Inflammatory Disease Arthritis Research Articles

P23 A case of visceral leishmaniasis presenting as seropositive erosive rheumatoid arthritis in an immunocompromised patient

Abstract Introduction Visceral leishmaniasis (VL) is a potentially fatal parasitic infection occurring primarily in the tropics, subtropics, and southern Europe. A strong humoral response can be observed in VL due to polyclonal activation of B-lymphocytes, and it can also result in the production of rheumatoid factor (RF), anti-CCP and anti-nuclear antibodies. We present this case here of visceral leishmaniasis presenting as seropositive RA on the background of HIV and hepatitis B infection. Case description We present a case of a 46-year-old Caucasian male with a two-year history of skin nodules, symmetrical arthralgia and weight loss. He was diagnosed with HIV a decade ago which was well controlled with bictegravir, emtricitabine and tenofovir alafenamide. He received pulmonary tuberculosis (TB) treatment in 2012 and had chronic e-antigen-positive hepatitis B. He previously resided in Ukraine and travelled frequently to Crimea and the Middle East. There was no history of Raynaud’s, chest pain, shortness of breath, sicca symptoms, mouth ulcers, genital ulcers, hair loss or photosensitivity. On examination, he was cachectic with generalised lymphadenopathy and multiple subcutaneous (1-2cm, firm, mildly tender, non-ulcerating) forearm nodules. There was synovitis on two joints but no tenosynovitis or joint deformity. Initial investigations revealed pancytopenia, hyperuricemia, proteinuria, positive RF (>200 IU/ml) and anti-CCP, positive ANA and anti-Ro antibody and erosion of proximal phalanx of the big toe bilaterally. His CD4 count was 166 (33%) with undetectable HIV viral load. Imaging showed lymphadenopathy and splenomegaly (17.5cm). A diagnosis of rheumatoid arthritis with possible connective tissue disease overlap was made and he was initiated on hydroxychloroquine. Because of systemic symptoms and atypical skin nodules, further investigation was undertaken including lymph node, bone marrow and skin biopsies, all of which confirmed a diagnosis of leishmaniasis. Blood PCR was positive for L. donovani complex, and serological analysis showed direct agglutination test and k39 Ag positivity. Treatment was initiated by the infectious diseases team initially with amphotericin B 40 mg/kg monotherapy, later on further amphotericin B 30 mg/kg and miltefisone. He responded well as evidenced by reduced splenomegaly, resolution of skin nodules and improvement in cytopenia. His joint symptoms also improved except for the recurrence of ankle pain for which he received intra-articular steroids. Discussion It has been widely reported in literature that leishmaniasis can trigger autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosis. There have also been multiple studies confirming the presence of rheumatoid factor, anti-CCP and ANA in patients with leishmaniasis without any presence of symptomatic autoimmune disease. The mechanisms involved in the pathophysiology of autoantibody productions are not yet fully understood. There is some evidence that these are related to activation of polyclonal B cells due to a decreased regulatory T cell activity. Another possible mechanism would be production of autoantigen in response to cross reaction between the parasite and the hoarse tissue antigens. There have been multiple case reports of leishmaniasis in patients with rheumatoid arthritis who were taking anti-TNF biologics. This represents the reactivation of leishmaniasis due to immunosuppression. There has been a long-known link between HIV infection and leishmaniasis. Our patient was a known case of HIV. Interestingly, not only did he have significantly positive rheumatoid factor, anti-CCP, ANA and anti-Ro antibodies, but he also had active synovitis on his joints and even erosions were seen on the X-ray. He fulfilled the criteria for rheumatoid arthritis. Our case was unique in the sense that this is a case of visceral leishmaniasis in an HIV patient who presented with rheumatoid arthritis. Skin nodules in this patient were appearing similar to rheumatoid nodules. Later on, the biopsy confirmed that these were due to leishmaniasis. It is also a challenge to manage RA in patients with HIV especially when have already an opportunistic infection like leishmaniasis. A high prevalence of hyperuricemia in HIV infection has been reported in multiple studies. Our case did have raised urate but his disease was not consistent with gout clinically. Key learning points • This is a rare case showing seropositive erosive RA coexisting with VL in an HIV patient, underscoring the link between autoimmune diseases and chronic infections. Chronic infections are always considered an important differential in inflammatory arthritis or connective tissue disease especially when they present with systemic features of fever, weight loss and organomegaly. • Although this disease is considered rare in the Western hemisphere, in the diverse, multiethnic and immigrant UK population this should be considered an important differential diagnosis. Another key element in clenching these diagnoses is detailed travel history. Multidisciplinary approach is key in managing such difficult cases. Our case was managed jointly by the rheumatology, dermatology and infectious disease teams, and the national leishmaniasis multidisciplinary team from University College London Hospitals. • It is important to do a holistic assessment for these patients and get help from other specialities especially in such challenging cases.

