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.

Extracellular mitochondrial components as new biomarkers for lupus nephritis.

Major reason for mortality among systemic lupus erythematosus patients is renal failure due to the deposition of immune complexes in the glomeruli. Being a chronic disease with multiple relapses and remissions across the lifespan, it's important to know the degree of nephritis for diagnosis as well as the long-term clinical management of the patients. Currently, renal biopsy is being used as the gold standard to diagnose and define the stages of the disease. However, renal biopsy being invasive only provides a localized picture of nephritis, and has the risk of bleeding. Additionally, it is also cost-intensive. Hence, a reliable, non-invasive biomarker is required for lupus nephritis. This study has evaluated extracellular mitochondrial components, including cell-free mitochondria, and cell-free mitochondrial DNA as probable biomarkers of the degree of nephritis. Both showed a significant correlation with proteinuria and protein-creatinine ratio. Our study substantiates their usage as clinical biomarkers of nephritis upon their validation in a larger cohort of lupus nephritis patients and other forms of nephritis. Although the current data suggest using cell-free mitochondria as a biomarker of lupus nephritis is better than the cell-free mitochondrial DNA.

SARS-CoV-2 seroprevalence in patients with autoimmune rheumatic diseases versus family controls: a multi-city cross-sectional survey.

There is uncertainty regarding the effect of the SARS-CoV-2 infection on patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressive drugs. We did a multicity cross-sectional seroprevalence study conducted in five different cities in India before COVID-19 immunization. Patients with a diagnosis of AIRD and DMARDs were included. Relatives of the patients, preferably staying in the same household with no known rheumatic diseases served as controls. Serum IgG antibodies to SARS-CoV-2 Receptor Binding Domain (RBD) of the spike protein and nucleoprotein (NP) were assayed in eight hundred and eighty nine sera (subjects with disease = 379 and in subjects without disease = 510). IgG antibodies to either RBD and/or NP were positive in 135 (36%) subjects with AIRD as compared to 196 (38%) controls. The seroprevalence of anti-RBD and anti-NP varied between different cities but was not significantly different between subjects with and without disease in Mumbai, Ahmedabad, Bengaluru and Bhubaneswar. However, the occurrence of IgG antibodies to RBD was significantly (p < 0.05) lower in subjects with disease (28/65;43%) as compared to subjects without disease (42/65;65%) in Kolkata, where the positivity rate was lower in connective tissue disease group than in inflammatory arthritis group. Overall, patients with rheumatic diseases on DMARDs have IgG antibodies to RBD and NP of SARSCoV-2 at a comparable level with that of subjects without disease, but the level of antibodies to RBD is lower in patients with connective tissue disease on immunosuppressive drugs in one centre.

Granulomatous nephritis: A rare presentation of juvenile-onset sarcoidosis.

Sarcoidosis is rare in children. Incidence and prevalence of sarcoidosis in India are not known. Renal involvement in childhood sarcoidosis is further rare with no clear data about prevalence. Here we report a case of a 13-year-old girl who presented with sarcoidosis with multi-system involvement including renal sarcoidosis. She initially presented with pyrexia of unknown origin and cervical lymphadenopathy - evaluation of which led to diagnosis of sarcoidosis. Later, after development of pulmonary involvement, she was treated with oral prednisolone and azathioprine. She again defaulted on medicines and later presented with renal failure and was diagnosed with a renal sarcoidosis. She was treated with oral prednisolone and mycophenolate mofetil with which she gradually improved with normal renal functions.

Clinical features, severity and outcome of acute pancreatitis in systemic lupus erythematosus.

