The contributions of deleterious rare alleles in NLRP12 and inflammasome-related genes to polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease characterized by arthralgia and myalgia of the shoulder and hip girdles, and fever. PMR is linked to autoimmune diseases and autoinflammatory disorders. Exome sequencing has revealed the roles of rare variants in some diseases. Causative genes for monogenic autoinflammatory disorders might be candidate genes for the selective exome analysis of PMR. We investigated rare variants in the coding and boundary regions of candidate genes for PMR. Exome sequencing was performed to analyze deleterious rare variants in candidate genes, and the frequencies of the deleterious rare alleles in PMR were compared with those of Japanese population controls. Deleterious rare alleles in the NLRL12 gene were associated with PMR (P = 0.0069, Pc = 0.0415, odds ratio [OR] 4.49, 95% confidence interval [CI] 1.79-11.27). A multigene analysis demonstrated the deleterious rare allele frequency of the candidate genes for autoinflammatory disorders was also increased in PMR (P = 0.0016, OR 3.69, 95%CI 1.81-7.54). The deleterious rare allele frequencies of the candidate genes including NLRP12 were increased in PMR patients, showing links to autoinflammatory disorders in the pathogenesis of PMR.

Serum metabolomic profiling identifies potential biomarkers in arthritis in older adults: an exploratory study.

BACKGROUND: Seronegative elderly-onset rheumatoid arthritis (EORA)neg and polymyalgia rheumatica (PMR) have similar clinical characteristics making them difficult to distinguish based on clinical features. We hypothesized that the study of serum metabolome could identify potential biomarkers of PMR vs. EORAneg. METHODS: Arthritis in older adults (ARTIEL) is an observational prospective cohort with patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples were compared at baseline with 18 controls. A thorough clinical examination was conducted. A Bruker Avance 600 MHz spectrometer was used to acquire Nuclear Magnetic Resonance (NMR) spectra of serum samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification.Student t-test, one-way ANOVA, binary linear regression and ROC curve, Pearson's correlation along with pathway analyses were conducted. RESULTS: Twenty-eight patients were diagnosed with EORAneg and 20 with PMR. EORAneg patients had a mean disease activity score (DAS)-Erythrocyte Sedimentation Rate (ESR) of 6.21 ± 1.00. All PMR patients reported shoulder pain, and 90% reported pelvic pain. Fifty-eight polar metabolites were identified. Of these, 3-hydroxybutyrate, acetate, glucose, glycine, lactate, and o-acetylcholine (o-ACh), were significantly different between groups. Of interest, IL-6 correlated with different metabolites in PMR and EORAneg suggesting different inflammatory activated pathways. Finally, lactate, o-ACh, taurine, and sex (female) were identified as distinguishable factors of PMR from EORAneg with a sensitivity of 90%, specificity of 92.3%, and an AUC of 0.925 (p < 0.001). CONCLUSION: These results suggest that EORAneg and PMR have different serum metabolomic profiles that might be related to their pathobiology and can be used as biomarker to discriminate between both diseases.

Baseline Characteristics and Clinical Presentation of Biopsy-Proven Giant Cell Arteritis in White Compared with Black Patients.

BACKGROUND: Giant cell arteritis (GCA) is the most prevalent systemic vasculitis in the elderly and can lead to permanent vision loss if left untreated. Most earlier studies have evaluated GCA in primarily white populations, and GCA was traditionally thought to occur at nearly negligible frequency in black populations. Our previous study showed that GCA may occur at similar rates in white and black patients, but little is known about the presentation of GCA in black patients. The purpose of this study is to examine baseline presentation of biopsy-proven GCA (BP-GCA) in a tertiary care center-based population with a sizeable proportion of black patients. METHODS: Retrospective study from a single academic institution of a previously described cohort of BP-GCA. Presenting symptoms, laboratory findings, and GCA Calculator Risk score were compared in black and white patients with BP-GCA. RESULTS: Among 85 patients with biopsy-proven GCA, 71 (84%) were white and 12 (14%) were black. White patients had higher rates of elevated platelet count (34% vs 0%, P = 0.04), whereas black patients had higher rates of diabetes mellitus (67% vs 12%, P < 0.001). There were no statistically significant differences in age, gender, biopsy classification (active vs healed arteritis), cranial symptoms, visual symptoms/ophthalmic findings, rates of abnormal erythrocyte sedimentation rate or C-reactive protein, unintentional weight loss, polymyalgia rheumatica, or GCA risk calculator score. CONCLUSIONS: Presenting features of GCA were similar between white and black patients in our cohort, except for rates of abnormal platelet level and diabetes. Physicians should feel comfortable relying on the usual clinical features for the diagnosis of GCA independent of race.