Long Term Outcomes of Pain, Disability and Quality of Life in Open vs Minimally Invasive Surgery of Transforaminal Lumbar Interbody Fusion

Objective: This study aims to evaluate the short- and long-term outcomes—specifically in terms of pain, disability, and quality of life—between minimally invasive surgery (MIS) and open transforaminal lumbar interbody fusion (TLIF) for treating lumbar spondylolisthesis. Study Design and Setting: A prospective cohort study was carried out at Liaquat National Hospital & Medical College, Karachi, and a teaching institution in South Asia. The study included patients with chronic back pain for over three months, unresponsive to medical treatment or accompanied by radicular symptoms, with MRI-confirmed grade I and II degenerative lumbar spondylolisthesis, lateral recess stenosis, and unilateral disc herniation. Patients with spinal metastasis, previous surgeries, inflammatory arthritis, or metabolic bone diseases were excluded. Methodology: The outcomes of MIS-TLIF and open-TLIF were assessed using the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and SF-36 quality of life scores at 1, 6, and 24 months postoperatively. Results: Among 93 patients, 35 underwent open-TLIF and 58 received MIS-TLIF. MIS-TLIF resulted in significantly less blood loss and faster recovery. At four weeks, the MIS group had lower VAS and ODI scores, and higher SF-36 scores. Similar trends continued at six months, with improvements in ODI and SF-36. By 24 months, the MIS group maintained lower ODI scores, though VAS and SF-36 scores were comparable. Conclusion: MIS-TLIF shows superior outcomes, especially in the early postoperative phase, with reduced morbidity and improved quality of life, making it a preferable option in resource-limited settings.

Acute phase reactants

The serum concentrations of certain proteins are altered in various conditions such as infection, trauma, inflammatory arthritis, malignancy, autoimmune and systemic inflammatory diseases. These proteins are known as positive or negative acute phase reactants. While albumin and transferrin belong to the negative acute phase reactants, alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-2-macroglobulin, C-reactive protein, ceruloplasmin, haptoglobin, serum amyloid A and fibrinogen are known as positive acute phase reactants. This review discusses the clinical use of C-reactive protein, erythrocyte sedimentation rate and procalcitonin.

Deficiency of interleukin-1 receptor antagonist in mice differentially affects bone properties under different genomic backgrounds

When IL-1 receptor antagonist (IL-1rn) is knocked out, mice have shown strain background dependent and major QTL regulated susceptibility to spontaneously inflammatory arthritis disease (SAD). The impact on bone properties resulting from the interactions of IL-1rn, genomic background strains, and the QTL locus, is unknown. Bone properties in the four specifically bred mouse strains with mutation of IL-1rn and variations in genomic components were investigated with high-resolution MicroCT and genomic analytical tools. Two congenic mouse strains were also measured to evaluate the influence on bone properties by a QTL in the region in chromosome 1. Our results reveal that several bone phenotypes, including bone mineral density (BMD), bone volume, tibial length, and cortical thickness of the tibia are different between wild type and IL-1rn knockout mice in both Balb/c and DBA/1 backgrounds, but IL-1rn knockout affects BMD differently between the two mouse strains. The absence of IL-1rn decreases BMD in Balb/c mice but increases BMD in DBA/1−/− mice compared to their respective wild type counterparts. A QTL transferred from the Balb/c genetic background which affects arthritis in congenic strains appears to also regulate BMD. While several genes, including Ctsg and Prg2, may affect BMD, Ifi202b is the most favored candidate gene for regulating BMD as well as SAD. In conclusion, the previously mentioned bone phenotypes are each influenced in different ways by the loss of IL-1ra when considered in mice from varying genomic backgrounds.

