Association of TPMT and NUDT15 gene polymorphisms with azathioprine-induced leukopenia: A case-control study in Eastern India.

BACKGROUND: Azathioprine (AZA) is a widely used immunosuppressant drug. Leukopenia is a serious adverse effect of the drug which often necessitates dose reduction or drug withdrawal. Predictors of leukopenia include genetic and nongenetic factors. Genetic polymorphism of AZA-metabolizing enzyme, thiopurine S-methyltransferase (TPMT) is well established. There is inconclusive evidence about the role of Nudix hydrolase (NUDT15) gene polymorphism. This case-control study assessed the association of genetic polymorphisms of NUDT15 and TPMT with leukopenia induced by AZA. MATERIALS AND METHODS: Cases were patients on AZA who developed leukopenia (white blood cell count <4000/µl) within 1 year of treatment initiation that necessitated dose reduction or drug withdrawal. Age and gender-matched patients without leukopenia within 1 year of treatment with AZA served as controls. TPMT (3 loci: c238G to C, c460G to A, c719A to G) and NUDT15 (c 415C to T, rs116855232) genotyping were done using TPMT strip assay and polymerase chain reaction-restriction fragment length polymorphism, respectively. Genotype frequencies were noted, and the odds ratio was calculated to determine the association between genotypes and leukopenia. RESULTS: Twenty-nine subjects (15 cases and 14 controls) were enrolled. Statistically significant differences were not observed in the TPMT genotype (*1/*1 and *1/*3C) (P = 0.23) between cases and controls. NUDT15 genotypes (*1/*1 and *1/*3) (P = 0.65) also showed no statistically significant difference between cases and controls. CONCLUSION: The above genotypes do not appear to be associated with AZA-induced leukopenia in an eastern Indian population.

Efficacy and safety of an early response-based tapering regimen of tocilizumab in children with systemic juvenile idiopathic arthritis.

INTRODUCTION: Systemic juvenile idiopathic arthritis (sJIA) is a distinct disease subset, with a poorer prognosis compared with other JIA subsets. Tocilizumab has an important role in the management of sJIA refractory to standard initial therapy. However, no specific guidelines exist for the tapering of tocilizumab therapy in sJIA, which could have implications on the overall cost and side effects of treatment. METHODS: This was an observational study which included 21 children with refractory sJIA, who were initially put on injection tocilizumab every 2 weekly, with subsequent dosing tapered to 4 weekly and 6 weekly intervals based on JIA ACR 70 responses at 12 and 24 weeks, respectively. The primary outcome at week 36 included JIA ACR 30, 50, 70, and 90 response rates with other efficacy and safety measures as secondary outcomes. RESULTS: At 36 weeks, JIA ACR 30, 50, 70, and 90 responses were observed in 90.5%, 90.5%, 71.4%, and 52.4% patients respectively along with significant improvement in hematological and inflammatory parameters. The mean prednisolone dose could be reduced from 0.54 to 0.13 mg/kg/day and around 29% patients were able to discontinue steroids altogether. No serious adverse events were recorded. With drug tapering, we could curtail on 26% of the total tocilizumab dose that would have been otherwise required on the continuous 2 weekly protocol. CONCLUSIONS: Tocilizumab, used in an early response-based tapering regimen, was both safe and efficacious in children with sJIA refractory to standard therapy. Larger and longer duration studies are required to further validate our observations.

Does post-COVID reactive arthritis exist? Experience of a tertiary care centre with a review of the literature.

