activity should be stringently controlled and all cardiovascular risk factors managed aggressively.

高齢発症関節リウマチの治療

In addition to population-growth in the elderly, development of new therapeutic agents for rheumatoid arthritis (RA) contributes to an increase in the number of elderly patients with RA. It is also reported that the age of RA onset is going higher. Elderly-onset RA (EORA) is defined as RA developing after the age of 60 years. In RA patients, significant damage can be detected radiographically within the first 2 years after the initial presentation of symptoms; therefore, appropriate treatment should be administered at the earliest. Meanwhile, caution should be exercised in prescribing disease-modifying antirheumatic drugs (DMARDs) to elderly patients because the associated risk of adverse effects and toxicity is elevated in the elderly. However, excessive caution may prevent elderly patients from being implemented the ideal therapy. Compared to young patients with RA, patients with EORA are less frequently treated with biological agents or multiple DMARDs treatment and more frequently treated with prednisone. Some patients with EORA do not receive optimal treatment during the early stage of RA, when the disease is highly active and joint destruction rapidly progresses. EORA should be treated with appropriate DMARDs instead of corticosteroids in order to maintain the risk of infection minimal and the patients' physical function maximal.

Elderly Onset Rheumatoid Arthritis

Elderly onset rheumatoid arthritis (EORA) has been considered a benign form of rheumatoid arthritis (RA). However, it most probably encompasses different subsets of patients with distinct outcomes. According to data reported in the most recent studies directly comparing older and younger RA patients, it seems that, overall, the prognosis of EORA patients is not very different from that of other patients with this disease. However, some cases with negative rheumatoid factor and polymyalgia-like symptoms appear to be a distinct subset with a different genetic basis and a more benign course. The differential diagnosis of EORA from other rheumatological disorders that are prevalent in this stratum of the population, such as polymyalgia rheumatica, crystal-induced arthritis or osteoarthritis, may be complicated because these disorders can present with signs and symptoms similar to those of RA in some circumstances. A prompt diagnosis of true RA is important because early treatment should be implemented. It is recommended that therapy of EORA be tailored according to disease activity, with the aim of achieving clinical remission or the lowest possible level of disease activity in order to minimize potential functional sequelae. Co-morbidities and drug toxicity profiles are major considerations when choosing the most suitable therapy for EORA patients. Prudent use and careful follow-up of all treatments are also required because of the increased risk of adverse events in elderly patients. However, no special contraindications to the use of disease-modifying antirheumatic drugs in this age group apply, and use of biological therapies currently used in younger RA patients has also been described in these patients. Therefore, a therapeutic strategy for first-line and subsequent treatment that is in accordance with the disease activity of patients with EORA is suggested.

Tumour Necrosis Factor-α Antagonists in the Management of Rheumatoid Arthritis in the Elderly

Rheumatoid arthritis (RA) is a chronic inflammatory disease that frequently affects people aged >or=65 years, causing significant impairment with pain and functional disability. Elderly RA patients have specific problems, including co-morbid diseases, numerous concomitant medications, greater number of damaged joints as a result of longer disease duration and often a more severe disease presentation in elderly-onset RA. These factors, together with an age-related decline in the immune defence mechanisms, make elderly patients more vulnerable. The new era of biologic medications has made intensive treatment of RA patients possible. Anti-tumour necrosis factor-alpha (anti-TNFalpha) agents can cause a dramatic improvement in disease activity and functional capacity, making complete remission of RA a possible target. TNFalpha has been shown to play an important role in both the healthy aging process and age-related diseases such as RA. Targeting this cytokine in elderly patients is therefore reasonable. However, it is not clear whether treatment effects can be reached to the same extent in both elderly and younger patients and whether anti-TNFalpha treatment specifically increases the risk of certain adverse events in elderly RA patients. This review discusses the currently available evidence relating to the efficacy and safety of anti-TNFalpha medication in RA patients aged >or=65 years treated in clinical trials and observational studies. Despite a slightly less robust effect in elderly patients, anti-TNFalpha treatment has a similar long-term efficacy in patients aged >or=65 years and patients aged <65 years. The majority of the study results showed that anti-TNFalpha treatment does not elevate the risk of infections beyond the risk found in age-matched controls. When a moderate increase in risk was found, this occurred equally in elderly and younger patients. Furthermore, whereas anti-TNFalpha agents were found to be relatively safe in the treatment of elderly RA patients, treatment with corticosteroids significantly elevated the risk of serious infections. Corticosteroids are frequently used in elderly patients, but the evidence suggests that preference should increasingly be given to anti-TNFalpha agents, for which the expected benefits will mostly outweigh the modestly increased risks of associated adverse events.