The mode of action of IL-23 in experimental inflammatory arthritic pain and disease

ObjectivesWe have previously reported using gene-deficient mice that the interleukin (IL)-23p19 subunit is required for the development of innate immune-driven arthritic pain and disease. We aimed to explore here, using a number of in vivo approaches, how the IL-23p19 subunit can mechanistically control arthritic pain and disease in a T- and B- lymphocyte-independent manner.MethodsWe used the zymosan-induced arthritis (ZIA) model in wild-type and Il23p19−/− mice, by a radiation chimera approach, and by single cell RNAseq and qPCR analyses, to identify the IL23p19-expressing and IL-23-responding cell type(s) in the inflamed joints. This model was also utilized to investigate the efficacy of IL-23p19 subunit blockade with a neutralizing monoclonal antibody (mAb). A novel IL-23-driven arthritis model was established, allowing the identification of putative downstream mediators of IL-23 in the control of pain and disease. Pain and arthritis were assessed by relative static weight distribution and histology, respectively.ResultsWe present evidence that (i) IL-23p19+ non-bone marrow-derived macrophages are required for the development of ZIA pain and disease, (ii) prophylactic and therapeutic blockade of the IL-23p19 subunit ameliorate ZIA pain and disease and (iii) systemically administered IL-23 can induce arthritic pain and disease in a manner dependent on TNF, GM-CSF, CCL17 and cyclooxygenase activity, but independently of lymphocytes, CGRP, NGF and substance P.ConclusionsThe data presented should aid IL-23 targeting both in the choice of inflammatory disease to be treated and the design of clinical trials.

Effects of the concentration of seeds, finite time-dependent supersaturations, and viscosity on the crystallization kinetics of monosodium urate monohydrate.

Although the crystallization of monosodium urate monohydrate (MSUM) has a crucial role in the occurrence of gout, which is an inflammatory arthritis disease, theoretical models have not been able to describe all features observed in its seeded growth kinetics. In contrast to previous modeling approaches, we show that our model can reproduce qualitative features typically observed in experiments. In particular, our results show that the higher the initial supersaturation and the lower the viscosity, the faster the crystallization kinetics, and they also indicate that there are distinct growth regimes for low and high concentrations of seeds. In this work, we introduce an alternative approach based on a master equation that allows us to incorporate hypotheses for the seeded growth crystallization of MSUM in a more transparent way. Such an approach includes not only effects that are related to the finite time-dependent supersaturation and concentration of seeds, but it can also be used to determine how the viscosity of the solution can affect the crystallization kinetics of MSUM molecules.

Prevalence and Risk Factors of Postacute Sequelae of COVID-19 in Adults With Systemic Autoimmune Rheumatic Diseases.

Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded > 12 weeks following the reported infection. Respondents were 91.6% female, 91.2% White, median (IQR) age was 48 (40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). Eighty-nine of 299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an effect on QOL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2 [2-3] vs 3 [2-3]; P < 0.001) and more reinfections (16.9% vs 5.7%; P = 0.004). In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections.

Incidence of checkpoint inhibitor-associated inflammatory arthritis, immunomodulation and mortality in cancer patients on immunotherapy: a retrospective cohort study.