BACKGROUND: Rheumatological manifestations following COVID-19 are various, including Reactive Arthritis (ReA), which is a form of asymmetric oligoarthritis mainly involving the lower limbs, with or without extra-articular features. The current case series describes the clinical profile and treatment outcome of 23 patients with post-COVID-19 ReA. METHODS: A retrospective, observational study of patients with post-COVID-19 arthritis over one year was conducted at a tertiary care centre in India. Patients (n=23) with either a positive polymerase chain reaction test for SARS-CoV2 or an anti-COVID-19 antibody test were included. Available demographic details, musculoskeletal symptoms, inflammatory markers, and treatment given were documented. RESULTS: Sixteen out of 23 patients were female. The mean age of the patients was 42.8 years. Nineteen patients had had symptomatic COVID-19 infection in the past. The duration between onset of COVID-19 symptoms and arthritis ranged from 5 to 52 days with a mean of 25.9 days. The knee was the most involved joint (16 out of 23 cases). Seven patients had inflammatory lower back pain and nine had enthesitis. Most patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids - either depot injection or a short oral course. Three patients required treatment with hydroxychloroquine and methotrexate which were eventually stopped. No relapse was reported in any of the patients. CONCLUSION: On combining our data with 21 other case reports of ReA, a lower limb predominant, oligoarticular, asymmetric pattern of arthritis was seen with a female preponderance. The mean number of joints involved was 2.8. Axial symptoms and enthesitis were often coexistent. Treatment with NSAIDs and intra-articular steroids was effective. However, whether COVID-19 was the definitive aetiology of the arthritis is yet to be proven.

Does post-COVID reactive arthritis exist? Experience of a tertiary care centre with a review of the literature / ¿Existe la artritis reactiva post-COVID?: experiencia de un centro de tercer nivel de atención con revisión de la literatura

Background: Rheumatological manifestations following COVID-19 are various, including Reactive Arthritis (ReA), which is a form of asymmetric oligoarthritis mainly involving the lower limbs, with or without extra-articular features. The current case series describes the clinical profile and treatment outcome of 23 patients with post-COVID-19 ReA. Methods: A retrospective, observational study of patients with post-COVID-19 arthritis over one year was conducted at a tertiary care centre in India. Patients (n=23) with either a positive polymerase chain reaction test for SARS-CoV2 or an anti-COVID-19 antibody test were included. Available demographic details, musculoskeletal symptoms, inflammatory markers, and treatment given were documented. Results: Sixteen out of 23 patients were female. The mean age of the patients was 42.8 years. Nineteen patients had had symptomatic COVID-19 infection in the past. The duration between onset of COVID-19 symptoms and arthritis ranged from 5 to 52 days with a mean of 25.9 days. The knee was the most involved joint (16 out of 23 cases). Seven patients had inflammatory lower back pain and nine had enthesitis. Most patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids – either depot injection or a short oral course. Three patients required treatment with hydroxychloroquine and methotrexate which were eventually stopped. No relapse was reported in any of the patients. Conclusion: On combining our data with 21 other case reports of ReA, a lower limb predominant, oligoarticular, asymmetric pattern of arthritis was seen with a female preponderance. The mean number of joints involved was 2.8. Axial symptoms and enthesitis were often coexistent. Treatment with NSAIDs and intra-articular steroids was effective. However, whether COVID-19 was the definitive aetiology of the arthritis is yet to be proven.(AU)

Antecedentes: Las manifestaciones reumatológicas posteriores al COVID-19 son diversas, entre ellas, la artritis reactiva, que es una forma de oligoartritis asimétrica que afecta principalmente a los miembros inferiores, con o sin características extraarticulares. La serie de casos actual describe el perfil clínico y el resultado del tratamiento de 23 pacientes con artritis reactiva posterior a COVID-19. Métodos: Se realizó un estudio observacional retrospectivo de pacientes con artritis post-COVID-19 durante un año en un centro de atención terciaria en India. Se incluyeron pacientes (n=23) con una prueba de reacción en cadena de la polimerasa positiva para SARS-CoV-2 o una prueba de anticuerpos anti-COVID-19. Se documentaron los detalles demográficos disponibles, los síntomas musculoesqueléticos, los marcadores inflamatorios y el tratamiento administrado. Resultados: Dieciséis de los 23 pacientes eran mujeres. La edad media de los pacientes fue de 42,8 años. Diecinueve pacientes habían tenido infección sintomática por COVID-19 en el pasado. La duración entre el inicio de los síntomas de COVID-19 y la artritis osciló entre 5 y 52 días, con una media de 25,9 días. La rodilla fue la articulación más comúnmente involucrada (16 de 23 casos). Siete pacientes tenían dolor lumbar inflamatorio y 9 tenían entesitis. La mayoría de los pacientes fueron tratados con medicamentos antiinflamatorios no esteroideos y esteroides, ya fuera una inyección de depósito o un ciclo oral corto. Tres pacientes requirieron tratamiento con hidroxicloroquina y metotrexato, que finalmente se suspendieron. No se reportaron recaídas en ninguno de los pacientes. Conclusión: Al combinar nuestros datos con otros 21 informes de casos de artritis reactiva, se observó un patrón de artritis oligoarticular asimétrico predominante en las extremidades inferiores con predominio femenino.(AU)

