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   Table of Contents - Current issue
September 2021
Volume 16 | Issue 3
Page Nos. 245-372

Online since Tuesday, September 21, 2021

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Gender disparity in indian rheumatology – The problem and the solution p. 245
Tanmayee Bichile, Grace C Wright
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Does gender gap exist in Indian rheumatology? Analysis of faculty gender representation at its annual conferences p. 248
Kavitha Mohansundaram, Velu Annamalai Sowndhariya, Vinod Ravindran
Background: Ensuring gender equality in faculty representation at medical academic meetings is important as it is linked to career development, building networks, increasing visibility, and reputation. The objective of this study was to analyze the gender representation among the faculty and abstract presenters at the Indian Rheumatology Association's (IRA) Annual Conferences (IRACONs). Methods: Gender representation among faculty (speakers and chairpersons from India and abroad) and the first author among abstract presenters in the past 10 years (IRACONs 2010–2019) was tabulated. Ratio and proportion of gender representation in these categories were calculated and compared in the two time frames of 2010–2014 and 2015–2019. Trends of female gender representation as faculty and abstract presenters were also compared with trend of enrollment of female life members of the IRA. Results: Female faculty from India constituted 127/627 (20%) and 91/567 (16%) as speakers and chairpersons respectively, with combined representation (speakers and chairpersons) of 18.5% ± 2.34% (mean) over the past 10 years with only few orations (4 out of 29). Widening of gender gap in speaker representation was noted in the latter 5 years' time period of 2015–2019 (23% [3.3:1] vs. 18% [4.6:1]). More females became life members of the IRA in the period 2015–2019, and though a similar positive trend was also noted in female abstract presenters, it was not seen in the female faculty representation. Conclusion: This study confirms that gender gap exists in the representation of female faculty at IRACONs. A systematic approach is required to address this issue by sensitizing the members and developing relevant policies.
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A prospective, randomized, single-center, two-arm, open-label study to evaluate the efficacy of biotherapi®, a two-strain bacillus probiotic blend, as an adjunctive therapy in the treatment of rheumatoid arthritis p. 254
Arindam Nandy Roy, Yarram Ashok Kumar, Syeda Sana Fatima
Objective: Probiotics have been shown to alleviate the symptoms of rheumatoid arthritis (RA) by normalizing the composition of gut microbiota. The objective of this study was to evaluate the effect of twice-daily Biotherapi® (Sanzyme Private Limited, India) as an adjunct to standard of care on disease activity and functional ability of patients with RA. Methods: In this prospective, randomized, single-center, two-arm, open-label study, patients were randomized (1:1) to receive twice-daily adjunctive Biotherapi® (n = 125) or standard of care alone (n = 125) for 12 weeks. The primary endpoint was the change from baseline to days 45 and 90 in the Disease Activity Score-28-erythrocyte sedimentation rate (DAS-28-ESR). Results: Standard of care alone and adjunctive Biotherapi® significantly reduced the mean DAS-28-ESR at days 45 and 90 (P < 0.05). However, the reduction from baseline was greater in patients receiving adjunctive Biotherapi® compared to standard of care alone at day 45 (–0.67 ± 0.77 vs. −0.15 ± 0.84, P < 0.0001) and day 90 (–1.21 ± 0.99 vs. –0.48 ± 0.69, P < 0.0001). Consequently, compared to standard of care, more patients achieved remission (4.3% vs. 23.6%) and showed good (6.52% vs. 35.45%) and moderate (31.5% vs. 41.81%) European League Against Rheumatism response at 90-day Biotherapi®. A similar pattern of improvement in the scores including Health Assessment Questionnaire was observed. No clinically significant changes in the laboratory parameters were reported during the study. Conclusion: Twice-daily supplementation with Biotherapi® probiotic blend as an adjunct to standard-of-care treatment for RA is beneficial for alleviation of severity and symptoms of the disease and results in improvement in patients' quality of life.
