Search Results (36)

Background: Immune checkpoint inhibitors (ICIs) transformed cancer treatment, producing significant survival benefits. However, ICIs can trigger toxicities called immune-related adverse events (irAEs), including inflammatory arthritis (IA) and polymyalgia rheumatica (PMR)-like syndromes. Our study aimed to systematically further characterize musculoskeletal ultrasound (MSKUS) findings in patients with ICI-IA and ICI-PMR, collectively referred to as “MSK-irAEs”, and explore the role of US in guiding treatment. Methods: The authors conducted a comprehensive chart review for patients receiving ICIs undergoing MSKUS at our center’s rheumatology clinics. US examinations were performed and reviewed by two MSKUS-certified rheumatologists. Descriptive statistics were performed to summarize demographic, clinical, and treatment-related variables. US findings were categorized with a novel scoring system: 0—no signs of inflammatory arthropathy or tendinopathy, 1—potential signs of inflammation (grayscale ≥ 2, effusion without power Doppler, synovial hypertrophy in the joint), and 2—active inflammation in joints and/or tendons (characterized by power Doppler) and signs of inflammation. Results: Twenty-three patients were included. The median age was 63 years, 52% were male, and 87% were White. Melanoma was the most common cancer (48%). MSK-irAEs were diagnosed in nineteen (83%), with MSKUS showing inflammation in seventeen (74%). Sixteen (70%) received escalation in MSK-irAE treatment after MSKUS. Four (17%) had erosive disease due to MSK-irAEs, while one had erosive osteoarthritis. Individuals with inflammatory erosive changes experienced prolonged intervals between symptom onset and MSKUS, ranging from 17 to 82 months, suggesting that erosions may reflect chronic, under-recognized inflammation. On MSK-irAE therapy, nine (47%) experienced symptomatic improvement, five (26%) achieved resolution, and in four (21%) cases, it was too early to assess the response. MSKUS detected other causes of MSK symptoms besides MSK-irAEs in several patients, allowing ICI resumption in one. Conclusions: Our study highlights the clinical utility of MSKUS not only as a diagnostic tool but also to guide therapeutic decision-making. Full article

Background: Polymyalgia rheumatica (PMR) has a multifaceted onset and course, and making a distinction between true PMR and so-called “polymyalgic syndrome” (that is, similar manifestations caused by different conditions) is far from easy in clinical practice. The existence of subsets within true PMR may further complicate the diagnostic question. Distinguishing PMR subsets from PMR-mimicking conditions does not just carry nomenclature value and speculative significance. Indeed, the correct diagnosis influences treatment, prognosis, epidemiological assessments, and health policies. Objectives: We aimed to (1) ascertain the presence of a definite and peculiar subset/subgroup/cluster of PMR in the scientific literature; (2) describe any possible subset/cluster/subgroup of PMR identified in at least two different studies. Methods: We performed a non-systematic (PRISMA protocol not followed) literature search on Embase and Medline (OVID interface). The following search terms were used: polymyalgia rheumatica, subset, cluster, subgroup, subclinical giant cell arteritis, mimicking conditions, polymyalgia rheumatica-like conditions, immunotherapy, checkpoint inhibitor, acute-phase reactants or acute-phase proteins, vaccination, infection, and calcium pyrophosphate deposition disease or chondrocalcinosis. Each paper’s reference list was scanned for additional publications meeting this study’s aim. Abstracts submitted at conferences or from non-peer-reviewed sources were not included. Results: The initial search yielded 2492 papers, of which 2389 articles were excluded based on title and abstract screening. A total of 103 articles underwent a full-length review, and 84 of them were finally assessed for eligibility. A total of seven large subsets of PMR could be identified: (1) PMR with normal acute-phase reactants; (2) PMR with an infection trigger; (3) PMR with a vaccination trigger; (4) PMR with subclinical giant cell arteritis (GCA); (5) PMR and calcium pyrophosphate deposition disease (CPPD); (6) PMR following immune checkpoint inhibitor (ICI) therapy; (7) PMR with peculiar clinical clusters (based on clinical or statistic clustering methods). Conclusions: PMR with normal baseline acute-phase reactants and PMR with an infection or a vaccination trigger could be categorized as subsets of disease. PMR with subclinical GCA and most cases of PMR/CPPD should be categorized as mimickers. Finally, further studies are required to better categorize some peculiar clinical subsets emerging from cluster analyses, and ICI-induced PMR. Full article

