-
Journal of Autoimmunity May 2024In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR...
OBJECTIVE
In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR symptoms in the metabolite signatures of peripheral blood from patients with PMR or the related disease, giant cell arteritis (GCA).
METHODS
Nuclear magnetic resonance spectroscopy was performed on serum from 40 patients with untreated PMR, 84 with new-onset confirmed GCA, and 53 with suspected GCA who later were clinically confirmed non-GCA, and 39 age-matched controls. Further samples from PMR patients were taken one and six months into glucocorticoid therapy to explore relationship of metabolites to persistent fatigue. 100 metabolites were identified using Chenomx and statistical analysis performed in SIMCA-P to examine the relationship between metabolic profiles and, disease, GC treatment or symptoms.
RESULTS
The metabolite signature of patients with PMR and GCA differed from that of age-matched non-inflammatory controls (R > 0.7). There was a smaller separation between patients with clinically confirmed GCA and those with suspected GCA who later were clinically confirmed non-GCA (R = 0.135). In PMR, metabolite signatures were further altered with glucocorticoid treatment (R = 0.42) but did not return to that seen in controls. Metabolites correlated with CRP, pain, stiffness, and fatigue (R ≥ 0.39). CRP, pain, and stiffness declined with treatment and were associated with 3-hydroxybutyrate and acetoacetate, but fatigue did not. Metabolites differentiated patients with high and low fatigue both before and after treatment (R > 0.9). Low serum glutamine was predictive of high fatigue at both time points (0.79-fold change).
CONCLUSION
PMR and GCA alter the metabolite signature. In PMR, this is further altered by glucocorticoid therapy. Treatment-induced metabolite changes were linked to measures of inflammation (CRP, pain and stiffness), but not to fatigue. Furthermore, metabolite signatures distinguished patients with high or low fatigue.
PubMed: 38797046
DOI: 10.1016/j.jaut.2024.103260 -
Journal of Personalized Medicine Apr 2024Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown etiology, sharing symptoms with giant cell arthritis (GCA) and rheumatoid arthritis (RA). The...
Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown etiology, sharing symptoms with giant cell arthritis (GCA) and rheumatoid arthritis (RA). The pathogenic inflammatory roots are still not well understood, and there is a lack of extensive biomarker studies to explain the disease debut and post-acute phase. This study aimed to deeply analyze the serum proteome and inflammatory response of PMR patients before and after glucocorticoid treatment. We included treatment-naïve PMR patients, collecting samples before and after 3 months of treatment. For comparison, disease-modifying antirheumatic drug (DMARD)-naïve RA patients were included and matched to healthy controls (CTL). The serum proteome was examined using label-free quantitative mass spectrometry, while inflammation levels were assessed using multiplex inflammatory cytokine and cell-free DNA assays. The serum proteomes of the four groups comprised acute phase reactants, coagulation factors, complement proteins, immunoglobulins, and apolipoproteins. Serum amyloid A (SAA1) was significantly reduced by active PMR treatment. Cell-free DNA levels in PMR and RA groups were significantly higher than in healthy controls due to acute inflammation. Complement factors had minimal changes post-treatment. The individual serum proteome in PMR patients showed over 100 abundantly variable proteins, emphasizing the systemic impact of PMR disease debut and the effect of treatment. Interleukin (IL)-6 and interferon-gamma (IFN-γ) were significantly impacted by glucocorticoid treatment. Our study defines the PMR serum proteome during glucocorticoid treatment and highlights the role of SAA1, IL-6, and IFN-γ in treatment responses. An involvement of PGLYRP2 in acute PMR could indicate a response to bacterial infection, highlighting its role in the acute phase of the immune response. The results suggest that PMR may be an aberrant response to a bacterial infection with an exacerbated IL-6 and acute phase inflammatory response and molecular attempts to limit the inflammation.
PubMed: 38793033
DOI: 10.3390/jpm14050449 -
Rheumatology (Oxford, England) May 2024Polymyalgia rheumatica (PMR) is an age-related inflammatory disease of unknown cause. We aimed to identify potentially modifiable risk factors and therapeutic targets...
OBJECTIVE
Polymyalgia rheumatica (PMR) is an age-related inflammatory disease of unknown cause. We aimed to identify potentially modifiable risk factors and therapeutic targets for preventing or treating PMR.
