Background: To assess the prevalence and risk factors associated with hydroxychloroquine (HCQ) retinopathy in patients with rheumatic and musculoskeletal diseases (RMD). Methods: Retrospective observational study was conducted on 984 patients using HCQ for RMD to detect prevalence of retinopathy by Humphrey visual field, spectral-domain optical coherence tomography, fundus autofluorescence test, and multifocal electroretinography (mfERG). Results: The patients' age ranged between 13 and 79 years and 85.8% were female. The prevalence of retinopathy was 13.5% in cases treated with HCQ. It was significantly more in the higher age group (>60 years) compared to lower age (<30 years), P = 0.033, but not significantly associated with gender, body mass index, hypertension, diabetes mellitus, hypothyroidism, and various RMD. In addition, retinopathy was not significantly associated with HCQ dose/day (P = 0.101), but was significantly associated with duration of HCQ treatment (12.2% prevalence with < 5 years treatment, while 19.8% with 5–10 years HCQ use; P = 0.017). A statistically significant difference was found between median duration of patients with and without retinopathy (36 vs. 30 months; P = 0.046). The mean cumulative HCQ dose in retinopathy patients was significantly high compared to nonretinopathy patients (283.79 g vs. 231.33 g; P = 0.006). Among the individual (possible retinopathy) tests, mfERG had the highest detection rate (11.4%) for retinopathy screening, whereas Humphrey visual field analyzer test (HVF) + mfERG had the highest detection rate among the combination (definite retinopathy) tests (12.8%). Conclusions: The high prevalence of retinal toxicity in patients with 1–5 years of HCQ therapy prompts the need for frequent ophthalmic screening, even before completion of 5 years of treatment.

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Background: Conversion of quiescent resident fibroblasts to activated myofibroblasts by transforming growth factor-beta 1 (TGF-β1) is the hallmark of fibrotic pathogenesis of systemic sclerosis (SSc). Myofibroblasts are characterized by increased alpha smooth muscle actin (α-SMA) expression and extracellular matrix (ECM) proteins production. Objective: The aim of this study is to evaluate anti-fibrotic potential of dual inhibition by phosphodiesterase5 (PDE5) inhibitor, sildenafil plus 5-HT_2Binhibitor, SB204741 in human adult dermal fibroblasts (HADFs) isolated from mid-forearm skin of a scleroderma patient. Materials and Methods: In disease-mimicking strategy, HADFs were incubated with TGF-β1 (10 ng/ml) for 1 hour, followed by TGF-β1 (10 ng/ml)/[sildenafil (10 μM) or SB204741 (1 μM)] or combination of the two for 24 hours. In pretreatment strategy, HADFs were pretreated with sildenafil (10 μM) or SB204741 (1 μM) or combination of the two for 1 hour and later with only TGF-β1 (10 ng/ml) for 24 hours. Real time quantitative polymerase chain reaction for pro-fibrotic (COL1A1, COL1A2, ACTA2, CCN2 and FN1) and anti-fibrotic genes (MMP2, TIMP1) was performed. Results: In TGF-β1 stimulated HADFs, upregulated expression of pro-fibrotic genes was observed (P < 0.05). Expression of pro-fibrotic genes in HADFs stimulated with TGF-β1 were significantly (P < 0.05) reduced by dual inhibition strategy with complete amelioration of ACTA2 in comparison to their respective individual treatments. Ratio of anti-fibrotic genes (MMP2/TIMP1) was restored significantly (P < 0.05). Conclusion: Dual inhibition strategy with sildenafil plus SB204741 leads to near complete amelioration of conversion of fibroblasts to myofibroblasts and thus may have the potential to treat fibrosis in scleroderma.

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Infections are closely associated with systemic lupus erythematosus (SLE). SLE patients require aggressive immunosuppression making them vulnerable to unusual or atypical presentations of common infections. They have an inherent immune abnormality predisposing them to infection. On the other hand, infection can act as a trigger for the immune system and lead to a newonset SLE or flare. Here, we present three-patients with SLE and uncommon infection. First case is of a chronic cytomegalovirus-infection that mimicked a 3-year long SLE-disease. Detection of infection and treating it led to withdrawal of all immunosuppressive therapy. There was no further SLE-activity on follow-up. Similarly, in the second case, tuberculosis presented as diffuse lower lobe pneumonitis, which triggered a mild-quiescent undiagnosed SLE (ANA positive with low platelet count) into a full-blown SLE (nephritis and autoimmune hemolytic anemia). Initially, a diagnosis of lupus pneumonitis was made but later complications of cavitation and nonhealing bronchopleural fistula led to a diagnosis of tuberculosis. Again, in this case, treating the infection led to complete resolution of SLE. The third case is of herpes-simplex virus esophagitis that was confused with steroid withdrawal symptoms. It led to a refractory SLE-flare that settled after treatment of infection. Thus, here, we have discussed the complex interplay of these infections with the diagnosis and management of SLE along with an intriguing phenomenon of treating the infection leading to near-cure of an aggressive systemic autoimmune disease.