Background: Among rheumatologic diseases following therapy with immune checkpoint inhibitors (ICIs), the cases of cancer patients diagnosed as having polymyalgia rheumatica (PMR), particularly with nivolumab and pembrolizumab, has been steadily rising in published reports. Objectives: We performed a systematic review of published case reports with the aim of answering these questions: (1) Is PMR following therapy with nivolumab and pembrolizumab an adverse drug reaction (ADR)? (2) Is there a difference between cases of PMR following therapy with nivolumab and those following therapy with pembrolizumab? Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search in three main bibliographic databases: MEDLINE (Ovid interface), EMBASE, and COCHRANE Library was carried out on 27 December 2024. This systematic review has no registration number. Results: Data were extracted from 12 patients. Namely, 5 cases followed treatment with nivolumab and 7 with pembrolizumab. Validated scales for ADR assessment—such as Naranjo’s scale—were not used in 10 out of the 12 patients. Additionally, validated diagnostic or classification criteria for PMR were used in the majority of case reports related to nivolumab. On the contrary, clinical judgment alone was the rule in almost all case reports on pembrolizumab. Finally, the time interval between PMR manifestations and nivolumab/pembrolizumab therapy ranged from one to 14 cycles (fully compatible with pharmacokinetics). Conclusions: Our literature review highlighted significant methodological blurred lines in the categorization of PMR following therapy with nivolumab or pembrolizumab. Full article

Background/Objectives: Polymyalgia Rheumatica (PMR) is an inflammatory condition that primarily affects individuals aged 50 and older, especially in Western countries. Although glucocorticoids are the cornerstone of PMR treatment, these drugs are associated with side effects, making it advisable to use them for the shortest duration possible. However, tapering or discontinuation of glucocorticoids often leads to disease relapses. In this review, we focus on the traditional management of PMR, as well as the potential for therapies that may reduce glucocorticoid use. Special attention is given to the efficacy of biologic agents in PMR management. Methods: A literature review, primarily based on articles published in PubMed, was conducted. In addition to discussing various glucocorticoids and conventional disease-modifying drugs used for the management of isolated PMR, this review specifically focused on the information reported regarding new therapies, with particular emphasis on biologic agents. Results: Prednisone or prednisolone at a dose ranging between 12.5 and 25 mg/day is the agreed-upon treatment for PMR. Due to the side effects associated with prolonged glucocorticoid use and the high frequency of relapses when glucocorticoids are tapered, glucocorticoid-sparing agents have emerged as tools in the management of PMR. Methotrexate has traditionally been the conventional disease-modifying antirheumatic drug (DMARD) unanimously recommended for use in PMR. Other conventional DMARDs, such as leflunomide, have shown promising results but require further study. The use of biologic agents has marked a significant step forward in the management of PMR. While anti-TNF agents failed to provide beneficial effects in isolated PMR, anti-IL-6 receptor agents, such as tocilizumab and sarilumab, have demonstrated efficacy in reducing relapse frequency, lowering the cumulative glucocorticoid burden, and achieving long-term remission of the disease. Other biologic agents, many of which have been used in giant cell arteritis, as well as Janus kinase (JAK) inhibitors, are currently under investigation. Conclusions: Glucocorticoids are the primary treatment for isolated PMR but are associated with comorbidities, especially in patients with pre-existing conditions or frequent relapses. Glucocorticoid-sparing agents, such as methotrexate and biologics, in particular tocilizumab and sarilumab, offer alternatives, improving symptoms and reducing glucocorticoid use. While biologic agents reduce long-term side effects and help achieve disease remission, their use must consider potential side effects and higher costs compared to traditional therapies. Full article

