Premature atrial contractions with multiple patterns of aberrant conduction followed by torsade de pointes in a patient with polymyalgia rheumatica: A case report.

RATIONALE: Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited. PATIENT CONCERNS: An 85-year-old Japanese woman with active PMR developed first syncope. DIAGNOSIS: Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP. INTERVENTIONS: Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective. OUTCOMES: Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia. LESSONS: IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy.

Temporal Arteritis Revealing Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A Case-Control Study.

OBJECTIVE: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. METHODS: In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). CONCLUSION: TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.

The pathophysiology of polymyalgia rheumatica, small pieces of a big puzzle.

Polymyalgia rheumatica (PMR) is a frequent rheumatic condition among people over 50 years of age. Despite its frequent association with giant cell arteritis (GCA), PMR can be isolated. Its pathophysiology is poorly understood. Nevertheless, many studies are ongoing; 98 studies are currently referenced in ClinicalTrials.org involving several conventional and targeted therapies. In this review, we synthetize the current knowledge about PMR pathophysiology according to genetic and immunogenetic, immunologic, antibody and aging data. Immunogenetic data are mainly related to the HLA system and the association between the HLA-DRB1 and PMR. Few studies are also about immunogenetics of proinflammatory interleukins (i.e. IL-6). The decrease of CD8+Tcells and the strong increase of IL-6 where the main elements of PMR's pathophysiology until the recent years. The disturbance of B cell homeostasis, the search for IL-6 secretion by the innate immune system, the role of aging, are new elements revealed by recent studies. Aging might be a key element to consider as PMR occurs in patients over 50 years of age. Aging may act by the increased susceptibility to infections, by immunological modifications or hormonal disturbances. The role of the cellular infiltration around the joints remains a crucial question. Only a handful of studies described this infiltration. Finally, this review reveals the gaps in available data and suggests new leads and in-depth studies for further research on PMR pathophysiology.

Cardiovascular risk factors associated with polymyalgia rheumatica and giant cell arteritis in a prospective cohort: EPIC-Norfolk Study.

OBJECTIVES: PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA. METHODS: Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards. RESULTS: In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P=0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P=0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets. CONCLUSION: PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk.

Subclinical atherosclerosis and endothelial dysfunction in patients with polymyalgia rheumatica: a pilot study.

Objective: The aim of the study was to investigate endothelial function in treatment-naïve polymyalgia rheumatica (PMR) patients and its modification during steroid therapy, in relation to changes in clinical and laboratory parameters.Method: This prospective observational study involved patients with a new diagnosis of PMR according to provisional American College of Rheumatology/European League Against Rheumatism 2012 criteria, who were naïve to steroid therapy, and control subjects matched for age, gender, and comorbidities. All participants underwent clinical and vascular ultrasound evaluations at baseline and after 1, 3, 6, and 12 months of steroid therapy. For the study of endothelial function, we evaluated the brachial artery reactivity, which has emerged as the most well-established technique used in adults, by assessing flow-mediated dilatation (FMD), which measures the endothelium-dependent vasodilatation.Results: Sixteen newly diagnosed PMR patients were compared with a population of 16 matched controls. FMD values in all subjects showed an inverse correlation with the values of erythrocyte sedimentation rate and C-reactive protein. At baseline, the FMD of PMR patients was significantly lower than controls and remained significantly lower with respect to controls until the sixth month of therapy, despite a clinical improvement already being evident after 1 month of therapy.Conclusions: PMR is characterized by an important chronic subclinical inflammatory component. This pilot study demonstrates that affected patients show endothelial dysfunction that slowly responds to steroid therapy. Further studies are needed to investigate the clinical relevance of these observations and, in particular, to monitor the cardiovascular risk profile of PMR patients.

Patient-reported involvement of the eighth cranial nerve in giant cell arteritis.

