Blockades in the Pathway of Specialty Care in Rheumatoid Arthritis: A Report Based on Indian Rheumatology Association Database.

AIM: The study aims to identify factors influencing referral patterns and delays in rheumatoid arthritis (RA) patients across clinical settings in India. MATERIALS AND METHODS: A prospective, multicenter, observational study collected data from eight centers using the Indian Rheumatology Association (IRA) database. Patient-related factors and referral factors were determined based on patient narration. The modified PRASAD scale categorized patients' socioeconomic status. RESULTS: The study included 4,643 RA patients from eight centers. Data from 35 patients were excluded due to inconsistent reporting of diagnosis and delay. Lack of awareness was the predominant factor causing the delay in referral. Approximately, 39% of patients were referred to the rheumatology specialty within 6 months of disease onset, while 26% reported later, and 34% reported over 2 years. Referral delays were linked to socioeconomic factors in Madhya Pradesh (21.43%) and West Bengal (28.57%). Lack of awareness about the disease and rheumatology specialty was highest in West Bengal (100%), followed by Delhi and Rajasthan (93.70%). Misconceptions about modern medicine, reluctance to refer patients to the rheumatologist, and previous treatment by other specialities were other factors influencing referral delay. Primary care clinicians' unawareness of the rheumatology specialty was the primary reason for referral delay in Gujarat (33.56%) and Delhi and Rajasthan (25.18%). CONCLUSION: Both patient and healthcare professional-related factors contribute to referral delays in RA patients. Major factors causing referral delays include reluctance to refer and inadequate knowledge about rheumatology among primary care physicians and the general public. Patients' education and occupation also influence the timing of referrals to specialty care.

MRI predictors of infectious etiology in patients with unilateral sacroiliitis.

BACKGROUND: Unilateral presentation of sacroiliitis is a diagnostic dilemma, especially between infection and inflammatory sacroiliitis associated with spondyloarthritis, requiring an early and accurate diagnosis. OBJECTIVE: To assess the utility of magnetic resonance imaging (MRI) in differentiating infective versus inflammatory etiology in unilateral sacroiliitis. MATERIALS AND METHODS: Retrospective review of the MRI of 90 patients with unilateral sacroiliitis, having an established final diagnosis. MR images were evaluated for various bone and soft tissue changes using predefined criteria and analyzed using univariate and multivariate regression analysis. RESULTS: Among the 90 patients, infective etiology was diagnosed in 66 (73.3%) and inflammatory etiology in 24 (26.7%). Large erosions, both iliac and sacral-sided edema, joint space involvement with effusion or synovitis, soft tissue edema, elevated ESR/CRP, and absence of capsulitis and enthesitis were associated with infection (p < .001). The independently differentiating variables favoring infection on multivariate analysis were-both iliac and sacral-sided edema (OR 4.79, 95% CI: 0.96-23.81, p = .05), large erosions (OR 17.96, 95% CI: 2.66-121.02, p = .003), and joint space involvement (OR 9.9, 95% CI: 1.36-72.06, p = .02). Exclusive features of infection were osteomyelitis, sequestra, abscesses, sinus tracts, large erosions, and multifocality. All infective cases had soft tissue edema, joint space involvement, elevated ESR, and no capsulitis. CONCLUSION: MRI evaluation for the presence and pattern of bone and joint space involvement, soft tissue involvement, and careful attention to certain exclusive features will aid in differentiating infectious sacroiliitis from inflammatory sacroiliitis.

A pilot study of childhood-onset Takayasu arteritis using whole exome sequencing suggests oligogenic inheritance involving classical complement, collagen, and autoinflammatory pathways.

