ANCA-associated vasculitis with muscle involvement mimicking polymyalgia rheumatica.

We report a case of a woman in her early 80s with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presented as myalgia mimicking polymyalgia rheumatica (PMR). She had positive results for the Neer and Hawkins-Kennedy impingement tests, and a normal serum creatine kinase (CK) concentration. At first, we suspected PMR; however, the patient did not strictly meet the classification criteria. Electromyography revealed an abnormal myogenic pattern, and muscle MRI revealed intramuscular and fascial hyperintensity. Moreover, chest CT revealed interstitial lung disease, and test results for ANCAs were positive. We diagnosed the patient with ANCA-associated vasculitis based on the criteria and treated her with corticosteroids and rituximab. Thus, ANCA-associated vasculitis can cause muscle involvement without elevation of the CK concentration and mimic PMR.

Investigational agents for polymyalgia rheumatica treatment: assessing the critical needs for future development.

INTRODUCTION: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder characterized by pain and stiffness in the shoulder and pelvic girdles, constitutional symptoms, and elevated acute-phase reactants. Glucocorticoids (GCs) remain the first-choice treatment for PMR, but relapses are common. Identification of steroid-sparing agents is therefore of utmost importance. AREAS COVERED: The efficacy of conventional immunosuppressive drugs is controversial. The use of interleukin (IL)-6 receptor inhibitors proved to be effective and safe in treating PMR patients. Currently, there are 12 ongoing clinical trials exploring potential treatments such as leflunomide, low-dose IL-2, rituximab, abatacept, secukinumab, Janus kinase inhibitors, and selective inhibitors like SPI-62 and ABBV 154. EXPERT OPINION: The high efficacy of IL-6 R receptor inhibitors as well as the numerous drug trials currently recruiting suggest that several therapeutic options will be available in the near future. Accurate diagnosis and early stratification of PMR patients according to the giant cell arteritis-PMR Spectrum Disease 'GPSD' and potential risk factors for relapsing disease or GC-related adverse events are crucial to identify patients who would benefit most from GC-sparing agents. The development of internationally accepted definitions for remission and relapse is urgently needed. Early referral strategies to specialist settings would improve disease stratification and personalized treatment.

Mortality associated with polymyalgia rheumatica in the United States in the 1999-2020 period: a multiple-cause-of-death study.

OBJECTIVE: Multicause-of-death methods were used to analyze mortality and leading causes of death associated with polymyalgia rheumatica (PMR) in the United States from 1999 to 2020. MATERIALS AND METHODS: We analyzed mortality data from the Centers for Disease Control and Prevention (CDC) Data analysis system and selected death certificates that listed PMR as the cause of death based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10) category code. Relevant mortality rates, number of deaths and historical trends were analyzed. The number of PMR-related deaths and age-standardized mortality rate (ASMR) trend charts were made using Excel 2010 version and trend lines were added. RESULTS: Over the last 22 years, the total number of PMR-related deaths in the United States was 15,421 women (89.8%), a ratio of about 1:9 men to women. When PMR is listed as the underlying cause of death, the ASMR for women and men (per 100,000 people) is approximately 1.8-5.1:1, and when it is listed as the non-underlying cause of death, it is 1.8-3.3:1. PMR deaths are more frequent in individuals aged 70 years and above, with patients aged 80 years and above being most affected. Among different ethnicities, the highest number of deaths was found in Caucasians, followed by Black or African American. When it comes to causes of death, heart disease still ranks first, followed by cancer. In addition, we also found that when PMR combined with malignant tumors as a multiple cause of death, the number of female deaths was higher than that of male deaths, the overall number of deaths of both showed an upward trend, and the overall ASMR of both showed a downward trend. CONCLUSIONS: In the past 22 years, we have observed a low mortality rate of PMR in the United States. However, for patients with PMR, especially elderly women, medical workers should be vigilant and pay attention to whether they are combined with other complications, such as malignant neoplasms, and make timely diagnosis and treatment to further reduce the mortality rate of patients with PMR.

