Safety and Efficacy of Golimumab in Indian Patients with Active Spondyloarthritis of Ankylosing Spondylitis or Psoriatic Arthritis: A Multicenter, Noncomparative, Open-Label, Real-World Study.

BACKGROUND: The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitor therapy for most common rheumatological diseases, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in controlled clinical trials is well-studied. This study evaluated subcutaneous (SC) golimumab in Indian patients with active spondyloarthritis (SpA) of AS or PsA in a real-world setting. MATERIALS AND METHODS: This phase 4, multicenter, prospective, non-comparative, interventional, 24-week study was performed in patients (age ≥18 years) with active SpA of AS or PsA (NCT03733925). Golimumab 50 mg was given subcutaneously to the patients every 4 weeks. Safety was assessed. The proportion of patients with AS and PsA achieving ≥20% improvement in the Assessment of SpA International Society 20 (ASAS20) criteria and American College of Rheumatology 20 (ACR20) responses, respectively, at weeks 14 and 24 were efficacy endpoints. RESULTS: Of the 100 patients enrolled (men: 78 [78.0%]; mean age: 36.7 [12.02] years), 94 (94.0%) patients completed the study. Treatment-emergent adverse events with golimumab were observed in 29/100 (29.0%) patients, and nasopharyngitis and upper respiratory tract infection (5.0% each) were the most common (≥5%). Deaths were not reported. At week 14, 74.5% (95% confidence interval [CI]: 59.7; 86.1%) of patients with AS and 84.6% (95% CI: 69.5; 94.1%) of patients with PsA achieved ASAS20 and ACR20 responses, which were sustained at week 24 (ASAS20: 66.0% [95% CI: 50.7, 79.1%]; ACR20: 93.2% [95% CI: 81.3, 98.6%]), respectively. CONCLUSION: Golimumab (50 mg) administered subcutaneously was safe and effective in Indian patients with active SpA of AS or PsA during the 24-week study period with no new safety signals.

Effect of neuronavigated repetitive Transcranial Magnetic Stimulation on pain, cognition and cortical excitability in fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep. METHODS: Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy (n = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy. RESULTS: Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity (P < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham. CONCLUSIONS: Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity.

HLA sequencing identifies novel associations and suggests clinical relevance of DPB1*04:01 in ANCA-associated Granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Major contributions of HLA genes have been reported; however, HLA typing-based diagnosis or risk prediction in GPA has not been established. We have performed a sequencing-based HLA genotyping in a north Indian GPA cohort and controls to identify clinically relevant novel associations. PR3-ANCA-positive 40 GPA patients and 40 healthy controls from north India were recruited for the study. Targeted sequencing of HLA-A,-B,-C,-DRB1,-DQB1, and -DPB1 was performed. Allelic and haplotypic associations were tested. Molecular docking of susceptibility HLA alleles with reported super-antigen epitopes was performed. The association of substituted amino acids located at the antigen-binding domain of HLA was evaluated. Genetic association of five HLA-alleles was identified in GPA. The novel association was identified for C*15:02 (p = 0.04; OR = 0.27(0.09-0.88)). The strongest association was observed for DPB1*04:01 (p < 0.0001; OR = 6.2(3.08-11.71)), previously reported in European studies. 35 of 40 GPA subjects had at least one DPB1*04:01 allele, and its significant risk was previously not reported from the Indian population. Significantly associated haplotypes DRB1*03:01-DQB1*02:01-DPB1*04:01 (p = 0.02; OR = 3.46(1.11-12.75)) and DRB1*07:01-DQB1*02:02-DPB1*04:01 (p = 0.04; OR = 3.35(0.95-14.84)) were the most frequent in GPA patients. Ranging from 89 % to 100 % of GPA patients with organ involvement can be explained by at least one DPB1*04:01 allele. A strong interaction between the HLA and three epitopes of the reported super antigen TSST-1 of Staphylococcus aureus was confirmed. Our study highlighted the potential applicability of HLA typing for screening and diagnosis of GPA. A large multi-centric study and genotype-phenotype correlation analysis among GPA patients will enable the establishment of HLA-typing based GPA diagnosis.

