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Journal of Autoimmunity Nov 2023The lack of disease-specific autoantibodies in giant cell arteritis (GCA) suggests an alternative role for B-cells readily detected in the inflamed arteries. Here we...
OBJECTIVE
The lack of disease-specific autoantibodies in giant cell arteritis (GCA) suggests an alternative role for B-cells readily detected in the inflamed arteries. Here we study the cytokine profile of tissue infiltrated and peripheral blood B-cells of patients with GCA. Moreover, we investigate the macrophage skewing capability of B-cell-derived cytokines.
METHODS
The presence of various cytokines in B-cell areas in temporal artery (n = 11) and aorta (n = 10) was identified by immunohistochemistry. PBMCs of patients with GCA (n = 11) and polymyalgia rheumatica (n = 10), and 14 age- and sex-matched healthy controls (HC) were stimulated, followed by flow cytometry for cytokine expression in B-cells. The skewing potential of B-cell-derived cytokines (n = 6 for GCA and HC) on macrophages was studied in vitro.
RESULTS
The presence of IL-6, GM-CSF, TNFα, IFNγ, LTβ and IL-10 was documented in B-cells and B-cell rich areas of GCA arteries. In vitro, B-cell-derived cytokines (from both GCA and HC) skewed macrophages towards a pro-inflammatory phenotype with enhanced expression of IL-6, IL-1β, TNFα, IL-23, YKL-40 and MMP-9. In vitro stimulated peripheral blood B-cells from treatment-naïve GCA patients showed an enhanced frequency of IL-6+ and TNFα+IL-6+ B-cells compared to HCs. This difference was no longer detected in treatment-induced remission. Erythrocyte sedimentation rate positively correlated with IL-6+TNFα+ B-cells.
CONCLUSION
B-cells are capable of producing cytokines and steering macrophages towards a pro-inflammatory phenotype. Although the capacity of B-cells in skewing macrophages is not GCA specific, these data support a cytokine-mediated role for B-cells in GCA and provide grounds for B-cell targeted therapy in GCA.
Topics: Humans; Giant Cell Arteritis; Cytokines; Macrophages; B-Lymphocytes; Female; Male; Aged; Temporal Arteries; Aged, 80 and over; Middle Aged
PubMed: 37703805
DOI: 10.1016/j.jaut.2023.103111 -
European Journal of Case Reports in... 2022Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are both rheumatological diseases of the elderly with a strong association with each other and which rarely...
UNLABELLED
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are both rheumatological diseases of the elderly with a strong association with each other and which rarely present with normal inflammatory markers. Here we present the case of a 61-year-old Caucasian woman who had typical symptoms of both diseases. At the time of presentation, her blood work showed normal inflammatory markers, but because of the high clinical suspicion for GCA, a temporal artery biopsy was done which was positive for giant cells and disruption of the internal elastic lamina. Our patient responded very well to treatment with oral steroids and steroid-sparing medication and was able to return to her normal life without experiencing any complications of the disease. By sharing our case, we aim to increase the awareness of medical personnel regarding the importance of focusing on the clinical presentation as well as the laboratory and pathological aspects of diagnosing GCA and PMR.
LEARNING POINTS
Normal levels of inflammatory markers like C-reactive protein and the erythrocyte sedimentation rate do not rule out the diagnosis of giant cell arteritis (GCA).We aim to increase clinician recognition and awareness of other parameters, particularly the clinical presentation, that should be considered when diagnosing GCA or polymyalgia rheumatica.If the index of suspicion for the disease is high, it is crucial to start treatment as early as possible for better management and to avoid harmful complications.
PubMed: 35265557
DOI: 10.12890/2022_003192 -
Reumatologia 2021
PubMed: 35280453
DOI: 10.5114/reum.2021.110221 -
Internal Medicine (Tokyo, Japan) Sep 2021
Topics: Diagnosis, Differential; Giant Cell Arteritis; Humans; Hypertrophy; Polymyalgia Rheumatica; Sternoclavicular Joint
PubMed: 33814497
DOI: 10.2169/internalmedicine.6860-20 -
Medicine Sep 2023Polymyalgia Rheumatica (PMR) is an inflammatory disease which does not have specific diagnostic tests or pathological symptoms and is identified based on clinical...
