ABSTRACT
Blau syndrome is an autosomal dominant chronic inflammatory disease, which may begin with skin manifestations in the first months of life, alerting physicians to the diagnosis. This case reports a patient diagnosed jointly by pediatric dermatology and rheumatology consultants at two years of age.
Subject(s)
Arthritis , Sarcoidosis , Synovitis , Uveitis , Humans , Synovitis/genetics , Synovitis/diagnosis , Uveitis/diagnosis , Sarcoidosis/diagnosis , Sarcoidosis/pathology , Arthritis/diagnosis , Child, Preschool , Male , Female , Arthritis, Infectious/diagnosis , Hereditary Autoinflammatory DiseasesABSTRACT
Background: Previous studies reported that endometriosis may have a higher risk of arthritis. However, it remains unclear whether the association between endometriosis and arthritis has genetic correlations, or the relationship is causal. Linkage Disequilibrium Score (LDSC) and Mendelian Randomization (MR) analyses use genetic variation as a natural experiment to explore genetic correlations and causal inferences from observational data, reducing unmeasured confounding factors. Method: Participants (aged 20-54 years, n = 2,915) for the cross-sectional study were obtained from the National Health and Nutrition Examination Survey (NHANES). Endometriosis and arthritis were diagnosed based on self-reported by reproductive health and medical condition questionnaire. Weighted multivariable logistic regression was used to explore the relationship between endometriosis and arthritis. LDSC and MR analysis were performed using the genome-wide association study (GWAS) summary statistics to identify the causal association. Result: A significant positive association between endometriosis and arthritis was found after multivariable adjustment (OR = 1.89; 95% CI: 1.33, 2.67). When exploring different types of arthritis, a positive association was revealed with rheumatoid arthritis (RA), other types of arthritis, and cases that the arthritis type were unknown, with an OR of 2.07 (95% CI: 1.03, 4.17), 2.78 (95% CI: 1.30, 5.95), and 2.06 (95% CI: 1.36, 3.11), respectively. However, genetic correlation analysis between endometriosis and RA did not reveal any significant findings (all P values > 0.05). Moreover, MR analysis also failed to identify a causal relationship between endometriosis and RA (all P values > 0.05). Conclusion: Cross-sectional study identified a significant positive association between endometriosis and arthritis among US women, especially among RA, while findings based on LDSC and MR analysis did not support a genetic correlation or causal role. These findings suggest that clinicians should pay more attention to the coexistence of RA in endometriosis patients and explore the shared pathophysiological mechanisms of these two disorders, with a particular focus on extrinsic factors rather than intrinsic genetic inheritance.
Subject(s)
Arthritis , Endometriosis , Genome-Wide Association Study , Mendelian Randomization Analysis , Nutrition Surveys , Humans , Endometriosis/genetics , Endometriosis/complications , Female , Adult , Middle Aged , Cross-Sectional Studies , Arthritis/genetics , Arthritis/epidemiology , Young Adult , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Linkage DisequilibriumABSTRACT
BACKGROUND: Previous observational studies indicated a complex association between frailty and arthritis. AIMS: To investigate the genetic causal relationship between the frailty index and the risk of common arthritis. METHODS: We performed a large-scale Mendelian randomization (MR) analysis to assess frailty index associations with the risk of common arthritis in the UK Biobank (UKB), and the FinnGen Biobank. Summary genome-wide association statistics for frailty, as defined by the frailty index, and common arthritis including rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PSA), and ankylosing spondylitis (AS). The inverse-variance weight (IVW) method served as the primary MR analysis. Heterogeneity testing and sensitivity analysis were also conducted. RESULTS: Our results denoted a genetic association between the frailty index with an increased risk of OA, the odds ratio (OR)IVW in the UKB was 1.03 (95% confidence interval [CI]: 1.01-1.05; P = 0.007), and ORIVW was 1.55 (95% CI: 1.16-2.07; P = 0.003) in the FinnGen. For RA, the ORIVW from UKB and FinnGen were 1.03 (1.01-1.05, P = 0.006) and 4.57 (1.35-96.49; P = 0.025) respectively. For PSA, the frailty index was associated with PSA (ORIVW = 4.22 (1.21-14.67), P = 0.023) in FinnGen, not in UKB (P > 0.05). However, no association was found between frailty index and AS (P > 0.05). These results remained consistent across sensitivity assessments. CONCLUSION: This study demonstrated a potential causal relationship that genetic predisposition to frailty index was associated with the risk of arthritis, especially RA, OA, and PSA, not but AS. Our findings enrich the existing body of knowledge on the subject matter.
