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   Table of Contents - Current issue
Coverpage
March 2022
Volume 17 | Issue 1
Page Nos. 1-105

Online since Tuesday, March 15, 2022

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EDITORIAL  

Which came first in lupus: The interferon or the infection? p. 1
TG Sundaram, Sakir Ahmed
DOI:10.4103/injr.injr_48_22  
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ORIGINAL ARTICLES Top

Infections in systemic lupus erythematosus: A study of incidence and risk factors in 100 patients from western India p. 4
Ankan Jha, Tridip Das, Sunilkumar Rajmani Singh, Jyotsna Oak
DOI:10.4103/injr.injr_65_21  
Aim: The present study was conducted to evaluate the incidence and characteristics of infections in patients of systemic lupus erythematosus (SLE) and determine the risk factors for infection. Materials and Methods: This is a prospective, observational study carried out at a single-center, tertiary care hospital. The study included all adult SLE patients diagnosed as per the revised American College of Rheumatology (ACR) criteria from January 2015 to October 2019. Episodes of infection and pathogens isolated were recorded. Results: A total of 100 patients with SLE were evaluated (94 females and 6 males). Forty-seven (47%) patients suffered from 54 episodes of infection. Urinary tract infections were most common (31.48%), followed by skin and mucous membrane (27.78%). Escherichia coli (E. coli) was the most common organism isolated in 9 (16.8%) cases. Tuberculosis was seen in 6 (11.1%) patients. Forty-three (79.6%) patients had a SLE disease activity index score of more than 5 at the time of infection. Significant risk factors for infection included use of prednisolone, prednisolone dose higher than 10 mg, use of cyclophosphamide within the preceding 3 months of infections, use of other immunosuppressive agents, and leukopenia. Renal lupus and presence of comorbidities did not have a significant association with occurrence of infections. The relative risk of infections in SLE patients was 4.7 compared to non SLE controls. Conclusion: Patients of SLE are at increased risk for various infections. Management of SLE needs vigilance for infection and judicious use of immunosuppressive drugs.
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Prospective study of patients with inflammatory back pain, clinical characteristics and treatment response in ankylosing spondylitis in two centers of rheumatology in South India p. 10
Subramanian Nallasivan, Dhivya Thiyagarajan, Abirami Manivannan
DOI:10.4103/injr.injr_121_21  
Introduction: Ankylosing spondylitis is inflammatory arthritis affecting the spine and peripheral joints more commonly in men of 15 years to 40 years of age and is a part of the spectrum of diseases called spondyloarthropathy. Psoriasis, uveitis, ulcerative colitis, and inflammatory bowel disease form part of the systemic manifestations. There exists a long delay between the onset of inflammatory back pain and being diagnosed with ankylosing spondylitis. Methodology: We set out to study the clinical profile, diagnosis, and management of patients with spondyloarthritis (SpA) prospectively and follow-up over 2 years period. All patients who had inflammatory back pain and diagnosed to have SpA were included in this prospective study in two different centers of Rheumatology. Clinical characteristics, magnetic resonance imaging (MRI)-spine and sacroiliac joints, disease activity using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and early treatment response were assessed. Other investigations including bloods, X-rays, and screening for biologics were done as and when indicated. We used both synthetic Disease-Modifying AntiRheumatic Drugs (DMARDS) and biosimilars as per the British Society of Rheumatology guidelines and patient choice. Patients were reviewed every 3 months for 1–2 years. The response to treatment was assessed and compared with other studies. Results: Forty -two patients were studied in this 2 years period (15 patients out of 57 lost to follow up). All patients had the diagnosis of ankylosing spondylitis as per Assessment of Spondylo Arthritis international Society (ASAS Score) criteria and MRI evidence of sacroiliitis and 22 patients had peripheral synovitis. HLA-B27 was positive in 11/19 patients. Eleven patients had been on anti-Tumor Necrosis Factor (TNF) drugs and 26 patients were on DMARDs. At the end of 24 weeks, disease activity indices including BASDAI and BASFI were low in remission and statistically significant. At the end of 2 years, most of them were in remission and 81% were continuing to work and maintain productivity. Patients who underwent treatment with biosimilar TNFs showed a significant reduction in disease activity and achieved remission earlier, as evidenced by BASDAI and BASFI scores, compared to others who were on DMARDS and supportive therapy. The usage of DMARDS was more than biosimilar drugs as they are expensive. Conclusion: This study shows the real-world data on the diagnosis and management of patients with ankylosing spondylitis, achieving remission, and maintaining the work-life balance. Early diagnosis with MRI and appropriate intervention with DMARDS are the important factors in this study.