Polymyalgia Rheumatica (PMR) is an inflammatory disease which does not have specific diagnostic tests or pathological symptoms and is identified based on clinical characteristics. Among acute phase reactants (APR), the erythrocyte sedimentation rate (ESR) and C-Reactive Protein (CRP) are laboratory findings used in diagnosis and follow-up. In this study, it was aimed to determine the incidence of normal ESH and CRP in patients diagnosed with PMR and identify the distinguishing characteristics of these patients. PMR patients who were clinically diagnosed at a single center were reviewed. After the presence of bursitis was demonstrated with ultrasonography in patients with normal ESR and CRP rates, they were accepted to have PMR. Among all 54 patients (63% female), ESR and CRP values were normal in 8 patients (14%), and serum amyloid A (SAA) was determined to be elevated in all these patients. In the comparisons of the groups with normal and high levels of ESR and CRP, it was found that the group with normal ESR and CRP values had a younger age of diagnosis (P = .027), a longer symptom duration (P < .001), and a lower comorbidity rate (P = .010). PMR patients can have normal ESR and CRP values at the time of their diagnosis. While bursitis can be demonstrated with ultrasonography in patients who are clinically evaluated to have PMR, APRs such as SAA other than ESR and CRP can also be used.
Topics: Humans; Female; Male; Polymyalgia Rheumatica; C-Reactive Protein; Blood Sedimentation; Giant Cell Arteritis; Bursitis; Serum Amyloid A Protein
PubMed: 37773830
DOI: 10.1097/MD.0000000000035385 -
Rheumatology (Oxford, England) Feb 2024To inform an international task force about current evidence on Treat to Target (T2T) strategies in PMR and GCA.
OBJECTIVES
To inform an international task force about current evidence on Treat to Target (T2T) strategies in PMR and GCA.
METHODS
A systematic literature research (SLR) was conducted in Medline, EMBASE, Cochrane Library, clinicaltrials.gov from their inception date to May 2022, and in the EULAR/ACR abstract database (2019-2021). Randomised clinical trials (RCTs) and non-randomised interventional studies published in English and answering at least one of the eleven PICO questions on T2T strategies, treatment targets and outcomes, framed by the taskforce, were identified. Study selection process, data extraction and risk of bias assessment were conducted independently by two investigators.
RESULTS
Of 7809 screened abstracts, 397 were selected for detailed review and 76 manuscripts were finally included (31 RCTs, eight subgroup/exploratory analyses of RCTs and 37 non-randomised interventional studies). No study comparing a T2T strategy against standard of care was identified. In PMR RCTs, the most frequently applied outcomes concerned treatment (90.9% of RCTs), particularly the cumulative glucocorticoids (GC) dose and GC tapering, followed by clinical, laboratory and safety outcomes (63.3% each). Conversely, the most commonly reported outcomes in RCTs in GCA were prevention of relapses (72.2%), remission as well as treatment-related and safety outcomes (67.0% each).
CONCLUSIONS
This SLR provides evidence and highlights the knowledge gaps on T2T strategies in PMR and GCA, informing the task force developing T2T recommendations for these diseases.
Topics: Humans; Giant Cell Arteritis; Polymyalgia Rheumatica; Glucocorticoids
PubMed: 37672017
DOI: 10.1093/rheumatology/kead471 -
Frontiers in Immunology 2022Although polymyalgia rheumatica (PMR) is a very common rheumatic inflammatory disease, current insight into the pathobiology of PMR is limited and largely based on...
BACKGROUND
Although polymyalgia rheumatica (PMR) is a very common rheumatic inflammatory disease, current insight into the pathobiology of PMR is limited and largely based on studies in blood. We investigated T helper 1 (T) and T helper 17 (T) cell responses in blood, synovial fluid and bursa tissue of patients with PMR.
MATERIALS AND METHODS
Blood samples were collected from 18 patients with new-onset PMR and 32 healthy controls. Synovial fluid was aspirated from the inflamed shoulder bursae or biceps tendon sheath of 13 patients. Ultrasound-guided biopsies of the subacromial-subdeltoid (SASD) bursa were obtained from 11 patients. T cells were examined by flow cytometry, immunohistochemistry and immunofluorescence staining.
RESULTS
Besides an increase of T (CD4IL-17IFN-γ) cells and T cytotoxic 17 (T; CD8IL-17IFN-γ) cells, no other major changes were noted in the circulating T cell compartment of patients with PMR. Absolute numbers of CD4 and CD8 T cells were similar in blood and synovial fluid of patients with PMR. Synovial fluid T cells showed an effector-memory (CD45ROCCR7) phenotype. Percentages of T (CD4IFN-γIL-17) cells and T/T (CD4IFN-γIL-17) cells, but not T or T cells, were increased in the synovial fluid. Bursa tissue biopsies contained a small number of T cells, which were mostly CD8 negative. The majority of bursa tissue T cells produced IFN-γ but not IL-17. For comparison, B cells were scarcely detected in the bursa tissue.
CONCLUSION
Although the circulating T cell pool is expanded in patients with PMR, our findings indicate that T cells are involved in the inflammation of bursae and tendon sheaths in this condition. Our study points towards the T cell pathway as a potential target for therapy in PMR.