Subject(s)
Frailty , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Frailty/genetics , Arthritis/genetics , Arthritis/epidemiology , Osteoarthritis/genetics , Osteoarthritis/epidemiology , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/epidemiology , Aged , Male , Female , Arthritis, Psoriatic/genetics , Arthritis, Psoriatic/epidemiology , Genetic Predisposition to Disease , Middle AgedABSTRACT
Immune responses demand the rapid and precise regulation of gene protein expression. Splicing is a crucial step in this process; ~95% of protein-coding gene transcripts are spliced during mRNA maturation. Alternative splicing allows for distinct functional regulation, as it can affect transcript degradation and can lead to alternative functional protein isoforms. There is increasing evidence that splicing can directly regulate immune responses. For several genes, immune cells display dramatic changes in isoform-level transcript expression patterns upon activation. Recent advances in long-read RNA sequencing assays have enabled an unbiased and complete description of transcript isoform expression patterns. With an increasing amount of cell types and conditions that have been analyzed with such assays, thousands of novel transcript isoforms have been identified. Alternative splicing has been associated with autoimmune diseases, including arthritis. Here, GWASs revealed that SNPs associated with arthritis are enriched in splice sites. In this review, we will discuss how alternative splicing is involved in immune responses and how the dysregulation of alternative splicing can contribute to arthritis pathogenesis. In addition, we will discuss the therapeutic potential of modulating alternative splicing, which includes examples of spliceform-based biomarkers for disease severity or disease subtype, splicing manipulation using antisense oligonucleotides, and the targeting of specific immune-related spliceforms using antibodies.
Subject(s)
Alternative Splicing , Arthritis , Alternative Splicing/genetics , Humans , Arthritis/genetics , Animals , Polymorphism, Single NucleotideABSTRACT
Ferroptosis is a form of iron-dependent regulated cell death caused by the accumulation of lipid peroxides. In this review, we summarize research on the impact of ferroptosis on disease models and isolated cells in various types of arthritis. While most studies have focused on rheumatoid arthritis (RA) and osteoarthritis (OA), there is limited research on spondylarthritis and crystal arthropathies. The effects of inducing or inhibiting ferroptosis on the disease strongly depend on the studied cell type. In the search for new therapeutic targets, inhibiting ferroptosis in chondrocytes might have promising effects for any type of arthritis. On the other hand, ferroptosis induction may also lead to a desired decrease of synovial fibroblasts in RA. Thus, ferroptosis research must consider the cell-type-specific effects on arthritis. Further investigation is needed to clarify these complexities.
Subject(s)
Ferroptosis , Osteoarthritis , Humans , Animals , Osteoarthritis/metabolism , Osteoarthritis/pathology , Chondrocytes/metabolism , Chondrocytes/pathology , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/pathology , Arthritis/metabolism , Arthritis/pathology , Fibroblasts/metabolism , Fibroblasts/pathology , Iron/metabolismABSTRACT
Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils' azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies.