MRI of shoulder girdle in polymyalgia rheumatica: inflammatory findings and their diagnostic value.

BACKGROUND: Non-synovial inflammation as detected by MRI is characteristic in polymyalgia rheumatica (PMR) with potentially high diagnostic value. OBJECTIVE: The objective is to describe inflammatory MRI findings in the shoulder girdle of patients with PMR and discriminate from other causes of shoulder girdle pain. METHODS: Retrospective study of 496 contrast-enhanced MRI scans of the shoulder girdle from 122 PMR patients and 374 non-PMR cases. Two radiologists blinded to clinical and demographic information evaluated inflammation at six non-synovial plus three synovial sites for the presence or absence of inflammation. The prevalence of synovial and non-synovial inflammation, both alone and together with clinical information, was tested for its ability to differentiate PMR from non-PMR. RESULTS: A high prevalence of non-synovial inflammation was identified as striking imaging finding in PMR, in average 3.4±1.7, mean (M)±SD, out of the six predefined sites were inflamed compared with 1.1±1.4 (M±SD) in non-PMR group, p<0.001, with excellent discriminatory effect between PMR patients and non-PMR cases. The prevalence of synovitis also differed significantly between PMR patients and non-PMR cases, 2.5±0.8 (M±SD) vs 1.9±1.1 (M±SD) out of three predefined synovial sites, but with an inferior discriminatory effect. The detection of inflammation at three out of six predefined non-synovial sites differentiated PMR patients from controls with a sensitivity/specificity of 73.8%/85.8% and overall better performance than detection of synovitis alone (sensitivity/specificity of 86.1%/36.1%, respectively). CONCLUSION: Contrast-enhanced MRI of the shoulder girdle is a reliable imaging tool with significant diagnostic value in the assessment of patients suffering from PMR and differentiation to other conditions for shoulder girdle pain.

Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment: Identification of metabolic correlates of fatigue.

OBJECTIVE: In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR symptoms in the metabolite signatures of peripheral blood from patients with PMR or the related disease, giant cell arteritis (GCA). METHODS: Nuclear magnetic resonance spectroscopy was performed on serum from 40 patients with untreated PMR, 84 with new-onset confirmed GCA, and 53 with suspected GCA who later were clinically confirmed non-GCA, and 39 age-matched controls. Further samples from PMR patients were taken one and six months into glucocorticoid therapy to explore relationship of metabolites to persistent fatigue. 100 metabolites were identified using Chenomx and statistical analysis performed in SIMCA-P to examine the relationship between metabolic profiles and, disease, GC treatment or symptoms. RESULTS: The metabolite signature of patients with PMR and GCA differed from that of age-matched non-inflammatory controls (R2 > 0.7). There was a smaller separation between patients with clinically confirmed GCA and those with suspected GCA who later were clinically confirmed non-GCA (R2 = 0.135). In PMR, metabolite signatures were further altered with glucocorticoid treatment (R2 = 0.42) but did not return to that seen in controls. Metabolites correlated with CRP, pain, stiffness, and fatigue (R2 ≥ 0.39). CRP, pain, and stiffness declined with treatment and were associated with 3-hydroxybutyrate and acetoacetate, but fatigue did not. Metabolites differentiated patients with high and low fatigue both before and after treatment (R2 > 0.9). Low serum glutamine was predictive of high fatigue at both time points (0.79-fold change). CONCLUSION: PMR and GCA alter the metabolite signature. In PMR, this is further altered by glucocorticoid therapy. Treatment-induced metabolite changes were linked to measures of inflammation (CRP, pain and stiffness), but not to fatigue. Furthermore, metabolite signatures distinguished patients with high or low fatigue.

Immune Checkpoint Inhibitor-induced Polymyalgia Rheumatica.