Refractory Takayasu arteritis with recurrent pyoderma gangrenosum: a therapeutic challenge with case-based review.

Takayasu arteritis (TA) is an uncommon chronic granulomatous large-vessel vasculitis affecting the aorta and its branches. Pyoderma gangrenosum (PG) is a chronic neutrophilic dermatosis characterized by rapidly developing painful ulcers. The association of PG with TA is relatively uncommon. We report a case of a 22-year-old lady with a history of recurrent pyoderma lesions for 4 months following which she developed right upper limb claudication. She underwent contrast-enhanced magnetic resonance angiography of the aorta and its branches and was initially diagnosed with type IIb TA. She was put on prednisolone and methotrexate but had a major relapse with new-onset lower limb claudication despite an appropriate course of immunosuppression. She was planned for tocilizumab infusion 8 mg/kg intravenous every 4 weeks. Following the first dose of tocilizumab, her vascular symptoms improved but she had a flare of PG. This was followed by another flare after the second dose. She was switched to tofacitinib which led to sustained remission of her TA activity and healing of her skin lesions, and the prednisolone dose could be reduced to 5 mg daily over the next 1 year. Various immunosuppressives were used to date for treating PG in TA. However, tofacitinib is being reported for the first time in literature for treating PG and controlling TA activity. The paradoxical flare of PG with tocilizumab is quite uncommon and is also reported in our case with literature review.

Does post-COVID reactive arthritis exist? Experience of a tertiary care centre with a review of the literature.

Background: Rheumatological manifestations following COVID-19 are various, including Reactive Arthritis (ReA), which is a form of asymmetric oligoarthritis mainly involving the lower limbs, with or without extra-articular features. The current case series describes the clinical profile and treatment outcome of 23 patients with post-COVID-19 ReA. Methods: A retrospective, observational study of patients with post-COVID-19 arthritis over one year was conducted at a tertiary care centre in India. Patients (n = 23) with either a positive polymerase chain reaction test for SARS-CoV2 or an anti-COVID-19 antibody test were included. Available demographic details, musculoskeletal symptoms, inflammatory markers, and treatment given were documented. Results: Sixteen out of 23 patients were female. The mean age of the patients was 42.8 years. Nineteen patients had had symptomatic COVID-19 infection in the past. The duration between onset of COVID-19 symptoms and arthritis ranged from 5 to 52 days with a mean of 25.9 days. The knee was the most involved joint (16 out of 23 cases). Seven patients had inflammatory lower back pain and nine had enthesitis. Most patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids - either depot injection or a short oral course. Three patients required treatment with hydroxychloroquine and methotrexate which were eventually stopped. No relapse was reported in any of the patients. Conclusion: On combining our data with 21 other case reports of ReA, a lower limb predominant, oligoarticular, asymmetric pattern of arthritis was seen with a female preponderance. The mean number of joints involved was 2.8. Axial symptoms and enthesitis were often coexistent. Treatment with NSAIDs and intra-articular steroids was effective. However, whether COVID-19 was the definitive aetiology of the arthritis is yet to be proven.

