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Introduction Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. Methods We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. Results Through the study period (April–December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. Conclusion Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort.

COVID-19; Registries; Vaccination COVID-19; Registros; Vacunación COVID-19; Registres; Vacunació Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups. HC is supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

Objectives The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in RA patients. Methods An online self-reported questionnaire (March–December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs). Descriptive and multivariable regression analyses were performed. Results Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA; they had a mean (s.d.) age of 50.7 (13.7) years, 74.2% were women and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both odds ratio [OR] = 0.7; 95% CI: 0.5, 0.9), and injection site pain (OR = 0.6; 95% CI: 0.5, 0.8) with similar major AE and hospitalization frequencies. Conclusion Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs, providing reassurance as to the safety of COVID-19 vaccination.

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in uncertainty and negative psychological outcomes for patients with autoimmune rheumatic diseases for several reasons. It is essential to understand the level of anxiety among rheumatic disease patients at the current situation of COVID-19. Objectives and Methods: A web-based cross-sectional multicenter survey was done across 5 rheumatology centers in India. The study duration was between 9th May and May 16, 2020. The questionnaire included consent, demographic details, medication history, opinion about tele rheumatology services, and anxiety score measured by Beck Anxiety Inventory. Results: The survey was sent to 2987 patients, there were 933 responses, and 581 were complete (male = 175). Complete responses were considered for data analysis. Rheumatoid arthritis was the most frequent (50.6%) diagnosis followed by other conditions. Most of the patients (43%) were on combination disease-modifying anti-rheumatic drug therapy, 12.7% of patients were on biological drugs, and 23.9% of patients were on glucocorticoids (GCs). Statistically significant higher anxiety scores were observed in females (8.79 ± 9.3), fibromyalgia patients (19.78 ± 14.8), patients on GCs (9.26 ± 8.8), and biological agents (10.65 ± 10.6). Difficulty in meeting rheumatologists and getting medications was expressed by 327 (56.2%) and 73 (29.7%) respondents, respectively. Conclusion: The findings of the study revealed that anxiety is a major concern in patients with autoimmune rheumatic diseases. Fibromyalgia patients and those who were on GC and biological drugs were found to have more anxiety levels compared to other groups of patients. There is a need to intensify the awareness and address the mental health issues.

Introduction Identifying factors predicting adverse pregnancy outcomes involving systemic lupus erythematosus (SLE) is a research priority. The aims of this study were to investigate (a) the maternal and fetal outcomes of pregnant lupus patients and the factors associated with adverse pregnancy outcomes, and (b) the effect of pregnancy on lupus disease activity of these patients. Methods This was an ambi-directional study collecting information from five multi-specialist referral centres across the state of Karnataka, India over 5 years (2013–2018). Clinical details of pregnancies and outcomes that were temporally associated with lupus disease were recorded using a structured pro forma. The Safety of Estrogen in SLE National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) was used to assess lupus activity during the 6 months prior to pregnancy and the intra- and post-partum periods. Modifications suggested in the SLE Pregnancy Disease Activity Index were considered while scoring. Results A total of 121 pregnancies in 80 SLE patients with a mean age of 27.1 (±4.5) years and with a mean disease duration of 4.6 (±4.1) years were reviewed. Largely patients were in clinical remission (109/121; 90.1%). Antiphospholipid antibody positivity was seen in 45/121 (37.2%) patients. A history of lupus nephritis was noted in 29/121 (24%) patients. Maternal complications (32%) were mainly due to hypertensive disorders of pregnancy (HDP; 19/121; 15.7%). Adverse fetal outcomes (58%) were mainly in the form of spontaneous first-trimester abortions (21/121; 16%), stillbirth (14/121; 11.6%) and prematurity (24/121; 20%). HDP is strongly associated with stillbirth and prematurity and is independent of active lupus. Disease activity was associated with a three-fold increased risk of adverse fetal outcome in univariate analysis. The risk of major flare during pregnancy is low (4.1%) when conception occurs during stable disease. Hydroxychloroquine (HCQ) use was associated with reduced risk of flare ( p = 0.001) in patients in remission at the time of conception. Conclusions The risk of major flare during pregnancy is low when conception happens during stable disease. HCQ use was associated with reduced risk of flare in patients in remission at the time of conception. HDP was strongly associated with stillbirth and prematurity and are independent of active lupus in our cohort.