Topics: Bursitis; CD8-Positive T-Lymphocytes; Giant Cell Arteritis; Humans; Polymyalgia Rheumatica; Tenosynovitis
PubMed: 36032100
DOI: 10.3389/fimmu.2022.943574 -
Clinical Rheumatology Jan 2022A systematic review and meta-analysis were conducted, according to the PRISMA methodology, to summarize current evidence on the prevalence and predictors of long-term... (Meta-Analysis)
Meta-Analysis Review
Long-term glucocorticoid treatment and high relapse rate remain unresolved issues in the real-life management of polymyalgia rheumatica: a systematic literature review and meta-analysis.
A systematic review and meta-analysis were conducted, according to the PRISMA methodology, to summarize current evidence on the prevalence and predictors of long-term glucocorticoid (GC) treatment and disease relapses in the real-life management of polymyalgia rheumatica (PMR).Out of 5442 retrieved studies, 21 were eligible for meta-analysis and 24 for qualitative analysis. The pooled proportions of patients still taking GCs at 1, 2, and 5 years were respectively 77% (95%CI 71-83%), 51% (95%CI 41-61%), and 25% (95CI% 15-36%). No significant difference was recorded by distinguishing study cohorts recruited before and after the issue of the international recommendations in 2010. The pooled proportion of patients experiencing at least one relapse at 1 year from treatment initiation was 43% (95%CI 29-56%). Female gender, acute-phase reactants levels, peripheral arthritis, starting GCs dosage, and tapering speed were the most frequently investigated potential predictors of prolonged GC treatment and relapse, but with inconsistent results. Only a few studies and with conflicting results evaluated the potential role of early treatment with methotrexate in reducing the GC exposure and the risk of relapse in PMR.This study showed that a high rate of prolonged GC treatment is still recorded in the management of PMR. The relapse rate, even remarkable, can only partially explain the long-term GC treatment, suggesting that other and not yet identified factors may be involved. Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies. Key Points: • High rate of long-term glucocorticoid (GC) treatment is recorded in polymyalgia rheumatica (PMR), being 77%, 51%, and 25% of patients still on GCs after respectively 1, 2, and 5 years. • A pooled relapse rate of 43% at 1 year, even remarkable, can only partially explain the long-term GC treatment in PMR. • Several studies have attempted to identify potential predictors of prolonged treatment with GCs and relapse, but with inconsistent results. • Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies.
Topics: Drug Administration Schedule; Female; Giant Cell Arteritis; Glucocorticoids; Humans; Polymyalgia Rheumatica; Recurrence
PubMed: 34415462
DOI: 10.1007/s10067-021-05819-z -
Frontiers in Medicine 2021Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and... (Review)
Review
Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.
PubMed: 34805229
DOI: 10.3389/fmed.2021.762247 -
Joint Bone Spine May 2024We aimed to describe the following in patients with polymyalgia rheumatica (PMR): (1) real-world glucocorticoid (GC) therapy, (2) improvement in inflammatory parameters...
OBJECTIVE
We aimed to describe the following in patients with polymyalgia rheumatica (PMR): (1) real-world glucocorticoid (GC) therapy, (2) improvement in inflammatory parameters associated with disease activity (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), and (3) incidence of GC-related adverse events (AEs).
METHODS
A cohort study was conducted using a Japanese electronic medical records database. We included newly diagnosed PMR patients aged≥50years with baseline CRP levels≥10mg/L and/or ESR>30mm/h and an initial GC dose of≥5mg/day. The outcomes were GC dose, inflammatory parameters, and GC-related AEs.
RESULTS
A total of 373 PMR patients (mean age, 77.3 years) were analyzed. The median initial GC dose was 15.0mg/day, which gradually decreased to 3.5mg/day by week 52. The median cumulative GC dose at week 52 was 2455.0mg. The median CRP level on day 0 was 64.3mg/L, which decreased during weeks 4-52 (1.4-3.2mg/L). At week 52, 39.0% of patients had a CRP level>3.0mg/L. The cumulative incidence of GC-related AEs at week 52 was 49.0% for osteoporosis, 30.2% for diabetes, 14.9% for hypertension, 12.2% for peptic ulcer, 11.3% for dyslipidemia, 2.9% for glaucoma, and 4.3% for serious infection. The incidence of osteoporosis and diabetes increased with the GC dose.
CONCLUSION
The incidence of GC-related AEs was associated with the GC dose in PMR patients. Further research is required to identify treatment strategies that can effectively control PMR disease activity while minimizing GC use.
Topics: Humans; Polymyalgia Rheumatica; Male; Female; Aged; Glucocorticoids; Middle Aged; Treatment Outcome; Cohort Studies; Aged, 80 and over; Japan; C-Reactive Protein; Retrospective Studies; Blood Sedimentation; Dose-Response Relationship, Drug; Severity of Illness Index
PubMed: 38143016
DOI: 10.1016/j.jbspin.2023.105680