Antecedentes: Las manifestaciones reumatológicas posteriores al COVID-19 son diversas, entre ellas, la artritis reactiva, que es una forma de oligoartritis asimétrica que afecta principalmente a los miembros inferiores, con o sin características extraarticulares. La serie de casos actual describe el perfil clínico y el resultado del tratamiento de 23 pacientes con artritis reactiva posterior a COVID-19. Métodos: Se realizó un estudio observacional retrospectivo de pacientes con artritis post-COVID-19 durante un año en un centro de atención terciaria en India. Se incluyeron pacientes (n = 23) con una prueba de reacción en cadena de la polimerasa positiva para SARS-CoV-2 o una prueba de anticuerpos anti-COVID-19. Se documentaron los detalles demográficos disponibles, los síntomas musculoesqueléticos, los marcadores inflamatorios y el tratamiento administrado. Resultados: Dieciséis de los 23 pacientes eran mujeres. La edad media de los pacientes fue de 42,8 años. Diecinueve pacientes habían tenido infección sintomática por COVID-19 en el pasado. La duración entre el inicio de los síntomas de COVID-19 y la artritis osciló entre 5 y 52 días, con una media de 25,9 días. La rodilla fue la articulación más comúnmente involucrada (16 de 23 casos). Siete pacientes tenían dolor lumbar inflamatorio y 9 tenían entesitis. La mayoría de los pacientes fueron tratados con medicamentos antiinflamatorios no esteroideos y esteroides, ya fuera una inyección de depósito o un ciclo oral corto. Tres pacientes requirieron tratamiento con hidroxicloroquina y metotrexato, que finalmente se suspendieron. No se reportaron recaídas en ninguno de los pacientes. Conclusión: Al combinar nuestros datos con otros 21 informes de casos de artritis reactiva, se observó un patrón de artritis oligoarticular asimétrico predominante en las extremidades inferiores con predominio femenino. El número medio de articulaciones afectadas fue de 2,8. A menudo coexistían síntomas axiales y entesitis. El tratamiento con antiinflamatorios no esteroideos y esteroides intraarticulares fue eficaz. Sin embargo, aún no se ha demostrado si el COVID-19 fue la etiología definitiva de la artritis.

Effect of vasodilator and immunosuppressive therapy on the endothelial dysfunction in patients with systemic sclerosis.

A comparative analysis of flow-mediated vasodilation (FMD), vasoactive angiogenic, and fibrogenic mediators between treatment-naive and treated systemic sclerosis (SSc) patients is an unmet need. (1)To assess the FMD and different pathogenic mediators in SSc patients about endothelial dysfunction. (2) To assess the proportion of circulating endothelial cells (CECs) in treatment-naïve patients. SSc patients were grouped into treatment-naïve (Group-I, n = 24) on vasodilator (Group-II, n = 10), on vasodilator + immunosuppressive (Group-III, n = 22)]. Age-sex matched healthy controls (n = 20) were included. Endothelial dysfunction (ED) was measured radiologically using FMD. Serum levels of NO, ET1, NO/ET1, sVCAM, sICAM, TGF, IL-6, and VEGF, as well as gene expressions of eNOS, iNOS, ET-1, and TGF, were measured to assess the status of ED in various study groups. CEC was measured in Group-I and HC. CEC was used as a marker to identify a key regulator of ED in SSc. FMD was significantly decreased in all SSc patients through receiving treatment. Upregulation of serum NO and ET concentrations was noted post-treatment with an unaltered NO/ET1 ratio. NO was positively correlated with FMD (r = 0.6) and negatively with TGFß (r = - 0.5). ET-1 showed a negative correlation with TGFß (r = - 0.5) but no significant correlation with FMD. Circulating endothelial cell (CEC) was significantly higher in Group-I (3.2%) than HC (0.8%) (p = 0.002), and it showed a good correlation with NO (r = - 0.7, p = 0.0001) and NO/ET1 (r = - 0.6, p = 0.007). Persistent ED was observed in all SSc patients irrespective of treatment. Dysbalance in NO/ET1 ratio might be the considering factor for the underlying progression of ED. Based on our findings, it may be hypothesized that reduced NO may be a contributing factor in the pathogenesis of endothelial dysfunction in SSc.

