Alakendu Ghosh

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.

The spectrum of thyroid disorders in systemic lupus erythematosus

To study the spectrum of thyroid disorders in systemic lupus erythematosus (SLE). Hundred SLE patients as per American Rheumatology Association(ARA) classification criteria underwent clinical examination, including assessment of disease activity (SLEDAI) and laboratory evaluation for serum triiodothyronine (T3),free thyroxine (FT4), thyroid stimulating hormone (TSH), antithyroperoxidase (TPO) antibody and antithyroglobulin (TG) antibody. Hundred age- and sex-matched apparently healthy individuals served as control. Thirty-six (36%) lupus patients had thyroid dysfunction when compared to 8 (8%) of controls and all of them were women. Primary hypothyroidism was the commonest dysfunction in 14 (14%), while subclinical hypothyroidism and subclinical hyperthyroidism was seen in 12 (12%) and 2 (2%), respectively. Eight (8%) had isolated low T3 consistent with sick euthyroid syndrome. Eighteen (50%) of thyroid dysfunction were autoimmune in nature (autoantibody positive) and rest 18 (50%) were non-autoimmune. Euthyroid state with the elevation of antibodies alone was seen in 12 (12%) of the lupus patients. In contrast, only 5 (5%) of controls had primary hypothyroidism and 3 (3%) had subclinical hypothyroidism, while none had hyperthyroidism. SLEDAI score and disease duration were compared between lupus patients with thyroid dysfunction to those with normal thyroid function. A statistically significant association was found between SLEDAI and thyroid dysfunction of sick euthyroid type.SLE disease duration had no statistically significant association with thyroid dysfunction. Prevalence of thyroid autoantibodies in lupus patients was 30% when compared to 10% of controls. Ninety-six (96%) of the SLE patients were ANA positive, while 4 (4%) of them were ANA negative but were anti-Sm antibody positive. There were no suggestions of any other autoimmune endocrine diseases like diabetes or Addison’s disease (clinically and on baseline investigations) in our lupus cohort and hence no further work up was done for these diseases. Thyroid disorders are frequent in SLE and are multifactorial with a definite higher prevalence of hypothyroidism as well as thyroid autoantibodies.

Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a debilitating autoimmune disease whose etiology remains unknown, but studies have consistently implicated a plethora of inflammatory mechanisms culminating in chronic symmetric and erosive synovitis. Importantly, reactive oxygen species (ROS) have been attributed to directly contribute towards the destructive, proliferative synovitis evident in RA. Accordingly, this study aimed to establish whether the degree of oxidative stress and disease activity score (DAS28) correlated with the downstream effects of oxidative damage. The redox status of neutrophils sourced from synovial fluid (SF) was measured by flow cytometry in terms of total ROS and hydroxyl radicals. Among the molecular damage markers, protein carbonylation and lipid peroxidation were detected by spectrophotometry and S-nitrosothiols by fluorimetry. Neutrophils constituted the major cellular component of the SF of patients with RA and their levels of ROS and hydroxyl radicals correlated strongly with protein carbonylation and lipid peroxidation. However, all the oxidative damage markers correlated positively with DAS28. Taken together, in patients with RA, the strong correlation between levels of ROS and DAS28 with markers of oxidative damage suggests that measurement of oxidative stress could serve as a biomarker for monitoring disease severity in RA.

Visceral afferent hypersensitivity in irritable bowel syndrome--evaluation by cerebral evoked potential after rectal stimulation.

OBJECTIVES:Gut hypersensitivity has been shown to be present in irritable bowel syndrome. The current study sought to determine the involvement or hypersensitivity of the gut afferents, objectively, by recording cerebral evoked potential after rectal stimulation.METHODS:In 13 patients with irritable bowel syndrome and nine healthy controls, rectal perception thresholds to electrical stimulation were measured, and cerebral evoked potentials were recorded from 2 cm behind vertex (Cz′) after rectal stimulation electrically (frequency 1 Hz, duration 0.5 ms) at an intensity 50% above perception threshold and with filter setting 1–250 Hz.RESULTS:Perception thresholds to rectal electrical stimuli in patients with irritable bowel syndrome were lower than controls (p < 0.05). Rectal stimulation led to recognizable and reproducible cerebral evoked potentials. P1, N1, P2 latencies in patients with irritable bowel syndrome were shorter than that in controls (p < 0.05). P1/N1 amplitude was greater in patients with irritable bowel syndrome than in controls (p < 0.05).CONCLUSIONS:The shorter latency and increased amplitude of cerebral evoked potential after rectal stimulation in patients with irritable bowel syndrome compared to controls provide objective evidence supporting visceral afferent hypersensitivity as the underlying mechanism in irritable bowel syndrome.