Polymyalgia rheumatica (PMR) is an inflammatory disease common in people aged 50 years and older. This condition is characterized by the presence of pain and stiffness involving mainly the shoulder and pelvic girdle. Besides the frequent association with giant cell arteritis (GCA), several conditions may mimic PMR or present with PMR features. Since the diagnosis is basically clinical, an adequate diagnosis of this condition is usually required. Positron emission tomography/computed tomography (PET-CT) has proved to be a useful tool for the diagnosis of PMR. The use of 18F-FDG-PET imaging appears promising as it provides detailed information on inflammatory activity that may not be evident with traditional methods. However, since PET-CT is not strictly necessary for the diagnosis of PMR, clinicians should consider several situations in which this imaging technique can be used in patients with suspected PMR. Full article

Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown etiology, sharing symptoms with giant cell arthritis (GCA) and rheumatoid arthritis (RA). The pathogenic inflammatory roots are still not well understood, and there is a lack of extensive biomarker studies to explain the disease debut and post-acute phase. This study aimed to deeply analyze the serum proteome and inflammatory response of PMR patients before and after glucocorticoid treatment. We included treatment-naïve PMR patients, collecting samples before and after 3 months of treatment. For comparison, disease-modifying antirheumatic drug (DMARD)-naïve RA patients were included and matched to healthy controls (CTL). The serum proteome was examined using label-free quantitative mass spectrometry, while inflammation levels were assessed using multiplex inflammatory cytokine and cell-free DNA assays. The serum proteomes of the four groups comprised acute phase reactants, coagulation factors, complement proteins, immunoglobulins, and apolipoproteins. Serum amyloid A (SAA1) was significantly reduced by active PMR treatment. Cell-free DNA levels in PMR and RA groups were significantly higher than in healthy controls due to acute inflammation. Complement factors had minimal changes post-treatment. The individual serum proteome in PMR patients showed over 100 abundantly variable proteins, emphasizing the systemic impact of PMR disease debut and the effect of treatment. Interleukin (IL)-6 and interferon-gamma (IFN-γ) were significantly impacted by glucocorticoid treatment. Our study defines the PMR serum proteome during glucocorticoid treatment and highlights the role of SAA1, IL-6, and IFN-γ in treatment responses. An involvement of PGLYRP2 in acute PMR could indicate a response to bacterial infection, highlighting its role in the acute phase of the immune response. The results suggest that PMR may be an aberrant response to a bacterial infection with an exacerbated IL-6 and acute phase inflammatory response and molecular attempts to limit the inflammation. Full article

The potential role of the COVID-19 vaccine and infection to induce autoimmunity is currently underestimated despite the literature emphasizing arthralgia as a common adverse event. We aimed to study the impact of rheumatological complications post-COVID-19 (PC) and post-COVID-19 vaccine (PCV), comparing undifferentiated arthritis (UA) to Polymyalgia Rheumatica, Horton’s Arteritis (PMR-HA) and isolated arthritis to UA with “connective-like” accompanying symptoms. We retrospectively included 109 patients with at least 6 months of follow-up, analyzing serum biomarkers, joint ultrasound (US), lung HRCT, DLCO, and HLA haplotypes. There were 87 UA patients showing increased gastrointestinal and lung involvement (p = 0.021 and p = 0.012), higher anti-spike protein IgG levels (p = 0.003), and anti-SARS-CoV-2 IgG positivity (p = 0.003). Among them, 66 cases progressed to ACR-EULAR 2010 early arthritis after 3 months, whereas PMR-HA patients were more commonly PCV (81.8%, p = 0.008), demonstrating higher CRP (p = 0.007) and ESR (p = 0.006) levels, a lower rate of ANA positivity (p = 0.005), and a higher remission rate after six months (p = 0.050). In UA patients, the prevalent HLA was DRB1*11 and C*07 (36.8% and 42.1%). Serum calprotectin, interleukin-6, and C*07 (p = 0.021, 0.041, 0.018) seemed more specific for isolated UA. Conversely, “connective-like” arthritis showed poorer DLCO (p = 0.041) and more frequent US synovitis (p = 0.041). In conclusion, UA is a frequent common PC and PCV complication and may persist over time when compared to PMR-HA. Full article