Highlights in clinical medicine-Giant cell arteritis, polymyalgia rheumatica and Takayasu's arteritis: pathogenic links and therapeutic implications.

Giant cell arteritis (GCA), frequently associated with polymyalgia rheumatica (PMR), and Takayasu's arteritis (TAK) are characterized by extensive vascular remodeling that results in occlusion and stenosis. The pathophysiological mechanisms underlying the onset of GCA/PMR and TAK are still hypothetical. However, similarities and differences in the immunopathology and clinical phenotypes of these diseases point toward a possible link between them. The loss of tolerance in the periphery, a breakdown of tissue barriers, and the development of granulomatous vasculitis define a disease continuum. However, statistically powered studies are needed to confirm these correlations. In addition to glucocorticoids, inhibition of the interleukin-6 axis has been proposed as a cornerstone in the treatment of GCA/PMR and TAK. Novel biologic agents targeting the pathogenic pathway at various levels hold promise to achieve glucocorticoid-free sustained remission.

Fracture Risk and Its Prevention Patterns in Korean Patients with Polymyalgia Rheumatica: a Retrospective Cohort Study.

BACKGROUND: To evaluate the incidence of fractures and fracture risk factors in Korean patients with polymyalgia rheumatica (PMR). METHODS: All PMR patients who visited a rheumatology clinic at a tertiary referral hospital between March 2005 and March 2018 were retrospectively assessed. We estimated bone mineral density (BMD) screening rate within 6 months of the first visit and classified the patients according to the performance and results of BMD screening. Incidence rates (IRs) of fractures were calculated in each group and risk factors for fractures were identified using Poisson regression analysis. RESULTS: A total of 95 PMR patients with median (interquartile range) age of 64.0 (56.0-72.0) years were included. Baseline BMD was assessed in only 55.8% of these patients (n = 53); 24 patients with osteoporosis, 20 with osteopenia, and 9 with normal BMD. During 433.1 person-years (PYs) of observation, 17 fractures occurred in 12 patients (IR, 3.93 [95% confidence interval (CI), 2.46-6.26]/100 PYs); 8.32 (95% CI, 4.09-16.90)/100 PYs in the osteopenia group, 3.40 (95% CI, 1.30-8.90)/100 PYs in the osteoporosis group, and 3.37 (95% CI, 1.53-7.39)/100 PYs in the no BMD test group. Risk factors for fractures were female sex, advanced age (≥ 65 years), longer follow-up duration, initial glucocorticoid dose ≥ 10 mg/day, and higher cumulative glucocorticoid dose over the first 6 months. CONCLUSION: The incidence rate of fractures in Korean patients with PMR was 3.93/100 PYs. Female sex, advanced age, longer follow-up duration, and increased glucocorticoid dose are risk factors for osteoporotic fracture.

"The added value of 18f-FDG PET/CT in the assessment of onset and steroid resistant polimyalgia rheumatica".

PMR is a common inflammatory rheumatic disease. Although its clinical characteristics are fully recognized, no specific test for its diagnosis has been established to date. Several studies have described a wide variety of diseases that present with polymyalgic symptoms. A 18FDG-PET/CT scan could help to deal with these differential diagnoses. The goal of our study is to describe the findings of the 18FDG-PET/CT scan in a cohort of PMR patients and to detail how the 18FDG-PET/CT scan improves accuracy when diagnosing other underlying conditions. This cross-sectional study enrolled patients with a diagnosis of PMR who underwent to a 18FDG-PET/CT scan to rule out other diagnosis. The 18FDG-PET/CT scan was performed either following clinical criteria at the onset of clinical symptoms or when the patient became PMR steroid resistant. Patients' demographic, clinical and analytical data at the moment of the 18FDG-PET/CT scan were recorded. The final diagnosis was confirmed according to clinical judgement. A total of 103 patients with PMR were included. In 49.51% of patients, the 18FDG-PET/CT scan was ordered to study resistance to steroid therapy. The final diagnoses of patients were PMR in 70.9% patients, large vessel vasculitis in 15.5%, neoplasms 4.8% and another diagnosis in the rest. The 18FDG-PET/CT scan is a very useful technique for the study of Polymyalgia Rheumatica, not only to help in the diagnostic process, but also due to its role in the identification of a variety of PMR-like patrons.