Polymyalgia rheumatica (PMR) immune-related adverse events (ICI-PMRs) represent a novel, distinct entity, despite many clinical, laboratory, and imaging similarities to classical PMR. Important questions remain in differentiating ICI-PMR from classical PMR, as well as other immune-related adverse events and PMR mimics. Despite this, ICI-PMR currently takes treatment cues from classical PMR, albeit with considerations relevant to cancer immunotherapy. Comparisons between ICI-PMR and classical PMR may provide further bidirectional insights, especially given that important questions remain unanswered about both diseases. The cause of classical PMR remains poorly understood, and ICI-PMR may represent a model of induced PMR, with important therapeutic implications.

Rheumatology: What You May Have Missed in 2023.

Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.

The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica-a prospective study of 101 patients.

PURPOSE: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. METHODS: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year. RESULTS: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. CONCLUSION: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

Recommendations of the French Society of Rheumatology for the management in current practice of patients with polymyalgia rheumatica.

OBJECTIVE: To develop recommendations for the routine management of patients with polymyalgia rheumatica (PMR). METHODS: Following standard procedures, a systematic review of the literature by five supervised junior rheumatologists, based on the questions selected by the steering committee (5 senior rheumatologists), was used as the basis for working meetings, followed by a one-day plenary meeting with the working group (15 members), leading to the development of the wording and determination of the strength of the recommendations and the level of agreement of the experts. RESULTS: Five general principles and 19 recommendations were drawn up. Three recommendations relate to diagnosis and the use of imaging, and five to the assessment of the disease, its activity and comorbidities. Non-pharmacological therapies are the subject of one recommendation. Three recommendations concern initial treatment based on general corticosteroid therapy, five concern the reduction of corticosteroid therapy and follow-up, and two concern corticosteroid dependence and steroid-sparing treatments (anti-IL-6). CONCLUSION: These recommendations take account of current data on PMR, with the aim of reducing exposure to corticosteroid therapy and its side effects in a fragile population. They are intended to be practical, to help practitioners in the day-to-day management of patients with PMR.

Polymyalgia rheumatica and giant cell arteritis following COVID-19 vaccination: Results from a nationwide survey.

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

Did the first description of patients with polymyalgia rheumatica take place in Scotland or in Denmark?

The first description of polymyalgia rheumatica (PMR) is generally attributed to Dr. Bruce. In an 1888 article entitled Senile rheumatic gout, he described five male patients aged from 60 to 74 years whom he had visited at the Strathpeffer spa in Scotland. In 1945, Dr. Holst and Dr. Johansen reported on five female patients examined over several months at the Medical Department of Roskilde County Hospital in Denmark. These patients suffered from hip, upper arms, and neck pain associated with elevated ESR and constitutional manifestations such as low-grade fever or loss of weight. In the same year, Meulengracht, another Danish physician, reported on two patients with shoulder pain and stiffness associated with fever, weight loss, and an increased erythrocyte sedimentation rate. As in the five patients reported by Dr. Holst and Dr. Johansen, a prolonged recovery time was recorded. On reading and comparing these three accounts, we question whether it is correct to attribute the first description of PMR to Dr. Bruce and put forward shifting this accolade to the three Danish physicians.

Anti-interleukin-6 receptor antibody for the treatment of remitting seronegative symmetrical synovitis with pitting oedema: a new outlook?

We present the case of an elderly man with a small-joint polyarthritis, accompanied by pitting oedema, involving hands and feet, raising clinical suspicion of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). Treatment with corticosteroids was initiated with significant improvement, but unacceptable iatrogeny ensued, and tapering was not possible without disease flare-up. A trial of tocilizumab allowed disease activity control, slow weaning of corticosteroids and, ultimately, its suspension. RS3PE is a rare rheumatological entity, initially thought to be a variant of rheumatoid arthritis (RA), with shared traits with polymyalgia rheumatica (PMR), and other seronegative spondyloarthropathies, thereby implying a shared pathophysiological background. Elevated levels of interleukin 6 (IL-6) are found in patients with RA, have shown to mirror disease activity in PMR and have also been described in the serum and synovial fluid of patients with RS3PE. Tocilizumab, an anti-IL-6 receptor antibody, shows auspicious results in several other rare rheumatic diseases other than RA.