Background We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs). Methods This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome. Results COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5–20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p Conclusions Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-05046-4.

There is limited evidence on the effects of myofascial release on fibromyalgia symptoms. This review aims to update the evidence on the effectiveness of myofascial release on pain, sleep, and quality of life in patients with fibromyalgia syndrome.The review was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Scopus, Cochrane Library, Physiotherapy Evidence Database, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature Complete, and ProQuest Medical library were searched from their inception to April 1, 2021 for randomized or nonrandomized clinical trials published in English. Studies consisting of myofascial release alone or in combination with exercise as the intervention were included. The quality of the studies was evaluated using Cochrane Risk of Bias 2.0.Six studies, including a total of 279 participants, were included in the review. The meta-analysis showed a large significant effect of myofascial release on pain posttreatment (-0.81[95% CI = -1.15 to -0.47], p 0.00001) and a moderate effect at 6 months post-treatment (-0.61, 95% CI = -0.95 to -0.28, p = 0.0003).The review demonstrated moderate evidence for the effect of therapist administered and self-myofascial release in improving pain, sleep subscales, and quality of life against sham and no treatment, respectively, in fibromyalgia syndrome patients. However, more high-quality randomized controlled trials with manual control group are required to be conducted at different geographical locations to generalize the findings.

Biologic disease-modifying anti-rheumatic drugs (bDMARD) have transformed the treatment paradigm of chronic autoimmune rheumatic diseases (ARDs), but they are often associated with adverse drug reactions. The present study evaluated the frequency, characteristics and type of infections, other than tuberculosis (TB), in ARD patients receiving bDMARDs. The multicentre, cross-sectional, retrospective, observational study was conducted across 12 centers in Karnataka, India, between January to August 2016. The study included patients receiving bDMARD therapy for various ARDs. Outcome variables considered were any infection, minor infections and major infections, other than TB. Clinical variables were compared between infection and no infection group, and the increase in the likelihood of infection with respect to various clinical variables was assessed. The study involved 209 subjects with a median (range) age of 41 (16–84) years and male to female ratio of 0.97:1. A total of 29 (13.88%) subjects developed infection following bDMARD therapy, out of whom a majority had minor infection (n = 26). The likelihood of developing any infection was noted to be more in subjects receiving anti-TNF (golimumab, P = 0.03) and those on three or more conventional synthetic (cs) DMARDs (P

Introduction: Biologics are widely used in Autoimmune rheumatologic diseases (AIRDs), however the need to capture real life data which monitors indications, adverse reactions cannot be over emphasized. Methods: This is a cross-sectional ambidirectional multi-center study conducted over 8 months from January 2016 to August 2016, across 12 tertiary care rheumatology centers in Karnataka, India conducted by members of the Karnataka Rheumatology Association. Results: The most common biologic prescribed is tumour necrosis factor antagonist etanercept. Commonest indication for biologics being Spondyloarthropathy group of disorders. The most common cause for stopping biologics is clinical improvement. Only 4.8% of patents discontinued biologics due to ADRs. Conclusion: The prescribing patterns, mode of use, prebiologics screening methods, and adverse event profile are similar across centres. Pre-screening for latent tuberculosis (TB) is consistent across centres, and TB prophylaxis appears to be effective in preventing its reactivation.

