Acute Calcific Tendinitis of the Flexor Hallucis Brevis Associated With Muay Thai.

Calcific tendinitis manifesting in the foot and toes is a rare condition that often goes unnoticed, even by podiatric specialists and healthcare practitioners. Characterized by an acute onset, this condition presents with pronounced local inflammatory indicators accompanied by pain, often complicating its differentiation from other conditions. We document our experience with a 27-year-old female patient presenting with calcific tendinitis in the flexor hallucis brevis (FHB), along with a review of the relevant literature.

Refractory Dupilumab-Induced Inflammatory Arthritis Treated by Upadacitinib: A 'Janus Kinase (JAK)' of All Trades.

Dupilumab, a monoclonal interleukin (IL)-4 receptor α antagonist, is used to treat moderate-to-severe atopic dermatitis. Uncommonly, inflammatory arthritis and enthesitis may occur upon initiation of dupilumab. Upadacitinib, a Janus kinase (JAK) inhibitor, is an alternative medication approved for moderate-to-severe atopic dermatitis but is also used to treat inflammatory arthritis. We report a case of dupilumab-induced inflammatory arthritis that was refractory to oral nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids and was successfully treated by upadacitinib, which also treated the atopic dermatitis. A 40-year-old female with moderate-to-severe atopic dermatitis was treated with dupilumab for 10 months, showing improvement in her skin. However, she then developed recurrent right knee effusions, polyarthritis in her hands, feet, and knees, and prolonged stiffness. She noticed swelling which developed abruptly in her right knee, then progressed to multiple joints including fingers, wrists, ankles, and persisted for four weeks prior to seeking additional medical care. She denied any recent preceding trauma. Joint pain was worsened by movement and morning stiffness lasted over two hours. Trials of ibuprofen or celecoxib and application of ice did not alleviate it. She had an elevated erythrocyte sedimentation rate of 29 mm/hr and C-reactive protein of 21.6 mg/dL. She tested negative for antinuclear antibody, rheumatoid factor, anti-cyclic citrullinated protein, human leukocyte antigen B27, Lyme enzyme-linked immunosorbent assay (ELISA), and Western blot. She was initially treated with a prednisone taper, but the symptoms returned upon reaching 10 mg daily. She continued on dupilumab for four weeks, but stopped as the joint symptoms progressed. With cessation, her atopic dermatitis also became active again. Despite stopping the dupilumab, she continued to have diffuse swelling and tenderness in her hands, feet, knees, and wrists over the next 12 weeks. Upadacitinib, within one month of initiating, led to improvement in both joints and skin. She was able to taper off the corticosteroids. At five months, she continued to not have swelling or tenderness in her joints, and her skin was well-controlled. We report the first successful use of upadacitinib for the treatment of refractory dupilumab-induced inflammatory arthritis as well as atopic dermatitis. The use of JAK inhibitors should be considered to treat this uncommon condition, given that they also treat atopic dermatitis.

The real experience of reporting electronic patient-reported outcomes in patients with inflammatory arthritis and factors influencing participation: a scoping review.

Inflammatory arthritis can result in pain, stiffness, fatigue, and reduce quality of life. Frequent monitoring of disease activity is necessary for patients with inflammatory arthritis, and electronic patient-reported outcomes (ePROs) play a crucial role in this process. This study aimed to investigate the real experience of reporting ePROs in patients with inflammatory arthritis, as well as to identify factors influencing participation. The ultimate goal was to inform targeted strategies and develop interventions to enhance the utilization of ePROs in clinical settings. A scoping review was performed using PubMed, Web of science, Embase, and the Cochrane library from 2000 to the present and the literature search focused on the experience of reporting ePROs in inflammatory arthritis and the factors that influence participation. Screening articles based on inclusion and exclusion criteria. A total of 1478 studies were identified, out of which 26 were included in the review. The top experience of applications/platforms in patients was that they were easy to use and that the applications were clear, logical and intuitive. A summary of 18 potential influencing factors were identified and there was inconsistent evidence for five of these factors. The participation of reporting ePROs is influenced by various factors, and the experience is a crucial aspect in patients with inflammatory arthritis. Analyzing patients' experience and influencing factors provides a theoretical basis for future interventions to facilitate the clinical application of ePRO. However, further research is needed to fully understand the association between influencing factors and intervention outcomes.