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Aortitis is not typically described in systemic lupus erythematosus (SLE).We describe two cases where aortitis was seen to occur concurrently with SLE or in its temporality. The possibility of an uncommon Takayasu-SLE overlap cannot be ruled out.

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Background: Impact of COVID-19 pandemic and consequential lockdown in India, on patients with chronic rheumatic diseases (CRD) pertaining these components of interest: (a) physical health, (b) mental health, (c) facets of social well-being, (d) health-care accessibility, and (e) COVID-19 related knowledge, attitude, and practices (KAP) was assessed. Methods: An online/onsite self-reported questionnaire-based cross-sectional survey was utilized to capture responses during May 20, 2020, to June 6, 2020, from CRD (both inflammatory and non-inflammatory) patients satisfying eligibility criteria, at a tertiary hospital in India. Adverse impact was defined as strong agreement/agreement on Likert scale to an impact on the individual components of interest. Results: From 1533 completed responses analyzed, adverse impact was noted on physical health (32.3%), mental health (42.9%), social health (54.8%), occupational life (55.9%), and financial condition (54.4%). Self-reported COVID-19 diagnosis (1.4%), flare/possible flare of CRD (41.3%), and symptoms of mental distress (64%) were also reported. Awareness and utilization of tele-video consultation (TVC) were 27.3% and 11.2%, respectively, with 89.9% expressing difficulty in procuring medication. COVID-19 KAP assessment revealed awareness of COVID-19 suspect symptoms and safety practices to be >60% and >70% respectively, with safety adherence being >75%. Conclusion: Majority of respondents reported adverse impact on social health, occupational life, financial condition, and interruption of CRD management, possibly complicated by the lack of awareness and low utilization of TVC. Although mental distress was greatly reported in the participants, a general preponderance toward self-education of current scenario and safety adherence was noted, indicating a favorable reception of future health-care directives.

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Takayasu arteritis (TAK) is a rare systemic large-vessel vasculitis. The evidence base to guide the medical management of TAK is sparse. This systematic review aims to synthesize the published literature on the use of disease-modifying antirheumatic drugs (DMARDs) in TAK. Scopus (which includes data from MEDLINE), Web of Science, PubMed central, the Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization International clinical trials registry platform shall be searched for relevant studies, both observational and interventional, on the use of DMARDs in TAK. Outcomes assessed shall be remission based on clinical, composite measures, inflammatory markers, angiographic assessment, and relapses. Screening of references and data extraction on predesigned pro formas shall be done in duplicate. Quality assessment of studies shall be done at the study level, using the Cochrane Risk of Bias 2 tool for interventional studies and the Newcastle–Ottawa scale for interventional studies. Publication bias shall be assessed wherever appropriate. Proportions of outcomes with DMARDs shall be pooled for uncontrolled observational studies. For controlled observational studies and interventional studies, pooled risk of outcomes versus comparator treatment or placebo shall be presented. Preplanned subgroup analyses are based on whether participants are adults or children with TAK. Certainty of evidence for DMARDs across studies shall be assessed by the GRADE profiler tool. The findings of the present systematic review shall help to understand better the current landscape of evidence for the use of DMARDs in TAK. This might help to guide future recommendations for the management of TAK. Future clinical trials on TAK might also be designed to avoid lacunae identified in the existing evidence for DMARD use on TAK.