A man in his 60s developed reactive arthritis following treatment with intravesical Bacillus Calmette-Guerin (iBCG) for papillary carcinoma of bladder. Evaluation revealed leucocytosis and raised inflammatory markers. HLA B27 was positive. Based on the temporal relationship, it was attributed to BCG-related reactive arthritis. iBCG was stopped. Treatment with non-steroidal anti-inflammatory drugs (NSAIDS) and glucocorticoids were ineffective. Prolonged course of disease-modifying antirheumatic drugs (DMARDS) was required which aided in alleviation of symptoms and sustained remission. Intravesical BCG therapy is a treatment for bladder cancer. It is rarely associated with reactive arthritis, which responds to discontinuation of iBCG and treatment with NSAIDS and/or short-term glucocorticoids. iBCG-related reactive arthritis commonly has an acute/subacute course. Chronic arthritis as observed in our case requiring prolonged treatment with DMARDS is rare.

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.

The aim was to study the prevalence of comorbidities in rheumatoid arthritis (RA) patients in everyday clinical practice and their association with disease-specific and demographic factors. The multi-center study recruited 3,247 (at 14 centers, and 265) were excluded due to incomplete data. The number of subjects considered for the analysis was 2982. The mean (±standard deviation) age was 48.98±12.64 years and the male-to-female ratio was 1:5. The data was collected based on a pre-structured pro forma by trained clinical research associates through interview and verification of charts and reports available in the patient records. The following comorbidities were studied: cardiovascular disease, hypertension, diabetes mellitus, hypercholesterolemia, thyroid disease, psychiatric diseases like depression, and pulmonary disease. Hypertension (20.7%), diabetes mellitus (14.4%) and thyroid disease (18.3%) were the most prevalent comorbidities. Hypercholesterolemia (5.3%), pulmonary diseases (2.1%), cardiovascular diseases (0.2%) and depression (0.03%) were prevalent in ≤5% of the study population. The overall presence of comorbidity increased with age and reduced with the duration of illness prior (DOIP). The age, gender, and DOIP differed significantly between groups with and without hypercholesterolemia. Females had a statistically increased prevalence of thyroid disease. The prevalence of comorbidities in RA patients from south India is around 40% and the incidence of comorbidity increased with age. As per the literature evidence, the prevalence in the current study subjects was higher when compared to prevalence of similar diseases occurring in the general south Indian population.

Aim Tuberculosis (TB) is one of the major adverse events of concern associated with the use of biologics for managing autoimmune inflammatory rheumatic diseases (AIRDs). The study presents the data on incidence of TB in relation to biologic used, screening test and TB prophylaxis in a real-world setting. Methods The cross-sectional, observational, retrospective study was conducted across 12 centres in Karnataka, India. The study included patients receiving biologics therapy for AIRDs, established based on the respective diagnostic criteria. The development of TB after receiving biologic therapy and other clinical variables and the predictability of the test performed for latent TB were evaluated. Results One hundred and ninety-five AIRDs patients with an average age of 41 years were initiated on biologic therapy. Twenty-one patients were latent TB positive and were given antitubercular prophylaxis, prior to biologics treatment. During follow-up, seven patients belonging to the negative test group (n = 174) developed TB. The negative predictive values noted for Mantoux test (n = 120) and quantiFERON TB gold test (n = 178) were 96.52% and 96.25%, respectively. Patients on anti-tumor necrosis factor were more likely to develop TB. Presence of comorbidities and steroid use increased the likelihood of developing TB by 1.5 and 4.6 times, respectively. Conclusion Close monitoring of patients receiving biologics is essential for early identification of adverse events, especially in test negative patients. Prophylaxis can effectively reduce the risk of developing TB in patients positive for screening.