Subject(s)
Arthritis , Biomarkers , Proteomics , Sarcoidosis , Synovitis , Tears , Uveitis , Humans , Tears/metabolism , Biomarkers/metabolism , Uveitis/metabolism , Uveitis/genetics , Uveitis/diagnosis , Female , Male , Arthritis/genetics , Arthritis/metabolism , Synovitis/metabolism , Synovitis/genetics , Sarcoidosis/genetics , Sarcoidosis/metabolism , Adult , Proteomics/methods , Nod2 Signaling Adaptor Protein/genetics , Nod2 Signaling Adaptor Protein/metabolism , Middle Aged , Mutation , Proteome/metabolism , Hereditary Autoinflammatory DiseasesABSTRACT
Objective: This study assessed the association between erectile dysfunction (ED) and arthritis. Methods: Weighted logistic regression and subgroup analyses were used to investigate the association between arthritis incidence and ED among participants in the 2001-2004 National Health and Nutrition Examination Survey database. Results: Among the participants, 27.8% and 18.5% had a self-reported history of ED and arthritis, respectively. ED was associated with arthritis (odds ratio [OR]=4.00; 95% confidence interval [CI]: 3.20-4.99; p<0.001], which remained significant after adjustment (OR=1.42, 95% CI: 1.00-1.96; p<0.001). Stratified by type of arthritis, after full adjustment, osteoarthritis remained significant (OR=1.11; 95% CI: 1.03-1.20; p=0.017), and rheumatoid arthritis (OR=1.03, 95% CI: 0.93-1.13; p= 0.5) and other arthritis (OR=1.04, 95% CI: 0.98-1.11; p=0.2) were not significantly correlated with ED. Multiple inference analyses confirmed the robustness of the results. Conclusion: Our study showed that arthritis was strongly associated with ED. There is an urgent need to raise awareness and conduct additional research on the reasons behind this association in order to implement more scientific and rational treatment programs for patients with ED and arthritis.
Subject(s)
Erectile Dysfunction , Nutrition Surveys , Humans , Male , Erectile Dysfunction/epidemiology , Erectile Dysfunction/complications , Erectile Dysfunction/etiology , Middle Aged , Adult , Risk Factors , Arthritis/epidemiology , Arthritis/complications , Aged , Incidence , United States/epidemiology , Cross-Sectional StudiesABSTRACT
BACKGROUND: Insulin resistance (IR) and arthritis are strongly associated, and the triglyceride-glucose (TyG) index combinations with obesity indicators [including TyG-BMI (glucose triglyceride-body mass index), TyG-WC (glucose triglyceride-waist circumference), and TyG-WHtR (glucose triglyceride-waist height ratio)] has recently been recognized as a more effective indicator for assessing IR. However, there is a lack of research on its association with arthritis, and it is also important to assess in different populations. METHODS: The analysis utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and the National Health and Nutrition Examination Survey (NHANES). Arthritis diagnosis relied on self-reporting confirmed by physicians. The association of TyG-BMI, TyG-WC, and TyG-WHtR with arthritis was analyzed through weighted logistic regression models, and exploring nonlinear effects with restricted cubic spline (RCS) models. Secondary and sensitivity analyses included receiver operating characteristic curve (ROC) analysis, comparisons of z score-related odds ratios, subgroup analyses, and multiple imputation. RESULTS: The study involved 6141 CHARLS participants and 17,091 NHANES participants. Adjusting for confounding variables, TyG-BMI and TyG-WHtR demonstrate a positive correlation with arthritis prevalence in both CHARLS (TyG-BMI: OR = 1.02, 95% CI 1.00-1.04; TyG-WHtR: OR = 1.13, 95% CI 1.03-1.24) and NHANES (TyG-BMI: OR = 1.07, 95% CI 1.06-1.08; TyG-WHtR: OR = 1.50, 95% CI 1.40-1.60). RCS regression analysis demonstrated a significant nonlinear association. ROC analysis indicated that TyG-BMI and TyG-WHtR were superior to TyG for the diagnosis of arthritis in both CHARLS and NHANES. CONCLUSIONS: TyG-BMI and TyG-WHtR demonstrate a positive correlation with arthritis prevalence in both Chinese and the U.S. populations, displaying superior diagnostic relevance compared to TyG.