INTRODUCTION: The frequency of eighth nerve lesions in patients with giant cell arteritis (GCA) has rarely been examined. However, sudden onset deafness has been recorded as a presenting feature of GCA on several occasions. This study sought to establish how common this and other symptoms of eighth nerve involvement are in a large retrospective survey. METHODS: We contacted 170 patients with GCA and 250 matched PMR patients, inviting them to participate in a questionnaire survey of symptoms of eighth nerve dysfunction. We compared the presence of deafness, tinnitus, loss of balance and vertigo in both groups and examined the relationship between the onset of these symptoms and other features of GCA. RESULTS: A total of 317 patients were recruited. The percentage of patients with symptoms of possible vestibulocochlear disease prior to commencement of steroid therapy was significantly greater among GCA patients than PMR patients for all domains. Hearing loss which was twice as common in GCA as in PMR (53% vs 26%) [p = 0.001]. Deafness was concurrent in 35% of GCA patients with other symptoms and 45% reported colocation with headache. Recovery with steroids occurred in 56% of these. CONCLUSION: Symptoms of eighth nerve dysfunction are present in over half of patients with GCA. Recovery with steroids was predicted by concurrence with headache in terms of both timing and location. It appears that eighth nerve involvement, especially acute hearing loss, is a not infrequent feature of GCA and often responds well to steroid therapy. Clinicians should enquire about these symptoms when evaluating a patient for possible GCA.Key Points• Deafness is a frequent presenting feature of giant cell arteritis.• Vertigo, tinnitus and loss of balance are also often reported by GCA sufferers.• Steroid therapy is more likely to relieve these symptoms if they are ipsilateral and concurrent with headache.

Toward a Core Outcome Measurement Set for Polymyalgia Rheumatica: Report from the OMERACT 2018 Special Interest Group.

OBJECTIVE: To report the progress of the Outcome Measures in Rheumatology (OMERACT) Polymyalgia Rheumatica (PMR) Working Group in selecting candidate instruments for a core outcome measurement set. METHODS: A systematic literature review identified outcomes measured and instruments used in PMR studies, and a respondent survey and raw data analysis assessed their domain match and feasibility. RESULTS: Candidate instruments were identified for pain [visual analog scale/numerical rating scale (VAS/NRS)], stiffness (VAS/NRS and duration), and physical function (Health Assessment Questionnaire-Disability Index/modified Health Assessment Questionnaire). Domain match and feasibility assessments were favorable; however, validation in PMR was lacking. CONCLUSION: Further assessment of candidate instruments is required prior to recommending a PMR core outcome measurement set.

Application of 2012 EULAR/ACR criteria for polymyalgia rheumatica to Korean patients previously classified by Chuang and Hunder criteria or Healey criteria.

AIM: To apply 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria to Korean patients previously classified as polymyalgia rheumatica (PMR) by Chuang and Hunder criteria or Healey criteria and investigated whether they might be still reclassified as PMR or not. METHODS: We retrospectively reviewed the medical records of 113 previously classified PMR patients. We applied 2012 EULAR/ACR criteria without ultrasonography to PMR patients, and fulfilment required at least 4 points. We evaluated odds ratios (OR) using logistic regression analyses. RESULTS: The mean age was 61.7 years. Seventy-one patients (62.8%) fulfilled Chuang and Hunder criteria, and 113 patients (100%) met Healey criteria. When we applied 2012 EULAR/ACR criteria, 98 patients fulfilled essential items (≥50 years, bilateral shoulder aching and abnormal C-reactive protein or erythrocyte sedimentation rate), and only 80 patients achieved points ≥4. Eight patients fulfilling the criteria exhibited higher frequencies of all the detailed items than those who did not. In multivariate logistic regression analysis, absence of rheumatoid factor or anti-citrullinated peptide antibodies was the only independent contributing item to the fulfilment of 2012 EULAR/ACR criteria (OR 23.571, 95% CI 6.357-87.407, P < .001). When we reclassified 33 excluded patients, the most common newly classified disease was generalized osteoarthritis (24.2%), followed by osteoporosis with compression fracture (15.2%). CONCLUSION: Eighty of 113 patients (81.6%) previously classified by Chuang and Hunder criteria or Healey criteria fulfilled 2012 EULAR/ACR criteria for PMR.

Preliminary concurrent validity of the Fitbit-Zip and ActiGraph activity monitors for measuring steps in people with polymyalgia rheumatica.

BACKGROUND: Activity monitors provide objective measurements of physical activity, however, the accuracy of these devices in people with polymyalgia rheumatica (PMR) is unknown. Therefore, this study aimed to obtain preliminary evidence of the accuracy of two activity monitors and explore if clinical and gait-related factors altered device accuracy in people with PMR. METHODS: The ActiGraph with low frequency extension (+LFE) and standard (-LFE) algorithms, Fitbit-Zip (waist) and Fitbit-Zip (shirt) were concurrently tested using a two-minute walk test (2MWT) and stairs test in 27 people with PMR currently treated with prednisolone. To determine accuracy, activity monitor step-count was compared to a gold-standard step-count (GSSC; calculated from video recording) using Bland-Altman plots. RESULTS: The Fitbit-Zip (waist) achieved closest agreement to the GSSC for the 2MWT (mean bias (95%CI): 10 (-3, 23); 95%LOA: -55, 74). The ActiGraph (+LFE) achieved closest agreement to the GSSC for the stairs test (mean bias (95%CI): 0 (-1, 1); 95%LOA: -5, 5). The ActiGraph (-LFE) performed poorly in both tests. All devices demonstrated reduced accuracy in participants with lower gait velocity, reduced stride length, longer double-limb support phase and greater self-reported functional impairment. CONCLUSION: Our preliminary results suggest that in controlled conditions, the Fitbit-Zip fairly accurately measures step-count during walking in people with PMR receiving treatment. However, device error was greater than data published in healthy people. The ActiGraph may not be recommended without activation of the LFE. We identified clinical and gait-related factors associated with higher levels of functional impairment that reduced device accuracy. Further work is required to evaluate the validity of the activity monitors in field conditions.

