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Journal of Internal Medicine Nov 2022Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2-3 times more common in women. The most... (Review)
Review
Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2-3 times more common in women. The most common symptoms are pain and morning stiffness in the shoulder and pelvic girdle and the onset may be acute or develop over a few days to weeks. General symptoms such as fatigue, fever and weight loss may occur, likely driven by systemic IL-6 signalling. The pathology includes synovial and periarticular inflammation and muscular vasculopathy. A new observation is that PMR may appear as a side effect of cancer treatment with checkpoint inhibitors. The diagnosis of PMR relies mainly on symptoms and signs combined with laboratory markers of inflammation. Imaging modalities including ultrasound, magnetic resonance imaging and positron emission tomography with computed tomography are promising new tools in the investigation of suspected PMR. However, they are still limited by availability, high cost and unclear performance in the diagnostic workup. Glucocorticoid (GC) therapy is effective in PMR, with most patients responding promptly to 15-25 mg prednisolone per day. There are challenges in the management of patients with PMR as relapses do occur and patients with PMR may need to stay on GC for extended periods. This is associated with high rates of GC-related comorbidities, such as diabetes and osteoporosis, and there are limited data on the use of disease-modifying antirheumatic drugs and biologics as GC sparing agents. Finally, PMR is associated with giant cell arteritis that may complicate the disease course and require more intense and prolonged treatment.
Topics: Antirheumatic Agents; Biological Products; Biomarkers; Female; Giant Cell Arteritis; Glucocorticoids; Humans; Inflammation; Interleukin-6; Polymyalgia Rheumatica; Prednisolone
PubMed: 35612524
DOI: 10.1111/joim.13525 -
Cleveland Clinic Journal of Medicine Aug 2020Polymyalgia rheumatica should be suspected in older patients with bilateral shoulder and hip stiffness that is worse in the morning and improves with use. An array of... (Review)
Review
Polymyalgia rheumatica should be suspected in older patients with bilateral shoulder and hip stiffness that is worse in the morning and improves with use. An array of nonspecific musculoskeletal complaints, constitutional symptoms, and elevated serum inflammatory markers may be present, so other conditions should also be considered. Prolonged glucocorticoids with patient-tailored dosing and duration are the mainstay of treatment. Corticosteroid-sparing therapy with adjunctive methotrexate may benefit select patients.
Topics: Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Blood Sedimentation; Diagnosis, Differential; Female; Giant Cell Arteritis; Glucocorticoids; Humans; Induction Chemotherapy; Male; Methotrexate; Middle Aged; Polymyalgia Rheumatica; Ultrasonography
PubMed: 32868305
DOI: 10.3949/ccjm.87a.20008 -
CMAJ : Canadian Medical Association... Nov 2021
Topics: Aged; Aged, 80 and over; Diagnosis, Differential; Female; Giant Cell Arteritis; Glucocorticoids; Humans; Incidence; Male; Medical History Taking; Middle Aged; Polymyalgia Rheumatica; Prednisone
PubMed: 34810164
DOI: 10.1503/cmaj.210541 -
Clinical & Experimental Optometry Sep 2020Temporal arteritis (TA), or giant cell arteritis, is a systemic autoimmune vasculitis affecting patients over 50 years of age. It can cause rapid, irreversible... (Review)
Review
Temporal arteritis (TA), or giant cell arteritis, is a systemic autoimmune vasculitis affecting patients over 50 years of age. It can cause rapid, irreversible bilateral vision loss in older adults and is therefore considered an ophthalmological emergency. Many of the symptoms and signs of TA can be vague, non-specific and gradual in onset, often leading to a delayed or inaccurate diagnosis. As such, it is important for a wide variety of primary optometrists and health practitioners to maintain a robust understanding of the clinical presentation, key investigations and time-sensitive management of this disease, as early initiation of treatment for TA can be vision- and life-saving.