Yoga maintains Th17/Treg cell homeostasis and reduces the rate of T cell aging in rheumatoid arthritis: a randomized controlled trial.

The pathogenesis of rheumatoid arthritis (RA) is characterized by a Th17/Treg cell imbalance. A pro-inflammatory cytokine milieu that promotes the continued proliferation of Th17 cells is related to the development of autoinflammation. In RA, T cells have several hallmarks of cellular aging, and they accumulate DNA damage, predisposing to the occurrence of mutations and epigenetic alterations. Since the onset, progression, and treatment response are influenced by a variety of external stressors and environmental factors, this study aimed to evaluate the impact of 8-week yoga practice on disease severity, T cell subsets, markers of T cell ageing and inflammation, epigenetic alterations and gene expression patterns in active RA patients on standard disease-modifying anti-rheumatic drugs (DMARDs). A total of 64 participants with active RA were randomized into 2 groups, yoga group (n = 32) or non-yoga group (n = 32); that were assessed for disease severity, at baseline and after 8 week duration, for Disease Activity Score (DAS28-ESR), T cell subsets [Th17 (CD3+ CD4+ IL17+ RORγt+) cells and Treg (CD3+ CD4+ CD25+ CD127-Foxp3+) cells], markers of T cell aging [aged Th17 cells (CD3+ CD4+ IL17+ RORγt+ CD28-) and aged Treg cells (CD3+ CD4+ CD25+ CD127-Foxp3+ CD28-)], pro-inflammatory markers [IL-6, and IL-17], anti-inflammatory markers [TGF-ß, and IL-10], epigenetic alterations [5-methyl cytosine, 5-hydroxymethyl cytosine, and HDAC1] and gene expression patterns [RORγt, FoxP3, IL-17, IL-6, TGF-ß, CXCL2, CXCR2, and JUN]. In yoga group, there was a significant improvement in DAS28-ESR scores at the end of 8-weeks of yoga program. The Th17 cells and aged T cell subsets showed a significant decline whereas Treg cell population showed a significant elevation in yoga group. There were significant improvements observed in epigenetic markers as well as inflammatory markers post 8-weeks of yoga practice. The yoga group showed downregulation of RORγt, IL-17, IL-6, CXCL2, CXCR2, and upregulation of FoxP3 and TGF-ß transcripts. Yoga enables the maintenance of immune-homeostasis as evident by increased Treg cell population and reduced Th17 cell population. Yoga reduces the rate of immunological aging in T cells, as seen by the reduction in population of aged Th17 cells and aged Treg cells. Yoga positively modifies transcriptome and epigenome by normalization of various inflammatory markers, gene expression patterns and epigenetic alterations. Taken together, yoga reduces RA severity, and aids in immune-modulation and hence can be beneficial as an adjunct therapy.

Anti-inflammatory potential of selective small compounds by targeting TNF-α & NF-kB signaling: a comprehensive molecular docking and simulation study.

Tumor necrosis factor alpha (TNF-α) is the major cause of inflammation in autoimmune diseases like rheumatoid arthritis (RA). It's mechanisms of signal transduction through nuclear factor kappa B (NF-kB) pathway via small molecules such as metabolite crosstalk are still elusive. In this study, we have targeted TNF-α and NF-kB through metabolites of RA, to inhibit TNF-α activity and deter NF-kB signaling pathways, thereby mitigating the disease severity of RA. TNF-α and NF-kB structure was obtained from PDB database and metabolites of RA were selected from literature survey. In-silico studies were carried out by molecular docking using AutoDock Vina software and further, known TNF-α and NF-kB inhibitors were compared and revealed metabolite's capacity to targets the respective proteins. Most suitable metabolite was then validated by MD simulation to verify its efficiency against TNF-α. Total 56 known differential metabolites of RA were docked with TNF-α and NF-kB compared to their corresponding inhibitor compounds. Four metabolites such as Chenodeoxycholic acid, 2-Hydroxyestrone, 2-Hydroxyestradiol (2-OHE2), and 16-Hydroxyestradiol were identified as a common TNF-α inhibitor's having binding energies ranging from -8.3 to -8.6 kcal/mol, followed by docking with NF-kB. Further, 2-OHE2 was selected because of having binding energy -8.5 kcal/mol, found to inhibit inflammation and the effectiveness was validated by root mean square fluctuation, radius of gyration and molecular mechanics with generalized born and surface area solvation against TNF-α. Thus 2-OHE2, an estrogen metabolite was identified as the potential inhibitor, attenuated inflammatory activation and can be utilized as a therapeutic target to disseminate severity of RA.