Acute pancreatitis (AP) is a rare but life threatening manifestation of Systemic Lupus Erythematosus (SLE). The current study aims to study the clinical characteristics, severity, mortality, and outcome of SLE-related AP in Indian population. We retrospectively reviewed medical records of patients with SLE who had AP in the past. Data from 13 rheumatology centers across India were compiled. All patients satisfied SLICC criteria for SLE and ATLANTA criteria for AP. AP was classified in to mild, moderate and severe using revised Atlanta classification. Patients with known risk factors like gall stone and alcohol were excluded.Sixty-six patients (six, children) were studied. Majority of patients were females (82%). The median age of presentation was 24 (11-63) years and most patients (57.5%) presented within first year of diagnosis of lupus. AP occurred mostly in the setting of active lupus (89%). Active nephritis was seen in 39% while a fourth had CNS disease. Patients with severe AP had lower C3. Ascites and sepsis were most common local and systemic complications, respectively. Mortality was 17%. Hypocalcemia, presence of sepsis and shock predicted mortality. In the multivariate analysis, only presence of shock remained as independent predictor of death (OR 63.0, 95% CI: 5.2-760.3). Pancreatitis is an early manifestation of SLE and is associated with active disease. Significant mortality is seen particularly with severe pancreatitis.

Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region.

BACKGROUND: Clinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates from multinational studies in the Asia-Pacific region are limited. We conducted a cross-sectional multicentric study to evaluate the clinical remission status and the related factors in RA patients in the Asia-Pacific region. METHODS: RA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries from APLAR RA SIG group. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine related factors of remission. FINDINGS: A total of 2010 RA patients was included in the study, the overall remission rates were 62•3% (DAS28-CRP), 35•5% (DAS28-ESR), 30•8% (CDAI), 26•5% (SDAI), 24•7% (Boolean), and 17•1% (CliDR), respectively, and varied from countries to countries in the Asia-Pacific region. Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prescription rate was low (17•9%). Compared to patients in non-remission, patients in remission had higher rates of b/tsDMARDs usage and lower rates of GC usage. The favorable related factors were male sex, younger age, fewer comorbidities, fewer extra-articular manifestations (EAM), and use of b/tsDMARDs, while treatment with GC was negatively related to remission. INTERPRETATION: Remission rates were low and varied in the Asia-Pacific region. Treatment with b/tsDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region.

The Role of Echocardiography in Evaluation of Takayasu's Arteritis: A Report of Two Cases.

Takayasu's arteritis (TA) is a large-vessel chronic inflammatory vasculitis that leads to thrombotic vascular occlusion. This can lead to varied presentations including limb claudication, ischemic stroke, hypertension, and heart failure. Although contrast computed tomography angiography is the main modality for imaging of the aorta and its branches, transthoracic echocardiography can be an easy-to-access, point-of-care, initial screening tool for evaluating the aorta and other cardiac structures. We present echocardiographic images from two cases that demonstrate the important cardiac structural and vascular afflictions of TA.

Tofacitinib in the treatment of Indian patients with rheumatoid arthritis: A post hoc analysis of efficacy and safety in Phase 3 and long-term extension studies over 7 years.

OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized tofacitinib efficacy/safety in Indian vs rest of the world (ROW; excluding India) RA patients. METHODS: Efficacy data were pooled for disease-modified antirheumatic drug (DMARD) inadequate responders from Phase (P)3 studies. For Indian patients, ORAL Solo and ORAL Scan; ROW (excluding India), these studies plus ORAL Step, ORAL Sync, and ORAL Standard. Safety data also included ORAL Start (P3; methotrexate-naïve) and ORAL Sequel (long-term extension [LTE] study; data cut-off March 2017) for Indian patients, and these studies plus A3921041 (LTE study; Japanese study) for ROW. Efficacy outcomes at months 3/6: American College of Rheumatology (ACR)20/50/70; Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission/low disease activity; change from baseline in Health Assessment Questionnaire-Disability Index. Incidence rates (IRs; patients with events/100 patient-years) for adverse events of special interest (AESIs) were assessed throughout. Descriptive data underwent no formal comparison. RESULTS: One-hundred-and-ninety-seven Indian and 3879 ROW patients were included. Compared with ROW patients, Indian patients were younger, had lower body mass index, shorter RA duration, and higher baseline disease activity; most Indian patients were non-smokers and all were biologic DMARD (bDMARD)-naïve. Month 3 ACR20 rates with tofacitinib 5 mg twice daily/10 mg twice daily/placebo were 67.4%/82.1%/40.9% (India) and 59.0%/66.1%/28.2% (ROW), and month 6 rates were 76.2%/92.1%/88.9% (India) and 69.0%/74.2%/66.5% (ROW). Month 3/6 improvements in other outcomes were generally numerically greater with tofacitinib vs placebo, and similar in both populations. Compared with ROW, Indian patients had numerically fewer AEs/serious AEs, and similar IRs for discontinuations due to AEs and AESIs, except that tuberculosis (TB) IR was higher in Indian (IR = 1.21; 95% CI 0.49, 2.49) vs ROW patients (IR = 0.17; 95% CI 0.11, 0.25). CONCLUSIONS: Tofacitinib efficacy/safety were similar in both populations, except TB IR, which was higher in Indian patients but in line with those in bDMARD-treated RA patients from high-risk countries (IR = 0.00-2.56; TB IR >0.05 [World Health Organization]). Limitations included the small Indian population and baseline differences between populations.