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Electrodiagnostic study in patients with fibromyalgia: Implication for central sensitization p. 263
Akram Mohammed Al-Mahdawi, Sara Ismael Sami, Farqad Bader Hamdan
Background: Fibromyalgia is a syndrome characterized by chronic pain, depression, fatigue, and sleep disturbance. Different hypotheses have emerged about its pathogenesis, but central sensitization, which plays an important role in the development of neuropathic pain, is considered to be the main mechanism. We aim to compare patients with fibromyalgia and healthy controls with different electrodiagnostic testing, and if present, to corroborate whether there is any relationship between electrodiagnostic measures. Also, we sought to test the diagnostic value of some of these measures. Methods: A case-control study of thirty-one patients with fibromyalgia with a duration of illness ranging from 5 months to 10 years were recruited for the study. Full medical history, clinical neurological examination, and electrodiagnostic tests of the upper and lower extremity including nerve conduction studies, needle electromyography, sympathetic skin response, cutaneous silent period and muscle fiber conduction velocity. Results: Sympathetic skin response latency and cutaneous silent period latency were not different between the patients and the control group. Cutaneous silent period duration was prolonged and the muscle fiber conduction velocity is faster in the subjects with fibromyalgia. The latter measures have similar diagnostic value. Sex has no significant impact on electrodiagnostic measures and the latter not correlated with patients' age. Conclusion: A central sensitization and concomitant deregulation of the efferent higher motor centers might be implicated in the pathogenic mechanism of fibromyalgia.
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Diagnostic validity of lung ultrasonogram in comparison with high-resolution computed tomography in interstitial lung disease associated with connective tissue disease p. 269
PV Lisha, N Safreena Mohamed, TP Rajagopal, Rennis Davis, Thomas Vadakkan Devassy
Background: Lung ultrasonography (LUS) may be a useful tool in identifying interstitial lung disease (ILD) in patients with Connective tissue disorder (CTD). The aim of the current study was to determine the diagnostic validity of LUS findings in comparison with high-resolution computed tomography (HRCT) in CTD-ILD and also determine the correlation between forced vital capacity (FVC) and 6-min walk test (6MWT) to LUS. Patients and Methods: Patients with connective tissue disorder and ILD diagnosed by HRCT were included and evaluated by physical examination, LUS, spirometry, and 6MWT. Results: Of 41 patients included, 38 (92.7%) were females. The mean age was 49.7 years. Systemic sclerosis was the most common diagnosis in 25 (61%) patients. LUS score was calculated as the total number of B-lines counted in all zones. The mean score was 20.83. B-line score showed a negative correlation with 6MWT distance (R = −0.501, P = 0.001) and FVC (R = −0.434, P = 0.005). There was a strong positive correlation between LUS and HRCT scores (R = 0.878, P = 0.0001). A LUS score of 39.5 or above has 83% sensitivity and 100% specificity (Youden index of 0.83, P = 0.001) for predicting a Class V HRCT pattern. Conclusions: There was a significant correlation between ILD with reticular pattern and honeycombing on HRCT and higher LUS B-line scores. LUS B-line scores also correlated significantly with functional parameters such as lower FVC values and 6MWT distance.
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Effect of type 2 diabetes mellitus on bone mineral density in patients with rheumatoid arthritis p. 276
Praveen Pratap Jadhav, Vivek Gajanan Patwardhan
Background: RA affection of bone manifests as low bone mineral density (BMD), generalised osteoporosis and increased risk of fragility fractures. Whereas, Type 2 Diabetes Mellitus (T2DM) produces many micro and macro vascular complications, its effects on bone and bone density is not very clear. The effect of coexistent RA and T2DM on BMD has not been well studied. Objective: The aim of this study was to investigate the effect of T2DM on BMD in patients with newly diagnosed RA. Methods: Patients diagnosed as RA were assigned to undergo BMD testing. Patients with T2DM were gathered from this population and formed a separate group. Healthy controls were drawn from subjects who came for a check-up. BMD was done with the GE Lunar DPX machine. Mean T Scores at spine, femur neck and total femur were recorded. Multivariate analysis was performed to compare T scores at various sites in the 3 groups. Age, gender, and steroid use were checked as confounding factors. Results: A total of 449 patients were diagnosed as RA during the period of 48 months. Of these, 337 (M-56, F-321) diagnosed as RA who had their BMD examined were enrolled in the study. Five hundred and one (M-248, F-253) healthy controls were enrolled. The mean T score values at femur neck, femur total and spine were -1.2+0.9, -0.8+1, -1.2+1.3 for controls, -2.4+0.8, -2.2+0.9, -2.9+0.9 for patients with RA and -1.7+1, -1.3+1, -1.7+1.2 for patients with RA+T2DM. The T scores at all sites in patients with additional T2DM were significantly better than those with only RA but significantly less than compared to controls. Similar results were obtained when separate analyses were done for males and females. Conclusion: Coexisting T2DM partly negates the low BMD measures and present with significantly higher values as compared to RA alone. In patients with this co morbidity, the BMD measures should be read with caution. With increasing evidence of diabetics having higher fragility fracture risk, measures other than the standard BMD need to be investigated which can quantify the exact fracture risk in patients with RA and T2DM.