A Movement Classification of Polymyalgia Rheumatica Patients Using Myoelectric Sensors.

Gait disorder is common among people with neurological disease and musculoskeletal disorders. The detection of gait disorders plays an integral role in designing appropriate rehabilitation protocols. This study presents a clinical gait analysis of patients with polymyalgia rheumatica to determine impaired gait patterns using machine learning models. A clinical gait assessment was conducted at KATH hospital between August and September 2022, and the 25 recruited participants comprised 18 patients and 7 control subjects. The demographics of the participants follow: age 56 years ± 7, height 175 cm ± 8, and weight 82 kg ± 10. Electromyography data were collected from four strained hip muscles of patients, which were the rectus femoris, vastus lateralis, biceps femoris, and semitendinosus. Four classification models were used-namely, support vector machine (SVM), rotation forest (RF), k-nearest neighbors (KNN), and decision tree (DT)-to distinguish the gait patterns for the two groups. SVM recorded the highest accuracy of 85% among the classifiers, while KNN had 75%, RF had 80%, and DT had the lowest accuracy of 70%. Furthermore, the SVM classifier had the highest sensitivity of 92%, while RF had 86%, DT had 90%, and KNN had the lowest sensitivity of 84%. The classifiers achieved significant results in discriminating between the impaired gait pattern of patients with polymyalgia rheumatica and control subjects. This information could be useful for clinicians designing therapeutic exercises and may be used for developing a decision support system for diagnostic purposes.

Concordance and agreement between different activity scores in polymyalgia rheumatica.

OBJECTIVE: The C reactive protein polymyalgia rheumatica activity score (CRP-PMR-AS) is a composite index that includes CRP levels and was developed specifically for PMR. As treatments such as interleukin-6 antagonists can normalise CRP levels, the erythrocyte sedimentation rate (ESR) of PMR-AS, the clinical (clin)-PMR-AS and the imputed-CRP (imp-CRP)-PMR-AS have been developed to avoid such bias. Our primary objective was to measure the correlation of these activity scores. Our secondary objective was to evaluate the concordance between different cutoffs of the PMR-ASs. METHOD: Data from the Safety and Efficacy of tocilizumab versus Placebo in Polymyalgia rHeumatica With glucocORticoid dEpendence (SEMAPHORE) trial, a superiority randomised double-blind placebo-controlled trial, were subjected to post hoc analysis to compare the efficacy of tocilizumab versus placebo in patients with active PMR. The CRP-PMR-AS, ESR-PMR-AS, clin-PMR-AS and imp-CRP-PMR-AS were measured at every visit. The concordance and correlation between these scores were evaluated using kappa correlation coefficients, Bland-Altman correlations, intraclass correlation coefficients (ICCs) and scatter plots. RESULTS: A total of 101 patients were included in the SEMAPHORE trial, and 100 were analysed in this study. The correlation between the PMR-ASs was excellent, as the ICC and kappa were >0.85 from week 4 until week 24 (CRP-PMR-AS ≤10 or >10). Bland-Altman plots revealed that the differences between the CRP-PMR-AS and the other threescores were low. The cut-off values for the clin-PMR-AS were similar to those for the CRP-PMR-AS 86% of the time. CONCLUSION: The correlation between all the PMR-ASs was excellent, reflecting the low weight of CRP. In clinical trials using drugs that have an impact on CRP, the derived activity scores can be used. TRIAL REGISTRATION NUMBER: NTC02908217.