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Health-related quality of life in children with juvenile idiopathic arthritis: A developing country perspective p. 16
Madhumita Nandi, Abhisek Majhi, Moumita Samanta, Tanmoy Sar, Sumantra Sarkar, Tapas Sabui
DOI:10.4103/injr.injr_259_20  
Objective: To assess the Health-Related Quality of Life (HRQoL) in domains of physical, emotional, social, and school functioning in children suffering from juvenile idiopathic arthritis (JIA). Materials and Methods: This hospital-based prospective observational study was undertaken in children from 2 to 12 years of age attending the Rheumatology clinic of a tertiary care teaching institute of Eastern India with a diagnosis of JIA for at least 6 months. Pediatric QoL inventory 4.0 generic core scale was used after obtaining the necessary permission. Results: Out of a total of 92 patients of JIA, 85 (male/female: 39/46) were taken up for the study polyarticular JIA was the commonest variety (54/85, 63.5%) followed by systemic JIA (sJIA) (25/85, 29.4%) and oligoarticular JIA (6/85, 7.0%). Male gender (P = 0.059, 0.000), better BMI (P = 0.004, 0.001), better disease control (P = 0.00, 0.00), sJIA subcategory (P = 0.002, 0.000), and longer duration of disease (P = 0.015, 0.000) correlated with better QoL in both child and parent scores whereas better socioeconomic status fared better only in parent scores (P = 0.017) and educational status of parents in child scores (child P = 0.000), Child and parent score were comparable across all domains and also overall scores. Conclusion: This study brings out certain important aspects of QoL in children suffering from JIA which may have some significant impact on disease control per se. Larger community-based multicentric studies would help us in delineating further this aspect of the disease and formulating guidelines for improving QoL in such children.
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A comparative study to assess vascular health in previously diagnosed patients of kawasaki disease p. 24
Malabika Maity, Debadatta Mukhopadhyay, Tapas Sabui, Rakesh Mondal, Jiban Krishna De
DOI:10.4103/injr.injr_263_20  
Background: Kawasaki disease, the commonest cause of multisystem vasculitis in children, was believed initially as a one-time disease. Long-term follow-up reveals that endothelial dysfunction persists in post-Kawasaki disease patients with and without coronary lesions and predisposes to atherosclerosis. Aims and Objectives: To establish the endothelial dysfunction and to correlate it with premature atherosclerosis in Kawasaki disease patients. Settings and Design: Prospective comparative study. Materials and Methods: Thirty patients of Kawasaki disease (age, 6 months to 20 years) were compared to the age matched control population and evaluated 2 times (1st F/U and 2nd F/U) at an interval of 6 months. USG Doppler was used to measure intimal thickness of carotid arteries CAD-IT, flow character and Resistive Index of anterior ATA-RI and posterior tibial arteries PTA-RI. Echocardiography was used to detect perivascular hyperintensity, dilatation and aneurysm of coronary arteries. Ongoing inflammation was documented by C- reactive protein (CRP) level. Coronary involvement (dilatation, small, medium, giant CAA) was determined by the z-scores adjusted to patients' body surface area (BSA) (AHA guidelines 2017). Statistical analysis used: Mean, paired t-test, GEE model, Odds ratio. Results: Significantly elevated CRP levels were observed in both the 1st follow up (p=0.0005) and 2nd follow up (p=0.000001) compared to control value. A significant rise (p<0.05) in total cholesterol, triglyceride levels, ATA-RI, PTA-RI and CAD-IT were seen. Seven patients developed coronary aneurysm of which three had persistent lesion. Conclusions: Kawasaki disease is not a one -time disease. Persistent endothelial dysfunction continues. CRP, total cholesterol, triglyceride, and USG doppler of coronary, carotids as well as peripheral arteries were found abnormal in follow up. So, these patients need to be followed up for a long period.