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High serum myostatin level suggests accelerated muscle senescence in active idiopathic inflammatory myositis p. 284
Anamika Kumari Anuja, Danveer Bhadu, R Naveen, Mantabya Kumar Singh, Mohit Kumar Rai, Vikas Agarwal, Latika Gupta
Introduction: Inflammation is the forerunner to fibrosis and premature aging in various systemic diseases. Hence, we hypothesized that idiopathic inflammatory myopathies (IIM) may exhibit accelerated senescence, and the serum myostatin (MSTN):follistatin system may be a reflection of early senescence events in the muscle. Methods: Patients with IIM (ACR/EULAR criteria) were recruited (2017–2019) for comparison with healthy and disease controls (DCs). Those with active infection, pregnancy, renal dysfunction, or chronic kidney disease were excluded from the study. MSTN and follistatin were estimated in sera using ELISA (R&D systems, USA). Juvenile myositis and young adults (18–40 years) were subsequently analyzed separately. Nonparametric tests were used for paired and unpaired analysis. Results expressed as median and interquartile range. Results: A total of 84 myositis (3 juvenile myositis, 40 DM, 30 PM, 11 overlap) patients (68 females) with median age 38 (27–47.0) years and median disease duration of 0.9 (2.3–5.1) years were included. Serum MSTN was lower in IIM than in healthy control (149.3 vs. 243.6 P < 0.0001) but higher in IIM as compared with DCs (149.3 vs. 85.11, P = 0.0174). MSTN levels were higher in active as compared with inactive myositis in young adults (189.6 vs. 115.8, P = 0.0349). Serum MSTN correlated with height (r = 0.3, P = 0.003) and weight (r = 0.2, P = 0.047) but not MMT8 or muscle enzymes. On follow-up, the serial MSTN estimation paralleled change in disease activity. Conclusion: Elevated serum MSTN levels in active myositis raise the possibility of accelerated senescence in the inflamed muscle tissues which need further investigation.
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The relationship between disease activity, quality of life, functional status, spinal mobility, heel enthesitis, and cartilage thickness in patients with axial spondyloarthritis: A cross-sectional study p. 290
Serdar Kaymaz, Hakan Alkan, Veli Cobankara, Ugur Karasu
Background: The aim of this study was to evaluate lower extremity cartilage thickness in axial spondyloarthritis (SpA) patients and healthy controls using ultrasound (US) and to determine the relationship between the indices, quality of life, enthesopathy, and cartilage thickness of patients with axial SpA. Materials and Methods: This study included 73 axial SpA patients and 30 healthy controls. The patients with axial SpA were divided into two groups as with and without heel enthesitis. Demographic data, disease duration, and medical treatments of patients were recorded. The cartilage (hip, talar, and knee), plantar fascia, and Achilles tendon thicknesses of both healthy controls and axial SpA patients were measured by US. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), patient global assessment (PGA), and Ankylosing Spondylitis Quality of Life (ASQoL) scores of patients were evaluated. Results: There was no difference between the groups in terms of demographic data and body mass index. The axial SpA groups with and without heel enthesitis were similar in terms of medical treatment and disease duration. The axial SpA patients with heel enthesitis had thinner cartilages than those without heel enthesitis (P < 0.05). The axial SpA patients without heel enthesitis had thinner cartilage thicknesses than the healthy control group (P < 0.05). There were statistically significant differences between the two groups in terms of the BASDAI, BASFI, BASMI, and ASQoL scores. These indices were negatively correlated with cartilage thickness (P < 0.05; r: −0.420). Conclusion: Lower extremity cartilage thickness is associated with disease activity, quality of life, and spinal mobility in patients with axial SpA.