Subject(s)
Arthritis , Blood Glucose , Body Mass Index , Obesity , Triglycerides , Humans , Female , Male , Triglycerides/blood , Middle Aged , Obesity/epidemiology , Obesity/blood , Arthritis/epidemiology , Arthritis/blood , Arthritis/diagnosis , Blood Glucose/analysis , Blood Glucose/metabolism , Aged , Nutrition Surveys , China/epidemiology , Longitudinal Studies , Insulin Resistance , Waist CircumferenceABSTRACT
Background: Perilunate fracture-dislocations are frequently associated with a high risk of developing post-traumatic arthritis. Current studies indicate that during mid-term follow-ups, radiological signs of arthritis do not appear to correspond with functional score. The aim of this study was to assess the occurrence of posttraumatic arthritis and the wrist function after perilunate dislocations (PLD) and fracture dislocations at a mid-term follow-up of 7 years. Methods: We report the clinical and radiological outcomes of 17 wrists treated for PLD or fracture-dislocation by open reduction and internal fixation through a dorsal approach with dorsal ligament repair. Functional outcomes were evaluated using the short version of the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), the Patient-Rated Wrist Evaluation questionnaire (PRWE) and the Mayo Wrist Score (MWS). Results of radiographs were assessed using the Herzberg Radiological Scoring Chart. Results: The MWS showed five excellent, five good, five fair and two poor results with an average score of 81%. Radiological analysis using the Herzberg classification revealed midcarpal and/or radiocarpal arthritis in 65% of cases, lunate collapse in 59% and an increase in the mean ulnar translocation ratio in 53% of the cases. Complications included one case of lunate osteonecrosis and one case of stage 3 scapholunate advanced collapse that required revision surgery. Conclusions: Although the clinical and functional outcomes are favourable at mid-term follow-up, radiological evaluation shows a progression towards osteoarthritis (OA). Further research is warranted to refine treatment strategies and investigate factors influencing the development of OA. Level of Evidence: Level IV (Therapeutic).
Subject(s)
Fracture Dislocation , Fracture Fixation, Internal , Lunate Bone , Humans , Male , Female , Adult , Follow-Up Studies , Lunate Bone/injuries , Lunate Bone/diagnostic imaging , Lunate Bone/surgery , Middle Aged , Fracture Fixation, Internal/methods , Fracture Dislocation/surgery , Fracture Dislocation/diagnostic imaging , Disability Evaluation , Young Adult , Wrist Injuries/surgery , Wrist Injuries/diagnostic imaging , Radiography , Wrist Joint/diagnostic imaging , Wrist Joint/surgery , Wrist Joint/physiopathology , Arthritis/etiology , Arthritis/diagnostic imaging , Arthritis/surgery , Open Fracture Reduction/methodsABSTRACT
Granulomatous mastitis (GM) is a long-term inflammatory disease of the breast that usually occurs in women of reproductive age. Autoimmune mastitis is one of the most common pathological breast conditions necessitating tailored treatment. However, GM as a first clinical manifestation of sarcoidosis is uncommon. Simultaneous occurrence of GM, erythema nodosum (EN), and arthritis, termed "GMENA" syndrome, is a rare clinical entity associated with autoimmune rheumatic diseases. Herein, we report the case of a 31-year-old female patient with GMENA syndrome, who presented with a painful nodule of the left breast. Initial treatment entailed antibiotics under the presumption of a breast abscess, yielding negligible improvement. During this period, the patient developed polyarthritis and bilateral EN on the lower extremities. Histopathologic examination of the breast tissue exhibited noncaseating granulomas. The patient responded positively to prednisolone and methotrexate treatment. Literature review revealed a coherent pattern across GMENA cases. Our findings suggest that the "GMENA" syndrome represents a unique acute manifestation of sarcoidosis and highlight the necessity for heightened awareness, accurate diagnosis, and tailored therapeutic approaches for GMENA syndrome. Further research is warranted to elucidate its cause and optimize patient management. This case highlights the importance of identifying and effectively managing such interrelated clinical presentations.