Objective: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are often overlapping conditions. We studied whether 18F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) is useful in identifying PMR in the setting of large vessel (LV) GCA. Methods: LV-GCA patients diagnosed by PET-CT at a tertiary care center for a population of 450,000 people over a two-year period were reviewed. Scoring was performed based on potential significant FDG uptake at up to 16 sites in nine different extravascular areas (SCORE 16). Differences in extravascular sites of significant FDG uptake were evaluated between LV-GCA with a clinical diagnosis of PMR or not. Results: Fifty-four patients were diagnosed with LV-GCA by 18F-FDG-PET-CT. Of them, 21 (38.8%) were clinically diagnosed with PMR. Significant extravascular FDG uptake was more frequently observed in those with a clinical diagnosis of PMR. In this sense, the SCORE 16 was higher in those with clinical PMR (5.10 ± 4.05 versus 1.73 ± 2.31 in those without a clinical diagnosis of PMR; p < 0.001). A SCORE 16 involving more than four sites of significant FDG uptake yielded a sensitivity of 52% and a specificity of 91% for establishing a clinical diagnosis of PMR associated with LV-GCA. The best areas of significant FDG uptake to clinically identify PMR in patients with LV-GCA were the shoulder, the greater trochanter, and the lumbar interspinous regions, with an area under the ROC curve of 0.810 (0.691–0.930). Conclusions: Significant extravascular 18F-FDG-PET-CT uptake may help establish a clinical diagnosis of PMR in patients with LV-GCA. These patients are more commonly diagnosed with PMR if they have significant FDG uptake in the shoulder, greater trochanter, and lumbar interspinous areas. Full article

(1) Objective:To assess the spectrum of PET-CT-related large vessel vasculitis (LVV) in a Spanish tertiary center and to determine whether FDG uptake by PET-CT differs between giant cell arteritis (GCA) with predominant cranial or extracranial phenotypes. (2) Methods: The spectrum of patients diagnosed with LVV by PET-CT in a tertiary referral hospital that cares for 450,000 people over a period of two years was reviewed. Moreover, differences in FDG uptake between LVV-GCA with predominantly cranial and extracranial phenotype were analyzed. (3) Results: Eighty patients were diagnosed with LVV by PET-CT. Most were due to systemic vasculitis (n = 64; 80%), especially GCA (n = 54; 67.5%). Other conditions included the presence of rheumatic diseases (n = 4; 3.2%), tumors (n = 9; 7.2%) and infections (n = 3; 2.4%). LVV-GCA patients with predominant extracranial GCA phenotype were younger (mean ± SD: 68.07 ± 9.91 vs. 75.46 ± 7.64 years; p = 0.017) and had a longer delay to the diagnosis (median [interquartile range] 12 [4–18] vs. 4 [3–8]; p = 0.006), but had polymyalgia rheumatica symptoms more frequently than those with predominantly cranial GCA phenotype (46.3% vs. 15.4%, p = 0.057). When FDG uptake was compared according to the two different disease patterns, no statistically significant differences were observed. However, patients with extracranial LVV-GCA showed a non-significantly higher frequency of vasculitic involvement of lower-extremity arteries. (4) Conclusions: Regardless of the predominant phenotype, LVV identified by PET-CT is more commonly due to GCA in the Spanish population. In these GCA patients, younger age, PMR, and a higher frequency of lower-extremity artery vasculitis suggest the presence of LVV. Full article

The immune system is vital for safeguarding the human body against infections and inflammatory diseases. The role of diet and meal patterns in modulating immune function is complex, and highlighting this topic is crucial for identifying potential ways to improve immune health. In Europe, the Mediterranean diet and Western diet are the most common dietary patterns, and gaining an understanding of how they affect immune function is essential for public health. There are numerous inflammatory diseases that are observed in younger and older people. Some of the common diseases include polymyalgia rheumatica (PMR), spinal muscular atrophy (SMA), vasculitis, sarcopenia, cirrhosis, cancer, and fibromyalgia, but the main focus in this review article is on irritable bowel disease (IBD). In general, dietary choices can have an immense impact on the microbial flora of the gut in people with inflammatory diseases. The intake of Mediterranean-style foods promotes the growth of healthy bacteria that enhances the function of the immune system. On the other hand, it is mostly seen that the intake of Western-style foods leads to the growth of harmful gut bacteria that contributes to inflammation and disease development by weakening the immune system. Additionally, inflammation in the gut can impact brain function, leading to mood disorders, such as anxiety and depression. Rare inflammatory diseases, such as psoriasis and sarcoidosis, are of main interest in this article. All the above-mentioned common and rare inflammatory diseases have a certain relationship with the microbiota of the gut. The gut microbiome plays a significant role in IBD; fiber and prebiotic interventions may represent promising adjunct therapies for pediatric IBD by targeting the gut microbiome. By advancing a good overall arrangement of microorganisms in the stomach through dietary mediations, working on the side effects and alleviating of diseases might be conceivable. The gut microbiota can be affected differently by various dietary fatty acid types. There is also an involvement of genetics in the progression of IBD, such as transcriptional factors, and one gene of interest is the LCT gene, which encodes for lactase, an enzyme responsible for digesting lactose in the gut. Full article