Aim Methotrexate (MTX) has the potential to cause serious adverse reactions and even mortality. We analyzed the predisposing factors and outcome in patients with MTX-induced pancytopenia admitted into our unit from 1996 to 2015. Methods Patients were identified by departmental database search. Pancytopenia was defined as white blood cell count (WBC) < 3500 cells/mm3, hemoglobin (Hb) < 11 g/dL and platelet count < 150 000 cells/mm3. Severe pancytopenia was defined as WBC < 2000 cells/mm3, Hb < 10 g/dL and platelet count < 50 000 cells/mm3. Results Forty-six patients were included in the study (female = 35). Twenty-four had been under the care of either primary care physicians or orthopedic surgeons and presented to us with pancytopenia. Sixteen patients had severe pancytopenia. Disease distribution was as follows: rheumatoid arthritis 33, psoriasis eight, systemic sclerosis two and others three. The median dose of MTX was 10 mg/week and median duration of treatment was 11 months. The median cumulative dose was 750 mg. Symptoms at presentation included: oral mucositis (n = 37); fever (n = 24); diarrhea (n = 12), bleeding gums (n = 5) and purpura (n = 3). The potential risk factors were: hypoalbuminemia (n = 23), renal insufficiency (n = 14), dosing errors (n = 13) and non-supplementation of folates (n = 7). Thirteen patients died. WBC at admission was found to determine survival (P < 0.05). Conclusion In patients on MTX, oral mucositis and fever can herald pancytopenia. MTX-induced pancytopenia is associated with high mortality. WBC at admission is the most important prognostic factor. There is need for increased awareness among physicians to minimize prescribing errors. A national guideline on monitoring of patients on MTX is desirable.

Aim The use of healthcare resources by rheumatoid arthritis (RA) patients can be related to the presence of disease, comorbid conditions, use of steroids, and the combined use of immunosuppressants. This study evaluated the risk factors associated with infection and hospitalization in RA. Methods This multicenter, cross-sectional study enrolled 3247 RA subjects fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria to examine the prevalence of hospitalization and episodes of documentable non-tubercular infections as a part of the "Karnataka rheumatoid arthritis comorbidity" study (KRAC). The study included 2081 subjects and 1166 were excluded due to incomplete data. Demographic, clinical and treatment variables were collected, and the events related to infections and hospitalization were extracted from the medical records. Comparative analysis and multivariate logistic regression were performed. Results Around 22% of the subjects had hospitalizations and 2.9% had infections. Infections were pertaining to dental (1.3%), urinary tract (1.6%) and candidiasis (0.2%). Skin- and soft tissue-related infections were found in 1.8% and 0.3% of patients, respectively. Increased need of hospitalization in RA patients was associated with advanced age (≥60 years), lower education, family income, and longer duration of RA. Presence of comorbidity, usage of three or more disease-modifying anti-rheumatic drugs (DMARDs) and family income influenced the likelihood of infection. Dental infections were less likely in working subjects and more likely in patients with increased disease duration, higher family income, comorbidities and those between the age group 40-59 years. Urinary tract infection was associated with DMARD usage. Conclusion Patient-specific risk factors should be considered to improve treatment strategies and to reduce the risk of infection and hospitalization in RA patients.

To study the prevalence of remission in rheumatoid arthritis (RA) patients and the influence of different factors like literacy, socioeconomic status, presence of comorbidity and treatment strategy in achieving remission.The study involved 1990 RA patients who were recruited for the Karnataka Rheumatoid arthritis comorbidity (KRAC) study. Based on the factors evaluated, the study participants were classified as follows: age,30 years, 30-39 years, 40-49 years, 50-59 years and ≥ 60 years; educational status, illiterate/no formal education, high school or less, graduate, post-graduate and doctorate; family income (₹ per annum),50 000, 50-100 000, 100-500 000, and500 000; duration of illness prior (DOIP): ≤ 6 months, 6-24 months, 24-120 months and120 months. Joint counts were performed by a rheumatologist or trained joint assessor. To assess the treatment outcome, the disease activity score was calculated using the Disease activity Score of 28 joints - erythrocyte sedimentation rate (DAS 28-3 ESR).As per the DAS 28-3 ESR score, around 20% (n = 397) of the study subjects achieved remission. The corresponding mean ± SD of DAS 28-3 ESR noted for remission and non-remission groups were 2.13 ± 0.42 and 4.32 ± 1.28. The majority of the patients were treated with double disease-modifying anti-rheumatic drugs (DMARDs) (60.7%). The likelihood of remission was found to be more in patients who reported DOIP ≤ 6 months. Furthermore, the chances of remission reduced with increase in patient's age and the highest remission rate was noted for 30-39 years age group (59%), followed by 40-49 years (35.4%) and 50-59 years (19.7%).The prevalence of remission noted was around 20%. Early treatment, escalating dose of DMARDs, and patient counseling are important contributing factors for attaining remission.