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.

Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement. The skin is the second most commonly affected organ. SLE with skin lesions can produce considerable morbidity resulting from painful skin lesions, alopecia, disfigurement, etc. Skin lesions in patients with lupus may be specific (LE specific) or may be non specific (LE non specific). Acute cutaneous LE (Lupus specific) has a strong association with systemic disease and non-specific skin lesions always indicate disease activity for which patients present to rheumatologists and internists. Therefore, a thorough understanding of the cutaneous manifestations of SLE is essential for most efficient management. Aims: The aims of this study were to evaluate the patterns and prevalence of skin lesions in patients with SLE and to assess the relationship between skin lesions and other systemic involvement. Materials and Methods: At the Department of Rheumatology and Clinical Immunology, IPGME&R in Kolkata, 150 patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatology Association (updated 1982) were examined and followed-up for cutaneous manifestations between January 2002 and January 2007. Results: Skin lesions were important clinical features. About 45 patients (30%) presented with skin lesions although all patients had skin lesions during the follow-up period. Skin changes noted were as follows: Lupus specific lesions: malar rash in 120 patients (80%), photosensitive dermatitis in 75 patients (50%), generalized maculopapular rash in 40 patients (26.67%), discoid rash in 30 patients (20%), subacute cutaneous lupus erythematosus (SCLE) in 5 patients (3.34%), lupus profundus in 5 patients (3.34%). The lupus non-specific lesions were non-scarring alopecia in 130 patients (86.67%), oral ulcers in 85 patients (56.67%), vasculitic lesions in 50 patients (33.34%), bullous lesions in 15 patients (10%), Raynauds phenomenon in 10 patients (6.67%), pyoderma gangrenosum in 2 patients (1.34%), erythema multiforme in 10 patients (6.67%), and nail fold infarcts in 2 patients (1.34%); however, mucosal discoid lupus, lichenoid discoid lupus, livedo reticularis, sclerodactyly, etc. were not detected. Patients having lupus-specific skin lesions e.g., malar rash were associated with systemic involvement, whereas those having lupus non-specific skin lesions were associated with disease flare. Conclusions: Skin lesions in patients with SLE are important disease manifestations and proper understanding is essential for diagnosis and efficient management.

Development of a colour Doppler ultrasound scoring system in patients of Takayasu’s arteritis and its correlation with clinical activity score (ITAS 2010)

OBJECTIVES The objectives of this study were to develop a scoring system with colour Doppler ultrasound (CDUS) in patients with Takayasus arteritis, to correlate the CDUS score with the Indian Takayasus Activity Score (ITAS) and to assess the degree of agreement between CDUS and angiogram in the diagnosis of Takayasus arteritis. METHODS Nineteen angiographically confirmed Takayasus arteritis patients fulfilling three or more of the 1990 ACR criteria were evaluated. Their ITASs were recorded. A CDUS scoring system, CDUS-Kolkata (CDUS-K), was devised based on the presence of stenosis and altered flow patterns. It was then correlated with the ITAS. An inter-rater agreement analysis was done between the CDUS-K scores and angiographic scores in selected arterial sites. RESULTS We found a significant degree of correlation between the ITAS and the CDUS-K score (r = 0.7144, 95% CI 0.3852, 0.8823, P = 0.0006). A high degree of correlation was found between the CDUS-K and angiographic scores in the selected arterial sites (κ-value = 0.725 on inter-rater agreement analysis). CONCLUSION CDUS imaging may be used as an objective tool for assessing disease severity in Takayasus arteritis. Development of a CDUS-K scoring system would be a supplementary tool to clinical scoring and the ITAS. CDUS imaging could be a cost-effective, non-invasive and reliable substitute for angiogram, especially for follow-up in Takayasus arteritis patients.