The Contribution of Macrophage Plasticity to Inflammatory Arthritis and Their Potential as Therapeutic Targets.

Inflammatory arthritis are common chronic inflammatory autoimmune diseases characterised by progressive, destructive inflammation of the joints leading to a loss of function and significant comorbidities; importantly, there are no cures and only 20% of patients achieve drug-free remission for over 2 years. Macrophages play a vital role in maintaining homeostasis, however, under the wrong environmental cues, become drivers of chronic synovial inflammation. Based on the current "dogma", M1 macrophages secrete pro-inflammatory cytokines and chemokines, promoting tissue degradation and joint and bone erosion which over time lead to accelerated disease progression. On the other hand, M2 macrophages secrete anti-inflammatory mediators associated with wound healing, tissue remodelling and the resolution of inflammation. Currently, four subtypes of M2 macrophages have been identified, namely M2a, M2b, M2c and M2d. However, more subtypes may exist due to macrophage plasticity and the ability for repolarisation. Macrophages are highly plastic, and polarisation exists as a continuum with diverse intermediate phenotypes. This plasticity is achieved by a highly amenable epigenome in response to environmental stimuli and shifts in metabolism. Initiating treatment during the early stages of disease is important for improved prognosis and patient outcomes. Currently, no treatment targeting macrophages specifically is available. Such therapeutics are being investigated in ongoing clinical trials. The repolarisation of pro-inflammatory macrophages towards the anti-inflammatory phenotype has been proposed as an effective approach in targeting the M1/M2 imbalance, and in turn is a potential therapeutic strategy for IA diseases. Therefore, elucidating the mechanisms that govern macrophage plasticity is fundamental for the success of novel macrophage targeting therapeutics.

Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area.

OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.

Cardiovascular comorbidities in psoriatic arthritis: state of the art.

Psoriatic arthritis (PsA) is a complex multi-system immune-mediated condition, characterised by a high comorbidity burden, one of the most prevalent of which is cardiovascular disease (CVD), affecting up to 80% of patients. This narrative review explores the current understanding of cardiovascular comorbidities in PsA, focusing on mechanistic pathways, risk assessment, and the impact of treatment choices on cardiovascular health. Here, we outline the role of inflammatory cytokines, immune system dysregulation, and genetic predispositions in PsA, not only as drivers of musculoskeletal manifestations but also atherosclerosis and endothelial dysfunction, giving rise to cardiovascular pathology. Given these insights, accurately assessing and predicting cardiovascular risk in PsA patients is a critical challenge. This review evaluates traditional risk calculators as well as innovative biomarkers and imaging techniques, emphasising their utility and limitations in capturing the true cardiovascular risk profile of PsA patients. There are multiple complexities surrounding the treatment of PsA in the context of concurrent CVD, and therapeutic choices must carefully balance efficacy in managing PsA symptoms with the potential cardiovascular implications. A multidisciplinary approach, integrating dermatological, rheumatological, and cardiological perspectives, amongst others, to optimise patient outcomes, is key. Overall, a heightened clinical awareness and research focus on cardiovascular comorbidities in PsA is warranted, aiming to refine risk assessment strategies and therapeutic interventions that holistically address the multifaceted needs of patients with PsA.

Converting an HLA-B27 flow assay from the BD FACSCanto to the BD FACSLyric.