Subject(s)
Arthritis , Erythema Nodosum , Granulomatous Mastitis , Sarcoidosis , Humans , Female , Erythema Nodosum/diagnosis , Erythema Nodosum/drug therapy , Erythema Nodosum/pathology , Adult , Granulomatous Mastitis/diagnosis , Granulomatous Mastitis/pathology , Granulomatous Mastitis/drug therapy , Sarcoidosis/diagnosis , Sarcoidosis/complications , Sarcoidosis/drug therapy , Sarcoidosis/pathology , Arthritis/diagnosis , Arthritis/drug therapy , Methotrexate/therapeutic use , Prednisolone/therapeutic use , SyndromeABSTRACT
Introduction: arthritis is a significant public health problem affecting many people globally. Exposure to various risk factors puts individuals at risk of developing arthritis. Therefore, this study aimed to assess the prevalence and predictors of arthritis among residents of a rural set-up in Nyamira County, Kenya. Methods: a community-based cross-sectional study design was employed. Simple random sampling was utilized to select households from a household list. All the residents of the sampled household above 40 years were included. Descriptive analysis was done to describe the study population. Bivariate and multivariate analysis was also done to identify statistically significant arthritis-related variables. Results: the prevalence of arthritis was 44.6%. Previous joint injury/infection [AOR=2.74; 95%CI=1.59-4.77; p<0.001], being unemployed [AOR=2.77; 95%CI=1.50-5.21; p=0.001], age above 51 years, and hypertension [AOR=1.90; 95%CI=1.03-3.53, p=0.040] were associated with an increased risk of arthritis. Conversely, being male [AOR=0.42; 95% CI=0.22-0.75; p=0.005], standing for > 2 hours [AOR=0.48; 95%CI=0.29-0.81; p=0.006], and constant shifting from sit to stand positions [AOR=0.45; 95% CI=0.26-0.76; p=0.003] were associated with a lower risk of arthritis. Most participants (75%) had an arthritis knowledge score of more than 66%. Conclusion: the study found a high prevalence of arthritis in the community. Arthritis was strongly associated with various risk factors under study. Therefore, there is a need to take preventive measures for modifiable factors to enhance a reduced prevalence of arthritis.
Subject(s)
Arthritis , Rural Population , Humans , Cross-Sectional Studies , Kenya/epidemiology , Male , Prevalence , Female , Adult , Arthritis/epidemiology , Middle Aged , Risk Factors , Rural Population/statistics & numerical data , Aged , Sex Factors , Age Factors , Hypertension/epidemiologySubject(s)
COVID-19 Vaccines , COVID-19 , Ultrasonography , Zygapophyseal Joint , Humans , COVID-19/prevention & control , Zygapophyseal Joint/diagnostic imaging , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/administration & dosage , SARS-CoV-2/immunology , Lumbar Vertebrae/diagnostic imaging , Male , Female , Middle Aged , Vaccination/adverse effects , Arthritis/diagnosisABSTRACT
In tumor cells, interleukin-6 (IL-6) signaling can lead to activation of the epidermal growth factor receptor (EGFR), which prolongs Stat3 activation. In the present experiments, we tested the hypothesis that IL-6 signaling activates EGFR signaling in peripheral and spinal nociception and examined whether EGFR localization and activation coincide with pain-related behaviors in arthritis. In vivo in anesthetized rats, spinal application of the EGFR receptor blocker gefitinib reduced the responses of spinal cord neurons to noxious joint stimulation, but only after spinal pretreatment with IL-6 and soluble IL-6 receptor. Using Western blots, we found that IL-6-induced Stat3 activation was reduced by gefitinib in microglial cells of the BV2 cell line, but not in cultured DRG neurons. Immunohistochemistry showed EGFR localization in most DRG neurons from normal rats, but significant downregulation in the acute and most painful arthritis phase. In the spinal cord of mice, EGFR was highly activated mainly in the chronic phase of inflammation, with localization in neurons. These data suggest that spinal IL-6 signaling may activate spinal EGFR signaling. Downregulation of EGFR in DRG neurons in acute arthritis may limit nociception, but pronounced delayed activation of EGFR in the spinal cord may be involved in chronic inflammatory pain.