Translational implications of humoral and cellular immune dysfunction in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a rare systemic ANCA (Anti-neutrophil cytoplasmic antibodies) associated vasculitis (AAV). In the last couple of decades, GPA has emerged as a disease of concern due to rapid increase in the prevalence and incidence especially in developing countries. Unknown aetiology and rapid progression have made GPA a critical disease. Thus, establishing specific tools to facilitate early and faster disease diagnosis and efficient disease management has immense importance. GPA may develop in genetically predisposed individuals on receiving the external stimulus (i.e. microbial pathogen, pollutant etc.) that triggers the immune response. B-cell activating factor (BAFF) produced by the neutrophils, promotes the B-cell maturation and survival which leads to increased ANCA production. Abnormal B-cell and T-cell proliferation and their cytokine response plays a major role in disease pathogenesis and granuloma formation. ANCA interacts with neutrophils and induces the neutrophil extracellular traps (NETs) formation and reactive oxygen species (ROS) production which leads to the endothelial cell injury. This review article summarizes the critical pathological events and how cytokines and immune cells shape the GPA pathogenesis. Decoding this complex network would facilitate in developing tools for diagnosis, prognosis and disease management. Recently developed specific monoclonal antibodies (MAbs) targeting cytokines and immune cells are being used for safer treatment and achieving longer remission.

Potential Role of Yoga Intervention in the Management of Chronic Non-malignant Pain.

Pain is an unpleasant and upsetting experience. Persistent pain has an impact on an individual's quality of life which causes stress and mood disorders. There are currently no pain-relieving techniques available that can eliminate pain and offer relief without causing any adverse effects. These factors draw attention to traditional treatments like yoga and meditation, which can reduce biological stress and hence increase immunity, as well as alleviate the psychological and emotional suffering produced by pain. Yoga reduces the stress response and the pain cascade via the downregulation of the hypothalamus-pituitary-adrenal (HPA) axis and vagal stimulation. Yoga is a cost-effective growing health practice that, unlike pharmaceuticals, has no side effects and can help patients stay in remission for longer periods of time with fewer relapses. Yoga not only reduces stress and depression severity but also improves functional status and reduces pain perception. This article highlights the impact of yoga on pain management and on a malfunctioning immune system, which leads to improved health, pain reduction, disease management, and improvement in overall quality of life.

Meta-analysis confirmed genetic susceptibility conferred by multiple risk variants from CTLA4 and SERPINA1 in granulomatosis with polyangiitis.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Smaller sample size and complex nature of the disease pathogenesis has made it challenging to perform well-powered genetic investigations. We performed a systematic review based meta-analysis in GPA to investigate the genetic susceptibility conferred by non-human leukocyte antigen (non-HLA) candidate genes. METHODS: A systematic review was performed using web-based literature search and eligible studies were included following inclusion-exclusion criteria. Studies were evaluated for their quality of evidence and study outcome was assessed using the Newcastle-Ottawa Scale and Grades of Research, Assessment, Development and Evaluation tools. Reviewer's agreement was accessed through Cohen's κ value. Meta-analyses were performed using RevMan 5 tool. Meta-odds ratio (meta-OR) and Z test P value were evaluated to estimate the genetic susceptibility for each of the variants. RESULTS: Eighteen studies were found eligible and 7 genetic variants from only 4 genes, namely CTLA4, PRTN3, SERPINA1 and PTPN22 could be studied for meta-analysis. rs231775-G (49-G) (Meta-OR = 1.42 [1.14-1.76]; P = .001) of CTLA4 and rs7151526-A (Meta-OR = 2.70 [1.51-4.85]; P = .0008) of SERPINA1 were confirmed to be predisposing alleles, and rs5742909-C (318-C) (Meta-OR = 0.65 [0.44-0.97]; P =.03) of CTLA4 was found to be protective for GPA. In concordance with the genetic association of rs7151526-A, serological marker for the same variant "Z" allele of SERPINA1 was found to be predisposing (Meta-OR = 12.60 [5.01-31.68]; P < .00001) for GPA. CONCLUSION: Genetic variants confirmed in this study play critical roles in T-cell mediated immune function and could be significantly implicated in GPA. Molecular pathology studies are warranted to confirm their role. These markers could be used for efficient patient classification and disease management.