HLA-B27 is a major histocompatibility complex (MHC) class I antigen which exhibits strong association (90%) with ankylosing spondylitis. HLA-B27 detection in patients by flow cytometry is a widely used clinical test, performed on many different flow cytometer models. We sought to develop and validate a test conversion protocol for the HLA-B27 test performed on the BD FACSCanto to BD's newer FACSLyric flow cytometers. The development and validation experiments were performed using anti-HLA-B27*FITC/CD3*PE antibody-stained whole blood patient specimens. The anti-HLA-B27*FITC logarithmic median fluorescence (LMF) results on the BD FACSCanto were converted to median fluorescence intensity (MFI) values on the BD FACSLyric. Clustering of the HLA-B27 positive and negative values, using a 3rd order polynomial equation, resulted in a conversion of the BD FACSCanto cutoff values, negative (<150 LMF) and positive (≥160 LMF), to negative (<4530 MFI) and positive (≥6950 MFI) on the BD FACSLyric. Accuracy was assessed by comparing the flow results obtained on the BD FACSCanto and BD FACSLyric to a molecular PCR based assay. Additional validation parameters (compensation verification, intra- and inter-assay precision, and instrument comparison) were performed per the recommendations outlined in the Clinical and Laboratory Standards Institute (CLSI) H62 guidelines for validation of flow cytometry assays.

CHIKV infection drives shifts in the gastrointestinal microbiome and metabolites in rhesus monkeys.

BACKGROUND: Many studies have demonstrated the association between intestinal microbiota and joint diseases. The "gut-joint axis" also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. RESULTS: CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. CONCLUSION: Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract.

Utility of common investigations for suspected inflammatory arthritis in adults.

Inflammatory arthritis may be the principal feature or one component of an inflammatory rheumatological disease. It is a clinical diagnosis, principally made based on the patient's history and examination. Specific investigations, such as rheumatoid factor and human leucocyte antigen B27 gene, may support the diagnosis in the context of a suggestive clinical presentation, but a diagnosis cannot be made based on these tests alone because positive results may also be seen in healthy individuals. To reduce the likelihood of false positive results, laboratory and radiological investigations should be tailored to the suspected diagnosis based on pretest probability. While musculoskeletal symptoms are a common presentation in general practice, specific features that increase suspicion of an inflammatory arthritis include prolonged morning stiffness (more than 1 hour) that is improved by exercise or movement. A broad 'rheumatological panel' increases the likelihood of false positive results and should be avoided to prevent unnecessary further investigations and treatment, and unwarranted anxiety in both the patient and the doctor.

Recent advances in the treatment of gout with NLRP3 inflammasome inhibitors.

Gout is an autoinflammatory disorder characterized by the accumulation of monosodium urate crystals in joints and other tissues, representing the predominant type of inflammatory arthritis with a notable prevalence and propensity for severe outcomes. The NLRP3 inflammasome, a member of the pyrin domain-containing NOD-like receptor family, exerts a substantial impact on both innate and adaptive immune responses and serves as a pivotal factor in the pathogenesis of gout. In recent years, there has been significant academic and industrial interest in the development of NLRP3-targeted small molecule inhibitors as a promising therapeutic approach for gout. To assess the advancements in NLRP3 inflammasome inhibitors for gout treatment, this review offers a comprehensive analysis and evaluation of current clinical candidates and other inhibitors targeting NLRP3 inflammasome from a chemical structure standpoint, with the goal of identifying more efficacious options for clinical management of gout.

Gabapentin alleviates peripheral nerve sensitization induced by inflammatory arthritis via ionotropic glutamate receptor NR2B subunit.

Inflammatory arthritis leads to peripheral nerve sensitization, but the therapeutic effect is often unsatisfactory. Our preliminary studies have found that in mice with inflammatory arthritis, the use of ionotropic glutamate receptor antagonists can produce a good analgesic effect without altering foot swelling, suggesting that pain relief may be related to the improvement of neuropathic pain. However, the underlying mechanisms remain unclear. To further investigate the effects of neuropathic pain medications on inflammatory arthritis and the impact of the ionotropic glutamate receptor NR2B subunit (NR2B) on inflammatory arthritis, this study employed gabapentin (GBP) treatment on the inflammatory arthritis mouse model (the adjuvant induced arthritis, AIA), and we found a significant reduction in pain. Further studies revealed that in AIA, the expression levels of NR2B, TRPV1, pain-related molecules (substance P, PGE2), inflammatory cytokines (IL-1, IL-6, TNF-α, and GM-CSF) and Ca2+ were elevated in the foot and dorsal root ganglia (DRG). GBP treatment was able to influence the downregulation of the expression levels of NR2B, TRPV1, pain-related molecules, inflammatory cytokines and Ca2+. Mechanistic studies have shown that GBP treatment affects the downregulation of NR2B, and the downregulation of NR2B expression leads to the downregulation of TRPV1, pain-related molecules and inflammatory cytokines, thereby alleviating pain. These results suggest that in peripheral sensitization caused by AIA, GBP can play a role in improving pain, and NR2B may be a key target of peripheral nerve sensitization induced by inflammatory arthritis. GBP provides a theoretical basis for the clinical treatment of inflammatory arthritis.