Prognostic impacts of glucocorticoid treatment in patients with polymyalgia rheumatica and giant cell arteritis.

Identifying comorbidities in polymyalgia rheumatica/giant cell arteritis (PMR/GCA) is crucial for patients' outcomes. The present study aimed to evaluate the impact of the inflammatory process and glucocorticoid treatment on aortic arterial stiffness and body composition in PMR/GCA. 77 patients with newly diagnosed PMR/GCA were treated with oral glucocorticoids and followed for 40 weeks. Aortic pulse wave velocity (PWV) was measured at baseline and during the follow-up period and compared to the results of temporal artery biopsy (TAB) and 18F-FDG PET/CT. Body composition was assessed by total body DXA at baseline and the end of the study. Of 77 patients (49 (63.6%) female, mean of age: (71.8 ± 8.0)), 64 (83.1%) had pure PMR, 10 (13.0%) concomitant PMR and GCA, and 3 (3.9%) pure GCA. Compared to baseline values, aortic PWV was initially decreased at week 16 (p = 0.010) and remained lower than baseline at week 28 (p = 0.002) and week 40 (p < 0.001), with no association with results of TAB and 18F-FDG PET/CT. Aortic PWV was significantly associated with age, male gender, left systolic and diastolic blood pressure, right diastolic blood pressure, and CRP. Total bone mineral content (BMC) was decreased in both genders (p < 0.001), while fat mass (FM) was significantly increased (p < 0.001). However, lean body mass did not significantly change during the study. Changes in FM were correlated with cumulative prednisolone dose (rho: 0.26, p = 0.031). Glucocorticoid treatment of patients with PMR/GCA had several prognostic impacts. Arterial stiffness was decreased due either to the treatment or a reduction in the inflammatory load. Additionally, treatment led to changes in body composition, including a decrease in BMC and FM excess.

Polymyalgia rheumatica in a melanoma patient 11 months after completion of immunotherapy with nivolumab.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of several cancers but can also lead to the development of immune-related adverse effects including dermatologic, gastrointestinal, endocrine, hepatic, pulmonary and less commonly, rheumatic toxicities. Toxicities associated with ICI therapy can occur several months or even years after initiation. Case reports of polymyalgia rheumatica (PMR) associated with nivolumab use are rare. We herein describe, for the first time, a case of PMR in a melanoma patient after cessation of treatment with nivolumab. CASE: An 88-year-old man with a history of stage IV M1c BRAF wild-type melanoma presented with a 1 month history of arthralgias and morning stiffness, predominantly affecting the shoulders and hips, associated with fatigue and weight loss. He had undergone wide local excision of a primary malignant melanoma in the left buttock region several years prior. Immunotherapy with nivolumab was initiated following disease relapse with multiple metastases. Nivolumab was discontinued due to demonstration of complete metabolic response on serial positron emission and computed tomography scans. Symptoms appeared 11 months after completion of treatment. A diagnosis of PMR was made and treatment with oral prednisone was initiated leading to complete resolution of symptoms within 1 week. We believe that the development of PMR in our patient was likely precipitated by nivolumab. CONCLUSION: This case demonstrates that PMR, although rare, may occur as an adverse effect both during and after treatment with nivolumab, leading to disabling symptoms and poor quality of life. Prompt diagnosis is crucial to enable timely commencement of corticosteroid therapy in order to avoid further impact on morbidity and mortality for cancer patients. This case highlights the importance of prompt referral to rheumatology, as well as the need for close collaboration between oncologists and rheumatologists to accurately diagnose and successfully manage these patients.

An exploratory cross-sectional study of subclinical vascular damage in patients with polymyalgia rheumatica.

The aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior-posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT (1.07/0.8-1.2 vs 0.8/0.8-1.05; p = 0.0001), CAVI (8.7/7.8-9.3 vs 7.6/6.9-7.8; p < 0.0001) and APAD values (21.15/18.1-25.6 vs 18/16-22; p = 0.0013) was found in PMR patients with respect to controls. No differences were reported in the prevalence of carotid artery stenosis or ABI values between the two groups. A significant correlation between IMT and CAVI in PMR and MCVRF subjects (r2 = 0.845 and r2 = 0.556, respectively; p < 0.01) was found. Leptin levels (pg/mL; median/25th-75th percentile) were higher in PMR than in MCVRF subjects (145.1/67-398.6 vs 59.5/39.3-194.3; p = 0.04). Serum levels of adiponectin (ng/mL) were higher in PMR patients (15.9/10.65-24.1 vs 6.1/2.8-22.7; p = 0.01), while no difference in serum levels of resistin (ng/mL) was found between PMR and MCVRF subjects (0.37/0.16-0.66 vs 0.26/0.14-1.24). Our study shows an increased subclinical vascular damage in PMR patients compared to those with MCVRF, paving the way for further studies aimed at planning primary cardiovascular prevention in this population.

High Relapse Rate in Patients with Polymyalgia Rheumatica despite the Combination of Immunosuppressants and Prednisolone: A Single Center Experience of 89 patients.

Polymyalgia rheumatica (PMR) is an inflammatory disorder in the elderly and is characterized by pain in the shoulders and lower back. Previous studies from western countries have shown that relapse is frequent; however, there are only a few reports on the relapse rate in Japan. Here we examined the relapse rate, and sought to identify factors that predict recurrence in patients with PMR. Of 110 patients who fulfilled the Bird's criteria for PMR between May 2011 and June 2019, 21 patients were excluded, and the remaining 89 patients were followed up until July 2019. Relapse was defined when clinical symptoms were exacerbated and serum C-reactive protein level increased. The relapse-free survival curves were plotted using the Kaplan-Meier method, and log-rank test was used for statistical analysis. The mean age of the 89 patients (50 males and 39 females) was 71.8 years. The mean dose of initial prednisolone (PSL) was 11.8 mg/day. The 1-, 3-, and 5-year relapse-free survival rates were 81.6%, 58.0%, and 52.3% (N = 59, 21, and 7), respectively. In patients who experienced recurrence, the 1- and 3-year second relapse-free survival rates were 58.3% and 27.3% (N = 18 and 3), respectively. Immunosuppressants, such as methotrexate and tacrolimus, were added to PSL in 19 of 30 patients who experienced relapse at the discretion of the attending physicians; however, none of the immunosuppressants worked for preventing second relapses and had steroid-sparing effects. These results indicate that effective immunosuppressants are required to suppress relapse in the treatment of PMR.

Association of mucosal-associated invariant T cells with different disease phases of polymyalgia rheumatica.

OBJECTIVES: Although T cells are thought to be involved in the pathogenesis of PMR, whether innate-like T cells are involved in the process remains unknown. METHODS: The serum levels of 27 cytokines/chemokines in patients with PMR were measured by a multiplex immunoassay (Bio-Plex Assay). The cytokine-producing capacity of T and innate-like T cells was assessed by intracellular cytokine staining and flow cytometry. The frequency and activated status of T and innate-like T cells were investigated by flow cytometry and their associations with clinical parameters were assessed. RESULTS: The levels of inflammatory cytokines were associated with disease activity in PMR. The cytokine-producing capacity by CD8+ T and innate-like T cells was associated with disease activity. The frequency of HLA-DR+ CD38+ cells among CD8+ T cells was increased in patients with active disease. The frequencies of HLA-DR+ CD38+ cells among CD4+ T, mucosal-associated invariant T (MAIT) and γδ T cells were higher in patients with inactive disease. The frequency of HLA-DR+ CD38+ MAIT cells was associated with the PMR activity score and CRP levels in patients in remission. CONCLUSION: The inflammatory cytokine-producing capacity and expression of activation markers of CD8+ T and innate-like T cells were associated with the disease activity of PMR. MAIT cell activation in patients in remission may contribute to the subclinical activity of the disease.

Differences of articular and extra-articular involvement in polymyalgia rheumatica: A comparison by whole-body FDG-PET/CT.