Topics: Biopsy; Diagnosis, Differential; Disease Management; Giant Cell Arteritis; Humans; Positron Emission Tomography Computed Tomography; Temporal Arteries
PubMed: 31663193
DOI: 10.1111/cxo.12975 -
BMJ (Clinical Research Ed.) Jan 2022To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.
DESIGN
Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design.
SETTING
Nationwide in the United States.
PARTICIPANTS
25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment.
INTERVENTIONS
Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence.
MAIN OUTCOME MEASURES
The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.
RESULTS
25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.
CONCLUSIONS
Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).
STUDY REGISTRATION
ClinicalTrials.gov NCT01351805 and NCT01169259.
Topics: Aged; Autoimmune Diseases; Cholecalciferol; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Treatment Outcome
PubMed: 35082139
DOI: 10.1136/bmj-2021-066452 -
Circulation Research Jan 2023Giant cell arteritis is an autoimmune disease of medium and large arteries, characterized by granulomatous inflammation of the three-layered vessel wall that results in... (Review)
Review
Giant cell arteritis is an autoimmune disease of medium and large arteries, characterized by granulomatous inflammation of the three-layered vessel wall that results in vaso-occlusion, wall dissection, and aneurysm formation. The immunopathogenesis of giant cell arteritis is an accumulative process in which a prolonged asymptomatic period is followed by uncontrolled innate immunity, a breakdown in self-tolerance, the transition of autoimmunity from the periphery into the vessel wall and, eventually, the progressive evolution of vessel wall inflammation. Each of the steps in pathogenesis corresponds to specific immuno-phenotypes that provide mechanistic insights into how the immune system attacks and damages blood vessels. Clinically evident disease begins with inappropriate activation of myeloid cells triggering the release of hepatic acute phase proteins and inducing extravascular manifestations, such as muscle pains and stiffness diagnosed as polymyalgia rheumatica. Loss of self-tolerance in the adaptive immune system is linked to aberrant signaling in the NOTCH pathway, leading to expansion of NOTCH1CD4 T cells and the functional decline of NOTCH4 T regulatory cells (Checkpoint 1). A defect in the endothelial cell barrier of adventitial vasa vasorum networks marks Checkpoint 2; the invasion of monocytes, macrophages and T cells into the arterial wall. Due to the failure of the immuno-inhibitory PD-1 (programmed cell death protein 1)/PD-L1 (programmed cell death ligand 1) pathway, wall-infiltrating immune cells arrive in a permissive tissues microenvironment, where multiple T cell effector lineages thrive, shift toward high glycolytic activity, and support the development of tissue-damaging macrophages, including multinucleated giant cells (Checkpoint 3). Eventually, the vascular lesions are occupied by self-renewing T cells that provide autonomy to the disease process and limit the therapeutic effectiveness of currently used immunosuppressants. The multi-step process deviating protective to pathogenic immunity offers an array of interception points that provide opportunities for the prevention and therapeutic management of this devastating autoimmune disease.
Topics: Humans; Giant Cell Arteritis; Inflammation; Arteries; Immunity, Innate; Giant Cells
PubMed: 36656970
DOI: 10.1161/CIRCRESAHA.122.322128 -
Medicina (Kaunas, Lithuania) Oct 2023Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA... (Review)
Review
Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA presents unique clinical features, including a more equitable distribution of sexes, a potential predilection for male involvement, a higher incidence of acute onset characterized by constitutional symptoms, a propensity for systemic manifestations, elevated sedimentation rates at disease onset, a reduced occurrence of rheumatoid factor positivity, increased titers of anti-citrullinated protein antibodies, a preference for involvement of large joints, elevated disease activity, the presence of bone erosions, and heightened patient disability. RA is recognized to consist of three partially overlapping subsets. One subset mirrors the classical RA clinical presentation, while the remaining subsets exhibit either a polymyalgia rheumatica-like phenotype or present with remitting seronegative symmetrical synovitis accompanied by pitting edema syndrome. In the initial stages of EORA management, non-steroidal anti-inflammatory drugs (NSAIDs) are not typically the first-line treatment choice, because seniors are much more prone to develop side effects due to NSAIDs, and the use of NSAIDs is in reality contraindicated to the majority of seniors due to comorbidities. Disease-modifying antirheumatic drugs (DMARDs), frequently methotrexate, are introduced immediately after the diagnosis is made. In cases where elderly patients demonstrate resistance to conventional DMARD therapy, the introduction of biological or targeted synthetic DMARDs becomes a viable treatment option. EORA presents a unique clinical profile, necessitating tailored treatment strategies. Our study emphasizes the challenges of NSAID use in seniors, highlighting the imperative shift toward DMARDs such as methotrexate. Future research should explore personalized DMARD approaches based on disease activity, comorbidities, and safety considerations, aiming to optimize treatment outcomes and minimize glucocorticoid reliance, thereby enhancing the quality of care for EORA patients.