Immune checkpoint inhibitor (ICI) associated inflammatory arthritis (ICI-IA) occurs in 4-6% of ICI-treated patients based on one observational study. We identified cases of ICI-IA using administrative claims to study its incidence and characteristics at the population level. We used the Medicare 5% sample to identify patients initiating ICIs. Cancer patients were identified by having ≥ 2 ICD-9/10-CM diagnosis codes from an oncologist for lung cancer, melanoma, or renal/urothelial cancer. ICI-IA was defined as having two Medicare claims ≥ 30 days apart with combinations of ICD-9/10-CM diagnosis codes that favored specificity. ICI-IA was identified in patients with a musculoskeletal diagnosis after ICI initiation, who had i.) no inflammatory arthritis or inflammatory rheumatic disease before ICI initiation ever, and ii) no musculoskeletal complaint in the one year prior to ICI. We examined DMARD utilization and visits to rheumatology in patients with ICI-IA. Landmark analysis and a time varying Cox proportional hazards model for overall survival was constructed. The incidence of ICI-IA was 7.2 (6.1-8.4) per 100 patient years. Patients with ICI-IA were mean (SD) age 73.5(7.0) years, 48% women, 91% white. Median(IQR) time from ICI initiation to first ICI-IA diagnosis was 124(56, 252) days. Only 24(16%) received care from a rheumatologist, and 24(16%) were prescribed a DMARD (46% by a rheumatologist). The HR for mortality in patients with ICI-IA was 0.86 (95% CI 0.59-1.26, p= 0.45). The incidence of ICI-IA identified in claims data is similar to that reported in observational studies, however, few patients are treated with a DMARD or see a rheumatologist. There was no difference in overall survival between ICI-treated patients with and without ICI-IA.

History and Familial Aggregation of Immune-Mediated Diseases in Sarcoidosis: A Register-Based Case-Control-Family Study

An autoimmune component in the cause of sarcoidosis long has been debated, but population-based data on the clustering of immune-mediated diseases (IMDs) and sarcoidosis in individuals and families suggestive of shared cause is limited. Do patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis? We conducted a case-control family study (2001-2020). Patients with sarcoidosis (N= 14,146) were identified in the Swedish National Patient Register using a previously validated definition (≥ 2 International Classification of Diseases [ICD]-coded inpatient or outpatient visits). At diagnosis, patients were matched to up to 10 control participants from the general population (N= 118,478) for birth year, sex, and residential location. Patients, control participants, and their first-degree relatives (FDRs; Multi-Generation Register) were ascertained for IMDs by means of ICD codes in the Patient Register (1968-2020). Conditional logistic regression was used to estimate ORs and 95%CIs of sarcoidosis associated with a history of IMDs in patients and control participants and in FDRs. Patients with sarcoidosis exhibited a higher prevalence of IMDs compared with control participants (7.7%vs4.7%), especially connective tissue diseases, cytopenia, and celiac disease. Familial aggregation was observed across IMDs; the strongest association was with celiac disease (OR, 2.09; 95%CI, 1.22-3.58), followed by cytopenia (OR, 1.88; 95%CI, 0.97-3.65), thyroiditis (OR, 1.72; 95%CI, 1.14-2.60), skin psoriasis (OR, 1.70; 95%CI, 1.34-2.15), inflammatory bowel disease (OR, 1.53; 95%CI, 1.14-2.03), immune-mediated arthritis (OR, 1.49; 95%CI, 1.20-1.85), and connective tissue disease (OR, 1.39; 95%CI, 1.00-1.93). IMDs confer a higher risk of sarcoidosis and they aggregate in families with sarcoidosis, signaling a shared cause between IMDs and sarcoidosis. Our findings warrant further evaluation of shared genetic mechanisms.

Identification of Drug Related Problems (DRPs) in Rheumatoid Arthritis Patients at Palembang City Hospital

Background: Rheumatoid arthritis is a chronic systemic inflammatory arthritis disease that affects mainly synovial joints. The incident of RA can lead to the emergence of complications or comorbidities, which then allows patients to receive a variety of therapies that can trigger the incidence of DRPs during the treatment. The prevalence of RA in Indonesia itself in 2018 has reached 7.30%, with the highest percentage occurring in the elderly age group and more prevalent in women. Objective: This study aimed to determine the incidence of DRPs in RA patients in Palembang city hospitals based on the category of DRPs identified as related to drug selection and dose selection problems, as the relationship between demographic factors and the incidence of DRPs. Methods: This research is non-experimental study conducted with a retrospective cross-sectional survey. Data collection was carried out by looking at patient medical record data at X and Y Hospital in Palembang from January 2021 to March 2023. Results: The results showed that the most frequent drps in the drug selection category were drug interactions (72.03%), while in the dose selection category were insufficient dosage regimens (60.74%). The results of bivariate analysis between the incidence of DRPs and gender (p=0.809), age (p=0.879), the number of drugs used (p=0.001), and comorbidities (p=0.089). Conclusion: There is no relationship between demographic factors and comorbidities with the incidence of DRPs, and there is a relationship between the number of drugs and the incidence of DRPs.