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Indigenous primary culture protocols for human adult skin fibroblast, pancreatic stellate cells, and peritoneal fibroblasts p. 298
Supriya Sharma, Gaurav Pande, Mohit Kumar Rai, Vikas Agarwal
Despite availability of commercially available cell lines, primary cultures of cells remain the best available natural resource for in vitro research work. However, establishing primary cultures is challenging and despite availability of many protocols for primary cell cultures reproducibility is lacking either due to cumbersome protocol, need for special reagents, and requirement of training. Herein, we present our simplistic least manipulative protocols for establishing primary human dermal fibroblasts, human pancreatic stellate cells, and human peritoneal fibroblasts that may be followed by other research laboratories for in vitro studies.
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Anxiety and depression in childhood rheumatologic conditions: A topical review p. 304
Mallet R Reid, Jacqueline Fabricius, Ashley Danguecan, Kaveh Ardalan, Andrea Knight, Natoshia R Cunningham
This topical review summarizes recent literature on mental health symptoms experienced by children diagnosed with rheumatologic conditions including childhood-onset systemic lupus erythematosus (cSLE), juvenile idiopathic arthritis (JIA), and juvenile dermatomyositis (JDM). Studies, while limited, generally indicate that anxiety and depressive symptoms may be more common among children diagnosed with rheumatologic conditions than non-chronically ill children. Although the rates of clinically significant symptoms are not consistently reported across studies, overall anxiety and depressive symptom rates in cSLE vary between 34%–37% and 6.7%–59%, respectively. A recent systematic review of JIA suggests between 7% and 64% of participants experienced elevated anxiety, and between 7% and 36% of participants reported clinically significant depressive symptoms. Approximately 40% of youth with JDM may experience general psychological distress, but more research is needed. In the available literature, there is mixed support for higher rates of anxiety in JIA as compared to cSLE, and higher rates of depressive symptoms in cSLE as compared to JIA, whereas mental health functioning in JDM is less well understood. Mental health functioning in youth with rheumatologic conditions may be related to increased disease-related impairment. Using consistent mental health screening measures with clinically validated cutoffs would enhance insight into the frequency and impact of anxiety and depressive symptoms experienced. Knowledge would also be enhanced by conducting studies with ethnically representative samples to identify potential disparities in care. An improved understanding of mental health functioning in pediatric patients presenting for rheumatologic care may inform the development and testing of tailored and effective treatments.
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Expert Panel consensus statements on the optimal usage of rituximab for the management of rheumatoid arthritis in India Highly accessed article p. 311
Keerthi Talari, Vinod Ravindran, Pradip Kumar, Pravin Patil, Sarath Chandra Mouli, Syamasis Bandyopadhyay, Balebail G Dharmanand, Abhrajit Ray, Shankaralingam Rajeshwari, Sanjiv N Amin, Jyotsna Oak, Ved Chaturvedi, Anand N Malaviya, Sukumar Mukherjee
Pharmacological management of rheumatoid arthritis (RA) includes synthetic and biological disease-modifying antirheumatic drugs (DMARDs). Biological DMARDs, also referred to as “biologics,” rapidly retard progression of the joint damage seen in RA. Rituximab is a well-established biologic for the management of RA with several biosimilar versions available. This document presents the consensus statements on the usage of rituximab for the management of RA developed by a group of 14 experienced rheumatologists from India. This expert panel identified areas of interests, collated and summarized relevant literature, developed, debated and refined and revised the statements which were voted upon at relevant stages. Subsequently, a wider consultative process including voting on the draft statements involved 18 more rheumatologists from across India. The approved final version has 28 consensus statements related to the following seven areas of rituximab therapy in RA, namely, contraindication, pretreatment screening, treatment schedule, evaluation of response, safety, and research agenda for future. It is envisaged that these consensus statements would help in optimizing the usage of rituximab in RA not only in India but also in other countries and benefit all stakeholders.