Vanished humeral head in a patient with rheumatoid arthritis: a case of Gorham’s disease

We report an 81-year-old female with rheumatoid arthritis who suVered from “vanishing bone disease or Gorham’s disease” involving the right humeral head. In 2003, she was diagnosed of elderly onset rheumatoid arthritis with high titer of rheumatoid factor, which was treated with leXunomide, hydroxychloroquine, and lowdose prednisolone. In October 2008, she presented with pain and swelling of the right shoulder which had persisted for 1 month. She had been doing farm work, but denied having experienced any major trauma. Around that time, her arthritis was controlled pretty well. On laboratory test, serum C-reactive protein level was 1.43 mg/dL (normal range, <0.3 mg/dL). Unexpectedly, humeral head was not visible (Fig. 1, short arrow) and soft tissue swelling was present on plain radiograph of the right shoulder. In addition, multiple calciWc materials were found adjacent to the proximal metaphysis of the right humerus (Fig. 1, long arrow). Ultrasonography revealed marked distension of the subacromial bursa and 65 ml of bloody Xuid was aspirated. On Xuid analysis, white blood cell count was 190/mm and red blood cell count 18,000/mm. Because she had been followed up in our rheumatology clinic, we had checked regular chest radiograph in June 2008, 3 months before her right shoulder pain developed. Notably, right humeral head was visible on that chest radiograph (Fig. 2, arrow). Based on the disappeared humeral head and multiple calciWc materials, rapid osteolysis of the humeral head seemed to have occurred during the 3-month period and the vanishing bone disease or Gorham’s disease was diagnosed. Because she was unwilling to undergo further treatment such as shoulder joint arthroplasty, conservative care was done. Vanishing bone disease, called Gorham’s disease, is a rare disease characterized by massive idiopathic osteolysis [1]. It can occur spontaneously or after trauma; however, precise etiology is still not known. In our patient, minor trauma seemed to be the most probable cause based on the hemorrhagic nature of the subacromial bursal Xuid. It was reported that excessive vascular proliferation and increased osteoclastic activity are thought to be the cause of the bone matrix destruction in Gorham’s disease and bone matrix is replaced by thinwalled vessels and Wbrous tissue [2]. Gorham’s disease can involve various bones such as ribs, vertebra, humerus, hip, foot, and even facial bones [3–8]. It can be progressive and spread to adjacent bones. The prognosis varies depending on which bones are involved. In most cases it is rarely fatal, but extension to spinal cord and/or internal organs can be life threatening when vertebra, scapula, rib or sternum are involved. As for the treatment, radiation therapy, chemotherapy, antiresorptive medications, and surgical intervention such as grafting have all been tried with diVerent degrees of success, but eVective therapy is not established yet [1]. So far, only H.-J. Ko · K.-S. Park (&) · C.-S. Cho · H.-Y. Kim Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea e-mail: pkyungsu@catholic.ac.kr

腫瘍合併リウマチ性多発筋痛症から高齢発症関節リウマチの診断に至った1例

The differential diagnosis between polymyalgia rheumatica and elderly-onset rheumatoid arthritis is difficult because these diseases share similar clinical findings, especially at onset. We report a case of elderly-onset rheumatoid arthritis that was distinguished from polymyalgia rheumatica with malignancy. A 77-year-old woman was admitted to our hospital because of pain and bilateral stiffness in her shoulders and her hips. Tests for rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative. Bone erosions and joint space narrowing were not detected radiographically, and polymyalgia rheumatica was suspected. Her arthralgia disappeared with a few days after treatment with prednisolone (10 mg per day) was started, and ESR and CRP were normalized. Computed tomographic scanning of the chest showed a nodular lesion in the right lower lobe, and biopsy revealed lung cancer. Positron-emission tomography with 18F-fluorodeoxyglucose (FDG) performed before lung surgery showed increased uptake of FDG in the bilateral shoulder joints and wrist joints. Enhanced MRI showed synovitis and bone erosions in the right acromioclavicular joint and bilateral carpal bones and also radiographically bone erosions were seen in the carpometacarpal joint of the right thumb. Therefore, a diagnosis of elderly-onset rheumatoid arthritis was made. In patients with polymyalgia rheumatica, the detection of rheumatoid synovitis should be routinely evaluated.