METHODS
We meta-analysed genetic association data from 8,156 cases of PMR (defined using diagnostic codes and self-report) and 416,495 controls of European ancestry from the UK Biobank and FinnGen. We then performed Mendelian randomization analyses to estimate the association between eight modifiable risk factors (using data from up to 1.2 million individuals) and 65 inflammation-related circulating proteins (up to 55,792 individuals), using the inverse variance weighted and pleiotropy robust methods.
RESULTS
We identified three novel genome-wide significant loci in the IL1R1, NEK6 and CCDC88B genes and confirmation of previously described associations with HLA-DRB1 and ANKRD55. Genetically predicted smoking intensity (OR 1.32; 95%CI 1.08-1.60; p = 0.006) and visceral adiposity (OR 1.22; 95%CI 1.10-1.37; p = 3.10x10-4) were associated with PMR susceptibility. Multiple circulating proteins related to IL-1 family signaling were associated with PMR. IL-1 receptor-like 2, also known as IL-36 receptor (OR 1.25; p = 1.89x10-32), serum amyloid A2 (OR 1.06, 9.91x10-10) and CXCL6 (OR 1.09, p = 4.85x10-7) retained significance after correction for multiple testing.
CONCLUSION
Reducing smoking and visceral adiposity at a population level might reduce incidence of PMR. We identified proteins that may play causal roles in PMR, potentially suggesting new therapeutic opportunities. Further research is needed before these findings are applied to clinical practice.
PubMed: 38788669
DOI: 10.1093/rheumatology/keae308 -
Cureus Apr 2024The primary treatment of choice for polymyalgia rheumatica (PMR) is corticosteroids, which are better avoided for elderly patients susceptible to PMR. The cases of five...
The primary treatment of choice for polymyalgia rheumatica (PMR) is corticosteroids, which are better avoided for elderly patients susceptible to PMR. The cases of five patients cured with only a small dosage of 600 mg/day ibuprofen without steroids or methotrexate are reported. Their clinical features were compared with those of the 26 PMR patients who had steroids and/or methotrexate in addition to ibuprofen. PMR was diagnosed based on the 2015 EULAR/ACR criteria. They were all females aged 73-80. They all had no giant cell arteritis or autoantibodies. Nonsteroidal anti-inflammatory drugs (NSAIDs) other than ibuprofen had not worked in four cases; for the one, ibuprofen was the first NSAID. Their serum CRP levels were 1.57-12.8 mg/dL at ibuprofen introduction. Colchicine was co-administered in two patients. At the next visit three to seven days after ibuprofen introduction, they all showed a clear recovery with a CRP level decrease. Ibuprofen tapering was started within three months, and no relapse was until two to five years' follow-up. Comparison with the 26 patients who had additional steroid and/or methotrexate showed that the disease duration until ibuprofen introduction was statistically significantly shorter in the five patients (1.40±0.65 vs 3.28±2.98 months). Ibuprofen would be the first-line drug for PMR, and its earliest use would be beneficial.
PubMed: 38784367
DOI: 10.7759/cureus.58778 -
Expert Review of Clinical Immunology May 2024Giant cell arteritis (GCA) is a large vessel (LV) vasculitis that affects people aged 50 years and older. Classically, GCA was considered a disease that involved... (Review)
Review
INTRODUCTION
Giant cell arteritis (GCA) is a large vessel (LV) vasculitis that affects people aged 50 years and older. Classically, GCA was considered a disease that involved branches of the carotid artery. However, the advent of new imaging techniques has allowed us to reconsider the clinical spectrum of this vasculitis.
AREASCOVERED
This review describes clinical differences between patients with the cranial GCA and those with a predominantly extracranial LV-GCA disease pattern. It highlights differences in the frequency of positive temporal artery biopsy depending on the predominant disease pattern and emphasizes the relevance of imaging techniques to identify patients with LV-GCA without cranial ischemic manifestations. The review shows that so far there are no well-established differences in genetic predisposition to GCA regardless of the predominant phenotype.
EXPERT COMMENTARY
The large branches of the extracranial arteries are frequently affected in GCA. Imaging techniques are useful to identify the presence of 'silent' GCA in people presenting with polymyalgia rheumatica or with nonspecific manifestations. Whether these two different clinical presentations of GCA constitute a continuum in the clinical spectrum of the disease or whether they may be related but are definitely different conditions needs to be further investigated.