Epidemiology and genetics of granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) previously known as Wegener's granulomatosis (WG) is a rare rheumatic disease affecting subjects of all ages. Prevalence and incidence of this systemic disease greatly varies across different ethnic groups. GPA is the commonest form of ANCA-associated vasculitis (AAV) with PR3 positivity among 85-95% of the cases. Scientific investigations of GPA is warranted because its severity, clinical heterogeneity, fast disease manifestation and end-organ damage. The etiology of GPA is still unknown. Major role of HLA and non-HLA genes with immune functions were identified, however, very limited replication was observed in different ethnic populations. In the present review, we have discussed the updates on the global epidemiology and contribution of HLA and major non-HLA genes/loci in GPA. We have also highlighted the cross disease association of GPA associated genes that may help in better disease management and predictive medicine. We proposed that high-resolution HLA typing and development of genetic risk model would help in early disease diagnosis and understanding the prognosis.

Yoga improves mitochondrial health and reduces severity of autoimmune inflammatory arthritis: A randomized controlled trial.

BACKGROUND: Oxidative stress (OS) and mitochondrial alterations have been implicated in the pathogenesis of rheumatoid arthritis (RA). Various environmental triggers like air pollutants, smoking, unhealthy social habits and sedentary lifestyle induce OS, which may compromise mitochondrial integrity. This trial was designed to explore the effect of 8-weeks yoga practice on mitochondrial health and disease severity in an active RA group compared with a usual-care control group. METHODS: A total of 70 subjects were randomized into two groups: yoga group and non-yoga group. Mitochondrial health was assessed by calculation of mitochondrial DNA copy number (mtDNA-CN), OS markers, mitochondrial activity, mitochondrial membrane potential (ΔΨm), circadian rhythm markers and transcripts associated with mitochondrial integrity: AMPK, TIMP-1, KLOTHO, SIRT-1, and TFAM. Parameters of disease activity and disability quotient were also assessed by disease activity score - erythrocyte sedimentation rate (DAS28-ESR) and health assessment questionnaire-disability index (HAQ-DI), respectively. RESULTS: In yoga group, there was a significant upregulation of mtDNA-CN, mitochondrial activity markers, ΔΨm, and transcripts that maintain mitochondrial integrity after 8-weeks of yoga. There was optimization of OS markers, and circadian rhythm markers post 8-weeks practice of yoga. Yoga group participants showed significant improvements in DAS28-ESR (p < 0.05) and HAQ-DI (p < 0.05) over the non-yoga group. CONCLUSION: Adoption of yoga by RA patients holds the key to enhance mitochondrial health, improve circadian rhythm markers, OS marker regulation, upregulation of transcripts that maintain mitochondrial integrity, reduce disease activity and its associated consequences on health outcome and hence can be beneficial as an adjunct therapy.

Correlating cognition and cortical excitability with pain in fibromyalgia: a case control study.