Neuropsychiatric symptoms in Systemic Lupus Erythematosus: mixed methods analysis of patient-derived attributional evidence in the international INSPIRE project.

Attribution of neuropsychiatric symptoms in systemic lupus erythematosus (SLE) relies heavily on clinician assessment. Limited clinic time, variable knowledge, and symptom under-reporting contributes to discordance between clinician assessments and patient symptoms. We obtained attributional data directly from patients and clinicians in order to estimate and compare potential levels of direct attribution to SLE of multiple neuropsychiatric symptoms using different patient-derived measures. Quantitative and qualitative data analysed included: prevalence and frequency of neuropsychiatric symptoms, response to corticosteroids, and concurrence of neuropsychiatric symptoms with non-neuropsychiatric SLE disease activity. SLE patients were also compared with controls and inflammatory arthritis (IA) patients to explore attributability of neuropsychiatric symptoms to the direct disease effects on the brain/nervous system. We recruited 2,817 participants, including 400 clinicians. SLE patients (n = 609) reported significantly higher prevalences of neuropsychiatric symptoms than controls (n = 463) and IA patients (n = 489). SLE and IA patients' quantitative data demonstrated multiple neuropsychiatric symptoms relapsing/remitting with other disease symptoms such as joint pain. Over 45% of SLE patients reported resolution/improvement of fatigue, positive sensory symptoms, severe headache, and cognitive dysfunction with corticosteroids. Evidence of direct attributability in SLE was highest for hallucinations and severe headache. SLE patients had greater reported improvement from corticosteroids (p= 0.008), and greater relapsing-remitting with disease activity (p< 0.001) in the comparisons with IA patients for severe headache. Clinician and patients reported insufficient time to discuss patient-reported attributional evidence. Symptoms viewed as indirectly related/non-attributable were often less prioritised for discussion and treatment. We found evidence indicating varying levels of direct attributability of both common and previously unexplored neuropsychiatric symptoms in SLE patients, with hallucinations and severe headache assessed as the most directly attributable. There may also be-currently under-estimated-direct effects on the nervous system in IA and other systemic rheumatological diseases.

Optimizing the Maastricht Work-Related Support intervention in clinical patient care: the value of integrating action research into intervention mapping

BackgroundHealthcare professionals (HCPs) are increasingly recommended to play an important role in supporting people with chronic disease in work participation. An intervention for HCPs to provide work-related support to their patients in clinical care was developed with intervention mapping (Maastricht Work-Related Support; Maastricht WRS). Action research proposes ‘combining research and practice’, which allows us to incorporate experiences of HCPs while implementing and to realize intervention’s full potential. Therefore, the aim of this study is to explore, by integrating action research into an intervention mapping approach, how experiences of HCPs with early implementation can be used to optimize the Maastricht WRS in clinical care.MethodsSemi-structured interviews were held with nine HCPs (response rate 82%), involved in care for people with inflammatory arthritis, knee problems or inflammatory bowel disease. Some of them were not yet trained in the Maastricht WRS while others had received the training and were providing the Maastricht WRS.ResultsAll participants regarded WRS an important part of clinical care. Untrained HCPs indicated a lack of knowledge and skills in providing the Maastricht WRS, and a need for tools. Trained HCPs were satisfied with the training and tools, but stressed that practical limitations hindered providing the Maastricht WRS. Action research showed that the intervention meets the needs of HCPs, but need some optimizations: (1) organizing ‘intervision’ for HCPs, (2) inform and activate patients to discuss work with their HCP, (3) update initial tools and (4) including patients’ work status in the electronic patient system.ConclusionsAction research integrated into intervention mapping proved to improve the Maastricht WRS intervention. By involving HCPs, the intervention could be optimized to provide to support people with chronic diseases in clinical care in healthy and sustainable work participation.

Reactive Granulomatous Dermatitis: A Descriptive Study of 10 Patients.