Methotrexate and theaflavin-3, 3'-digallate synergistically restore the balance between apoptosis and autophagy in synovial fibroblast of RA: an ex vivo approach with cultured human RA FLS.

BACKGROUND: Imbalance between apoptosis and autophagy in fibroblast-like synoviocytes (FLS) is one of the pathogenic mechanisms responsible for their abnormal proliferation in rheumatoid arthritis (RA). Methotrexate (MTX) demonstrated limited efficacy in amending this imbalance in fluid-derived (fd)-FLS. The active compound of black tea Theaflavin 3,3'-digallate (TF3) may be effective in restoring apoptosis-autophagy imbalance in (fd)-FLS. The combined effect of MTX + TF3 upon the same is yet to be elucidated. OBJECTIVE: To evaluate the effect of MTX + TF3 on fd-FLS to induce apoptosis and inhibit autophagy through Endoplasmic Reticulum (ER) stress-mediated pathways. METHODS: FLS from synovial fluid of 11 RA and 10 osteoarthritis patients were cultured after treatment with MTX/TF3 or a combination of MTX (125 nM) and TF3(10 µM) and the following parameters were evaluated. C-reactive protein, cytokines (TNF-α, IL-6), angiogenic markers were quantified by ELISA. fd-FLS viability was determined by MTT assay and apoptosis by flow cytometry. ER stress markers were estimated by RT-PCR (IRE1A, spliced-XBP-1) and immunoblotting (Grp78, Hsp70, CHOP, HIF-1α). Immunoblot studies were done to evaluate apoptotic (Bcl-2, Bax, Caspases) and autophagic (Beclin1, LC3b, p62) proteins. RESULTS: MTX (IC25) and TF3 (IC50) both in single doses could down-regulate the levels of pro-inflammatory and angiogenic markers. Combinatorial treatment modulated autophagosomal proteins in fd-FLS and induced apoptosis by regulating ER stress response. CONCLUSION: Disruption in homeostasis between apoptosis and autophagy in fd-FLS might be an underlying phenomenon in the progression of pathophysiology in RA. Co-administration of MTX + TF3 successfully restored the homeostasis by inducing apoptosis.

Incidence and effect of insulin resistance on progression of atherosclerosis in rheumatoid arthritis patients of long disease duration.

BACKGROUND: The continued atherosclerotic risk in rheumatoid arthritis (RA) has been inadequately explained by conventional factors. Chronic inflammation and endothelial activation seems responsible for developing insulin resistance (IR). The study was aimed to assess the role of inflammation and endothelial activation causing IR in long term RA patients leading to increased atherosclerotic risk. METHODS: Fifty (25 long-duration and 25 short-duration) RA patients and twenty-three healthy controls were recruited excluding potential confounding co-morbidities. Fasting insulin, proinflammatory cytokines, endothelial stress markers and adipokines were quantified by ELISA. Homeostasis Model Assessment (HOMA)-IR calculated using glucose and insulin values. Atherosclerotic indices were measured using ultrasound. RESULTS: Lipid profile was comparable among groups. Mean carotid intima media thickness (cIMT) was significantly higher in both RA groups (p = 0.0062) compared to controls. HOMA-IR was significantly higher in long-duration RA (p = 0.005); it showed significant associations with DAS 28 (p = 0.01) and hsCRP (p = 0.03) in this subset. Mean cIMT for short-duration RA (p = 0.02) and long-duration RA (p = 0.0006) respectively was also significantly associated with HOMA-IR. Pro-inflammatory markers like TNF-α, resistin and leptin were highest in long-duration RA, higher in short-duration RA when compared to control group respectively. HOMA-IR was significantly dependent on TNF-α (p = 0.008), resistin (p = 0.031), leptin (p = 0.0054). Mean cIMT showed association with all parameters mainly with TNF-α (p = 0.001), iNOS (p = 0.001), resistin (p = 0.008) and leptin (p = 0.04). CONCLUSIONS: Persistent inflammation leads to altered adipokine secretion promoting IR in RA patients with long disease duration. Treatment with conventional disease modifying anti-rheumatic drugs (DMARDs) is incomplete to control chronic inflammation and limit progression of atherosclerosis.