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Humoral responses to SARS-CoV-2 vaccination in rituximab-treated patients depend on peripheral B cell re-population rather than the timings of the dosing p. 30
Rashwith Umesh, Aby Paul, Veena Shenoy, Sakir Ahmed, Somy Cherian, Arya Prasad, Padmanabha Shenoy
DOI:10.4103/injr.injr_215_21  
Introduction: Previous exposure to Rituximab affects the immunogenicity of vaccination including that against coronavirus disease (COVID-19). However, dynamics of the effect of rituximab on vaccination are not well understood. This study aims to assess the role of timing of vaccine dosing and B-cell repopulation on vaccine seroconversion. Methods: Autoimmune rheumatic disease (AIRD) patients treated with rituximab who had completed two doses of COVID-19 vaccination were enrolled. Peripheral B-cell counts were estimated along with the titer of immunoglobulin G antibody-directed against the receptor-binding domain of spike1 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Antibody titers of participants were compared against B-cell re-population. Results: Out of the 33 participants with available prevaccination B-cell counts, 11 did not have any detectable peripheral B cells before vaccination, and out of these patients, only 1 developed antibodies postvaccination, whereas, of the remaining 22, 18 (81.8%) had a positive seroconversion. Although all patients who had received the last dose of Rituximab at least 1 year before vaccination had antibodies, there was no direct correlation between time from the last dose and antibody positivity. B-cell re-population was strongly associated with seroconversion (P = 0.0001). Conclusion: In rituximab-treated patients, humoral responses to SARS-CoV-2 vaccination depend on peripheral B-cell re-population rather than the timing of the vaccination postrituximab infusion.
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Sleep quality in rheumatoid arthritis p. 34
Anil Kumar, Rohini Handa, Sundeep Kumar Upadhyaya, Sirinder Jit Gupta, Deepak Ramchandra Malgutte
DOI:10.4103/injr.injr_151_21  
Background: Patients with rheumatoid arthritis (RA) often have sleep dysfunction. This may adversely impact quality of life. Despite being common, sleep dysfunction is uncommonly assessed in the clinic. No data on sleep quality in RA patients is available from India. In this study we examined the sleep quality and factors influencing it in Indian patients with RA. Methods: This cross-sectional study evaluated sleep quality in 110 patients with RA using the Pittsburgh sleep quality index (PSQI) or its validated Hindi version (PSQI-H). The risk of sleep apnea was assessed by the Berlin questionnaire while the assessment of pain and fatigue was done on a visual analogue scale (VAS). Disease activity was assessed by simplified disease activity index, functional disability was assessed by the health assessment questionnaire disability index-Centre for Rheumatic Diseases version, and quality of life was evaluated by World Health Organization quality of life-BREF (WHOQOL-BREF). Socioeconomic status was assessed by modified Kuppuswamy scale. Results: Sixty four percent of our patients with RA demonstrated poor sleep quality. The mean global PSQI score was of 6.41 ± 3.07 (range 1–17). A high risk of sleep apnea was present in 26% of the study population. The use of glucocorticoids, high risk of sleep apnea, high disease activity, pain VAS, fatigue VAS, and functional disability were more common in poor sleepers. Multivariate logistic regression analysis revealed that high risk of sleep apnea, fatigue, and poor physical health domain of WHOQOL-BREF were independent risk factors for poor sleep quality. Conclusions: Patients with RA had a high prevalence of poor sleep quality. High risk of sleep apnea, fatigue and physical health domain of WHOQOL-BREF were identified as independent predictors of poor sleep quality. Clinic evaluation of patients with RA should incorporate the domain of sleep quality.