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Trillions of commensal bacteria colonizing humans (microbiome) have emerged as essential player(s) in human health. The alteration of the same has been linked with diseases including autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Gut bacteria are separated from the host through a physical barrier such as skin or gut epithelial lining. However, the perturbation in the healthy bacterial community (gut dysbiosis) can compromise gut barrier integrity, resulting in translocation of bacterial contents across the epithelial barrier (leaky gut). Bacterial contents such as lipopolysaccharide and bacterial antigens can induce a systemic inflammatory environment through activation and induction of immune cells. The biggest question in the field is whether inflammation causes gut dysbiosis or dysbiosis leads to disease induction or propagation, i.e., it is inside out or outside in or both. In this review, we first discuss the microbiome profiling studies in various autoimmune disorders, followed by a discussion of potential mechanisms through which microbiome is involved in the pathobiology of diseases. A better understanding of the role of the microbiome in health and disease will help us harness the power of commensal bacteria for the development of novel therapeutic agents to treat autoimmune disorders.

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Background: The international consensus on antinuclear antibody (ANA) patterns (ICAP) guidelines recommends that non-nuclear patterns should be reported as positive for ANA. Therefore, a prospective study was planned to investigate the frequency of cytoplasmic and mitotic ANA patterns in routine reporting in a high-throughput lab in a tertiary referral center in Northern India. Materials and Methods: Whole blood samples received were centrifuged and serum was separated within 4 hours of collection. Sera were subjected to indirect immunofluorescence (IIF) assay on HEp-2 cells for ANA determination in a dilution of 1:40, per standardized protocol in our laboratory. IIF staining patterns and intensity were evaluated and the results interpreted. Results: Over a 3-month period, of the 3796 serum samples received for ANA testing, 81 (4.9%) samples were positive for cytoplasmic, 7 (0.4%) for mitotic, and 2 (0.1%) for DNA topoisomerase I (Topo I)-like pattern. The most frequent cytoplasmic fluorescence pattern was dense fine speckled (2%) and the most frequent mitotic pattern was NuMA-like (0.2%). The prevalence of total positive ANA in our study population was found out to be 43.6%. Conclusions: Implementation of ICAP guidelines into routine ANA reporting helped us in detecting important cytoplasmic antibodies such as antimitochondrial antibodies, anti-ribosomal P protein antibodies, anti-Jo-1antibodies, anti-Topo I antibodies and allowed us to introduce more specific and confirmatory tests for the same. The new format for ANA reporting also encouraged clinician-laboratory crosstalk.

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Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterized by circulating autoantibodies, widespread inflammation, and tissue destruction. The association between cancer and SLE is intriguing in view of their common pathophysiological pathways. It is established that there is an increased risk for overall malignancies in SLE, with standardized incidence ratios ranging from 1.14 to 3.6. Hematological malignancies are more common than solid organ malignancies in SLE. Malignancy when associated with lupus usually follows the diagnosis, but can occur concurrently or even predate the diagnosis of SLE. Neoplasms of dendritic cells (DCs), the key antigen-presenting cells, are rare, and they account for <1% of all lymph node tumors. Interdigitating DC sarcoma (IDCS) is a rare hematological malignancy of DCs, with only a few over 100 cases being reported in literature. IDCS is usually seen in elderly males in their sixth decade. Here, we report a rare case of SLE and IDCS occurring together in a 5-year-old girl. The persistence of lymphadenopathy despite improvement in other lupus-specific features following the initiation of treatment led to a suspicion of malignancy which was proven on histopathology. Another unique feature of our case was that remission and relapse of both SLE and IDCS occurred synchronously. Although this presentation is rare, clinicians must be aware of the possibility of SLE and malignancies occurring together, especially in the presence of atypical clinical manifestations such as persistent lymphadenopathy. This knowledge helps in early diagnosis and effective treatment of both these conditions.

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A 36-year-old lady presented with insidious onset, gradually progressive neuropathic pain, sensory loss, and weakness of the right upper limb. Her brachial, ulnar, and radial pulses were not palpable on the right side and feeble on the left. She had an irregular, ill-localized 8 cm × 6 cm pulsatile swelling in the right supraclavicular region with thrill on palpation and bruit on auscultation. Motor system examination revealed grade 4 power with wasting of thenar muscles. Nerve conduction studies were suggestive of pan-brachial plexus involvement. Computed tomography angiogram images revealed thickening of the aortic arch, irregular narrowing of the descending aorta, and aneurysm of the right subclavian artery. She was diagnosed to be suffering from right brachial plexopathy due to compression by aneurysm of the right subclavian artery secondary to Takayasu's arteritis. The case is rare as no such presentation has been reported earlier.

