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Clinical Nephrology. Case Studies 2023We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of...
PURPOSE
We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition.
OBSERVATIONS
We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis.
CONCLUSION AND IMPORTANCE
These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).
PubMed: 38169875
DOI: 10.5414/CNCS111088 -
Mediterranean Journal of Rheumatology Dec 2023Polymyalgia Rheumatica (PMR) and Giant Cell Arteritis (GCA) are chronic inflammatory disorders that usually affect older people. Although the aetiology of these diseases...
Polymyalgia Rheumatica (PMR) and Giant Cell Arteritis (GCA) are chronic inflammatory disorders that usually affect older people. Although the aetiology of these diseases remains unknown, genetic, environmental, and immune factors have been implicated. Specific cytokines such as the IL-6, IL-1β, IL-12, IL-17, and interferon -γ seem to play an essential role. The diagnosis of the disease is usually based on clinical manifestations and the use of histology or imaging, while disease monitoring is based on physical examination, laboratory, and imaging findings. However, there is the unmet need in identifying possible biomarkers that could help the diagnosis and the monitoring as well. The present study aims to investigate the epidemiological, clinical, and immunological characteristics of PMR and/or GCA patients in the region of northwest Greece and to evaluate the role of specific molecules associated with the pathogenesis of the diseases, giving evidence to possible future biomarkers.
PubMed: 38282939
DOI: 10.31138/mjr.050923.csa -
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 -
International Medical Case Reports... 2023Polymyalgia rheumatica (PMR) is a systemic inflammatory disease of the elderly population that increases in incidence as age advances. It is characterised by the sudden...
Polymyalgia rheumatica (PMR) is a systemic inflammatory disease of the elderly population that increases in incidence as age advances. It is characterised by the sudden or sub-acute onset of symptoms affecting the shoulder and pelvic girdles, often accompanied by constitutional symptoms. Due to the lack of consensual diagnostic criteria and specific laboratory or radiological investigations for PMR, its diagnosis can be very challenging, particularly because it can be mimicked or masked by other geriatric syndromes. PMR responds well to glucocorticoid treatment, but if left untreated, can lead to morbidity and poor quality of life. We present the case of an 87-year-old male who presented with a one-week history of localised pain in the left hip joint, later involving the contralateral hip. Previously able to ambulate unaided, his mobility was now severely impaired. Due to his Alzheimer's dementia and multiple comorbid geriatric conditions, extensive investigations were undertaken before a diagnosis of atypical PMR was reached. Treatment with a low dose of prednisolone led to a full recovery. This case highlights the inconsistency between an atypical presentation and the classic presentation of PMR and draws attention to the possibility of missed diagnosis in older, frail patients. Atypical symptomatology on top of cognitive impairment and language barriers can be easily overlooked and left untreated and could lead to severe adverse outcomes. Accurate diagnosis is crucial, as PMR is readily diagnosed, but the treatment with glucocorticoids, though generally straightforward, can pose challenges, particularly when dealing with polypharmacy and multiple coexisting health conditions.
PubMed: 38163043
DOI: 10.2147/IMCRJ.S440486 -
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 -
Rheumatology Advances in Practice 2024The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to...
OBJECTIVES
The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina.
METHODS
A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed. Results are expressed as medians and interquartile ranges [25th-75th (IQR)] for continuous variables and percentages for categorical ones. The two treatment groups were compared using χ test for categorical variables, Mann-Whitney U test for continuous variables and the log-rank test for time-to-event data. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. In all cases, a -value <0.05 was considered statistically significant.
RESULTS
One-hundred and eighty-six patients (79% female) with a median age of 72 years (IQR, 65-77 years) were included. One-hundred and forty-three patients (77%) were prescribed MTX (15, IQR 10-15) and 43 (23%) LEF (20 mg, fixed dose). Flare-ups (relapses and recurrences) occurred in 13 patients (7%) and were comparable between both groups. Persistent GCSD intake was observed in 145 patients (78%). Glucocorticoid (GC) withdrawal was achieved in 67 of these 145 patients (46%) and this occurred more frequently in the LEF group (). Furthermore, time until prednisone discontinuation was shorter in the LEF-treated patients (4.7 months, IQR 3-20 on LEF versus 31.8 months, IQR 10-82 on MTX, ). Remission was found more frequently in the LEF group (). In the multivariate analysis, the probability of remission was higher with LEF therapy (=0.010) and this finding persisted in the subgroup analysis who were followed up < 40 months (OR 3.12, 95% CI = 1.30-7.47, = 0.011).