BACKGROUND: Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal symptoms, primarily attributed to sensitization of somatosensory system carrying pain. Few reports have investigated the impact of fibromyalgia symptoms on cognition, corticomotor excitability, sleepiness, and the sleep quality - all of which can deteriorate the quality of life in fibromyalgia. However, the existing reports are underpowered and have conflicting directions of findings, limiting their generalizability. Therefore, the present study was designed to compare measures of cognition, corticomotor excitability, sleepiness, and sleep quality using standardized instruments in the recruited patients of fibromyalgia with pain-free controls. METHODS: Diagnosed cases of fibromyalgia were recruited from the Rheumatology department for the cross-sectional, case-control study. Cognition (Mini-Mental State Examination, Stroop color-word task), corticomotor excitability (Resting motor threshold, Motor evoked potential amplitude), daytime sleepiness (Epworth sleepiness scale), and sleep quality (Pittsburgh sleep quality index) were studied according to the standard procedure. RESULTS: Thirty-four patients of fibromyalgia and 30 pain-free controls were recruited for the study. Patients of fibromyalgia showed decreased cognitive scores (p = 0.05), lowered accuracy in Stroop color-word task (for color: 0.02, for word: 0.01), and prolonged reaction time (< 0.01, < 0.01). Excessive daytime sleepiness in patients were found (< 0.01) and worsened sleep quality (< 0.01) were found. Parameters of corticomotor excitability were comparable between patients of fibromyalgia and pain-free controls. CONCLUSIONS: Patients of fibromyalgia made more errors, had significantly increased reaction time for cognitive tasks, marked daytime sleepiness, and impaired quality of sleep. Future treatment strategies may include cognitive deficits and sleep disturbances as an integral part of fibromyalgia management.

Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX). METHODS: This 52-week, multicentre, double-blind, placebo-controlled and active-controlled phase III trial evaluated once-daily oral filgotinib in patients with RA randomised 3:3:2:3 to filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100), subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), all with stable weekly background MTX. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Additional efficacy outcomes were assessed sequentially. Safety was assessed from adverse events and laboratory abnormalities. RESULTS: The proportion of patients (n=1755 randomised and treated) achieving ACR20 at week 12 was significantly higher for FIL200 (76.6%) and FIL100 (69.8%) versus placebo (49.9%; treatment difference (95% CI), 26.7% (20.6% to 32.8%) and 19.9% (13.6% to 26.2%), respectively; both p<0.001). Filgotinib was superior to placebo in key secondary endpoints assessing RA signs and symptoms, physical function and structural damage. FIL200 was non-inferior to adalimumab in terms of Disease Activity Score in 28 joints with C reactive protein ≤3.2 at week 12 (p<0.001); FIL100 did not achieve non-inferiority. Adverse events and laboratory abnormalities were comparable among active treatment arms. CONCLUSIONS: Filgotinib improved RA signs and symptoms, improved physical function, inhibited radiographic progression and was well tolerated in patients with RA with inadequate response to MTX. FIL200 was non-inferior to adalimumab. TRIAL REGISTRATION NUMBER: NCT02889796.

Correlating cognition and cortical excitability with pain in fibromyalgia: a case control study

Abstract Background: Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal symptoms, primarily attributed to sensitization of somatosensory system carrying pain. Few reports have investigated the impact of fibromyalgia symptoms on cognition, corticomotor excitability, sleepiness, and the sleep quality — all of which can deteriorate the quality of life in fibromyalgia. However, the existing reports are underpowered and have conflicting directions of findings, limiting their generalizability. Therefore, the present study was designed to compare measures of cognition, corticomotor excitability, sleepiness, and sleep quality using standardized instruments in the recruited patients of fibromyalgia with pain-free controls. Methods: Diagnosed cases of fibromyalgia were recruited from the Rheumatology department for the cross-sectional, case-control study. Cognition (Mini-Mental State Examination, Stroop color-word task), corticomotor excitability (Resting motor threshold, Motor evoked potential amplitude), daytime sleepiness (Epworth sleepiness scale), and sleep quality (Pittsburgh sleep quality index) were studied according to the standard procedure. Results: Thirty-four patients of fibromyalgia and 30 pain-free controls were recruited for the study. Patients of fibromyalgia showed decreased cognitive scores (p = 0.05), lowered accuracy in Stroop color-word task (for color: 0.02, for word: 0.01), and prolonged reaction time (< 0.01, < 0.01). Excessive daytime sleepiness in patients were found (< 0.01) and worsened sleep quality (< 0.01) were found. Parameters of corticomotor excitability were comparable between patients of fibromyalgia and pain-free controls. Conclusions: Patients of fibromyalgia made more errors, had significantly increased reaction time for cognitive tasks, marked daytime sleepiness, and impaired quality of sleep. Future treatment strategies may include cognitive deficits and sleep disturbances as an integral part of fibromyalgia management.(AU)