Subject(s)
ErbB Receptors , Interleukin-6 , Sensory Receptor Cells , Spinal Cord , Animals , Female , Mice , Rats , Arthritis/metabolism , Arthritis, Experimental/metabolism , Cell Line , ErbB Receptors/metabolism , Ganglia, Spinal/metabolism , Gefitinib/pharmacology , Interleukin-6/metabolism , Receptors, Interleukin-6/metabolism , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/drug effects , Signal Transduction , Spinal Cord/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
Arthritis is associated with health challenges. Lifestyle traits are believed to influence arthritis development and progression; however, data to support personalized treatment regimens based on holistic lifestyle factors are missing. This study aims to provide a comprehensive list of associations between lifestyle traits and the health status of individuals with arthritis in the Canadian population, using binary logistic regression analysis on data from the Canadian Community Health Survey, which includes 104,359 respondents. Firstly, we explored the association between arthritis and various aspects of health status including self-reported lifestyle factors. Secondly, we examined the associations between self-reported dietary intake and smoking status with general, mental, and oral health, and sleep disturbance among individuals both with and without arthritis. Our analysis revealed that individuals with arthritis reported considerably poorer general, mental, and oral health, and poorer sleep quality compared to those without arthritis. Associations were also found between self-reported dietary intake and various measures of health status in individuals with arthritis. Smoking and exposure to passive smoking were associated not only with arthritis but also with compromised sleep quality and poorer general, mental, and oral health in people with and without arthritis. This study highlights the need for personalized and holistic approaches that may include a combination of dietary interventions, oral health improvements, sleep therapies, and smoking cessation for improved arthritis prevention and care.
Subject(s)
Arthritis , Health Surveys , Life Style , Mental Health , Oral Health , Sleep Quality , Smoking , Humans , Male , Cross-Sectional Studies , Female , Canada/epidemiology , Middle Aged , Oral Health/statistics & numerical data , Arthritis/epidemiology , Adult , Smoking/epidemiology , Aged , Diet , Health Status , Self Report , Sleep Wake Disorders/epidemiology , EatingABSTRACT
Importance: Epidemiologic studies indicate a high rate of autoimmune conditions among patients with obsessive-complusive disorder and other psychiatric conditions. Furthering the understanding of the inflammatory diatheses of psychiatric conditions may open doors to new treatment paradigms for psychiatric disorders. Objectives: To evaluate whether pediatric acute-onset neuropsychiatric syndrome (PANS) is associated with an inflammatory diathesis by assessing signs of immune activation and vasculopathy during a psychiatric symptom exacerbation (flare), estimating the risk of developing arthritis and other autoimmune diseases, and characterizing subtypes of arthritis. Design, Setting, and Participants: This retrospective cohort study used longitudinal clinical data on 193 consecutive patients with PANS followed up within the Stanford Immune Behavioral Health Clinic from September 1, 2012, to December 31, 2021. Main Outcomes and Measures: Medical records were reviewed, and a predefined set of immune markers that were measured during a flare and the features and imaging findings of arthritis and other autoimmune diseases were collected. Immune activation markers included (1) autoimmunity signs (antinuclear antibody, antihistone antibody, antithyroglobulin antibody, C1q binding assay, and complement levels [C3 and C4]); (2) immune dysregulation or inflammation signs (leukopenia, thrombocytosis, C-reactive protein, and erythrocyte sedimentation rate); and (3) vasculopathy signs (livedo reticularis, periungual redness and swelling, abnormally prominent onychodermal band, palatal petechiae, high von Willebrand factor antigen, and high d-dimer). Last, the cumulative risk of developing arthritis and autoimmune diseases was estimated using product limit (Kaplan-Meier) survival probability. Results: The study included data from 193 children (112 boys [58.0%]) who had PANS at a mean (SD) age of 7.5 (3.5) years. They were followed up for a mean (SD) of 4.0 (2.1) years. Among those tested for immune activation markers, 54.2% (97 of 179) had nonspecific markers of autoimmunity, 12.0% (22 of 184) had nonspecific signs of immune dysregulation or inflammation, and 35.8% (69 of 193) had signs of vasculopathy. By 14 years of age, the estimated cumulative incidence of arthritis was 28.3% (95% CI, 20.8%-36.3%), and the estimated cumulative incidence of another autoimmune disease was 7.5% (95% CI, 4.0%-12.4%). Novel findings in the subgroup with arthritis include joint capsule thickening (55.0% [22 of 40]), distal interphalangeal joint tenderness (81.8% [45 of 55]), and spinous process tenderness (80.0% [44 of 55]). Among the 55 patients with arthritis, the most common subtypes of arthritis included enthesitis-related arthritis (37 [67.3%]), spondyloarthritis (27 [49.1%]), and psoriatic arthritis (10 [18.2%]). Conclusions and Relevance: This study found that patients with PANS show signs of immune activation and vasculopathy during psychiatric symptom flares and have an increased risk of developing arthritis and other autoimmune diseases compared with the general pediatric population. The most common arthritis subtype was enthesitis-related arthritis. These findings suggest that PANS may be part of a multisystem inflammatory condition rather than an isolated psychiatric or neuroinflammatory disorder.