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease among people over 50 and occurs with symptoms such as musculoskeletal pain and stiffness in the neck, shoulders, and hips. To date, corticosteroids represent the cornerstone of PMR treatment. However, it is well known that their prolonged use is associated with several adverse effects, making it crucial to find therapeutic alternatives. The purpose of this case report was to describe the effectiveness of 10 whole-body cryostimulation (WBC) sessions on a 74-year-old woman suffering from PMR. An improvement in disease impact, fatigue, pain, quality of sleep, and total physical activity was observed after WBC. Moreover, the patient reduced her daily drug intake by 67% following WBC treatments. Given the increasing prevalence of PMR and considering the side effects that drug treatments can lead to, WBC could represent a valuable adjuvant and well-tolerated alternative for treating PMR. Full article

Background: There is little literature on the paraneoplastic value of the absence of long-lasting morning stiffness (MS) at the time of diagnosis of polymyalgia rheumatica (PMR). We investigated whether and to what extent this finding was related to the probability of diagnosing a neoplasia. Patients and Methods: This was an observational, retrospective, single-center cohort study. We enrolled all patients consecutively referred to our rheumatologic outpatient clinic between January 2015 and December 2020, who could be classified as PMR according to 2012 EULAR/ACR criteria. In particular, we assessed all patients scoring a minimum of five points with a combination of clinical and ultrasound (US) criteria. The exclusion criteria were as follows: (a) follow-up duration <two years; (b) malignancy prior to PMR; (c) first-degree familiarity of malignancy; (d) incomplete data; and (e) diagnostic change during follow-up in different rheumatologic diseases. Results: 143 patients (108 women; median age: 71.5 years) were enrolled, and 35 of them did not have long-standing MS at the time of PMR diagnosis. In 10 patients (6.9%), a neoplasia was diagnosed in the first 6 months of follow-ups; among these, 7 did not have long-lasting MS. Among the remaining 133 PMR patients without subsequent malignancy, 28 did not have long-lasting MS. The odds of cancer were 0.114 (C.I. 95% 0.028, 0.471). Long-lasting MS was inversely associated with the development of neoplasias. In all eight PMR patients diagnosed with solid cancers during follow-ups, the removal of the neoplastic mass led to a fast disappearance of clinical, ultrasound and laboratory findings, thus supporting the diagnosis of paraneoplastic PMR. Finally, a positive response to glucocorticoids (GCs) was present in 100% of the 28 PMR patients without long-lasting MS at the time of diagnosis and without neoplasia during their follow-ups. On the contrary, a positive response to GCs was present in 71% of PMR patients without long-lasting MS and neoplasias during follow-up. Among the variables we assessed, a positive response to GCs was the only one that was statistically significant (p < 0.0001). These data suggested that an inadequate response to GCs in PMR patients without long-lasting MS at the time of diagnosis should strengthen investigations to rule out neoplasias. Conclusions: The absence of long-standing MS at the time of diagnosis can be a paraneoplastic warning in patients classified as PMR. A thorough investigation is therefore needed in this subset of patients to rule out neoplasia, before diagnosing an idiopathic PMR and starting treatment with GCs. Full article