Reactive granulomatous dermatitis (RGD) is a rare and misunderstood skin disorder. It includes interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: 2 entities of the same spectrum. Multiple associations are described with RGD in the literature, including autoimmune diseases, malignancy, and drugs. To report and describe the suspected associations with RGD at the time of diagnosis and in the following year. We retrieved and described cases of RGD confirmed by skin biopsy and clinicopathologic correlation. All patients were evaluated in the Centre Hospitalier Universitaire de Québec-Université Laval between January 2000 and December 2020. Collected data include the systemic diseases (autoimmune disease, malignancy) and suspected drugs, in addition to the clinical presentation and prescribed treatments. Out of the 10 patients with RGD, 7 patients were known to have an autoimmune disease at the time of diagnosis. They either had inflammatory arthritis (3/10) or inflammatory bowel disease (4/10). There was a clinical suspicion of a possible association with a tumor necrosis factor (TNF) inhibitor in 2 of these 7 patients. Among the 3 patients with idiopathic RGD at the time of diagnosis, 1 patient developed a high-grade B-cell lymphoma 6 months later. There was no new association identified in the following year for patients with a known autoimmune condition. This descriptive study supports RGD and its previously described systemic associations, particularly autoimmune diseases, malignancy, and certain drugs (specifically TNF inhibitors). The majority of patients already had one of these associations identified at the time of histopathological diagnosis.

Inflammatory arthritis and eye diseases: a Mendelian randomization study.

The aim of this study was to determine causal associations between inflammatory arthritis and eye diseases (disorders of sclera, cornea, iris, and ciliary body [DSCIC] and disorders of choroid and retina [DCR]). Genome-wide association studies' summary data of rheumatoid arthritis (RA) from a large-scale meta-analysis were used to identify genetically predicted RA. UK Biobank source data predicted ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA). Furthermore, data from the FinnGen Biobank were used to identify genetically predicted eye diseases. Two-sample Mendelian randomization analysis was used to assess the causal relationship between inflammatory arthritis and eye diseases in the European population. Inverse-variance weighting (IVW) was used as the primary method, while MR-Egger, weighted median, and MR-PRESSO outlier test were used to detect heterogeneity and pleiotropy. Genetically determined RA was indeed observed to have a causal effect on DSCIC (odds ratio [OR] = 1.084, p = 2.353 × 10-10) and DCR (OR = 1.151, p = 1.584 × 10-19). AS was causally associated with DSCIC (OR = 1.068, p < 2.024 × 10-8). In addition, PsA was also found to have a causal association with an increased risk of 17.9% for the development of DSCIC (OR = 1.179, p = 0.003). On the flip side, DSCIC increased the risk of JIA (OR = 2.276, p = 0.003). Our study provided genetic evidence for the causal associations of RA, AS, and PsA with an increased risk of DSCIC, and a causal association between RA and DCR was also identified. In addition, DSCIC greatly increased the risk of JIA.

Occupational impacts of early inflammatory arthritis: results from the National Early Inflammatory Arthritis Audit.

Inflammatory arthritis causes significant work disability. Studies regarding this frequently fail to report important contextual information such as employment type. Our objective was to explore work participation, by gender and occupation type, in early inflammatory arthritis. Data are from the National Early Inflammatory Arthritis Audit for 2018-2020. At diagnosis, clinicians collected information on demographics, inflammatory arthritis disease activity, and working status. Participants completed patient-reported outcomes at baseline, 3 months and 12 months, including occupation and Work Productivity and Activity Impairment (WPAI). Descriptive analyses of work participation and WPAI scores by occupational class at all time points were performed. Regression models were used to examine associations between WPAI score and occupation. In all, 12 473 people received a diagnosis of inflammatory arthritis and reported employment status, among whom 5999 (47%) were in paid work for at least 20 hours/week. At diagnosis, the working cohort had statistically significant lower measures of disease activity (P < 0.001). Occupational data were available for 3694 individuals. At diagnosis, 2793 completed a WPAI; 200 (7.2%) had stopped work and 344 (12.3%) changed jobs because of inflammatory arthritis symptoms. There was a high burden of absenteeism (30%) and presenteeism (40%). Compared with managerial or professional workers, the burden of work disability was greater among those in routine (manual) occupations. During follow-up, 9.4% of WPAI completers stopped work and 14.6% changed roles. Work drop-out occurred almost entirely among people doing routine jobs. It is easier to retain work in certain employment sectors. Participation in routine jobs is more affected, which may widen health inequalities.