Subject(s)
Autoimmune Diseases , Obsessive-Compulsive Disorder , Humans , Child , Autoimmune Diseases/epidemiology , Autoimmune Diseases/immunology , Autoimmune Diseases/complications , Male , Female , Retrospective Studies , Adolescent , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/immunology , Child, Preschool , Arthritis/epidemiology , Arthritis/immunologyABSTRACT
Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize an induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. We show that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Likely owing to the unique features of the collagen triple helix, this accumulation is not recognized by the unfolded protein response. Gly1170Ser procollagen-II interacts to a greater extent than wild-type with specific ER proteostasis network components, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the easily expandable cartilage model will enable rapid testing of therapeutic strategies to restore proteostasis in the collagenopathies.
Subject(s)
Collagen Type II , Endoplasmic Reticulum , Procollagen , Unfolded Protein Response , Endoplasmic Reticulum/metabolism , Humans , Procollagen/metabolism , Collagen Type II/metabolism , Mutation , Induced Pluripotent Stem Cells/metabolism , Cartilage/metabolism , Cartilage/pathology , Protein Folding , Arthritis/metabolism , Arthritis/genetics , Osteoarthritis/metabolism , Osteoarthritis/genetics , Osteoarthritis/pathology , Animals , Chondrocytes/metabolismABSTRACT
Cuboid injuries, including fractures, are rare and infrequently occur in isolation. Often, cuboid injuries can be treated nonoperatively. However, when surgery is indicated, appropriate management is necessary for maintaining the associated biomechanics of the midfoot. Current procedures for surgical management of the cuboid include open reduction and internal fixation, application of external fixation, or primary arthrodesis of the calcaneocuboid joint. Secondary procedures for symptomatic or poor outcomes of nonoperative and operative cuboid injuries consist of corrective osteotomy, bone resection, and interpositional arthroplasty. We present a novel surgical technique using a patient-specific three-dimensional-printed total cuboid replacement. This is an alternative treatment for post-traumatic arthritis of the cuboid along with a shortened lateral column. A single case example is given as well as details and discussion of the surgical technique.
Subject(s)
Printing, Three-Dimensional , Humans , Tarsal Bones/injuries , Tarsal Bones/surgery , Male , Arthritis/etiology , Arthritis/surgery , AdultABSTRACT
Inflammatory Bowel Disease-Associated Arthritis (IBD-associated arthritis) poses a significant challenge, intertwining the complexities of both inflammatory bowel disease (IBD) and arthritis, significantly compromising patient quality of life. While existing medications offer relief, these drugs often initiate adverse effects, necessitating the requirement for safer therapeutic alternatives. Artemisia herba-alba, a traditional medicinal plant known for its anti-inflammatory properties, emerges as a potential candidate. Our computational study focused on examining 20 bioactive compounds derived from A. herba-alba for potential treatment of IBD-associated arthritis. These compounds detected in A. herba-alba include camphor, alpha-thujone, eucalyptol, cis-chrysanthenyl acetate, vicenin-2, 4,5-di-O-caffeoylquinic acid, chlorogenic acid, hispidulin, isoschaftoside, isovitexin, patuletin-3-glucoside, vanillic acid, rutin, schaftoside, lopinavir, nelfinavir, quercetin, artemisinin, gallic acid, and cinnamic acid. Following rigorous analysis encompassing pharmacokinetics, toxicity profiles, and therapeutic targets, compounds with favorable, beneficial characteristics were identified. In addition, comparative analysis with disease-gene associations demonstrated the interconnectedness of inflammatory pathways across diseases. Molecular docking studies provided mechanistic insights indicating this natural plant components potential to modulate critical inflammatory pathways. Overall, our findings indicate that A. herba-alba-derived compounds may be considered as therapeutic agents for IBD-associated arthritis, warranting further experimental validation and clinical exploration.