Association of Angiogenic and Inflammatory Markers with Power Doppler Ultrasound Vascularity Grade and DAS28-CRP in Early Rheumatoid Arthritis: A Comparative Analysis.

OBJECTIVE: Upregulation of various proinflammatory and angiogenic mediators orchestrates the typical pathological synovial alterations in rheumatoid arthritis (RA). DAS28-CRP is commonly used for assessment of RA disease activity and power Doppler ultrasonography (PDUS) is an important modality for assessing synovial vascularity. This study was intended to look for the association of various inflammatory and angiogenic mediators, with respect to different PDUS vascularity grades and disease activity status, in early RA patients. METHODS: 50 early RA patients (<6 months disease duration) with either moderate or high disease activity and 30 healthy controls were included in this study. RA patients were subcategorized based on PDUS vascularity grading of wrist joints. Serum levels of proinflammatory cytokines [tumor necrosis factor-α (TNF- α); interleukin-6(IL-6)] and angiogenic markers [angiopoietin-1 and 2 (Ang-1 and Ang-2); vascular endothelial growth factor (VEGF) ] were measured and compared among different patient subgroups. RESULTS: Among 50 patients, 22 and 28 patients had moderate and high DAS28-CRP score, respectively. Patients with grade 3 PDUS score, even with moderate DAS value, showed a significant rise in Ang-1 (p<0.02), VEGF (p<0.008), Ang-2 (p <0.001), and TNF-α (p<0.005) level compared to grade 2 PDUS patients with high DAS values. CONCLUSION: Higher serum level of angiogenic and inflammatory markers was noted among patients with moderate disease activity but with advanced PDUS vascularity (grade 3) in comparison to high disease activity group with less severe PDUS vascularity (grade 2). PDUS vascularity grading better reflects some markers of angiogenesis and inflammation, than composite disease activity index.

Sensitivity and specificity of ultrasonographic features of gout in intercritical and chronic phase.

AIM: This study aimed to assess the sensitivity and specificity of ultrasonographic features of gout in intercritical and chronic stages and compared ultrasonographic features of gout between patients with persistent high serum uric acid (SUA) and patients with low SUA. METHODS: Adult patients with gout confirmed by demonstration of monosodium urate crystals were recruited, if they were in intercritical or chronic stage clinically. Ultrasonographic examination of the first metatarsophalangeal joints (MTPJs) and the knee joints of both sides were done by a blinded rheumatologist trained in musculoskeletal ultrasound. RESULTS: Sixty-two patients with gout and 30 control subjects were examined. The double contour sign (DCS) was found in 71 (57.3%) first MTPJs and tophi were found in 54 (43.5%) first MTPJs. DCS was present in 43 (69.4%) gout patients but none in the control group (P < 0.001). Sensitivity and specificity (95% CI) of DCS in gout patients were 69.4% (56.4-80.4%) and 100% (88.3-100%), respectively, while of tophi they were 66.1% (53-77.7%) and 100% (88.3-100%), respectively. The sensitivity of DCS increased to 100% in high the SUA subgroup (SUA ≥ 7 mg/dL). The low SUA (SUA < 7 mg/dL) gout subgroup showed significantly higher occurrence of erosions (40%) and tophi (50%) in first MTP joints than the control group. CONCLUSION: MSUS is useful for diagnosis of gout in intercritical or chronic stages, especially in patients with persistently high SUA level.

A Study of Clinical Profile of Vitamin B12 Deficiency with Special Reference to Dermatologic Manifestations in a Tertiary Care Hospital in Sub-Himalayan Bengal.