PubMed: 38757894
DOI: 10.1080/1744666X.2024.2356741 -
Internal Medicine Journal May 2024
Topics: Humans; Giant Cell Arteritis; Polymyalgia Rheumatica; Australia; Aged; Female; Male; Aged, 80 and over; Time Factors; Middle Aged; Retrospective Studies
PubMed: 38757207
DOI: 10.1111/imj.16400 -
Tidsskrift For Den Norske Laegeforening... May 2024A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a...
BACKGROUND
A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review.
CASE PRESENTATION
The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level.
INTERPRETATION
Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.
Topics: Humans; Medication Errors; Female; Methotrexate; Aged; Dyspnea; Leucovorin; Antidotes; Antirheumatic Agents
PubMed: 38747669
DOI: 10.4045/tidsskr.23.0657 -
International Journal of Rheumatic... May 2024Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used...
BACKGROUND
Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination.
METHODS
A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio.
RESULTS
Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs.
CONCLUSION
This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination.
Topics: Humans; Male; Female; Middle Aged; COVID-19 Vaccines; Autoimmune Diseases; Cross-Sectional Studies; COVID-19; Aged; Adult; Vaccination; Risk Factors; SARS-CoV-2
PubMed: 38742751
DOI: 10.1111/1756-185X.15178 -
Rheumatology (Oxford, England) May 2024
Comment on: Immune checkpoint inhibitor-mediated polymyalgia rheumatica versus primary polymyalgia rheumatica: comparison of disease characteristics and treatment requirement. Reply.
PubMed: 38741187
DOI: 10.1093/rheumatology/keae261 -
Vaccine Jul 2024A large vaccination campaign was initiated worldwide in December 2020 in order to prevent infection with SARS-CoV-2 and severe Covid-19 disease. However, long-term...
BACKGROUND
A large vaccination campaign was initiated worldwide in December 2020 in order to prevent infection with SARS-CoV-2 and severe Covid-19 disease. However, long-term adverse effects of vaccination remain unclear. Therefore, our objective was to examine the association between vaccination and the incidence of autoimmune diagnoses in the first year after vaccine uptake.
METHODS
This retrospective cohort study based on Clalit Health Services (CHS) comprehensive database compared the rates of immune-mediated diagnoses among BNT162b2 vaccinated versus unvaccinated individuals. As a reference, a secondary cohort compared individuals infected with Sars-CoV-2 versus uninfected individuals. The minimum follow-up period was 4 months. The cohorts were divided into 4 age groups (12-17, 18-44, 45-64, 65 years or older). Multivariate Cox proportional hazard regression models were applied, followed by a correction for multiple comparisons using the False Discovery Rate (FDR) method, hence accounting for the investigation of multiple clinical outcomes.
RESULTS
Increased risk for immune-mediated diagnoses following vaccination with BNT162b2 was observed for psoriasis in all age groups (HR 1.41-1.69), colitis among patients younger than 65 years (HR 1.38-1.93), vitiligo in patients aged 45-64 (HR 2.82, 95 %CI: 1.57-5.08) and for polymyalgia-rheumatica in patients aged 65 years or older (HR 2.12, 95 % CI: 1.3-3.47). In the reference cohort, patients who were infected by Covid-19 were at increased risk for fibromyalgia (HR 1.72, 95 % CI: 1.36-2.19 in individuals aged 18-44; HR 1.71, 95 % CI: 1.31-2.22 in individuals aged 45-64), and hypothyroidism (HR 1.54, 95 % CI: 1.15-2.07 in individuals aged 65 years or older).
CONCLUSIONS
The BNT162b2 vaccine was associated with increased risk (though rare) for psoriasis, colitis and polymyalgia rheumatica. These findings should be considered as a part of the risk-benefit assessment when planning future vaccination programs for various population groups.
Topics: Humans; BNT162 Vaccine; Middle Aged; Retrospective Studies; Male; Adult; Female; COVID-19; Aged; Adolescent; Young Adult; Incidence; Child; Vaccination; SARS-CoV-2; Comorbidity; Autoimmune Diseases; COVID-19 Vaccines; Psoriasis
PubMed: 38729910
DOI: 10.1016/j.vaccine.2024.04.097