Juvenile arthritis damage index (JADI) consists of two parts which measure articular (JADI-A) and extra-articular (JADI-E) damage in patients with juvenile idiopathic arthritis (JIA). It does not include assessment of cardiac dysfunction and joint areas commonly affected in enthesitis-related arthritis (ERA) category of JIA. We have tried to study if modification of JADI will improve its performance in JIA-ERA. We studied 101 consecutive patients of JIA-ERA. JADI-A was modified (JADI-AM) to include damage assessment of tarsal joints and lumbar spine. JADI-E was modified (JADI-EM) to include assessment of symptomatic cardiac dysfunction. The performances of the modified and standard JADI were compared. Ninety-seven patients were male. The median age was 18 years (9–36). At a median disease duration of 6 years (1–24), joint damage was observed in 47 as assessed by JADI-A. JADI-AM could identify 11 more patients (N = 58) with articular damage. JADI-AM had good correlation with number of joints with limitation of movement (Spearman’s [rS] = 0.9) and low to moderate correlation (rS

Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease (KFD) is a rare, benign and self-limiting disorder that characteristically presents with fever and cervical lymphadenopathy. Articular manifestations in the form of arthralgias are common but frank arthritis is distinctly rare and dactylitis has not been reported yet. Herein, we describe a young boy who presented with arthritis and dactylitis as the initial manifestation of KFD. A 14-year-old boy presented with a two-week history of fever, generalized lymphadenopathy and asymmetric polyarthritis, enthesitis and dactylitis of the toes. Two years earlier he presented with arthritis of the knee and ankle joints, which lasted for 12 months. However, he had been asymptomatic for one year. Investigations revealed anemia, leukopenia and raised acute phase reactants. Work-up for infectious etiology, systemic lupus erythematosus and leukemia and lymphoma was negative. Excision biopsy of the cervical lymph node confirmed KFD. Fever, lymphadenopathy and leukopenia dissipated with nonsteroidal anti inflammatory drug therapy, but the arthritis persisted. A trial of methotrexate led to the resolution of the arthritis.

Methotrexate (MTX) has gained wide acceptance among both patients and rheumatologists due to its efficacy and safe therapeutic window in a variety of inflammatory rheumatological disorders. However, it has the potential to cause serious, life-threatening complications and even mortality. In the present series, we have reviewed our data of five patients who developed serious pancytopenia after the use of MTX, including one who died. Two of these resulted from prescription errors by primary care physicians. The clinical, laboratory, and outcome profile of all five cases are discussed with a brief review of the literature about MTX-induced pancytopenia. There is an urgent need to increase awareness in primary care physicians, patients, and pharmacists toward informed prescribing, dispensing, and monitoring of MTX to prevent such mishaps in the future.