Arthritis in sarcoidosis: A multicentric study from India.

INTRODUCTION: Ten to 15% of patients with sarcoidosis have associated arthritis. Chronic arthritis is fairly uncommon. There is a paucity of data on articular manifestations of the disease from India. METHODS: Case records of adult patients with sarcoidosis presenting to 11 rheumatology centers from 2005 to 2017 were retrospectively reviewed. Joint involvement was assessed clinically, classified as acute or chronic depending on duration of symptoms less or greater than 6 months, respectively. RESULTS: A total of 117 patients with sarcoid arthritis were reviewed. Forty-five patients were classified as having Lofgren's syndrome. The pattern of joint involvement revealed the ankle to be most commonly affected in both the groups. Shoulder, wrist, metacarpophalangeal, proximal interphalangeal joints of hands and knee joint involvement were significantly more common in chronic sarcoid arthritis. Peripheral lymphadenopathy and uveitis were significantly more frequent in chronic sarcoid arthritis. Forty out of 49 patients with acute arthritis followed up over a median of 1.8 years had achieved complete remission. Twelve out of 16 chronic sarcoid arthritis (median follow up 2.5 years) had achieved complete remission with 15, 12 and five patients on steroids, methotrexate and hydroxychloroquine, respectively. One patient with acute sarcoid arthritis with concomitant interstitial lung disease had died due to lung infection. CONCLUSION: Acute oligoarthritis was the commonest presentation with the ankle being the most commonly affected joint. Upper limb joint (predominantly distal) and knee involvement were more common as reported in our largest series worldwide of chronic sarcoid arthritis in adults. Hilar adenopathy and erythema nodosum were common extra-articular features in both acute and chronic sarcoid arthritis. A limitation of the study was the retrospective nature of the analysis.

Smoking cessation advice by rheumatologists: results of an international survey.

OBJECTIVE: The aim of this study was to understand practices regarding smoking cessation among rheumatologists for patients with inflammatory rheumatic diseases. METHODS: A survey was sent to the rheumatologists participating in the multinational Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) group. The survey inquired about the clinical practice characteristics and practices regarding smoking cessation (proportion of smokers with inflammatory rheumatic diseases given smoking cessation advice, specific protocols and written advice material, availability of dedicated smoking cessation clinic). RESULTS: Rheumatologists from 44 departments in 25 countries (16 European) completed the survey. The survey involved 395 rheumatologists, of whom 25 (6.3%) were smokers, and 199 nurses for patient education, of whom 44 (22.1%) were smokers. Eight departments (18.1 %) had a specific protocol for smoking cessation; 255 (64.5%) rheumatologists reported giving smoking cessation advice to all or almost all smokers with inflammatory diseases. In a regression model, early arthritis clinics (P = 0.01) and high gross domestic product countries (P = 0.001) were both independently associated with advice by the rheumatologist. Nurse gives advice to most patients in 11 of the 36 (30.5%) departments with nurses for patient education. CONCLUSION: Advice for smoking cessation within rheumatology departments is not homogeneous. In half of the departments, most doctors give advice to quit smoking to all or almost all patients with inflammatory diseases. However, only one in five departments have a specific protocol for smoking cessation. Our data highlight the need to improve awareness of the importance of and better practice implementation of smoking cessation advice for inflammatory rheumatic disease patients.