Elderly onset rheumatoid arthritis

Elderly-onset rheumatoid arthritis (EORA), defined as rheumatoid arthritis (RA) with the onset at the age > or =60 differs sligthy at presentation from younger-onset RA (YORA) by a more equal sex distribution, a higher frequency of an acute onset, more frequent involvement of large joints, especially of the shoulder, and higher disease activity. Longitudinal studies have shown greater disease activity, more severe radiographic damage and functional decline in patients with EORA than in those with YORA. These differences were only found in seropositive patients. In seronegative EORA patients a less severe course of the disease and a better outcome have been observed, with the clinical manifestations of polymyalgia rheumatica or remitting seronegative symmetrical synovitis with pitting edema. This article is a review of available data concerning differences between EORA and YORA.

Interleukin-1RN gene polymorphisms in elderly patients with rheumatic inflammatory chronic conditions: Association of IL-1RN*2/2 Genotype with polymyalgia rheumatica

The objective of this study was to investigate whether there is an association between IL1RN polymorphism and disease susceptibility for three age-related inflammatory conditions: polymyalgia rheumatica (PMR), giant cell arteritis (GCA), and elderly-onset rheumatoid arthritis (EORA). A tandem-repeat polymorphism within IL1RN intron 2 was analyzed in 139 PMR, 69 GCA, and 156 RA patients (75 with EORA) as well as in 437 healthy subjects, together with the in vitro production of IL-1β. Our results showed that the IL1RN*2/2 genotype was more frequent in PMR patients compared with controls ( p = 0.032, odds ratio = 1.785, 95% confidence interval = 1.047–3.044) and GCA patients ( p = 0.008, odds ratio = 4.661, 95% confidence interval = 1.352–16.065). We found no difference in the distribution of genotypes between PMR and EORA or between EORA and controls. However, the frequency of the IL-1RN*2/2 genotype had a tendency to be higher in patients with EORA compared with young onset RA. The presence of IL1RN*1 or IL1RN*2 allele was not associated with severity of the disease in PMR and GCA patients and did not influence the production of IL-1β. In conclusion, the IL1RN*2 polymorphism in a homozygous state was associated with an increased susceptibility to PMR and may give some clues for a differential therapy with GCA.

Proinflammatory Cytokine Profiles of Patients with Elderly-Onset Rheumatoid Arthritis: A Comparison with Younger-Onset Disease

Background: Little is known about the differences in the immunopathogenesis between elderly-onset rheumatoid arthritis (EORA) and younger-onset RA (YORA) and the factors responsible for their clinical characteristics. Objective: It was the aim of this study to investigate proinflammatory cytokines of EORA patients and compare them with those of YORA patients. Methods: Serum levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were determined by cytometric bead array in 86 patients with active EORA, in 76 patients with active YORA and in 30 healthy controls. Disease activity of RA was assessed using the 28-joint disease activity score. Erosion scores were recorded using a modified version of the Sharp method. Levels of anti-cyclic citrullinated peptide antibodies were determined by ELISA, and levels of rheumatoid factor-IgM and C-reactive protein were measured by nephelometry. Results: A higher proportion of men and a higher frequency of acute onset with constitutional symptoms and comorbidities were observed in EORA compared with YORA patients. Increased levels of serum IL-1β, IL-6, TNF-α, IFN-γ and IL-8 were positively correlated with the 28-joint disease activity score, and elevated levels of IL-1β and TNF-α were positively correlated with erosion scores for both groups of RA patients. Significantly higher IL-6 levels and lower TNF-α levels were found in EORA compared with YORA patients. Higher levels of serum IL-6 were found in EORA patients with polymyalgia rheumatica-like symptoms than in those without and were also noted in male patients with EORA compared with female patients. Multivariate analysis showed that high levels of TNF-α were associated with the occurrence of constitutional symptoms, and high levels of IL-1β were associated with the presence of anti-cyclic citrullinated peptide antibodies in EORA patients. Conclusion: EORA patients appear to have differences in clinical characteristics and the patterns of proinflammatory cytokines when compared with YORA patients.

Coexistence of the monostatic Paget’s disease, sensorimotor neuropathy and elderly onset rheumatoid arthritis

Paget's disease is a chronic focal disease of the skeleton that affects up to 2-3% of the population over the age of 60. Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder, pelvic girdle and the neck. There are two incompletely overlapping subsets of RA that have been recognized: one exhibits the classical RA clinical picture, while the other has a PMR-like onset in later ages of life. We reported a rare case of monostatic Paget's disease, sensorimotor neuropathy and elderly onset rheumatoid arthritis in an elderly women.

Report on a case of elderly-onset rheumatoid arthritis differentiated from polymyalgia rheumatica by the detection of acromioclavicular joint synovitis

Report on a case of elderly-onset rheumatoid arthritis differentiated from polymyalgia rheumatica by the detection of acromioclavicular joint synovitis

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.