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Background: B-cell hyperactivity is believed to have a central role in the pathogenesis of systemic lupus erythematosus (SLE). B-cell-activating factor (BAFF) is a cytokine that plays a role in accelerating maturation, differentiation, and survival of B-cells. The purpose of this study is to determine whether there is a significant association between the serum BAFF levels and disease activity in SLE patients. Subjects and Methods: This study uses bivariate analysis with a cross-sectional design. The statistical analysis test used is Pearson's and Spearman's correlation coefficient test, as well as Mann–Whitney test. Participants were 44 SLE patients with active disease (SLEDAI 2K >2) in the rheumatology clinic and in-patient wards of Hasan Sadikin General Hospital, Department of Internal Medicine, Bandung, during the period of December 2016–March 2017. Results: Forty-four participants of the study were women with a mean age of 28 ± 8 years. Renal (93.2%) and mucocutaneous (93.2%) involvements were the most common manifestations. Median of disease activity based on SLEDAI-2K score was 8 (4–23). Median serum BAFF level was 1.218 ng/ml (0.476–10.835). There was a weak positive correlation between serum BAFF levels and SLEDAI-2K (r = 0.327, P = 0.015). There was also a significant correlation with weak relation found between serum BAFF levels and anti-dsDNA and complement C3 levels. Conclusion: There is a significant correlation between the serum levels of BAFF and SLE disease activity. However, the strength of the relationship is weak. Therefore, disease activity in lupus can be influenced by other factors.

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Background: Tenascin-C (TN-C) is a pro-inflammatory glycoprotein with various biological functions. TN-C plays a major role in cell adhesion, migration, proliferation, and cellular signaling through the induction of pro-inflammatory cytokines. Aim of the Work: This study was designed to investigate the relationship between serum TN-C levels and disease activity in patients with systemic lupus erthromatosus. Subjects and Methods: This is a case–control observational study that was carried out on 68 participants and divided into two groups. Group A included 34 systemic lupus erythematosus (SLE) patients and Group B included (34) apparently healthy volunteers. They were age and sex matched with the patients. Clinical examination as well as routine laboratory investigations confirmed their healthy status. All patients were subjected to full history taking, through clinical examination, laboratory investigations as C-reactive protein, erythrocyte sedimentation rate, C3, C4, ANA, and anti-dsDNA. Serum TN-C estimation of serum TN-C was done for SLE patients and the control group using double-antibody sandwich enzyme-linked immunosorbent assay. Disease activity of SLE patients was assessed according to SLE disease activity index 2000 score. Results: Serum level of TN-C was higher in SLE patients than healthy control but with no statistically significant difference (P > 0.05). There was highly statistically significant difference (P < 0.001) between active and inactive SLE patients regarding TN-C level. Conclusion: Serum TN-C level is elevated in SLE patients and correlates with disease activity which indicates its possible role in SLE pathogenesis. Thus, TN-C may provide a novel research target for the pathogenesis and therapy of SLE.

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Background: Leptin is an adipokine that has an important role in body weight regulation and endocrine function. Leptin also acts as a pro-inflammatory cytokine by inducing the production of Th1 cytokines. The aim of our study was to estimate the serum leptin levels in systemic lupus erythematosus (SLE) patients and analyze its associations with clinical manifestations of lupus and disease activity. Materials and Methods: This study was conducted on 80 patients who satisfied Systemic Lupus International Collaborating Clinics 2012 criteria for SLE and 40 healthy controls. Demographic, clinical, and laboratory parameters were recorded. SLE disease activity index (SLEDAI) was scored for all SLE patients. Serum leptin levels (ng/dl) were estimated by enzyme-linked immunosorbent assay and the results were analyzed by SPSS. Results: Baseline characteristics were comparable in both cases and controls. SLE patients had higher serum leptin levels as compared to controls (mean 16.01 vs. 5.86 ng/ml) which were statistically significant (P < 0.00001). Cutaneous lupus (85%) was the most common manifestation observed in patients with elevated leptin levels. Patients with lupus nephritis had high serum leptin levels (P = 0.04) in comparison to patients with nonrenal lupus. Serum leptin levels correlated positively with higher body mass index (BMI), higher uric acid levels, and lower high-density lipoproteins (HDL) cholesterol levels (P < 0.0001). Serum leptin levels showed no correlation with disease activity markers such as erythrocyte sedimentation rate, C-reactive protein, anti-double-stranded deoxyribonucleic acid titers, complements C3 and C4, and SLEDAI. Conclusion: Patients with SLE had high serum leptin levels. High leptin levels were seen predominantly in mucocutaneous lupus and lupus nephritis. Serum leptin levels correlated positively with BMI and serum uric acid and negatively with serum HDL cholesterol levels but showed no correlation with disease activity markers.