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Cone-Beam Computed Tomography: Fractal Analysis of Osseous Changes in Temporomandibular Joint for Rheumatoid Arthritis Patients: A Retrospective Study p. 41
S Jayachandran, Nivethitha Nagarajan, M Archana
DOI:10.4103/injr.injr_315_20  
Background: Rheumatoid arthritis (RA) is a chronic systemic disorder which is autoimmune, inflammatory, and erosive joint disease affecting all the joints in the body. Temporomandibular joint (TMJ) is involved in advanced cases. Trabecular bone of TMJ has higher metabolic activity and shows higher alterations in RA. Aim and Objectives: This study evaluated and compared the trabecular bone changes of TMJ in patients with RA using fractal dimension (FD) analysis on cone-beam computed tomography (CBCT). Materials and Methods: A total of 25 (n = 25) CBCT images of RA patients were included for the study. Mid-sagittal section image was selected, and FD assessment of TMJ was done in the bilateral condylar head, condylar neck, and articular eminence. Statistical Analysis: SPSS® 25.0 (Statistical Package for the Social Sciences) – independent t-test, one-way ANOVA followed by Tukey's post hoc test was used. Results: The condylar head had lowest FD values and condylar neck had highest FD values on both the sides. The overall mean values of FD of condylar head, condylar neck, and articular eminence were lower for female than males. Conclusion: Fractal analysis showed that trabecular bone density was altered in condylar head, condylar neck, and articular eminence. Condylar head was the most affected region followed by articular eminence. Condylar neck was the least affected region in both the sides. Hence, FD analysis of CBCT can potentially be considered as an aid in evaluating osseous changes in trabecular bone architecture of the TMJ and to assess the severity of disease.
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Histone deacetylase-2 inducer like theophylline has a potential to improve glucocorticoid responsiveness in severe uncontrolled asthma by reducing P-glycoprotein/MRP-1 p. 47
Ravi Mishra, Zia Hashim, Mansi Gupta, Rachna Chaturvedi, Harshit Singh, Alok Nath, Durga Prasanna Misra, Ajmal Khan, Mohit Kumar Rai, Shivani Srivastava, Saurabh Chaturvedi, Vikas Agarwal
DOI:10.4103/injr.injr_85_21  
Background: Epigenetic factors play an essential role in regulating the action of steroids in asthma. Steroids suppress inflammation by recruiting histone deacetylase-2 (HDAC-2), which removes the acetyl group of the nuclear factor kappa B-enabled inflammatory gene complex and disables its action. P-glycoprotein (P-gp)/Multidrug resistance-associated protein 1 (MRP-1), the energy-dependent efflux pumps, reduces the bioavailability of steroids in the cell by pumping it out. The expression of P-gp/MRP-1 and HDAC-2 has been linked to regulating the action of steroids in asthma. Therefore, the use of HDAC-2 inducer like theophylline might improve asthma control by improving steroid responsiveness. Objective: HDAC-2 inducer, theophylline, can improve glucocorticoid responsiveness in severe uncontrolled asthma (UA). Materials and Methods: We classified subjects into severe UA (n = 7, age: 52.36 ± 11.94 years), controlled asthma (CA) (n = 23, age: 50.65 ± 16.11 years), and treatment-naïve patients (n = 10, age: 50.60 ± 14.38 years). Peripheral blood mononuclear cells (PBMCs) were isolated and treated with theophylline (1 μM) and Trichostatin-A (TSA) (0.8 μM) for 48 h, for induction/suppression of HDAC-2, respectively. The messenger RNA (mRNA) expression extracted from PBMCs was studied for HDAC-2and P-gp/MRP-1 by quantitative real-time polymerase chain reaction. Results: The mRNA expression of P-gp/MRP-1 was higher, whereas HDAC-2 mRNA levels were significantly lower in UA at baseline. Exposure to theophylline reduced mRNA expression of P-gp/MRP-1 (fold change: 2.57/2.15 in UA; 1.27/1.26 in CA, respectively, P < 0.0001), but the HDAC-2 mRNA expression increased (fold change: 5.56 in UA; 6.85 in CA, respectively, P < 0.0001). However, TSA treatment resulted in higher mRNA levels for P-gp/MRP-1 (fold change: 7.45/7.26 in UA; 3.34/3.29 in CA, respectively, P < 0.0001), whereas it significantly lowered expression for HDAC-2(fold change: 1.39 in UA; 2.46 in CA, respectively, P < 0.0001). Conclusion: HDAC-2 inducer theophylline has a potential to induce response against steroid resistance in severe UA.