BACKGROUND: Vitamin B12 deficiency is thought to be uncommon in the eastern parts of India including Bengal and the eastern states as compared to the northern and southern parts of India. The importance of cutaneous features in relation to vitamin B12 deficiency is not well described in literature. AIM: To know the clinical profile of vitamin B12 deficiency in this region and to find out if there is any relationship between dermatologic manifestations with vitamin B12 deficiency. MATERIALS AND METHODS: All symptomatic patients of anemia requiring blood transfusions who had either raised mean corpuscular volume (MCV) or bicytopenia/pancytopenia on complete blood count or were symptomatic in the form of skin hyperpigmentation were screened for vitamin B12 deficiency. RESULTS: Twenty-five patients were tested for vitamin B12 deficiency. Of them 19 patients were found to be having vitamin B12 deficiency. CONCLUSIONS: Vitamin B12 deficiency is not uncommon in the eastern parts of India, contrasting the previous thoughts that it was uncommon in this area, though larger studies are required to know it better. This study included only those requiring blood transfusions, thus a much higher prevalence is expected in this area. Patients with vitamin B12 deficiency do present with severe anemia requiring blood transfusions and often have skin hyperpigmentation.

Cutaneous manifestations of mixed connective tissue disease: study from a tertiary care hospital in eastern India.

CONTEXT: Mixed connective tissue disorder is an uncommon disease. Some scientists are reluctant to recognize it as a separate entity. Some others have defined this ailment. Cutaneous features of this condition are unique. Researchers from India have described these features to relate to those described in the studies from other parts of the globe. AIMS: This study aims to delineate the skin manifestations of clearly defined mixed connective tissue disease (MCTD) patients, to compare them with those established as overlap syndrome, and to relate them with studies from other parts of the globe. SETTINGS AND DESIGN: Successive patients who fulfilled the specific criteria for MCTD presenting in the skin outpatient department of a tertiary care hospital in eastern India were clinically examined from 2009 for 3 years. MATERIALS AND METHODS: The number of participants was 23 and the dermatological features of these were compared with 22 patients with overlap syndrome. The antibody to uridine-rich U1 ribonucleoprotein was measured for all patients. STATISTICAL ANALYSIS USED: SPSS (Version 17) and MedCalc (Version 11.6). RESULTS: THE MALE: Female ratio among the MCTD patients was 1:6.67 and that of the overlap syndrome was 1:10. Twenty patients of the MCTD group presented with synovitis as against only seven in the overlap group. Raynaud's phenomenon was present in some of the subjects. Puffy fingers were rare in our study. Facial numbness was reported by four of those suffering from MCTD. Antinuclear antibody (ANA) was essentially of a speckled pattern in this disease. CONCLUSIONS: Cutaneous indicators of MCTD are distinct from overlap syndrome. Knowledge of these manifestations prevalent in a region may lead to early diagnosis of the disease.

Effects of disease modifying anti-rheumatic drugs on subclinical atherosclerosis and endothelial dysfunction which has been detected in early rheumatoid arthritis: 1-year follow-up study.

OBJECTIVE: The study was designed to explore the effect of disease modifying anti-rheumatic drugs (DMARDs) on synovial inflammation as well as on atherosclerotic indices in patients with early rheumatoid arthritis (RA). METHODS: The study included 35 early RA patients (disease duration <12 months). Inflammatory variables, like erythrocyte sedimentation rate (ESR) and high sensitivity C-reactive protein (hsCRP) were measured. Carotid intima-media thickness (cIMT) and endothelial dependent flow-mediated vasodilatation (ED-FMD) were measured by high-resolution ultrasonography. Disease activity of RA was assessed by disease activity score (DAS28) and quality of life was determined by Health Assessment Questionnaire-Disability Index (HAQ-DI) Score. All the above parameters were assessed both at baseline and follow-up after 1 year. Patients were treated with methotrexate (MTX), hydroxycholoroquine (HCQ) and sulfasalazine (SSZ) depending on their disease activity. RESULTS: After a year of treatment, variables like ESR, hsCRP, DAS28 and HAQ-DI showed significant improvement (p < 0.0001 for each variable). However, there was no such significant change observed in the lipid profile after 1 year from the baseline. Average body mass index (BMI) of patients remained same at the one year follow-up. The cIMT values after 1 year decreased significantly [0.43 ± 0.08mm] from the baseline [0.50 ± 0.16mm] [p = 0.002]. Similarly, in case of FMD%, the post-1-year treatment values [7.57 (4.04-13.03)] improved significantly from the baseline [5.26 (2.9-10.6)] [p = 0.041]. CONCLUSION: Subclinical atherosclerosis and endothelial dysfunction are demonstrable features even in early RA which improved after therapy. Early intervention of RA with DMARDs not only controls the disease but also retards the atherosclerotic progression.