Takayasu arteritis (TA) is a chronic granulomatous inflammatory disease affecting the aorta and its branches. Paediatric TA (pTA) may present from 6 months after birth till the adolescent age group. Genetics and pathogenesis of pTA are not fully understood. Earlier studies reported monogenic mutation in NOD2, XIAP, and STAT1 genes in patients with pTA. TA, a relatively rare disease, is more common in geographical pockets, including India. We hypothesized that South Asian patients with pTA, namely, those of Indian subcontinent origin, may have clinically relevant and unique pathogenic variants involving one or more genes, especially those linked to genetically driven vasculitic illnesses, including autoinflammatory pathologies. Children with pTA fulfilling EULAR/PRINTO/PReS classification criteria and presenting with clinical symptoms to the Paediatric Rheumatology clinic of Christian Medical College, Vellore, were included. Blood samples were collected after getting informed consent from parents or guardians and assent forms from children. DNA was extracted from whole blood using the Qiagen DNA extraction kit. Initially, the common variant in Indian population, namely, ADA2 c.139G > A; p.Gly47Arg, was screened, followed by whole exome sequencing. Fourteen children were recruited for the study. Median age of patients was 11 years (4 months-14 years) with a male-to-female ratio of 4:10. Distribution of angiographic subsets by Numano's classification of included children were as follows: type 5 (n = 7), type 4 (n = 5), and type 3 (n = 2). We identified novel variants in ten different genes. This include variants in genes of classical complement pathway, namely, C2, C3, C6, C7, and C9, and other genes, namely, CYBA, SH3BP2, GUCY2C, CTC1, COL5A1, and NLPR3. Two of 14 patients have heterozygous pathogenic variants; this implies that combination of heterozygous variants in C3 and COL5A1 might lead to disease development, suggesting digenic inheritance. One patient has a homozygous variant in CYBA. None of the patients were identified to have ADA2 variants. Whole exome sequencing reveals combination of rare variants in genes C3, COL5A1, and CYBA associated with disease development in children with Takayasu Arteritis. Key Points • We identified novel variants in genes of classical complement pathway, namely, C2, C3, C6, C7, and C9, and other genes, namely, CYBA, SH3BP2, GUCY2C, CTC1, COL5A1, and NLPR3. • Two of 14 patients have heterozygous pathogenic variants in C3 and COL5A1; this may have implications in disease development, suggesting digenic inheritance. • One patient has homozygous variant in CYBA. • None of the patients were identified to have ADA2 variants.

Study of pathogenic T-helper cell subsets in Asian Indian patients with Takayasu arteritis.

The relapses and refractory disease are a challenge in the management of patients with Takayasu arteritis (TAK). We quantified pathogenic CD4 + memory T helper cells bearing surface markers CD161 and/or p-glycoprotein (MDR1) in patients with TAK. Peripheral blood mononuclear cells of 21 patients with TAK and 16 age-matched controls were stained with anti-CD3, anti-CD4, anti-CD45RA, anti-CD161 and anti-p-glycoprotein antibodies and subjected to flow cytometry by FACS ARIAIII. Eighteen patients underwent follow-up immunophenotyping. Intracellular staining for interleukin-17 and interferon-γ was performed for 18 patients and 11 controls. Surgical arterial biopsies of 6 TAK and 5 non-inflammatory controls were subjected to immunohistochemistry with anti-CD161 and anti-p-glycoprotein. At baseline the frequency of MDR1 + CD4 + and CD161 + MDR1 + CD4 + memory T cells was higher in TAK than controls (p = 0.002 and 0.01, respectively). After stimulation, the frequency of IFN-y + CD161 + cells was higher in TAK than controls (p = 0.028). Modal fluorescence intensity of CD161 + MDR1 + CD45RA - CD4 + cells was higher in active as compared with stable disease (p = 0.041). At 6 months, MDR1 + and CD161 + MDR1 + memory CD4 + T cells decreased significantly only in patients who had complete/partial response to treatment (p = 0.047 and 0.02, respectively). To conclude, MDR1 + and MDR1 + CD161 + CD4 + memory T-helper cells are increased in patients with TAK. These cells decreased only in patients with response to treatment during subsequent follow-up.

Coalition for Health and Gender Equity (CHANGE)-a protocol for a global cross-sectional survey of health and gender equity in rheumatology.

Objectives: The primary aim of the CHANGE survey is to determine the current state of gender equity within rheumatology, and secondarily, to review the physician perspective on bullying, harassment and equipoise of opportunities within rheumatology. Methods: The CHANGE e-survey is a cross-sectional self-reported questionnaire adapted from EULAR's gender equity in academic rheumatology task force. The survey was launched in January 2023; it is available in six languages and distributed widely via rheumatology organizations and social media. Eligible participants include rheumatologist physicians and rheumatology health-care professionals. Survey responses will undergo descriptive analysis and inter-group comparison aiming to explore gender-based discrimination using logistic regression, with subgroup analyses for country/continent variations. Conclusion: This e-survey represents a comprehensive global initiative led by an international consortium, aimed at exploring and investigating the gender-related disparities and obstacles encountered by rheumatologists and rheumatology health-care professionals across diverse communities and health-care environments. By pursuing this initiative, we aim to take the broader rheumatology community a step closer to understanding the underlying origins of inequities and their determinants. Such insights are pivotal in identifying viable interventions and strategies to foster gender equity within the field. Ultimately, our collective objective is to ensure equitable access to opportunities for every individual, irrespective of gender, thereby promoting inclusivity and fairness across the entire spectrum of professional practice and career development.