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Scientific Reports Jan 2024Polymyalgia rheumatica (PMR) is a chronic inflammatory disease characterized by arthralgia and myalgia of the shoulder and hip girdles, and fever. PMR is linked to...
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.
Topics: Humans; Polymyalgia Rheumatica; Inflammasomes; Alleles; Giant Cell Arteritis; Gene Frequency; Intracellular Signaling Peptides and Proteins
PubMed: 38177227
DOI: 10.1038/s41598-024-51320-3 -
European Journal of Case Reports in... 2024We describe a case of a patient treated with pembrolizumab (an immune checkpoint inhibitor) for metastatic scalp melanoma. He had a previous history of colorectal...
CASE DESCRIPTION
We describe a case of a patient treated with pembrolizumab (an immune checkpoint inhibitor) for metastatic scalp melanoma. He had a previous history of colorectal cancer, prostatic cancer and chronic polymyalgia rheumatica. The patient was known to have a stable ascending aortic aneurysm of 4.5 cm. However, he developed a rapid expansion of the ascending aortic aneurysm with the size crossing the threshold for surgery. The patient was referred to the cardiothoracic surgery service for intervention and he subsequently underwent surgery. The patient was electively admitted one week later for resection of aortic aneurysm, aortoplasty and external graft fixation. Pathologically, gross evidence of dissection was not identified; however, the histological analysis of the media showed laminar medial necrosis, multifocal in nature, with occasional clusters of histiocytic cells appreciated at their edge reminiscent of that seen in an inflammatory aortitis (granulomatous/giant cell type).
DISCUSSION
Immune checkpoint inhibitor-induced aortitis is becoming increasingly evident, and its presentation can vary. It has been discovered incidentally on surveillance imaging with the use of nivolumab. In other cases, patients have been symptomatic to severely symptomatic. Atezolizumab with carboplatin and etoposide has been reported to cause abdominal aortitis which was responsive to corticosteroids and subsequent discontinuation of atezolizumab. Pembrolizumab has been linked to a case of transverse aortic arch aortitis. In our case, the inflammatory aortitis due to pembrolizumab was the cause of the rapid expansion of the ascending aortic aneurysm.
CONCLUSION
Patients with known aortic aneurysms should undergo careful surveillance when commencing immune-checkpoint inhibitor therapy.
LEARNING POINTS
Immune checkpoint inhibitors are being increasingly used in the treatment of metastatic malignancy. However, they are a relatively new group of medications, and the side effect profile of each is yet to be fully recognised. Aortitis has occurred with several different immune checkpoint inhibitors.Patients with known aortic aneurysms should undergo careful surveillance when commencing immune checkpoint inhibitors.All interventional therapeutic options should be considered early in these patients on the development of aneurysmal expansion.
PubMed: 38715880
DOI: 10.12890/2024_004419 -
Clinical and Experimental Rheumatology Apr 2024Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only...
OBJECTIVES
Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey.
METHODS
We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician.
RESULTS
The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up.
CONCLUSIONS
In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.
Topics: Humans; Giant Cell Arteritis; Retrospective Studies; Female; Aged; Male; Turkey; Recurrence; Middle Aged; Registries; Glucocorticoids; Treatment Outcome; Remission Induction; Time Factors; Immunosuppressive Agents; Aged, 80 and over
PubMed: 37976117
DOI: 10.55563/clinexprheumatol/zr7s0g -
Acta Medica Portuguesa May 2024
Topics: Humans; Polymyalgia Rheumatica; COVID-19 Vaccines; Male; Female; Aged; Databases, Factual; COVID-19; Middle Aged
PubMed: 38607657
DOI: 10.20344/amp.20952 -
Journal of the American Heart... Mar 2024Chronic inflammatory disease (CID) accelerates atherosclerosis and the development of aortic stenosis. Data on long-term outcomes after transcatheter aortic valve...
BACKGROUND
Chronic inflammatory disease (CID) accelerates atherosclerosis and the development of aortic stenosis. Data on long-term outcomes after transcatheter aortic valve implantation (TAVI) in those patients are missing. The aim of this study was to investigate the clinical long-term outcomes of patients with and without autoimmune-related CID undergoing TAVI for the treatment of severe aortic stenosis.