Determinants of discordance in patients' and physicians' rating of rheumatoid arthritis disease activity.

OBJECTIVE: To assess the determinants of patients' (PTGL) and physicians' (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them. METHODS: A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0-10-cm visual analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within ±2 cm), higher patient rating group (PTGL exceeding MDGL by >2 cm), and lower patient rating group (PTGL less than MDGL by >2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance. RESULTS: The mean ± SD VAS scores for PTGL and MDGL were 4.01 ± 2.70 and 2.91 ± 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher, and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels. CONCLUSION: Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the "disease experience" of patients, particularly pain and fatigue, is warranted for effective care of RA.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study.

INTRODUCTION: Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. METHODS: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. RESULTS: At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. CONCLUSIONS: Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

IL1RN*2 allele of IL-1receptor antagonist VNTR polymorphism is associated with susceptibility to ankylosing [corrected] spondylitis in Indian patients.

Despite strong linkage of ankylosing spondylitis (AS) with human leukocyte antigen (HLA) B27, its contribution to disease susceptibility is only 15%, and additional genetic factors are likely to be involved in AS. Interleukin (IL)-1 locus has been linked to AS in European population. Thus, we studied IL-1 receptor antagonist polymorphism in Indian patients with AS. One hundred and sixty-two patients with AS and ethnically matched healthy controls were included. IL-1Ra variable number tandem repeat polymorphism was studied by polymerase chain reaction (PCR). HLA B27 was done by amplification refractory mutation system PCR. Clinical details regarding severity of articular disease, presence of peripheral arthritis, and extra-articular manifestations were collected. The mean age of these 162 patients was 35 years, and the mean duration of disease was 10.8 years. Of these 162 patients, 137 were HLA B27 positive. The commoner alleles--IL-1RN*1 and IL-1RN*2--together accounted for 99.5% of the IL-1RN alleles in the control population and 98.5% of the cases. The allele frequency as well as the carriage rate of allele IL-1RN*2 were significantly higher in patients with AS than the control populations (26.3 vs 16.2% and 41.97 vs 22.5%, respectively; p=0.015 and 0.0002). The IL-1RN*2 allele was not associated with any difference in clinical disease expression. The IL-1RN*2 allele is a susceptibility marker for AS in the Indian population but does not influence disease phenotype.

Wegener's granulomatosis--an etiology of acute pancreatitis.

Wegener's granulomatosis is a systemic disease that usually involves the upper respiratory tract and kidneys. We report a 47-year-old man with Wegener's granulomatosis that presented as acute pancreatitis.

Methotrexate twice weekly vs once weekly in rheumatoid arthritis: a pilot double-blind, controlled study.

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatoid drug used in patients with rheumatoid arthritis. It is usually given on a weekly schedule, but as the half-life of its active compound, the polyglutamate MTX, is 3 days, we did a pilot study to see if MTX twice weekly is superior to MTX once weekly. Eighty patients with rheumatoid arthritis (RA) fulfilling the American College of Rheumatology (ACR) criteria were enrolled into a double-blind, controlled trial of 16-week duration. Patients achieving ACR scores of 20 and 50 were determined at 8 and 16 weeks. In addition, the incidence of hepatotoxicity was also studied. Of the 80 patients, 66 completed 8 weeks of study, whereas 53 completed 16 weeks of study. Most withdrawals were because of inefficacy. At 8 weeks, ACR 20 response (24/34 in once weekly and 22/32 in twice weekly) and ACR 50 response (16/34 in once weekly and 16/32 in twice weekly) in both groups were similar. Even at 16 weeks, there was no significant difference in ACR 20 and ACR 50 responses. Intent-to-treat analysis also yielded similar results. Five patients in each group had a mild reversible rise in transaminases. Our study suggests that MTX twice weekly has no advantage over once weekly regarding efficacy, and thus the currently used once weekly regimen is good enough till alternate dosing schedules are evaluated in a large multicentric trial.