Association between characteristics of pain and stiffness and the functional status of patients with incident polymyalgia rheumatica from primary care.

This paper aims to examine the relationship between different characteristics of pain and stiffness and the functional status of patients with newly diagnosed polymyalgia rheumatica (PMR). Baseline analysis of an inception cohort study was conducted. Patients aged ≥18 years, with a new diagnosis of PMR were recruited from 382 English general practices. Participants were mailed a baseline questionnaire, including separate pain and stiffness manikins and numerical rating scales (NRS), a question on their ability to raise their arms above their head and the modified Health Assessment Questionnaire (mHAQ) to examine participants' functional status. Linear regression analysis, reported as regression co-efficients (95% confidence intervals (95% CI)), was used to assess the association of pain and stiffness with function, initially unadjusted and then adjusted for age, gender, deprivation status, smoking status, BMI, anxiety and depression. Six hundred fifty two patients responded to the baseline survey (88.5%). The majority (88.2%) reported no, or mild impairment in their functional status. Adjusted linear regression analysis demonstrated that high (NRS ≥8) pain (0.20 (95% CI 0.10-0.28)) or stiffness (0.18 (0.09-0.26)) ratings, an increasing number of sites of pain (0.18 (0.06-0.29)) or stiffness (0.19 (0.08-0.31)) and shoulder pain (0.18 (0.05-0.31)), stiffness (0.10 (0.01-0.20)) and difficulty raising arms above one's head (0.19 (0.10-0.28)) were all associated with increased functional impairment. The majority of newly diagnosed PMR patients reported no or minimal functional difficulty. However, those who experience severe or widespread pain or stiffness often have significant functional limitation in performing their daily activities and may be a subset worthy of additional focus in primary care.

Assessment of 2012 EULAR/ACR new classification criteria for polymyalgia rheumatica in Japanese patients diagnosed using Bird's criteria.

AIM: The 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for polymyalgia rheumatica (PMR) were published in 2012. The present study aimed to assess the 2012 EULAR/ACR classification criteria for PMR in Japanese patients diagnosed with PMR using Bird's criteria. METHODS: The study included 75 patients diagnosed using Bird's criteria. The patients were divided into fulfilled and not-fulfilled groups according to whether they met the 2012 EULAR/ACR classification criteria for PMR. The factors in the new criteria were morning stiffness duration > 45 min, hip pain or limited range of motion, absence of rheumatoid factor or anti-citrullinated protein antibody, and absence of other joint involvement. RESULTS: Thirty-two of the patients diagnosed with PMR using Bird's criteria met the new EULAR/ACR classification criteria, while the remaining 43 patients did not meet the new criteria. Among the factors, only morning stiffness duration > 45 min was an independent predictive factor. CONCLUSIONS: A morning stiffness duration > 45 min is the only independent predictive factor for differentiating patients diagnosed according to the new 2012 EULAR/ACR classification criteria for PMR.

Polymyalgia rheumatica and giant cell arteritis-three challenges-consequences of the vasculitis process, osteoporosis, and malignancy: A prospective cohort study protocol.

INTRODUCTION: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are common inflammatory conditions. The diagnosis of PMR/GCA poses many challenges since there are no specific diagnostic tests. Recent literature emphasizes the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to assess global disease activity in inflammatory diseases. 18F-FDG PET/CT may lead to the diagnosis at an earlier stage than conventional imaging and may also assess response to therapy. With respect to the management of PMR/GCA, there are 3 significant areas of concern as follows: vasculitis process/vascular stiffness, malignancy, and osteoporosis. METHODS AND ANALYSIS: All patients with suspected PMR/GCR referred to the Rheumatology section of Medicine Department at Svendborg Hospital, Denmark. The 4 separate studies in the current protocol focus on: the association of clinical picture of PMR/GCA with PET findings; the validity of 18F-FDG PET/CT scan for diagnosis of PMR/GCA compared with temporal artery biopsy; the prevalence of newly diagnosed malignancies in patients with PMR/GCA, or PMR-like syndrome, with the focus on diagnostic accuracy of 18F-FDG PET/CT scan compared with conventional workup (ie, chest X-ray/abdominal ultrasound); and the impact of disease process, and also steroid treatment on bone mineral density, body composition, and vasculitis/vascular stiffness in PMR/GCA patients. ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethics Committee of the Region of Southern Denmark (identification number: S-20160098) and Danish Data Protection Agency (J.nr 16/40522). Results of the study will be disseminated via publications in peer-reviewed journals, and presentation at national and international conferences.