Topics: Aged; Humans; Male; Middle Aged; Methotrexate; Arthritis, Rheumatoid; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Treatment Outcome
PubMed: 37893596
DOI: 10.3390/medicina59101878 -
Deutsches Arzteblatt International Jun 2022Polymyalgia rheumatica (PMR) is among the most common inflammatory rheumatic diseases in older adults. Presumed risk factors include female sex, previous infections, and... (Review)
Review
BACKGROUND
Polymyalgia rheumatica (PMR) is among the most common inflammatory rheumatic diseases in older adults. Presumed risk factors include female sex, previous infections, and genetic factors. No epidemiological data on PMR in Germany have been available until now.
METHODS
This review is based on publications retrieved by a selective literature search in PubMed. Moreover, the administrative incidence and prevalence of PMR in the years 2011-2019 was determined from data of the AOK Baden-Württemberg statutory health insurance carrier for insurees aged 40 and older. In addition, we quantified the number of consultations with physicians involved in the diagnosis.
RESULTS
The annual age- and sex-standardized incidence and prevalence of PMR from 2011 to 2019 were 18.6/100 000 persons and 138.8/100 000 persons, respectively. The incidence was higher in women than in men (21.8/100 000 vs. 12.8/100 000 persons per year). 60% of the cases were diagnosed in primary care practices. The treatment of PMR with orally administered glucocorticoids usually results in a treatment response within a few days to weeks. Approximately 43% of patients experience recurrent symptoms within a year, requiring adjustment of the glucocorticoid dose. For older patients with impaired physical ability, additional non-pharmacological treatment with exercise programs plays an important role.
CONCLUSION
PMR usually takes an uncomplicated course under treatment and can be managed in primary care, but these patients are often multimorbid and require frequent follow-up. Along with research on the etiology of the disease, further studies are needed to identify the risk factors for a chronic course and to evaluate the potential effects of non-pharmacological measures.
Topics: Adult; Aged; Female; Giant Cell Arteritis; Glucocorticoids; Humans; Incidence; Male; Middle Aged; Polymyalgia Rheumatica; Prevalence
PubMed: 35635433
DOI: 10.3238/arztebl.m2022.0218 -
Annals of the Rheumatic Diseases Jan 2021Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the...
BACKGROUND
Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.
METHODS
First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.
RESULTS
The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies.
CONCLUSION
These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.
Topics: Advisory Committees; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthralgia; Arthritis, Psoriatic; Arthritis, Reactive; Autoantibodies; Decision Making, Shared; Deprescriptions; Europe; Glucocorticoids; Humans; Immune Checkpoint Inhibitors; Immunoglobulins, Intravenous; Immunologic Factors; Medical Oncology; Methotrexate; Myalgia; Myocarditis; Myositis; Neoplasms; Plasma Exchange; Polymyalgia Rheumatica; Rheumatic Diseases; Rheumatology; Severity of Illness Index; Societies, Medical; Tumor Necrosis Factor Inhibitors
PubMed: 32327425
DOI: 10.1136/annrheumdis-2020-217139