1Departments of Radiodiagnosis, 2Immunology, 3Neurology, 4Microbiology, Sanjay Gandhi postgraduate Institute of Medical Sciences, Lucknow, India. Correspondence: Dr. Vikas Agarwal, email: vikasagr@sgpgi.ac.in Dear Editor Cerebral infections are a major cause of morbidity and mortality in systemic lupus erythematosus (SLE).1 Susceptibility to infection may be due to abnormalities in complements, mannose binding lectin, phagocytes, T or B lymphocytes or due to immuosuppressive treatment.2 Patients are predisposed to viral, bacterial, and fungal infections.3 Cryptococcal meningitis has been rarely reported in SLE. It may mimic neuropsychiatric SLE.4 Because of the protean clinical manifestations, magnetic resonance imaging (MRI) may be performed early to detect possible aetiology. MRI is more sensitive than computerized tomography for the diagnosis of cryptococcal meningitis. However, MRI may be normal even during active CNS infection. Herein we present two cases of SLE with cryptococcal meningitis whose MRI was normal at presentation.

Objective.Membrane-bound receptor for advanced glycation endproducts (mRAGE) is overexpressed in response to increasing concentrations of its ligand (e.g., S100A12) and triggers an inflammatory immune response. In contrast, soluble RAGE (sRAGE) acts as a decoy receptor and downmodulates inflammation. Decreased sRAGE levels are associated with autoimmune diseases; however, limited data are available in juvenile idiopathic arthritis (JIA). We studied sRAGE levels in patients with JIA [enthesitis-related arthritis (ERA) category].Methods.sRAGE levels were estimated in the serum of patients with ERA JIA (n = 101), systemic-onset JIA and polyarticular JIA (n = 10 each), and healthy controls (n = 45). Synovial fluid (SF) sRAGE was measured in patients with ERA, rheumatoid arthritis, reactive arthritis, and osteoarthritis (n = 10). Levels of S100A12 were also measured. Twenty-four patients with ERA were followed for 4 months. Disease activity was assessed by swollen joint count (SJC), tender joint count (TJC), and erythrocyte sedimentation rate (ESR). All levels are expressed as median (range).Results.The serum sRAGE (pg/ml) level was significantly lower in patients compared to healthy controls [515 (64–1887) vs 1542 (627–3159); p < 0.0001]. In paired samples, SF had lower levels compared to corresponding plasma level [102 (51–799) vs 481 (134–1006); p < 0.0001]. The level of S100A12 (ng/ml) was higher in SF (1042; 573–1415) than serum (638; 208–779). Serum sRAGE correlated negatively with S100A12 levels (r = −0.474; p < 0.01.), ESR (r = −0.306; p < 0.01), and SJC (r = −0.237; p < 0.05), but not with TJC (r = −0.134; p = NS). The levels of sRAGE remained stable over time in patients with stable disease.Conclusion.Levels of sRAGE are reduced in patients with ERA and correlate negatively with disease activity and S100A12 levels. sRAGE may be a modulator of inflammation in these patients.

Objective.Enthesitis-related arthritis subtype of juvenile idiopathic arthritis (JIA-ERA) clinically resembles reactive arthritis (ReA). In patients with ReA the immune response is targeted at the outer membrane protein (OMP) ofSalmonella typhimurium. We studied the immune response in JIA-ERA toS. typhimuriumOMP.Methods.Synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) were isolated from blood and SF of patients with JIA-ERA. Lymphocyte transformation test was done withS. typhimuriumOMP and crude bacterial lysates ofYersinia enterocolitica,Shigella flexneri, andS. typhimurium. IgG and IgA ELISA were performed in serum and SF usingS. typhimuriumOMP as antigen and compared with sera from healthy controls.Results.In PBMC samples (n = 25) an antigen-specific proliferative response was seen in 13 patients and a cross-reactive response in 6. Among these 19 patients, 12 showed response to OMP. In SFMC (n = 15) antigen-specific responses were seen in 3 patients and cross-reactive responses in 9. Among these 12 patients, 11 showed response to OMP. The IgG and IgA anti-OMP antibody concentrations in serum and SF were similar in patients and controls.Conclusion.In JIA-ERA, OMP is the major antigenic target recognized by both SFMC and PBMC. Response to OMP is independent of specific bacterial response, suggesting that OMP is the immunodominant antigen. In these patients, absence of significant humoral response suggests response to OMP is mainly T cell mediated.