METHODS AND RESULTS
From a prospective registry, consecutive patients with TAVI were included. Baseline clinic and imaging data (echocardiographic and computed tomography) were analyzed. Long-term (up to 5 years) clinical and echocardiographic outcomes were studied. Of 1000 consecutive patients (mean age 81±6 years, 46% female), 107 (11%) had CID; the most frequent entities included polymyalgia rheumatica (31%) and rheumatoid arthritis (28%). Patients with CID were predominantly female (60% versus 44%, =0.002) and more often had pulmonary disorders (21% versus 13%, =0.046) and atrial fibrillation (32% versus 20%, =0.003). The presence of CID was associated with a higher rate of postinterventional infection (5% versus 1%, =0.007) and further emerged as a risk factor for rehospitalization for bleeding or infection (hazard ratio, 1.93 and 1.62, respectively). Premature valve degeneration, endocarditis, and all-cause mortality were not increased among patients with CID.
CONCLUSIONS
This real-world analysis found that patients with CID undergoing TAVI were associated with a higher risk of postinterventional infectious complications and rehospitalization due to infection. However, valve durability and survival seem not to differ between patients with TAVI with versus without CID.
Topics: Humans; Female; Aged; Aged, 80 and over; Male; Transcatheter Aortic Valve Replacement; Aortic Valve; Treatment Outcome; Aortic Valve Stenosis; Risk Factors; Atrial Fibrillation; Chronic Disease; Heart Valve Prosthesis; Registries
PubMed: 38390801
DOI: 10.1161/JAHA.123.032250 -
Annals of the Rheumatic Diseases Feb 2024Glucocorticoids used in the treatment of inflammatory rheumatic conditions can impact on health-related quality of life. An underpinning qualitative study developed a...
OBJECTIVES
Glucocorticoids used in the treatment of inflammatory rheumatic conditions can impact on health-related quality of life. An underpinning qualitative study developed a long-list of candidate items for a treatment-specific patient-reported outcome (PRO) measure. The objective of this paper is to determine scale structure and psychometric properties of the Steroid PRO.
METHODS
A cross-sectional survey of adults from the UK, USA, Australia and New Zealand, taking glucocorticoids for a rheumatic disease. Initial survey collected demographics, clinical information, 40 Steroid PRO candidate items and EuroQol-5 Dimensions- 5 levels (EQ-5D-5L). Follow-up, 3-5 days later, collected Steroid PRO candidate items and a condition-change ('transition') question. Analysis included Rasch measurement model, exploratory factor analysis (EFA), and hypothesis testing for discriminative validity, convergence validity and test-retest reliability.
RESULTS
Total responses 946: UK n=743 (79%); USA n=139 (15%); Australia/New Zealand n=64 (7%); mean age 57.6 (SD=13.6); 833 (88%) women. Participants with inflammatory arthritis n=197 (21%), connective tissue disease and/or vasculitis n=402 (42%), giant cell arteritis and/or polymyalgia rheumatica n=347 (37%). Twenty-five items were removed due to lack of fit to Rasch model. Of the remaining items, EFA suggested four subscales: Social impact (4 items); Impact on appearance (3 items); Psychological impact (5 items); Treatment concerns (3 items). Rasch modelling supported a four-subscale structure and total score, confirming construct validity and reliability. Hypothesis testing confirmed discriminant and convergence validity. Intraclass correlation coefficient (total score) was 0.809 demonstrating excellent (test-retest) reliability.
CONCLUSIONS
The Steroid PRO is a 15-item, valid and reliable scale for measuring the impact of glucocorticoid therapy in people with rheumatic diseases.
Topics: Adult; Humans; Female; Middle Aged; Male; Quality of Life; Glucocorticoids; Reproducibility of Results; Cross-Sectional Studies; Rheumatic Diseases; Surveys and Questionnaires; Patient Reported Outcome Measures; Psychometrics; Steroids
PubMed: 37949468
DOI: 10.1136/ard-2023-224946 -
Frontiers in Medicine 2024Giant cell arteritis (GCA) is characterized by inflammation of large and medium vessels. First-line therapy for the treatment of GCA are glucocorticoids, which are...