Association of Interleukin-6 and Tumor Necrosis Factor-alpha Gene Polymorphisms with Gnetic Susceptibility of Psoriatic Arthritis in Kuwaiti Arab Patients

Background: Psoriatic arthritis (PsA) is an inflammatory arthritic disease in which joint inflammation occurs with psoriasis. It results from a complex interplay between genetic, immunological and environmental factors. In PsA, the activation of T cells is considered as a crucial step in the disease process. The T-lymphocytes affect the proliferation of epidermal skin cells and result in abnormal differentiation. Altered cytokine networks have been shown to play a central role in the pathogenesis of PsA. Psoriasis is characterized by Th-1 type cytokine pattern in which there is a marked variation in the secretion of interleukin-6 (IL6), interleukin-13 (IL13) and Tumor necrosis factor-alpha (TNF-alpha). This study investigated the association of IL6, IL13 and TNF-alpha gene polymorphisms with genetic susceptibility of PsA in Kuwaiti patients. Methods: The genotypes of IL6 gene (-174G/C; rs1800795), IL13 gene (R130Q; rs20541) and TNF-alpha gene (-308A/G’ rs1800629) polymorphisms were detected in 113 Kuwaiti PsA patients and were compared to that in 104 healthy controls. The PsA patients were diagnosed on the basis of the presence of inflammatory arthritis with psoriasis with no rheumatoid factor in the serum. The genotypes for IL6, IL13 and TNF-alpha gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods and were confirmed by DNA sequencing. Results: The frequency of IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G’ rs1800629) polymorphisms manifested a statistically significant difference between Kuwaiti PsA patients and controls. However, the frequency of IL13 gene (R130Q; rs20541) polymorphism did not show a significant difference between Kuwaiti PsA patients and the controls. Conclusion: Our data show an association of two cytokine gene polymorphisms in IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G’ rs1800629) with PsA in Kuwaiti patients highlighting their significant contribution to genetic susceptibility of this chronic disease possibly along with other factors.

Are Patients With Systemic Sclerosis Subject to an Increased Risk of Developing Superficial Erosion of Atherosclerotic Plaques?

Various inflammatory rheumatic diseases (RDs) are associated with an increased risk of developing cardiovascular (CV) disease. Increased cardiovascular morbidity and mortality has been reported in inflammatory arthritis (including rheumatoid arthritis, psoriatic arthritis, gout, and spondyloarthritis) and connective tissue disease (including vasculitis, systemic lupus erythematosus, and systemic sclerosis [SSc]).

Circ_0002984 promotes proliferation, migration and inflammatory cytokine secretion and inhibits apoptosis of rheumatoid arthritis fibroblast-like synoviocytes by inducing PCSK6 through miR-543

BackgroundRheumatoid arthritis (RA) is inflammatory arthritic disease, and circular RNA is involved in RA development. The aim of the present work is to analyze the role of circ_0002984 in the process of RA fibroblast-like synoviocytes (RAFLSs) and the underlying mechanism.MethodsCirc_0002984, miR-543, and proprotein convertase subtilisin/kexin type 6 (PCSK6) expression levels were analyzed by quantitative real-time polymerase chain reaction or western blotting. Cell proliferation, migration, inflammatory response, and apoptosis were investigated through 5-Ethynyl-2′-deoxyuridine assay, wound-healing assay, enzyme-linked immunosorbent assay, and flow cytometry analysis. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to assess the binding relationship.ResultsCirc_0002984 and PCSK6 expression were increased, while miR-543 expression was decreased in the synovial tissues of RA patients and RAFLSs. Circ_0002984 introduction facilitated RAFLS cell proliferation, migration and inflammatory response and repressed apoptosis, but circ_0002984 knockdown had an opposite role. Circ_0002984 targeted miR-543, and PCSK6 was targeted by miR-543. MiR-543 downregulation or PCSK6 overexpression restored the effects of circ_0002984 interference on RAFLS phenotypes.ConclusionCirc_0002984 promoted RAFLS proliferation, migration and inflammatory cytokine secretion and inhibited apoptosis by binding to miR-543 to induce PCSK6 production, providing a potential target for RA therapy.