Sir,Anaemia in scleroderma may be due to disease activity,malabsorption secondary to bacterial overgrowth or gastro-intestinal dysmotility, nutritional, drug-related, associatedoverlap syndromes, association with autoimmune hemolyticanaemia, microangiopathic hemolytic anaemia secondaryto renal crisis and blood loss from the gut secondary to gas-tric ulcers or vascular ectasias. A 37-year-old female diagnosed for diffuse scleroderma 2 years back, with Reynaud’s phenomenon, skin thickening,digital ulcers, gastro-esophageal reflux and interstitial lungdisease. She was treated with cyclophosphamide for herlung disease. She presented with progressive dyspnoea ofNYHA Class III, generalised weakness and dizziness for 1 month. She had severe pallor, with pulse rate 120/min,blood pressure 110/70mmHg, respiratory rate 22/min, nor-mal JVP, normal heart sounds and coarse crepts in lowerzones of the lungs. Investigation revealed that her haemo-globin level was 3.2g/dL and microscopic hypochromic redblood cells. Stool for occult blood was positive. The uppergastrointestinal endoscopy revealed hiatus hernia, gastro-esophageal reflux disease and linear erythematous streaks

Objective. Membrane-bound receptor for advanced glycation endproducts (mRAGE) is overexpressed in response to increasing concentrations of its ligand (e.g., S100A12) and triggers an inflammatory immune response. In contrast, soluble RAGE (sRAGE) acts as a decoy receptor and downmodulates inflammation. Decreased sRAGE levels are associated with autoimmune diseases; however, limited data are available in juvenile idiopathic arthritis (JIA). We studied sRAGE levels in patients with JIA [enthesitis-related arthritis (ERA) category]. Methods. sRAGE levels were estimated in the serum of patients with ERA JIA (n = 101), systemic-onset JIA and polyarticular JIA (n = 10 each), and healthy controls (n = 45). Synovial fluid (SF) sRAGE was measured in patients with ERA, rheumatoid arthritis, reactive arthritis, and osteoarthritis (n = 10). Levels of S100A12 were also measured. Twenty-four patients with ERA were followed for 4 months. Disease activity was assessed by swollen joint count (SJC), tender joint count (TJC), and erythrocyte sedimentation rate (ESR). All levels are expressed as median (range). Results. The serum sRAGE (pg/ml) level was significantly lower in patients compared to healthy controls [515 (64–1887) vs 1542 (627–3159); p < 0.0001]. In paired samples, SF had lower levels compared to corresponding plasma level [102 (51–799) vs 481 (134–1006); p < 0.0001]. The level of S100A12 (ng/ml) was higher in SF (1042; 573–1415) than serum (638; 208–779). Serum sRAGE correlated negatively with S100A12 levels (r = −0.474; p < 0.01.), ESR (r = −0.306; p < 0.01), and SJC (r = −0.237; p < 0.05), but not with TJC (r = −0.134; p = NS). The levels of sRAGE remained stable over time in patients with stable disease. Conclusion. Levels of sRAGE are reduced in patients with ERA and correlate negatively with disease activity and S100A12 levels. sRAGE may be a modulator of inflammation in these patients.

Availability of veterinary services is very important for development of livestock sector in India. In many locations apart from state veterinary services other veterinary services are also available and the veterinary service users have the choice available with them regarding the service providers. The preference of service providers depend upon the location, distance, livestock holding and capacity to pay and quality of services. A study was conducted among the livestock owners of Sangli district in Maharastra to assess the preference of the livestock owners towards a particular veterinary service provider. Majority of large farmers preferred state veterinary services and cooperative veterinary services where it had strong presence. Cooperative veterinary service can be a good alternative to the state veterinary services and the private veterinary service providers are still not preferred in the rural area.