BACKGROUND
Giant cell arteritis (GCA) is characterized by inflammation of large and medium vessels. First-line therapy for the treatment of GCA are glucocorticoids, which are effective while potential adverse effects should be considered, especially during long-term use. The aim was to investigate the incidence of glucocorticoids' adverse effects and potential predictors for them.
MATERIALS AND METHODS
138 GCA patients were retrospectively evaluated for newly developed glucocorticoid adverse effects in 2020. Potential predictors, defined as initial glucocorticoid pulse therapy, relapse of GCA and concomitant polymyalgia rheumatica as well as parameters of inflammation and endothelial dysfunction, including pulse-wave velocity and intima-media-thickness, were measured in 2012.
RESULTS
Potential new glucocorticoid adverse effects per patient was 1 (25th-75th 0-3) of which chronic kidney disease progression (29%), bone fractures (23.2%), cataracts (18.1%), dementia, and arterial hypertension (each at 12.3%) were most commonly recorded. Significant associations were found between occurrence of any relapse and new diabetes mellitus and between initial glucocorticoid pulse therapy and new dementia (all with < 0.05). In multivariate regression analysis, any relapse was a predictor for developing diabetes mellitus (OR 9.23 [95% CI 1.33-64.05], = 0.025). However, no correlations were observed between endothelial dysfunction or inflammatory parameters and development of new glucocorticoid adverse effects.
CONCLUSION
GCA relapses may be associated for development of diabetes mellitus potentially by increasing glucocorticoid doses. Parameters of inflammation and endothelial dysfunction are not suited predictors for glucocorticoid adverse effects.
PubMed: 38841591
DOI: 10.3389/fmed.2024.1382946 -
Journal of Clinical Medicine Nov 2023Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are often overlapping conditions. We studied whether 18F-fluorodeoxyglucose (FDG) positron emission...
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; < 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.
PubMed: 38002597
DOI: 10.3390/jcm12226983 -
Cureus Aug 2023Giant cell arteritis, or temporal arteritis, is a chronic granulomatous vasculitis that affects large- and medium-sized arteries. An elderly male of 61 years presenting...
Giant cell arteritis, or temporal arteritis, is a chronic granulomatous vasculitis that affects large- and medium-sized arteries. An elderly male of 61 years presenting with chronic headaches for the past one year had been misdiagnosed as having migraine because of the similarity in symptoms. General examination revealed the presence of bilateral large, tortuous temporal arteries without any scalp tenderness, diminished arterial pulsations, or skin changes over the dilated arteries. A temporal artery biopsy revealed giant cell arteritis and was treated with steroids. This case report highlights the importance of considering secondary headaches, especially giant cell arteritis, in the differential diagnosis of new-onset headaches or worsening headaches in the elderly.
PubMed: 37750130
DOI: 10.7759/cureus.44107 -
Cureus Dec 2023Japanese spotted fever (JSF) poses a significant public health challenge, mainly due to its atypical presentation in specific demographics. This report details a unique...
Japanese spotted fever (JSF) poses a significant public health challenge, mainly due to its atypical presentation in specific demographics. This report details a unique case of JSF in an 89-year-old female who was admitted to a rural hospital exhibiting generalized pain and rapid cognitive decline but no rash. Initially misdiagnosed as polymyalgia rheumatica, her condition was complicated by thrombocytopenia and altered mental state, prompting consideration of tick-borne illnesses. Subsequent serological analysis confirmed JSF despite the absence of its hallmark rash. The patient's condition escalated to include bacteremia and aseptic meningitis. Treatment involved a regimen of minocycline and meropenem, along with endoscopic cauterization of a bleeding rectal ulcer. After treatment, the patient showed improvement and was transferred for rehabilitation. This case highlights the criticality of considering JSF in elderly patients within endemic areas, even when classic symptoms like erythema and petechiae are absent. It underscores the necessity for broad diagnostic perspectives, especially in atypical presentations, and the integration of comprehensive care approaches. The involvement of caregivers and relatives in early detection and seeking medical care promptly is crucial. The report illustrates the complexities in diagnosing and managing advanced JSF cases and stresses the importance of early serological testing and adaptive treatment strategies in managing such challenging cases.
PubMed: 38229818
DOI: 10.7759/cureus.50681