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REVIEW ARTICLES Top

Personalized medicine in India: Mirage or a viable goal? p. 57
Somashree Chakraborty, Anisha Wagh, Pranay Goel, Sanat Phatak
DOI:10.4103/injr.injr_152_21  
Personalized medicine refers to using individual patient characteristics including phenotype and genotype, to tailor the therapeutic strategy. This approach seeks to challenge the “one-size-fits-all” method to patient management. In the bargain, it reduces adverse drug reactions, improves compliance, and reduces the economic burden of disease management. Traditionally, as extrapolated from usage in oncology, the term applied to using genomic, metabolomic, and epigenomic data in selecting medications; however, even simpler data such as clinical phenotype can aid therapeutic decision making. Autoimmune diseases provide many such data points, owing to the multi-organ nature of clinical manifestations as well as the availability of a wide variety of tests for antibodies as well as cytokines. Rheumatologists already use personalization intuitively, based on various factors such as organ involvement, comorbidities, fertility concerns, and costs. However, in a literature search, few studies look at tailoring treatment regimens to individual characteristics. Building coherent databases can help in better analysis of data and answering locally relevant questions in the future.
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CASE BASED REVIEW Top

Autoinflammation with arthritis and dyskeratosis an inflammasomopathy: Case report and review of literature p. 65
Nayan Patel Sureja, Liza Rajasekhar
DOI:10.4103/injr.injr_17_21  
Inherited disorders of the inflammasome pathway causes dysregulated inflammasome activation, which presents with inflammation and other clinical features linked to the defective protein. Eight mutations have been previously described in the NLRP1 inflammasome protein, causing different inflammatory skin disorders. Two of these mutations are associated with “autoinflammation with arthritis and dyskeratosis (AIADK),” a novel Mendelian auto-inflammatory disorder, in the 2017 International Union of Immunological Societies phenotypic classification for primary immunodeficiencies. We report a 22-year-old female, with recurrent generalized urticaria, periodic fever and pain abdomen, inflammatory polyarthritis, cutaneous lesions over the extremities, and persistently elevated inflammatory markers. On next-generation sequencing, a heterozygous missense mutation in exon 4 of the NLRP1 gene (chr17:G.5461839C>T) was detected, which results in the amino acid substitution of glutamine for arginine at codon 726 (c.2177G>A; p.Arg726Gln). A probable diagnosis of AIADK, possibly caused by this mutation was proposed, and patient responded well to colchicine.
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An unusual case of vomiting and arthritis: A diagnostic enigma p. 69
Shivraj Padiyar, Daisy Doley, Ramesh Babu, John Mathew
DOI:10.4103/injr.injr_359_20  
Sarcoidosis is a multisystem inflammatory disorder, which can have a myriad of presentations, with atypical presentation not being uncommon. Unless the clinician has a strong suspicion of sarcoidosis, it can be easily missed out. Here, we present an interesting case of a 44-year-old gentleman who had presented with inflammatory arthritis and vomiting. His serum cortisol levels were low. On further evaluation, he was found to have panhypopituitarism. Magnetic resonance imaging brain showed infiltrative disease involving the pituitary stalk. Imaging of the chest revealed mediastinal nodes which showed nonnecrotizing granulomatous inflammation on histopathology. After ruling out infectious causes a diagnosis of sarcoidosis was made, and the patient had a full recovery with steroids and methotrexate. Sarcoidosis can be a great mimicker presenting with a myriad of complications. Clinicians must be aware of the atypical presentations to diagnose the disease earlier.
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Antisynthetase syndrome with anti-oj antibody: A Case report and review of literature p. 73
Nayan Patel Sureja, Sandeep Nandamuri
DOI:10.4103/injr.injr_338_20  
Antisynthetase syndrome (ASS) is a rare autoimmune disease characterized by the presence of an anti-aminoacyl transfer RNA synthetase antibody with one or more clinical features. The prevalence of anti-OJ antibodies in ASS is 2%–5%. Information regarding the clinical presentation and evolution of these patients is limited. We report a case of ASS with anti-OJ antibody in a 45-year-old female from India, who presented with arthritis and interstitial lung disease (ILD). She was managed with corticosteroids and intravenous cyclophosphamide. We also described the clinical details of 69 previously reported ASS patients with anti-OJ antibody. Data from these patients including our patient showed that isolated ILD was the most common form of presentation (24%) followed by myositis with ILD (16%), isolated arthritis (15%), and isolated myositis (13%). The prevalence of arthritis, myositis, and ILD, at the disease onset, was 33%, 42%, and 70%, respectively, whereas the overall prevalence was 44%, 77%, and 83%, respectively.