Physical Activity and Sports for Children With Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, presenting clinically as inflammatory arthritis in children younger than 16 years. To date, while evidence supports physical activity for children with JIA, there is limited evidence on the recommended approach to physical activity and sports participation in this population, and no single structured therapeutic exercise program has been established as best practice. This review article presents what is known on the management of physical activity in children with JIA, including recommendations from the pediatric rheumatology and rehabilitation literature, where available, for sports participation, structured therapeutic exercise programs, and return to activity.

Diet affects inflammatory arthritis: a Mendelian randomization study of 30 dietary patterns causally associated with inflammatory arthritis.

Background: The causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown. Objective: In this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR). Methods: We analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran's Q tests. FDR correction was used to correct the p-values. Results: IVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360-6.021, p = 0.006, p_fdr < 0.05] was positively associated with rheumatoid arthritis(RA); Dried fruit intake (OR = 0.522; 95% CI, 0.349-0.781, p = 0.002, p_fdr < 0.05), and Iron intake (OR = 0.864; 95%CI, 0.777-0.960, p = 0.007, p_fdr < 0.05) were negatively associated with RA, all of which were evidence of significance. Fresh fruit intake (OR = 2.528. 95% CI, 1.063-6.011, p = 0.036, p_fdr > 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367-0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100-0.565, p = 0.001, p_fdr < 0.05) was negatively associated with reactive arthritis (ReA), a protective factor, and significant evidence. All exposure data passed the heterogeneity check (Cochrane's Q test p > 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results. Conclusion: Our study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.

Transient/Toxic Synovitis.

Transient synovitis (TS) is a self-limiting inflammatory condition of the joints, predominantly affecting children and characterized by symptoms such as pain, swelling, warmth, and erythema. It is often triggered by an immune response to a viral infection, leading to acute inflammatory arthritis. Diagnosis involves a combination of patient history, physical examinations, imaging techniques, and laboratory tests, although there are no specific laboratory tests for TS. Treatment primarily consists of symptom management through rest, analgesics, and nonsteroidal anti-inflammatory drugs. The condition underscores the importance of distinguishing TS from more serious joint diseases to prevent unnecessary interventions and to ensure appropriate management.

Total Joint Arthroplasty in the Patient with Inflammatory Arthritis: A Review.

Inflammatory arthritis is a family of conditions including rheumatoid arthritis, juvenile inflammatory arthritis, and spondyloarthropathies affecting both the large and small joints. Total joint arthroplasty is commonly used for surgical management of end-stage disease. Preoperative and postoperative considerations as well as perioperative medical management and intraoperative treatment of patients with inflammatory arthritis undergoing total joint arthroplasty are reviewed. Although individualized, multidisciplinary approaches to treatment are necessary due to the complex nature of the disease and the varying levels of severity, patients generally have favorable outcomes with respect to pain scores and functional outcomes.

Efficacy and safety of culture-expanded mesenchymal stromal cell therapy in the treatment of 4 types of inflammatory arthritis: A systematic review and meta-analysis of 36 randomized controlled trials.