Protective effects of Glycyrrhiza glabra supplementation against methotrexate-induced hepato-renal damage in rats: An experimental approach.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine, Glycyrrhiza glabra, commonly known as liquorice, is known to possess promising pharmacological properties including anti-oxidative, anti-inflammatory, gastro, hepato and nephro-protective activities. AIM: The present study investigated the protective effects of Glycyrrhiza glabra rhizome extract (GGE) on MTX-induced hepato-renal damage in Wistar albino rats. MATERIALS AND METHODS: Rats were pre-treated with GGE (100, 200 or 400 mg/kg) from day 1 to 15 and administered MTX (20 mg/kg) on day 4. Methotrexate-induced hepato-renal damage was assessed by serum toxicity biomarkers (AST, ALT, BUN and creatinine), oxidative stress estimation (MDA, GSH, SOD, CAT, peroxidase and glutathione reductase), interleukins profiling (TNF-α, IL-1ß, IL-6 and IL-12), tissue histopathology and immunohistochemical (caspase-3 and NFkB) examination. RESULTS: MTX induced hepato-renal damage resulted in elevated serum levels of AST, ALT, BUN and creatinine, increased pro-inflammatory cytokines concentration and accumulation of MDA and reduced levels of GSH, SOD, CAT, peroxidase and glutathione reductase. Conversely, co-treatment with GGE dose-dependently ameliorated oxidative stress, serum interleukins, hepato-renal toxicity biomarkers (p < 0.001), preserved tissue architecture and downregulated both caspase-3 and NFkB expression in hepato-renal tissue. CONCLUSION: The above results suggested that GGE can alleviate MTX-induced hepato-renal damage by decreasing oxidative stress and suppressing the ensuing activation of pro-apoptotic and pro-inflammatory pathways.

Repetitive transcranial magnetic stimulation of the prefrontal cortex for fibromyalgia syndrome: a randomised controlled trial with 6-months follow up.

OBJECTIVES: Fibromyalgia Syndrome (FMS), is a chronic pain disorder with poorly understood pathophysiology. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been recommended for pain relief in various chronic pain disorders. The objective of the present research was to study the effect of low frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) on pain status in FMS. METHODS: Ninety diagnosed cases of FMS were randomized into Sham-rTMS and Real-rTMS groups. Real rTMS (1 Hz/1200 pulses/8 trains/90% resting motor threshold) was delivered over the right DLPFC for 5 consecutive days/week for 4 weeks. Pain was assessed by subjective and objective methods along with oxidative stress markers. Patients were followed up for 6 months (post-rTMS;15 days, 3 months and 6 months). RESULTS: In Real-rTMS group, average pain ratings and associated symptoms showed significant improvement post rTMS. The beneficial effects of rTMS lasted up to 6 months in the follow-up phase. In Sham-rTMS group, no significant change in pain ratings was observed. CONCLUSION: Right DLPFC rTMS can significantly reduce pain and associated symptoms of FMS probably through targeting spinal pain circuits and top-down pain modulation . TRIAL REGISTRATION: Ref No: CTRI/2013/12/004228.

Repetitive transcranial magnetic stimulation of the prefrontal cortex for fibromyalgia syndrome: a randomised controlled trial with 6-months follow up