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Familial hypercholesterolemia mimicking juvenile idiopathic arthritis p. 78
Pooja Dhaon, Utkarsh Bansal, Dileep Jain
DOI:10.4103/injr.injr_22_21  
Juvenile idiopathic arthritis (JIA) seen in children is a diagnosis of exclusion, as many systemic and metabolic diseases have similar presentation. Here, we present a case of a 14-year-old female girl who presented with polyarthralgia, fever, and nodules over body. She was diagnosed as JIA initially without any response to treatment. On further assessment, she had xanthelasma on eyelids, and a very high and low-density lipoprotein-cholesterol, a second-degree relative also with similar findings. The histopathology of the nodule was suggestive of xanthoma. Thus, she was diagnosed as familial hypercholesterolemia (FH) and was given statins. Articular manifestations are not very uncommon in patients of FH, and sometimes, they are the presenting symptoms in these patients. There are number of causes of arthritis with subcutaneous nodules in children apart from JIA which have been enumerated. Thus, FH must also be considered as a differential diagnosis in such patients.
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IMAGES IN RHEUMATOLOGY Top

Subcutaneous calcinosis as a harbinger of infection in a patient with relapsing dermatomyositis p. 82
Ansh Bhatia, Pallavi Prasad, Koshy Nithin Thomas, Latika Gupta
DOI:10.4103/injr.injr_87_21  
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Unstable psoriasis in the setting of psoriatic arthritis: A rare presentation p. 84
Roma Raj, Abir Saraswat, Koshy Nithin Thomas, Latika Gupta
DOI:10.4103/injr.injr_128_21  
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LETTERS TO EDITOR Top

New onset of Juvenile Dermatomyositis during Tumor Necrosis Factor Inhibitor (Adalimumab) Therapy p. 86
Sunil V Kapur, Jitendra S Oswal
DOI:10.4103/injr.injr_266_20  
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Hyperpigmentation heralding relapse of active dermatomyositis in an indian patient p. 89
Mahathi Kunduru, Latika Gupta
DOI:10.4103/injr.injr_92_21  
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Organic anxiety syndrome in a patient of lupus p. 91
Kunal Chandwar, Prasanna Dogga, Rasmi Ranjan Sahoo, Anupam Wakhlu
DOI:10.4103/injr.injr_26_21  
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Extensive calcinosis in a patient with raynaud's phenomenon and anti-ku antibody positivity p. 93
Kunal Chandwar, Digvijay Ekbote, Juhi Dixit, Kriti Kishor, Rasmi Ranjan Sahoo, Anupam Wakhlu
DOI:10.4103/injr.injr_203_21  
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Trend of global and indian biomedical retracted literature p. 95
Himel Mondal, Shaikat Mondal, Sarika Mondal
DOI:10.4103/injr.injr_126_21  
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Theory of Planned Behavior – The Need of the Hour? p. 97
Roma Raj, Supriya Agarwal, Latika Gupta
DOI:10.4103/injr.injr_252_20  
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India and the conundrum of booster dose in immunocompromised patients p. 99
Kunal Chandwar, Chandani J Shah, Puja Srivastava
DOI:10.4103/injr.injr_202_21  
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Perspectives on poetry in rheumatology p. 101
Sreoshy Saha, Ansh Bhatia, Latika Gupta
DOI:10.4103/injr.injr_1_21  
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Gender disparity in Indian rheumatology p. 103
Suma Balan
DOI:10.4103/injr.injr_94_21  
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BOOK REVIEW Top

Ankylosing spondylitis–Axial spondyloarthritis - 2nd edition p. 104
Subramanian Nallasivan
DOI:10.4103/injr.injr_252_21  
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