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Pregnancy counseling in rheumatic diseases: Where science meets the steps Highly accessed article p. 322
Anu Balakrishnan, Pankti Mehta, Latika Gupta
Most rheumatic diseases (RDs) have a predilection for women in the reproductive age group. Common drugs used in rheumatology practice have identified risks to the fetus; thus, adequate pregnancy counseling is of utmost importance. Contraception and adequate preparation for the same can enhance the experience of motherhood and decrease intra as well as peripartum complications. The knowledge, as well as practices of contraception in autoimmune diseases, are low and varied in various populations. The challenges faced in different RDs are unique and keen understanding can be fruitful toward better patient care. A multi-disciplinary team effort between the patient, obstetricians, and the rheumatologist is the key to better maternal and fetal outcomes.
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Spontaneous recovery in a case of lupus with severe COVID-19 pneumonia; Do we need to reconsider treatment Protocol? p. 333
Pradeepta Sekhar Patro, Samir Sahu, Shawaz Iqbal, Ishwar Chandra Behera, Priyanka Samal, Satyasundar Mohapatra
Individuals with inflammatory rheumatic diseases such as lupus are considered at risk for severe COVID-19 infection due to their immunocompromised state and the use of immunosuppressive treatment. Its impact on lupus is yet to be determined. Herein, we report a case of COVID-19 pneumonia in a 40-year-old female with a history of hypothyroidism and mild pulmonary hypertension who presented with a 4-day history of fever and breathlessness. COVID-19 infection was confirmed by real-time polymerase chain reaction (RT-PCR). On examination, she had a malar rash, short hair, and crepitations on the right side infrascapular and infraaxillary areas. Investigations revealed to have anemia, thrombocytopenia, transaminitis, high ferritin, and low fibrinogen, which were suggestive of cytokine release syndrome. Her antinuclear antibody (ANA) by indirect immunofluorescence on Hep-2 cells was 4+ homogeneous in 1:100 titer dilution and extractable nuclear antigen panel showed antibodies positive for histone, nucleosome, Ro, and smith antigens. The patient was diagnosed with systemic lupus erythematosus (SLE) with severe COVID-19 pneumonia with cytokine release syndrome and managed conservatively without specific antivirals or steroids. Her clinical condition and laboratory parameters improved afterward. On the 12th day, her RT-PCR for COVID-19 was negative and the patient was discharged. This would probably a reference case which showed conservative management can be helpful at times where no definite antiviral therapy has been approved with judicious use of immunosuppressants. Close monitoring of clinical conditions and laboratory parameters are recommended for such autoimmune disorders with COVID-19 infection.
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Fever, uveitis, and myocarditis as the initial presentation of Behcet's Disease: A case report and review of the literature p. 338
Vishal Mangal, Yogendra Mishra, Amar Tej Atal, Divya Kochhar, Durga Madhab Tripathy, Manish Manrai
Behcet's disease (BD) is an inflammatory disease characterized by recurrent aphthous ulcers, genital ulcers, and eye involvement. The involvement of the vascular system, heart, lungs, gastrointestinal tract, and the brain is less common, and BD myocarditis is very rare, with only a few cases reported in the literature. The prevalence of BD is variable globally, with Turkey having the highest prevalence, with 370 cases/100,000 population. Out of the 17 criteria proposed for the diagnosis of BD, the most commonly used criteria are the International Study Group (ISG) on BD criteria and the “International Criteria of BD” (ICBD) criteria. We present a case of a 40-year-old female who presented with fever of unknown origin, oral ulcers, odynophagia, and a rash over the face, extremities, and trunk. She developed acute-onset bilateral painful red eyes in the hospital with marked diminution of vision and persistent tachycardia. On evaluation, she was diagnosed to have bilateral intermediate uveitis based on the clinical finding of conjunctival congestion, and 1+ cells in the anterior chamber of both eyes, dispersion of iris pigments on the anterior surface of lens bilaterally, and Grade 1 vitreous haze on slit-lamp examination. The patient had persistent tachycardia for which an electrocardiogram was done, which revealed nonspecific ST-changes. Echocardiography was done, which showed a left ventricular ejection fraction of 40%, with global hypokinesia, suggestive of myocarditis. Our patient fulfilled the ICBD criteria, and she tested positive for human leukocyte antigen B51. She also had persistent transaminitis, and on evaluation, she was found to have occult hepatitis B infection with possible reactivation. The final diagnosis of BD with myocarditis and occult hepatitis B infection was established. She was managed with oral glucocorticoids, colchicine, azathioprine, and entecavir with a favorable outcome. BD causing myocarditis is an infrequent presentation, and we could find only 15 cases reported in the literature since 1947 when Dr. Hulusi Behcet first described the disease.