OBJECTIVE: This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis. METHODS: Two researchers conducted a comprehensive search of Chinese and English databases from their inception until July 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. RESULTS: A total of 36 relevant RCTs, involving 2,076 participants, were ultimately included in this study. These RCTs encompassed four types of inflammatory arthritis, namely rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic sclerosis (SSc). The results demonstrated that MSC therapy exhibited improvements in the Visual Analog Scale (VAS) for pain in OA patients (bone marrow: SMD=-0.95, 95 % CI: -1.55 to -0.36, P = 0.002; umbilical cord: SMD=-2.03, 95 % CI: -2.99 to -1.07, P < 0.0001; adipose tissue: SMD=-1.26, 95 % CI: -1.99 to -0.52, P = 0.0009). Specifically, MSCs sourced from adipose tissue showed enhancements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (P = 0.0001), WOMAC physical function (P = 0.001), and total WOMAC scores (P = 0.0003). As for MSC therapy in RA, AS, and SSc, the current systematic review suggests a potential therapeutic effect of MSCs on these inflammatory arthritic conditions. Safety assessments indicated that MSC therapy did not increase the incidence of adverse events. CONCLUSION: MSCs have the potential to alleviate joint pain and improve joint function in patients with inflammatory arthritis. Moreover, MSC therapy appears to be relatively safe and could be considered as a viable alternative treatment option for inflammatory arthritis.

Comparisons of infection events associated with tumor necrosis factor inhibitors in patients with inflammatory arthritis: A systematic review and network meta-analysis.

Objective: To compare the risk of infection in inflammatory arthritis patients treated with tumor necrosis factor (TNF) inhibitors. Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to 28 December 2023 for randomized controlled trials (RCTs) assessing TNF inhibitors and reporting infections. Subsequently, pairwise and network meta-analyses were conducted to determine odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Results: A total of 61 RCTs involving 20,458 patients were included. Pairwise meta-analysis revealed that certolizumab pegol was significantly associated with an increased risk of serious infection compared to placebo (OR:2.28, 95% CI: 1.13-4.62). Both adalimumab and certolizumab pegol were also significantly associated with an increased risk of any infection compared to placebo (OR:1.18, 95% CI: 1.06 to 1.30 and OR:1.40, 95% CI: 1.11 to 1.76, respectively). Moreover, a network meta-analysis indicated that certolizumab pegol and infliximab were associated with a higher risk of serious infection compared to other TNF inhibitors. In the cumulative ranking of any infection risk, certolizumab pegol had the highest risk compared with others. TNF inhibitors increased the risk of tuberculosis but not that of herpes zoster. Conclusion: Available evidence indicates etanercept and golimumab are likely associated with a lower risk of infection compared to other TNF inhibitors in inflammatory arthritis. For patients at a heightened risk of infection, prioritizing the use of etanercept and golimumab may be advisable to minimize patient risk. Systematic Review Registration: identifier CRD42022316577.

Pneumococcal vaccine uptake in patients with inflammatory arthritis: a single centre cohort study.

INTRODUCTION: Current guidelines recommend pneumococcal vaccination in individuals who are over the age of 65 or are immunosuppressed due to a disease or treatment. The objective of this study was to assess vaccine uptake rates in people with inflammatory arthritis for the pneumococcal, influenza and Covid-19 vaccines and factors determining uptake. METHODS: We conducted a retrospective single centre cohort study in the UK of individuals with rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis between October and December 2023. Data were collected for age, gender, co-morbidities, immunosuppressive therapies, and dates of vaccines. Logistic regression was used to evaluate predictors of vaccine uptake, with adjustments for demographic and clinical factors. RESULTS: 906 individuals were identified. 46% were receiving treatment with csDMARD, 26% on biologic monotherapy, and 23% were on both biologic and csDMARDs. 316 individuals (35%) received a pneumococcal vaccine, lower than uptake for influenza (63%) and Covid-19 (87%) vaccines. Predictors of pneumococcal vaccine uptake included age, with older patients more likely to be vaccinated (odds ratio [OR] for age ≥ 65 years: 1.67, 95% CI 1.21-2.29). Those on biological therapy demonstrated higher likelihood of vaccination (OR for biologic therapy: 1.81, 95% CI 1.33-2.47). Additional Joint committee for immunisation and vaccination (JCVI) Green Book indicators also positively influenced vaccine uptake (OR: 1.67, 95% CI 1.19-2.33). CONCLUSION: Pneumococcal vaccine uptake in inflammatory rheumatic diseases is low, especially in younger patients and those not on biological therapy. The study highlights the need for a focused approach, distinct from strategies for other vaccines, to address this public health challenge.