Concomitant Polymyalgia Rheumatica and Giant Cell Arteritis Associated with Cystic Echinococcosis: A Rare Geriatric Case.

INTRODUCTION: Parasitic infections could be an important triggering factor for autoimmune diseases. We present a clinical case of concomitant polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) induced with cystic echinococcosis (CE). CASE PRESENTATION: A 74-year-old male was admitted with a 2-month history of progressive pain at the shoulders and hip, movement restriction, and constitutional symptoms. As a result of the examinations performed due to rheumatological complaints, PMR and GCA were diagnosed. The cystic appearance, which was incidentally detected in the liver 6 months ago and not examined at that time, was found to be hydatid cyst. Medical treatment was initiated for all three conditions and the patient's symptoms improved significantly. DISCUSSION: Parasite infections may cause various autoimmune diseases because of molecular mimicry or sustained immune activation. Echinococcus granulosus is a very complex multicellular parasite and highly immunogenic for humans. Some body parts of the parasite, the outer surface and secreted particles, stimulate the host immune system strongly. CONCLUSION: The first case in the literature of coexistence of PMR and GCA associated with CE. Autoimmune diseases should be evaluated in patients with CE. Furthermore, CE should be considered in patients with autoimmune diseases in the presence of a cyst.

Should all patients with polymyalgia rheumatica have a vascular ultrasound assessment?

There is a growing appreciation that both giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely interrelated conditions that have significant overlap in aetiology, clinical characteristics and treatment regimens. Subclinical GCA in PMR is becoming increasingly recognised, and there is evolving evidence that this may be a more aggressive disease phenotype than PMR. Ultrasound (US) lends itself well as a screening tool for GCA in PMR; it is inexpensive, non-invasive, widely available, lacks ionising radiation, may be performed at the bedside and is recommended by EULAR as a first-line investigation for suspected GCA. There is insufficient evidence to currently recommend that all patients with PMR should have a US assessment for vascular involvement. However, as clinical and laboratory parameters alone do not accurately diagnose patients with subclinical GCA, we suggest that vascular US will be increasingly performed by rheumatologists in practice to identify these patients with PMR, preferably as part of larger prospective outcome studies.

The usefulness of 18F-FDG-PET/CT in detecting musculoskeletal and vascular involvement in patients with polymyalgia rheumatica receiving glucocorticoids.

OBJECTIVE: Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT is a promising diagnostic tool for polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV). PET/CT performance is recommended before the onset of steroid therapy because glucocorticoids (GC) may decrease the intensity of FDG uptake. However, this is not always possible in clinical practice. Our aim was to assess if PET/CT could be also useful to detect musculoskeletal and vascular involvement in patients receiving GC. METHODS: Single-center study of patients with PMR diagnosis based on 2012 EULAR/ACR criteria who underwent a PET/CT scan due to LVV suspicion. We compared the musculoskeletal and vascular FDG uptake between two groups: (a) steroid-naïve and (b) steroid-resistant patients. A sub-analysis was conducted in patients who were receiving GC to discern if the cumulative prednisone dose influences the FDG uptake. RESULTS: We evaluated 75 patients (27 men/ 48 women); mean age±SD: 68.2 ± 10.7 years. PET/CT was performed in 14 steroid-naïve and 61 steroid-resistant patients. Patients under GC had received a median cumulative prednisone dose of 1.8 [0.6-3.9] g. The pattern of musculoskeletal FDG uptake was similar in steroid-naïve and steroid-resistant patients. FDG uptake in the vessel wall was more frequently detected in steroid-naïve patients. However, PET/ CT was also useful to detect LVV in 62.3 % of the patients who were receiving GC. The percentage of patients who had positive PET/CT scans tended to decrease with higher cumulative prednisone doses. CONCLUSION: Even though GC therapy may decrease the 18-FDG uptake, PET/CT continues to be a useful tool to detect musculoskeletal and LVV involvement in PMR.