[Polymyalgia rheumatica: diagnostic and therapeutic issues of an apparently straightforward disease.] / La polimialgia reumatica: difficoltà diagnostiche e terapeutiche per una malattia apparentemente "banale".

Polymyalgia rheumatica (PMR) is an inflammatory disease characterized by aching and stiffness in the girdles, which affects typically people over 50 years old and could overlap with giant cell arteritis (GCA) in about 15-20% of cases. Although the diagnosis of PMR is usually considered straightforward, clinicians facing this disease should be aware of its atypical manifestations, which can hamper the correct identification of PMR and, conversely, should be aware of other diseases which may present with polymyalgic features. The aim of this review is to synthetize current knowledge about clinical presentations of PMR, the differential diagnoses, the relationship with cancer, the clues to the presence of a concomitant GCA, the role of ultrasonography at the onset and in the follow-up and, finally, treatment approaches. Besides evidence from the literature, this review will highlight some "tips&tricks" useful in everyday clinical practice. The awareness of the different presentations and pitfalls of PMR could improve patients' management and avoid complications consequent upon unrecognized diseases or, conversely, overtreatment.

[A rare concurrence of polymyalgia rheumatica and AA-amyloidosis]. / Redkoe sochetanie revmaticheskoi polimialgii s AA-amiloidozom.

Polymyalgia rheumatica (PMR) is a rare chronic inflammatory disease. It predominantly affects the elderly. The disease has a slow onset, pain and stiffness in the muscles of the shoulder and pelvic girdle, fever, weight loss, and a high acute-phase inflammatory response. The disease is concurrent with giant cell arteritis in a quarter of cases, which allows some authors to consider them as two different manifestations of the same pathological process. The kidneys are rarely involved. This disease is rarely complicated by AA amyloidosis. The authors describe a case of RPM in a patient who has developed secondary AA amyloidosis.

Síndrome paraneoplásico: a propósito de dos casos / Paraneoplastic syndrome: report of two cases

El dolor poliarticular es muy frecuente en la consulta diaria del médico de Atención Primaria. El diagnóstico de la patología articular es fundamentalmente clínico y la anamnesis es la herramienta diagnóstica más importante de la que disponemos. Algunos de estos casos pueden ser la manifestación reumática de algún tipo de cáncer y su curso clínico habitualmente es paralelo al del tumor (AU)

Polyarticular pain is very common in the daily practice of primary care physicians. The diagnosis of the articular pathology is fundamentally clinical and the anamnesis is the most important diagnostic tool we have. Some of these cases can be the rheumatic manifestation of some type of cancer and their clinical course is usually parallel to the tumor (AU)

Stiffness Is the Cardinal Symptom of Inflammatory Musculoskeletal Diseases, Yet Still Variably Measured: Report from the OMERACT 2016 Stiffness Special Interest Group.

OBJECTIVE: The objectives of the Outcome Measures in Rheumatology (OMERACT) Stiffness special interest group (SIG) are to characterize stiffness as an outcome in rheumatic disease and to identify and validate a stiffness patient-reported outcome (PRO) in rheumatology. METHODS: At OMERACT 2016, international groups presented and discussed results of several concurrent research projects on stiffness: a literature review of rheumatoid arthritis (RA) stiffness PRO measures, a qualitative investigation into the RA and polymyalgia rheumatica patient perspective of stiffness, data-driven stiffness conceptual model development, development and testing of an RA stiffness PRO measure, and a quantitative work testing stiffness items in patients with RA and psoriatic arthritis. RESULTS: The literature review identified 52 individual stiffness PRO measures assessing morning or early morning stiffness severity/intensity or duration. Items were heterogeneous, had little or inconsistent psychometric property evidence, and did not appear to have been developed according to the PRO development guidelines. A poor match between current stiffness PRO and the conceptual model identifying the RA patient experience of stiffness was identified, highlighting a major flaw in PRO selection according to the OMERACT filter 2.0. CONCLUSION: Discussions within the Stiffness SIG highlighted the importance of further research on stiffness and defined a research agenda.