CONCLUSIONS
This study demonstrated the clinical effectiveness of LEF and even its superiority in achieving remission when compared with MTX as GCSD in PMR patients. Further research is needed to support these findings.
PubMed: 38560643
DOI: 10.1093/rap/rkae033 -
Seminars in Arthritis and Rheumatism Oct 2023To examine the test-retest reliability of four measurement instruments in polymyalgia rheumatica (PMR): pain severity visual analogue scale (VAS) / numerical rating...
OBJECTIVE
To examine the test-retest reliability of four measurement instruments in polymyalgia rheumatica (PMR): pain severity visual analogue scale (VAS) / numerical rating score (NRS), stiffness severity VAS/NRS, the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the modified Health Assessment Questionnaire (mHAQ).
METHOD
Two prospectively collected datasets were used. All participants had a diagnosis of PMR and only those with stable disease were included in analyses. Measurement instruments were administered twice, with a testing interval of two to six weeks. The intra-class correlation coefficient (ICC) was calculated using a two-way mixed effects model looking for absolute agreement. ICC values of 0.8-0.9 were deemed representative of good test-retest reliability, whilst values >0.9 were representative of excellent test-retest reliability.
RESULTS
From the first dataset, 38 participants were analysed. The ICC between baseline and 2 weeks for pain VAS, stiffness VAS, HAQ-DI and mHAQ were 0.84, 0.82, 0.92 and 0.92 respectively. From the second dataset, 58 participants were included in the analysis for pain NRS, 59 for stiffness NRS and 78 for mHAQ. The ICC between baseline and follow-up for pain NRS, stiffness NRS and mHAQ were 0.80, 0.83 and 0.87 respectively.
CONCLUSION
Pain severity VAS/NRS, stiffness severity VAS/NRS, HAQ-DI and mHAQ all demonstrate good to excellent test-retest reliability in a PMR patient population.
Topics: Humans; Polymyalgia Rheumatica; Reproducibility of Results; Giant Cell Arteritis; Pain; Surveys and Questionnaires
PubMed: 37429139
DOI: 10.1016/j.semarthrit.2023.152239 -
Rheumatology (Oxford, England) Nov 2023Giant Cell Arteritis-(GCA) is an inflammatory disease following a chronic, relapsing course. The metabolic alterations related to the intense inflammatory process during...
OBJECTIVES
Giant Cell Arteritis-(GCA) is an inflammatory disease following a chronic, relapsing course. The metabolic alterations related to the intense inflammatory process during the active phase and to the rapid impact of steroid treatment, remain unknown. The study aims to investigate the serum metabolome in active and inactive disease state.
METHODS
110 serum samples from 50 patients [33-GCA and 17-Polymyalgia rheumatica-(PMR)] at 3 time points, 0-(V1: active disease), 1 and 6 months-(V2 and V3: remission) of treatment with glucocorticosteroids (GCs), were subjected to Nuclear Magnetic Resonance (NMR)-based metabolomic analysis. Multi- and univariate statistical analyses were utilized to unveil metabolome alterations following treatment.
RESULTS
Distinct metabolic profiles were identified between activity and remission, independently to disease type. N-acetylglycoproteins and cholines of bound phospholipids, emerged as predictive markers of disease activity. Altered levels of 4 out of the 21 small molecules were also observed, including increased levels of phenylalanine, and decreased of glutamine, alanine, and creatinine in active disease. Metabolic fingerprinting discriminated GCA from PMR in remission. GCA and PMR patients exhibited characteristic lipid alterations as a response and/or adverse effect of GCs treatment. Correlation analysis showed that several identified biomarkers were further associated with acute phase reactants, C-Reactive Protein and Erythrocyte Sedimentation Rate.
CONCLUSION
The NMR profile of serum metabolome could identify and propose sensitive biomarkers of inflammation. Metabolome alterations, following GCs treatment, could provide predictors for future steroid-induced side effects.
PubMed: 37935429
DOI: 10.1093/rheumatology/kead590 -
Zeitschrift Fur Rheumatologie Mar 2024
Topics: Humans; Polymyalgia Rheumatica; Giant Cell Arteritis; Antibodies, Monoclonal, Humanized
PubMed: 38240818
DOI: 10.1007/s00393-024-01474-2