Abstract Objectives Fibromyalgia Syndrome (FMS), is a chronic pain disorder with poorly understood pathophysiology. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been recommended for pain relief in various chronic pain disorders. The objective of the present research was to study the effect of low frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) on pain status in FMS. Methods Ninety diagnosed cases of FMS were randomized into Sham-rTMS and Real-rTMS groups. Real rTMS (1 Hz/1200 pulses/8 trains/90% resting motor threshold) was delivered over the right DLPFC for 5 consecutive days/week for 4 weeks. Pain was assessed by subjective and objective methods along with oxidative stress markers. Patients were followed up for 6 months (post-rTMS;15 days, 3 months and 6 months). Results In Real-rTMS group, average pain ratings and associated symptoms showed significant improvement post rTMS. The beneficial effects of rTMS lasted up to 6 months in the follow-up phase. In Sham-rTMS group, no significant change in pain ratings was observed. Conclusion Right DLPFC rTMS can significantly reduce pain and associated symptoms of FMS probably through targeting spinal pain circuits and top-down pain modulation . Trial registration: Ref No: CTRI/2013/12/004228.(AU)

Can aberrant spinal nociception be a marker of chronicity of pain in fibromyalgia syndrome?

Pain sensitivity is a recognized feature of fibromyalgia syndrome (FMS) but the contribution of spinal nociceptive circuitry to this phenomenon is unknown. Therefore, the objectives were to study the changes in spinal nociception i.e. nociceptive flexion reflex (NFR) in patients with FMS and to investigate correlation if any, between NFR threshold, pain duration and tender points in FMS. One hundred and three patients with FMS and 74 healthy volunteers participated in the study. To record NFR, sural nerve was stimulated in the retro malleolar region and the reflex response was recorded from the short head of biceps femoris muscle. NFR was elicited at significantly lower [21.0(18.0-25.0)V] thresholds in FMS group when compared to healthy subjects [30.0(24.75-35.0)V; p = 0.001] indicating hyperalgesic response to electrocutaneous stimulation in FMS patients. The latency and other parameters of NFR were comparable in both the groups. No significant correlation was found among NFR threshold and pain duration or tender points. On the basis of results of present study, it may be concluded that the functional deficit of the spinal nociceptive system can contribute to hyperalgesia in FMS. This is first study that correlates a marker of central hyper-excitability (NFR threshold) with clinical symptoms (pain duration and tender points) of FMS.

Infectious versus non-infectious causes of oligoarticular inflammatory arthritis: A prospective study from a tertiary care hospital in north India.

Oligoarticular arthritis (inflammation of upto 4 joints) has a wide range of infectious and non-infectious etiologies. The aim of our study was to identify the features which could help in the differentiation of infectious from non-infectious arthritis. The study was prospective and observational, and included 100 patients with oligoarticular inflammatory arthritis. The final diagnosis was made using standard diagnostic criteria and the patients were categorized into infectious and non-infectious groups. Among the 100 patients who were recruited, the following final diagnosis were made: peripheral spondyloarthritis (n = 37), axial spondyloarthritis (n = 11), tuberculosis (n = 19), brucellosis (n = 6), septic arthritis (n = 6), gouty arthritis (n = 5), early rheumatoid arthritis (n = 5), non-tubercular mycobacteria (n = 2), SLE (n = 2), post-chikungunya arthritis (n = 2), acute lymphocytic leukaemia (n = 1), pachydermoperiostosis (n = 1), sarcoidosis (n = 1) and juvenile idiopathoic arthritis (n = 1). The patients were categorized into two groups: infectious (33) and non-infectious (60). The presence of monoarthritis, clinically-significant weight loss, hepatomegaly, splenomegaly and erosive arthritis were significantly more common in the infectious group as compared to the non-infectious group.

Unravelling the NERDS syndrome.

A 22-year-old man presented with symmetric polyarthritis, pruritus and deviation of angle of mouth to the right side since the last 7 years. His symptoms were persistent despite receiving ayurvedic medications and symptomatic therapy. Examination revealed dry skin, cutaneous nodules, xanthelasma, periarticular non-tender swellings, pitting oedema of hands and feet and lower motor neuron type right facial palsy. Haematological investigations revealed eosinophilia and skin biopsy had cutaneous eosinophilic infiltration. The constellation of above findings comprises the nodules, eosinophilia, rheumatism, dermatitis and swelling syndrome. It a rare syndrome with few reported cases in literature. The patient was started on oral corticosteroids which was subsequently tapered and methotrexate therapy. His polyarthritis and skin rashes resolved with therapy. He has been followed-up for 2 years and is presently asymptomatic for the last 1 year.