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Background: Efficacy and safety of orally administered rebamipide was assessed in treating dry eye disease (DED) and xerostomia in Sjögren syndrome (SS) patients. Methods: Patients of SS with bilateral DED and xerostomia were offered a choice between either oral rebamipide (100 mg BID) with topical 0.5% carboxymethylcellulose (CMC) (R + CMC group) or CMC alone (CMC group), for 3 months, in a quasi-experimental study. Outcome measures were tear-film break-up time (TBUT) and xerostomia symptoms (XS), Schirmer's test (ST), Lissamine green staining grade (LGSG) and goblet cell density (GCD), Saxon salivary secretion test (SSST), and Ocular Surface Disease Index (OSDI). Results: Twenty patients were enrolled in each group. Those who preferred oral rebamipide had worse ST (P = 0.04), LGSG (P = 0.04), SSST (P = 0.006), and GCD (P = 0.009). At 1, 2, and 3 months, the mean increase in TBUT were, respectively, 3.4, 2.9, and 3.45 s in R + CMC, higher than CMC (P < 0.001). Improvement in ST was significantly higher in R + CMC (from 6.75 ± 0.43 to 12.6 ± 1.23 mm) than CMC (P < 0.001). The improvement in OSDI, LGSG, and XS was higher in R + CMC group (all P < 0.001), while that in SSTT (P = 0.6) and GCD (P = 0.7) was similar. No serious adverse events were seen. Conclusion: The dry eye and mouth showed improvement with oral rebamipide, proving its dual therapeutic action in SS.

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Background: Inflammatory polyarthritis is seen in ~80% of patients with systemic lupus erythematosus (SLE); yet, there is no validated “instrument” for its assessment. The commonly used measures of disease activity, namely SLE Disease Activity Index 2000 (SLEDAI2K) and British Isles Lupus Assessment Group are complex and impractical for routine use in busy outpatient clinics. This “proof of concept” study's primary aim was to test clinical disease activity index (CDAI) as a possible instrument for measuring the joint disease in SLE that may have a face value and sensitivity to change. The secondary aim was to determine the efficacy of low-dose methotrexate in the SLE joint disease. Materials and Methods: This open-label study included the Systemic Lupus International Collaborating Clinics criteria classifiable thirty patients with SLE with inflammatory polyarthritis as the main manifestation. SLE disease activity and the joint disease activity were assessed using SLEDAI2K and CDAI, respectively, at the baseline and in the follow-up. The CDAI and the SLEDAI2K scores were compared between the first and the last visit, as well as compared with each other, using a nonparametric test (Wilcoxon signed-rank test). Results: CDAI scores improved significantly on treatment from a mean of 19.30 to 1.58 and in SLEDAI2K from 7.83 to 0.6, respectively; the pre- and the postintervention scores were statistically highly significant (P < 0.001) for both the CDAI and the SLEDAI2K. The degree of improvement as shown by SLEDAI2K change in scores and CDAI was statistically insignificant (P > 0.05), indicating similarity in their sensitivity to change. A significant number of patients achieved low disease activity status or remission in their joint disease. Conclusion: CDAI appears to be sensitive to change with treatment. Therefore, it could be used as a tool for assessing inflammatory arthritis in SLE.

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The coronavirus disease 2019 (Covid-19) has been implicated in a Cytokine Release Syndrome (CRS) in adults. Initial reports of Covid-19 suggested a milder disease course and better prognosis in children. However, a new inflammatory syndrome, reminiscent of Kawasaki Disease (KD) is associated with covid-19 in a proportion of children. This has been variously referred to as Kawasaki-like disease, multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV2 (PIMS-TS). Similar to KD, these patients have frequent cardiac involvement and are responsive to steroids and intravenous immunoglobulins (IVIG). But there are important distinctions in that, they are older, often have gastrointestinal manifestations, and more profound lymphopenia, and acute phase response. In this review, we underline the important takeaways from various published case series, and describe clinical characteristics, speculated pathogenetic mechanisms, implications for treatment and future directions for this novel syndrome.

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