Pradyot Sinhamahapatra

Background and objectives: There is limited data on prescription behaviour and compliance with interstitial lung disease (ILD) guidelines among pulmonologists. This study aimed to evaluate ILDs treatment prescription behaviour in India. Methods: Prescriptions of treatment-naive ILD patients from 13 tertiary care hospitals were reviewed and classified as guideline compliant (GCP) or non-compliant (GNCP) for pharmacological and non-pharmacological components. Change in forced vital capacity (FVC), diffusing capacity (DLCO), and six-minute walk distance (6-MWD) at 6 and 12 months were compared between GCP and GNCP. Results: After screening 720 participants, 425 treatment-naïve ILD patients (56.7% female; mean age 51.7 years) were included. Connective tissue associated-ILD (CTD-ILD) was the most common diagnosis (36.2%), followed by hypersensitivity pneumonitis (17.4%), idiopathic pulmonary fibrosis (IPF, 13.9%), interstitial pneumonia with autoimmune features (13.9%), and sarcoidosis (8.2%). GCP rates for ILD specific pharmacotherapy were 83%, 74.7%, and 93.5% for IPF, CTD-ILD, and sarcoidosis, respectively. In IPF, patients with GCP had significantly lower FVC decline at 12 months compared to the GNCP (0.06 L vs. 0.25 L; p = 0.02). There was huge care-gap in non-pharmacological advice with 13.2%, 7.1%, 10.2% and 4.2% of eligible cases were advised vaccination, pulmonary rehabilitation, antigen avoidance, and lung transplantation counselling, respectively. Interpretation and conclusions: India-ILD care study revealed a huge care gap with significantly under-prescription of non-pharmacological components. These results highlight the urgent need for organized implementation strategies including dissemination of guidelines, and a greater emphasis on a structured management protocol that includes both pharmacological and non-pharmacological treatment to optimize outcomes for ILD in India.

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.

Background: Microvascular dysfunction is one of the major clinical challenges in systemic sclerosis (SSc) and mesenchymal transformation of the major event for micovascular dysfunction. Recent studies have shown epigenetic regulation of long non coding RNAs (lncRs) in different disease pathophysiology. Objectives: To study the differential expressions of lncRs in patients with SSc and to study their associations with regulatory molecules of fibrosis Methods: Peripheral Blood were collected from 15 diffused cutaneous SSc patients (dSSc) [ACR, 2013] and 10 age-sexes matched healthy controls. RNA was isolated from the peripheral blood & cDNAs were prepared and the Relative mRNA expressions were measured with respect to an endogenous control gene by real-time PCR. Protein expressions were measured by ELISA. Results: Increased expression of MEG3, MALAT1and NEAT1 (3.5, 3, 4fold respectively) has been found in SSc patients with respect to healthy individuals and they are mutually correlated (MEG3 and NEAT1: r=0.9, p MALAT1and NEAT1: r=0.7, p MEG3 and MALAT1 r=0.7, p). The expression of NEAT1 is significantly higher (p= 0.0009) in case patients with disease duration (DD) >5 years compare to the patients with DD≤5 years. No significant difference was found in the expression of MEG3 andMALAT1 between these two subpopulations. Modified Rodnan’s skin score (mRDss): the clinical parameter of measuring fibrosis, was significantly up regulated (p=0.004) in patients with long disease duration (>5 years) and also have a positive correlation with DD(r=0.2,p=0.2) and the regulatory RNAs: MEG3 (r=0.4,p=0.003), MALAT1 (r=0.2, p=0.2), and NEAT1(r=0.3, p=0.009). The master regulator of fibrosis TGFβ which is significantly up regulated at both transcriptional (pp=0.0009) level has significant positive correlation with MEG3 (r=0.3, p=0.02), MALAT1 (r=0.5, p=0.0005), and NEAT1(r=0.3p=0.006).MEG3, MALAT1and NEAT1 also have significant high correlation (r=0.7, p; r=0.6 pr=0.7pr=0.3, p=0.03; r=0.3, p=0.03 and r=0.3 p=0.03 respectively). In multivariate analysisMEG3 and NEAT1 together could explain 37.5% variability of fibrotic marker and NEAT1 alone could explain 35.5% of the same. Conclusion: mRDSS probably does not reflect the underlying fibrotic process occurring sub-clinically, as no significant correlation was observed either with the disease duration or with the pro-fibrotic molecules (TGFβ, αSMA, and collagen1). The strong inter-correlation of NEAT1, MALAT1 and MEG3 suggest that any one of them might well be studied as specific marker of sub-clinical fibrosis.The long non coding RNAs (MALAT1, MEG3, NEAT1) better reflects the sub-clinical fibrosis occurring in the patients, suggested by strong correlation with fibrotic markers (TGFβ, αSMA, collagen1). The linear regression values suggest that NEAT1 could be an important biomolecule in SSc pathogenesis. References: [1]Asano Y, Sato S., Vasculopathy in scleroderma. Semin Immunopathol. 2015 Sep;37(5):489-500. doi: 10.1007/s00281-015-0505-5. Disclosure of Interests: None declared

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. 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. 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. MSUS is useful for diagnosis of gout in intercritical or chronic stages, especially in patients with persistently high SUA level.

Background: Vitamin B ₁₂ 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 B ₁₂ deficiency is not well described in literature. Aim: To know the clinical profile of vitamin B ₁₂ deficiency in this region and to find out if there is any relationship between dermatologic manifestations with vitamin B ₁₂ 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 B ₁₂ deficiency. Results: Twenty-five patients were tested for vitamin B ₁₂ deficiency. Of them 19 patients were found to be having vitamin B ₁₂ deficiency. Conclusions: Vitamin B ₁₂ 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 B ₁₂ deficiency do present with severe anemia requiring blood transfusions and often have skin hyperpigmentation.

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.