Objectives: To clarify differences in incidences of articular and extra-articular involvement in patients with polymyalgia rheumatica (PMR) using FDG-PET/CT.Methods: Twenty PMR patients were enrolled in this retrospective study. We compared frequency, degree, and patterns (diffuse or non-diffuse) of abnormal FDG accumulation in the proximal and distal articular structures (PAS, DAS), and extra-articular synovial structures (ESS). Regional analyses were performed for the large joints (shoulder, hip, and knee).Results: The incidences of positive FDG accumulation were significantly higher in the PAS (96.7%) and ESS (91.4%) than in the DAS (31.8%, p < .0001), although, the incidence in the knees (96.2%) was exceptionally high. PAS (2.79 ± 0.61) and ESS (2.52 ± 0.85) had significantly higher visual scores than DAS (0.89 ± 1.33, p < .0001). Shoulder, hip, and knee joints each had a different accumulation pattern. Strong FDG accumulation was frequently observed in the medial-to-subscapular part of the shoulder joints, the lateral part of the hip joints, and the medial part of the knee joints.Conclusion: ESS were found to be the main affected areas in PMR patients as well as PAS. DAS involvement occurred with low frequency except in the knee joints. Each large joint showed a different accumulation pattern and its own characteristically strongly affected areas.

Discovery of IL-6 and Development of Anti-IL-6R Antibody.

A series of our studies on IL-6 have revealed that it has a pleiotropic activity in various tissues and cells and its deregulated expression is responsible for several chronic inflammations and hemopoietic malignancies.Humanized antibody against 80kd IL-6R (Tocilizumab) has shown significant therapeutic effect in RA, JIA, Castleman's diseases and several other autoimmune inflammatory diseases, such as, giant cell arteritis, reactive arthritis, polymyalgia rheumatica and adult still's disease. Cytokine storm induced by CAR-T cell therapy has been shown to be controlled by Tocilizumab.Therapeutic effect of Tocilizumab confirmed that over and constitutive-production of IL-6 is responsible for the pathogenesis of autoimmune diseases.Then, the question to be asked is how is IL-6 production regulated. We identified a novel molecule called Arid5a which binds with the 3'-UTR of IL-6 mRNA and protects its degradation by competing with Regnase-1. Interestingly, this molecule is present in nuclei and inflammatory stimulation induced translocation of Arid5a from nuclei into cytoplasm and it competes with Regnase-1 for the protection of mRNA of IL-6.Our study indicates that Arid5a is one of the key molecules for inflammation as well as the development of septic shock.The results also suggest the therapeutic potential of anti-agonistic agents for Arid5a in the prevention of various inflammatory diseases and septic shock.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are associated with disease activity in polymyalgia rheumatica.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are indicators of systemic inflammation and are useful as markers in systemic rheumatic diseases. In this study, we compared the NLR, PLR, and MLR among patients with polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA), and explored possible associations with clinical features, disease activity, and prognosis in patients with PMR. METHODS: The study enrolled 94 patients with PMR and 242 patients with RA who were initially diagnosed at the rheumatology clinic of a university-based tertiary hospital. Symptoms, physical examination, and medical histories were collected with the results of laboratory tests. RESULTS: Neutrophil-to-lymphocyte ratio (4.5 ± 3.3 vs 2.8 ± 1.8), PLR (222.7 ± 115.5 vs 159.7 ± 78.1), and MLR (0.4 ± 0.3 vs 0.3 ± 0.2) were higher in patients with PMR compared with patients with RA (all P < .001). NLR, PLR, and MLR were correlated with specific laboratory values, including CRP and albumin, in patients with PMR. After disease activity resolved, NLR (2.95 ± 2.32, P < .001), PLR (137.5 ± 82.3, P < .001), and MLR (0.26 ± 0.16, P < .001) decreased significantly. By comparing patients according to the disease course, swollen joint counts were higher in the chronic course group compared with the remission group (P = .03), while the NLR, PLR, and MLR were similar. CONCLUSIONS: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio levels were associated with disease activity and specific clinical features, although they could not predict prognosis in patients with PMR.

Differences in clinical manifestations and prognosis of Chinese giant cell arteritis patients with or without polymyalgia rheumatica.