Ultrasound is a useful adjunct in diagnosis of eosinophilic fasciitis

This 28-year-old male presented with progressive skin tightening and limited joint mobility for 11 months, involving legs up to mid-shin and forearms up to elbows, preceded by painless swelling involving affected regions, sparing fingers and toes. Systemic features were absent. There was peripheral eosinophilia (leucocytes: 11 600/ml, eosinophils 52%, absolute eosinophil count: 6032/ml), raised acute-phase reactants and hypergammaglobulinaemia. Nail-fold capillaroscopy was noncontributory. RP, digital ulcers, dysphagia, reflux and pulmonary arterial hypertension were absent. ANA was positive, and Scl70 and anticentromere antibodies were negative. High-resolution US of legs (Fig. 1A and C) using an 18-MHz linear array transducer showed thickening and altered echointensities afflicting the fascia, alongside deranged echotexture of subcutaneous fat (Fig. 1B is from a healthy person for comparison). MRI of legs (Fig. 1D) showed thickening of fascia, along with increased contrast enhancement of the myofascial plane, corroborating US findings. He was diagnosed as having eosinophilic fasciitis (EF) and put on prednisolone. Apart from histology, MRI is also useful for the diagnosis of EF [1]. The role of US elastography has been studied in scleroderma, and has demonstrated reduction of strain in the dermis of the forearm due to loss of elasticity [2]. Here we present a case of EF characterized ultrasonographically with MRI corroboration.

Ultrasonography as a useful modality for documenting sacroiliitis in radiographically negative inflammatory back pain: a comparative evaluation with MRI

OBJECTIVES The aims of this study were to identify and characterize features of sacroiliitis in patients with non-radiographic inflammatory low back pain by ultrasonography (USG) and to correlate the findings with that of MRI. METHODS MRI and USG of SI joints were performed on 29 patients who fulfilled the definition of inflammatory low back pain according to the Assessment of SpondyloArthritis International Society 2009 criteria for axial SpA but were X-ray negative for sacroiliitis. Increased vascularity, low resistive index (RI) and hyperechogenicity of the joint space were considered USG features of sacroiliitis. The findings were compared with those of 32 controls. USG features of sacroiliitis were compared with MRI by κ statistics. RESULTS Receiver operating characteristic analysis revealed cut-off values for flow signals and RI of 3 and 0.605, respectively. There was a significant difference in the number of flow signals, RI and echogenicity of the SI joint between MRI-proven cases and controls. The Cohens κ for flow signals, RI and hyperechogenicity when compared with MRI were 0.816 (95% CI 0.676, 0.937) and 0.821 (95% CI 0.662, 0.965) and 0.403 (95% CI 0.108, 0.695). Taking both flow signals and RI parameters as criteria for determining sacroiliitis, comparison with MRI returned a κ of 0.816 (95% CI 0.601, 0.963). CONCLUSION Three or more flow signals and a RI ≤0.605 can be applied as USG criteria for sacroiliitis. USG can be a cost-effective and non-inferior modality compared with MRI in documenting sacroiliitis in early SpA.

Tuberculous arthritis—the challenges and opportunities: observations from a tertiary center

Abstract Tuberculosis (TB) arthritis accounts for approximately 1–3% of all cases of tuberculosis and for approximately 10–11 % of extrapulmonary cases. The most common presentation is chronic monoarthritis. The Poncets disease is a reactive symmetric form of polyarthritis that affects persons with visceral or disseminated TB. TB arthritis primarily involves the large weight-bearing joints, in particular the hips, knees, and ankles, and occasionally involves smaller nonweight-bearing joints. The diagnosis of TB arthritis is often delayed due to lack of awareness, insidious onset, lack of characteristic early radiographie findings and often lack of constitutional or pulmonary involvement. A high index of suspicion is necessary, especially in the context of persistent monoarthritis and synovial biopsy and prompt anti-tubercular therapy with adequate doses and duration prevents joint damage and preserves joint function. Surgical procedures should be restricted to joints with severe cartilage destruction, large abscesses, joint deformity or atypical mycobacteria.