Introduction: We aimed to evaluate the utility of FDG-PET/CT in diagnosing polymyalgia rheumatica (PMR) and associated large-vessel vasculitis (LVV). Methods: We analyzed FDG-PET/CT completed between 2015 and 2019 on patients diagnosed with PMR. For comparisons, patients with PMR were matched 1:1 to controls based on age and gender. FDG-PET/CT had been completed on the controls over the same period. The FDG uptake was scored visually for 17 articular or periarticular sites and 13 vascular sites using a semi-quantitative scoring system (score of 0–3). Results: Eighty-one patients with PMR and eighty-one controls were included (mean age 70.7 (9.8) years; 44.4% women). Significant differences between the PMR and control groups were found at all articular and periarticular sites for the following: (i) the FDG uptake score (p < 0.001 for all locations); (ii) the number of patients per site with significant FDG uptake (score ≥ 2); (iii) the global FDG articular uptake scores (31 [IQR, 21 to 37] versus 6 [IQR, 3 to 10], p < 0.001); and (iv) the number of sites with significant FDG uptake (score ≥ 2) (scores of 0–17) (11 [IQR, 7 to 13] versus 1 [IQR, 0 to 2], p < 0.001). No significant differences in the global FDG vascular uptake scores were found between the patients who were considered isolated PMR and the control groups. Conclusions: The FDG uptake score and the number of sites with significant FDG uptake could be pertinent criteria for the diagnosis of PMR. Unlike others, we did not confirm the presence of vascular involvement in patients with isolated PMR. Full article

[¹⁸F]Fluorodeoxyglucose positron emission tomography (FDG-PET) is increasingly used to demonstrate inflammation in specific sites typical for polymyalgia rheumatica (PMR). Scoring systems based on FDG uptake have been proposed to increase diagnostic accuracy. Methods: Retrospective inclusion of 198 consecutive patients ≥40 years of age referred for FDG-PET from the Department of Rheumatology. We assessed the degree of FDG uptake in predilection sites visually, as well as semiquantitatively, and through logistic regression analyses, we evaluated the performance of existing scoring systems as well as a new, simplified scoring system, against the final clinical diagnosis at 6 months after the FDG-PET scan. Results: We found high diagnostic accuracy for the diagnosis of PMR (range 0.74–0.91) using most of the existing scoring systems in glucocorticoid-naïve patients. A simplified scoring system including only periarticular FDG uptake in the shoulders and the ischiogluteal bursae retained high sensitivity and specificity (0.92 and 0.86, respectively). We found a detrimental effect on diagnostic accuracy in all scoring systems in patients treated with glucocorticoids within 4 weeks prior to FDG-PET. Conclusion: Most FDG-PET scoring systems perform well for the diagnosis of PMR, and there is no loss of either sensitivity or specificity in the simplest scoring systems evaluating FDG uptake in only a few selected anatomical regions. However, systemic glucocorticoid treatment up to 4 weeks prior to FDG-PET has a markedly detrimental effect on the diagnostic accuracy of all scoring systems. Full article

Elderly-onset rheumatoid arthritis (EORA) is prevalent among older patients, and its incidence is increasing due to aging societies. However, differentiating between EORA and polymyalgia rheumatica (PMR) is challenging for clinicians and hinders the initiation of effective treatment for rheumatoid arthritis among older generations, thereby allowing its progression. Therefore, we conducted a qualitative synthesis of narrative reviews via meta-ethnography regarding seronegative EORA diagnosis to clarify the methods to differentiate seronegative EORA from PMR. Three databases (PubMed, EMBASE, and Web of Science) were searched for relevant reviews published between January 2011 and October 2022. The extracted articles were synthesized using meta-ethnography, and 185 studies were selected following the protocol. Seven reviews were analyzed, and four themes and nine concepts were identified. The four themes included difficulty in differentiation, mandatory follow-up, and factors favoring rheumatoid arthritis and those favoring PMR. Factors favoring seronegative EORA and PMR should be considered for effective diagnosis and prompt initiation of disease-modifying anti-rheumatic drugs. Mandatory and long follow-ups of suspected patients are essential for differentiating the two diseases. The attitude of rheumatologists toward tentatively diagnosing seronegative EORA and flexibly modifying their hypotheses based on new or altered symptoms can aid in effective management and avoiding misdiagnosis. Full article