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A tale of two great mimickers: leprosy or sarcoidosis? A case-based review p. 345
Shivraj Padiyar, Reena Kharkele, Ramesh Babu Telugu, S Rima, John Mathew
Leprosy and sarcoidosis are chronic multisystem disorders, with clinical features overlapping with each other. The diagnosis requires a thorough clinical, laboratory, histopathological, and radiological examination. Although it is possible to conclude on one particular diagnosis most of the time, in some cases, even after extensive evaluation, it is difficult to differentiate between the two diseases. In such scenarios, treating both the conditions is warranted. Here, we present a case with a diagnostic dilemma between Hansen's disease and sarcoidosis and systematically discuss the specific pointers which can help to differentiate between the two diseases.
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Quadriparesis in lupus: A clinical challenge p. 349
Rashmi Roongta, Sumantro Mondal, Alakendu Ghosh
Neuropsychiatric manifestations are commonly seen in lupus and limb paresis is commonly due to noncompressive spinal etiology. Here, we report a case of a 50-year-old female with Jaccoud's arthropathy who had presented with quadriparesis for 3 months. She was diagnosed with lupus during her hospital stay. Her magnetic resonance imaging of the spine showed the presence of a soft-tissue mass in the cervical spine with atlantoaxial dislocation causing severe cord compression. This case highlights the importance of suspecting compressive myelopathy secondary either to infection or inflammation due to disease process in the cervical spine of patients with lupus, especially with Jaccoud's arthritis, presenting with weakness of limbs.
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Levamisole-Induced immune phenomenon and its various clinical manifestations in children: Two case reports along with review of literature p. 353
Anu Punnen Kocheril, T Sathish Kumar, Dharshini Sathishkumar
In literature, levamisole-induced immune manifestations were described mostly in association with its use in treatment of rheumatoid arthritis, malignancies, and recently, in relation to the use of illicit cocaine contaminated with levamisole among adults. Even though levamisole has been proven to be an inexpensive, safer, and effective drug with minimal side effects among children, it is not possible to undermine its potential side effects. The objective of this study was to describe levamisole-induced immune phenomenon and its manifestation in children. We describe two children with levamisole-induced immune phenomenon, leading to limb ischemia resulting in a gangrene and autoamputation of toes in the first child and an isolated microscopic hematuria in the second child along with a thorough review of available knowledge on this rare manifestation in children. Increased awareness of these rare but severe manifestations will remind clinicians to keep a high index of suspicion, its early recognizing, and withdrawal of offending drug before severe morbidity occurs in those children on levamisole.
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Fibrodysplasia ossificans progressiva: “A skeleton within a skeleton” p. 359
Kasturi Hazarika, Digvijay Gajanan Ekbote, Rasmi Ranjan Sahoo, Abilash Krishnan, Anupam Wakhlu
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Colour Doppler ultrasonography of temporal artery in treatment naive takayasu arteritis: A pilot study p. 361
Ripal Shah, Sathiyamoorthy Jothy, Shivraj Padiyar, Ramaswamy Subramanian, Shyamkumar N Keshava, George Joseph, Debashish Danda
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Narrowing the gender gap: Will Indian rheumatology pave the way? p. 364
Benzeeta Pinto, KM Mahendranath
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Comment on: Assessing the risk of retinopathy in indian patients using hydroxychloroquine for rheumatic and musculoskeletal diseases: A retrospective observational study p. 365
Manesh Manoj, Rasmi Ranjan Sahoo, Anupam Wakhlu
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Correspondence on “assessing the risk of retinopathy in Indian patients using hydroxychloroquine for rheumatic and musculoskeletal diseases: A retrospective observational study” p. 367
Nikunjkumar V Dadhaniya, Sundeep Upadhyaya, Sirinder J Gupta, Rohini Handa
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Correspondence on “assessing the risk of retinopathy in indian patients using hydroxychloroquine for rheumatic and musculoskeletal diseases: A retrospective observational study” – Reply p. 369
Arindam Nandy Roy, Vinitha Samala, Yarram Ashok Kumar, Syeda Sana Fatima
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Toward voice detection for screening rheumatology patients p. 371
Or Aharonov
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