High-sensitivity cardiac troponin T is associated with disease activity in patients with inflammatory arthritis.

To investigate whether high-sensitivity cardiac troponin T (hsTnT) correlates to markers of disease activity in inflammatory arthritis (IA), and whether antirheumatic treatment influences hsTnT levels. We assessed 115 patients with active IA (64 rheumatoid arthritis (RA), 31 psoriatic arthritis and 20 ankylosing spondylitis) before and after using methotrexate (MTX) alone or tumor necrosis factor inhibitor (TNFi) with or without MTX co-medication (TNFi±MTX). All patients starting with TNFi had been previously unsuccessfully treated with MTX monotherapy. HsTnT (measured in serum by electro-chemiluminescence immunoassay (Roche Elecsys® Troponin T- high-sensitivity)), and other clinical and laboratory parameters were evaluated at baseline, and after 6 weeks and 6 months of treatment. Of markers of disease activity, baseline levels of hsTnT positively correlated with Physicians' Global Assessment Score of disease activity in the total patient cohort (p = 0.039). In RA group, hsTnT positively correlated with swollen joints, Disease Activity Score for 28 joints with ESR and serum tumor necrosis factor levels (p = 0.025, p = 0.008, p = 0.01, respectively). Median hsTnT at baseline was 5.0 ng/L, and did not change significantly at 6-week visit (6.0 ng/L, p = 0.37) and 6-month visit (6.0 ng/L, p = 0.18) with either antirheumatic therapy. HsTnT levels were associated with inflammatory markers for IA disease activity. However, while inflammatory markers significantly improved after antirheumatic treatment, hsTnT did not change during the 6-month follow-up period.

Perceptions towards biologic and biosimilar therapy of patients with rheumatic and gastroenterological conditions

BackgroundBiologic and targeted synthetic disease modifying agents (b/tsDMARDs) have broadened the treatment landscape for autoimmune diseases particularly in patients refractory to conventional DMARDs. More recently, the introduction of biosimilars has reduced the price of bDMARDs, potentially improving accessibility. Though efficacy and safety have been described, patient attitudes to b/tsDMARDs are not well-understood. We aim to investigate patients’ beliefs about biologic and biosimilar therapy, and the factors influencing their perceptions.MethodsPatient consumer groups (Arthritis Australia, Crohn’s and Colitis Australia) assisted in advertising an online questionnaire for people with a self-reported diagnosis of inflammatory arthritis (IA) or inflammatory bowel disease (IBD). The questionnaire incorporated the Belief about Medicines Questionnaire (BMQ) and the single-item literacy screener (SILS). Sources and favourability of biologic/biosimilar information were analysed, using the chi-square and a non-parametric trend test for unordered and ordered categorical variables respectively, comparing respondents with IA and IBD.ResultsEight hundred and thirty eight people (686–IA, 144–IBD, 8 both) responded. 658 (79%) used b/tsDMARDs. The BMQ demonstrated high necessity belief (median 4.2) with moderate concerns (median 2.8) about biologics. 95% of respondents obtained medication information from specialists though most used multiple sources (median 4). The most positive resources were specialists and specialist nurses. 73/141 (52%) respondents with IBD obtained information from specialist nurses compared with 202/685 (29%) with IA (p = 0.012). Respondents with limited reading ability on SILS were more likely to discuss information with a general practitioner or pharmacist. Younger respondents and those with higher BMQ concern scores more frequently consulted less reliable sources (e.g. social media). 502 respondents (60%) answered the biosimilar questions. Only 23 (4.6%) reported currently using a biosimilar and 336 (66.9%) were unsure if biosimilars were available in Australia. Specialist recommendation was the most frequent factor that would influence a patient to change from originator to biosimilar (352/495, 71.1%).ConclusionsThere is a high level of trust in specialists’ recommendations about b/tsDMARDs, although most people also utilise additional information sources. Contextual factors influencing resource selection include age, reading ability and degree of concern about medicines. People with IA and IBD have similar attitudes though those with IBD more frequently access specialist nurse advice.