BACKGROUND: The symptoms of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) frequently overlap in the elderly. Whether there are differences in clinical features or prognosis between GCA patients with or without PMR remains unknown. AIMS: To identify differences in clinical manifestation and prognosis between Chinese GCA patients with or without PMR. METHODS: A retrospective study of patients diagnosed with GCA in Peking Union Medical College Hospital (PUMCH) during the last 20 years was conducted. Clinical data was collected and analyzed accordingly, and follow-up was performed. RESULTS: A total of 50 patients had PMR, while 41 patients did not, with no significant differences in age, gender, and disease course between the two groups. GCA patients with PMR presented with higher risks of family history of malignancy (p = 0.048). Patients without PMR had higher proportion of hearing loss (p = 0.006), ANCA positive (p = 0.024), and abnormal imaging findings illustrating the involvement of arteries under aortic arch (p = 0.018). Before treatment, total lymphocyte counts in patients without PMR were lower than those with PMR, and monocyte counts in both groups were higher than normal. Acute phase reactants in patients without PMR were higher than the other group. No significant differences were found in prognosis during follow-up. CONCLUSIONS: GCA patients with or without PMR have different clinical characteristics. Patients with PMR present myalgia or arthralgia more frequently, while those without PMR have higher inflammatory markers, lower lymphocyte counts, and wider involvement of arteries under aortic arch.

Drug therapies for polymyalgia rheumatica: a pharmacotherapeutic update.

INTRODUCTION: Polymyalgia rheumatica (PMR), a common disease in individuals older than 50 in the western world, is characterized by bilateral inflammatory pain involving the shoulder girdle and less commonly the neck and pelvic girdle. The main goals of the currently available treatment are to induce remission and prevent relapse. AREAS COVERED: This review briefly presents the main epidemiological and clinical features of PMR and discusses in depth both its classical management as well as new therapies used in PMR. EXPERT OPINION: In general, patients with isolated PMR experience a rapid response (in less than seven days) to 12.5-25 mg/prednisone/day. Methotrexate is the conventional disease-modifying antirheumatic drug most commonly used for disease management, especially for relapses of the disease. However, this agent often yields a modest effect. Randomized controlled trials do not support the use of antitumor necrosis factor agents in PMR. Several case series and retrospective studies have highlighted the efficacy of the anti-interleukin-6 receptor antibody tocilizumab in PMR. However, controlled trials are needed to fully establish the efficacy of this biologic agent in PMR. The potential beneficial effect of the Janus-kinase inhibitors remains to be determined.

Torsades de Pointes in Patients with Polymyalgia Rheumatica.

Polymyalgia rheumatica (PMR) represents the most common inflammatory rheumatic disease of the elderly. It is characterized by synovitis of proximal joints and extra-articular synovial structures, along with chronic high-grade systemic inflammation. PMR is closely related to giant cell arteritis (GCA), a large-vessel vasculitis that involves the major branches of the aorta, particularly the extracranial branches of carotid artery including temporal arteries. It is currently believed that PMR and GCA may represent different manifestations of the same disease process. Chronic systemic inflammation is presently recognized as one of the key pathogenic mechanisms underlying cardiovascular disease and associated complications, including cardiac arrhythmias and sudden death. In this regard, several studies demonstrated that besides promoting structural heart disease, inflammatory activation may also be per se arrhythmogenic, via cytokine-mediated effects on cardiac electrophysiology. In particular, increasing evidence points to inflammation as a novel risk factor for QTc prolongation and related life-threatening arrhythmias, specifically Torsade de Pointes (TdP). Starting from the report of two cases of TdP occurring in PMR patients with active disease and elevated circulating IL-6 levels, we here reviewed literature data regarding heart involvement and arrhythmic events in PMR/GCA, as well as TdP risk in inflammatory diseases. Potential underlying mechanisms were dissected, by focusing on the driving role of inflammatory activation.

Management of difficult polymyalgia rheumatica and giant cell arteritis: Updates for clinical practice.

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) represent a family of systemic inflammatory diseases occurring in adults aged 50 years and above. Clinical presentation of PMR/GCA can be variable, making diagnosis at times challenging. There has been an increased appreciation of the role of various large-vessel imaging modalities to help confirm a diagnosis of GCA. Systemic corticosteroids (CS) remain the mainstay of treatment for both PMR and GCA, yet both relapses and CS-related side effects are common. Recent research has demonstrated efficacy of certain biologic agents in these diseases, with particular emphasis on the role of interleukin-6 (IL-6) blockade in GCA. This chapter discusses the latest updates on the diagnosis and treatment of PMR/GCA, with an emphasis on clinical care.