Subclinical atherosclerosis and endothelial dysfunction in patients with early rheumatoid arthritis as evidenced by measurement of carotid intima-media thickness and flow-mediated vasodilatation: an observational study.

OBJECTIVE: In this study, we aimed to investigate the frequency of endothelial dysfunction and subclinical atherosclerosis in early rheumatoid arthritis (RA) patients by carotid intima-media thickness (cIMT) and endothelial-dependent flow mediated vasodilatation (ED-FMD) as compared with healthy controls. METHODS: The study included 35 early RA patients (disease duration <12 months) and 35 healthy controls. Intima-media thickness of common carotid artery and ED-FMD of brachial artery were measured by high-resolution ultrasonography. Disease activity of RA was assessed by Disease Activity Score and activities of daily living were determined by Health Assessment Questionnaire-Disability Index Score. RESULTS: RA patients (age 38.3 ± 10.6 years) had average disease duration of 0.46 ± 0.28 years and 22 patients (62.9%) were rheumatoid factor (RF) positive (RF titer >9.56 IU/mL). There were no significant differences between age, sex, and lipid profiles of patient and control group. cIMT was significantly higher in RA patients (0.50 ± 0.16 mm) than in controls (0.44 ± 0.09 mm) (P = 0.007). Similarly, FMD% was significantly lower in RA patients [5.26 (2.9-10.6)] as compared with controls [10.34 (7.4-14.3)] (P = 0.004). Age, systolic blood pressure, tender joint count, and swollen joint count had significant correlations with patient cIMT. RF titer came out to be the major risk factor for increased cIMT of the patients. CONCLUSIONS: Compared with controls, early RA patients have higher cIMT and lower FMD%, denoting premature atherosclerosis. Our data suggest that early determination of FMD% and cIMT may be useful tools to assess cardiovascular risk even in early RA patients.

Prevalence of rheumatic conditions in patients with diabetes mellitus in a tertiary care hospital.

Musculoskeletal disorders are common in diabetic subjects. The pathophysiology of these disorders in diabetic patients is not obvious. It could be due to connective tissue disorders, glycosylated end products, vasculopathy, neuropathy or combinations. A wide range of musculoskeletal syndromes have been described in association with diabetes, namely diabetic cheiro-arthropathy, adhesive capsulitis of shoulder, carpal tunnel syndrome, Dupuytren's contracture, hyperostosis, osteo-arthritis, hyperuricaemia, etc. This study was undertaken to find out the prevalence of these conditions in diabetes mellitus and to look for any associations with diabetic complications or therapy. A tertiary care centre-based cross-sectional study was carried out among 100 consecutive diabetic patients (WHO criteria) attending medicine department who were enrolled. The study was done at Calcutta National Medical College and Hospital, Kolkata, from March 2008 to February 2009. The diagnoses of the rheumatic conditions were made by unbiased clinical observations on the basis of standardised case definitions or criteria. Limited joint mobility (29%), adhesive capsulitis (18%), and osteo-arthritis of knee (27%) or hand (17%) were the most common rheumatic conditions in diabetics. Trigger finger (flexor tenosynovitis) and carpal tunnel syndrome were also present in 7% and 5% cases of diabetics respectively. Although hyperuricaemia was present in 9%, clinical gout was present in only 4%. There was no clear association of these syndromes with diabetic renal disease or micro-albuminuria. Most of these conditions were noted in chronic long duration diabetic subjects.