Subject(s)
Artemisia , Inflammatory Bowel Diseases , Molecular Docking Simulation , Plant Extracts , Artemisia/chemistry , Inflammatory Bowel Diseases/drug therapy , Humans , Plant Extracts/chemistry , Plant Extracts/pharmacology , Arthritis/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistryABSTRACT
AIM: Existing studies on the cost of inflammatory arthritis (IA) and osteoarthritis (OA) are often cross-sectional and/or involve patients with various disease durations, thus not providing a comprehensive perspective on the cost of illness from the time of diagnosis. In this study, we therefore assessed the cost of lost productivity in an inception cohort of patients with IA and OA in the year before and after diagnosis. METHODS: Employment status, monthly income, days absent from work, and presenteeism were collected at diagnosis and 1 year later to estimate the annual costs of unemployment, absenteeism, and presenteeism using human capital approach. Non-parametric bootstrapping was performed to account for the uncertainty of the estimated costs. RESULTS: Compared to patients with OA (n = 64), patients with IA (n = 102, including 48 rheumatoid arthritis, 19 spondyloarthritis, 23 psoriatic arthritis, and 12 seronegative IA patients) were younger (mean age: 52.3 vs. 59.5 years) with a greater proportion receiving treatment (99.0% vs. 67.2%) and a greater decrease in presenteeism score (median: 15% vs 10%) 1 year after diagnosis. Annual costs of absenteeism and presenteeism were lower in patients with IA than those with OA both in the year before (USD566 vs. USD733 and USD8,472 vs. USD10,684, respectively) and after diagnosis (USD636 vs. USD1,035 and USD6,866 vs. USD9,362, respectively). CONCLUSION: Both IA and OA impose substantial cost of lost productivity in the year before and after diagnosis. The greater improvement in productivity seen in patients with IA suggests that treatment for IA improves work productivity.
Subject(s)
Absenteeism , Cost of Illness , Efficiency , Osteoarthritis , Presenteeism , Humans , Middle Aged , Male , Female , Osteoarthritis/economics , Osteoarthritis/diagnosis , Osteoarthritis/therapy , Presenteeism/economics , Time Factors , Adult , Aged , Unemployment , Employment/economics , Arthritis/economics , Arthritis/diagnosis , Arthritis/therapy , Arthritis, Rheumatoid/economics , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , IncomeABSTRACT
OBJECTIVE: To examine the burden of non-communicable diseases (NCDs) among women of reproductive age in Kenya, highlighting the prevalence and risk factors. DESIGN: Cross-sectional design based on the 2022 Kenya Demographic and Health Survey. SETTING: Kenya. PRIMARY OUTCOMES: Predict the burden of hypertension, diabetes, heart disease, lung disease, arthritis, depression, anxiety, breast and cervical cancer. RESULTS: Overall, 15.9% of Kenyan women aged 15-49 years were living with at least one NCD. The most prevalent NCD among this cohort was hypertension (8.7%) followed by arthritis (2.9%) and depression (2.8%). Our findings revealed that increasing age, increasing wealth, being married or formerly married, being overweight or obese, consuming alcohol and some occupations were risk factors of NCDs among women of reproductive age in Kenya. CONCLUSION: We conclude that hypertension is the most prevalent NCD among women of reproductive age in Kenya. The findings underscore the multifaceted nature of NCD risk factors in Kenya, emphasising the importance of targeted interventions that consider age, economic status, education, marital status, occupation and lifestyle factors.