Topical Application of Galgeunhwanggeumhwangryeon-Tang Recovers Skin-Lipid Barrier and Ameliorates Inflammation via Filaggrin-Thymic Stromal Lymphopoietin-Interleukin 4 Pathway

Background and objectives: The purpose of this study was to confirm the effect of Galgeunhwanggeumhwangryeon-tang (GGRT) on the skin barrier integrity and inflammation in an atopic dermatitis-like animal model. Materials and Methods: The model was established using lipid barrier elimination (LBE) in BALB/c mice. Ceramide 3B, a control drug, and GGRT were applied to the skin of LBE mice. Gross observation and histological examination were combined with measurement of skin score, trans-epidermal water loss, and pH. The expression of filaggrin, kallikrein-related peptidase 7 (KLK7), protease-activated receptor-2 (PAR-2), thymic stromal lymphopoietin (TSLP), and interleukin 4 (IL-4) was examined. Results: The effect of GGRT on atopic dermatitis was estimated in silico using two individual gene sets of human atopic dermatitis. In animal experiments, GGRT treatment reduced atopic dermatitis-like symptoms, as confirmed via gross and histological observations, skin score, pH change, and trans-epidermal water loss. The expression level of filaggrin increased in the skin of GGRT-treated mice compared to that in the LBE group. The expression levels of KLK7, PAR2, TSLP, and IL-4 were decreased in GGRT-treated mice skin compared to those in LBE mice. Conclusions: We demonstrated that GGRT restored the skin barrier and reduced inflammatory reactions in a murine model of atopic dermatitis.

Skin score as a predictor of prolonged QTc in systemic sclerosis.

Background Systemic sclerosis is an autoimmune disease characterized by endothelial dysfunction and fibrosis of the skin and internal organs. Cardiac involvement during systemic sclerosis can be primary or secondary to pulmonary arterial hypertension and renal pathology. Among the disorders in systemic sclerosis, prolongation of QTc time is also associated with more anti-RNA polymerase III antibodies, longer duration and severity of disease. Methods This case-control study was performed on 35 patients with systemic scleroderma who filled in the American Society of Rheumatism (ACR / EULAR criteria) and 35 healthy subjects prior to entering the study. Then, the QTc distance was extracted from the electrocardiogram and calculated using the formula. The measured QTc distance in the electrocardiogram, QTc> 440ms in men and QTc> 460ms in women, was defined as QTc long. Then the patients and the control group underwent echocardiography and changes in QTc interval and its relation with echocardiographic findings was evaluated. Results The results of this study indicated a significant relationship between QTc distance in patients with scleroderma compared with healthy controls. There was also a significant relationship between QTc and Skin Score of patients. However, there was no significant correlation between QTc distance and age, gender, duration of disease, Anti-Centromere, Anti-Scl70, and pulmonary artery pressure. Conclusion This study concludes that patients with scleroderma are at high risk for cardiac conduction impairment. The only factor that significantly correlated with QTc was the Skin Score of the patients.

RNA-Seq analysis identifies novel roles for the primary cilia gene SPAG17 and the SOX9 locus non-coding RNAs in systemic sclerosis

Systemic sclerosis (SSc) is characterized by immune activation, vasculopathy, and unresolving fibrosis in the skin, lungs, and other organs. We performed RNA-Seq analysis on skin biopsies and peripheral blood mononuclear cells (PBMCs) from SSc patients and controls to better understand SSc pathogenesis. We analyzed these data to 1) test for case-control differences, and 2) identify genes whose expression levels correlate with SSc severity as measured by local skin score, modified Rodnan skin score (MRSS), forced vital capacity (FVC), or diffusion capacity for carbon monoxide (DLCO). We found that PBMCs from SSc patients showed a strong type 1 interferon signature. This signal replicated in the skin, with additional signals for increased extracellular matrix (ECM) genes, classical complement pathway activation, and the presence of B cells. Notably, we observed a marked decrease in the expression of SPAG17, a cilia component, in SSc skin. We identified genes that correlated with MRSS, DLCO, and FVC in SSc PBMCs and skin using weighted gene co-expression analysis (WGCNA). These genes were largely distinct from the case/control differentially expressed genes. In PBMCs, type 1 interferon signatures negatively correlated with DLCO. In SSc skin, ECM gene expression positively correlated with MRSS. Network analysis of SSc skin genes correlated with clinical features identified the non-coding RNAs SOX9-AS1 and ROCR, both near the SOX9 locus, as highly connected,"hub-like" genes in the network. These results identify non-coding RNAs and SPAG17 as novel factors potentially implicated in SSc pathogenesis.

Nail Fold Capillaroscopy in a Cohort of Egyptian Dermatomyositis/Polymyositis Patients

ABASTRACT Background Nailfold capillaroscopy (NC) has been demonstrated to be an important tool in the diagnosis and treatment of patients with juvenile dermatomyositis (JDM) and systemic sclerosis. However, NC has been scarcely studied in adult patients with DM. Objectives Is to visualize capillary changes in DM/PM patients, trying to find a specific capillary pattern and its correlation if any- with disease activity in those patients. Methodology This is a cross sectional observational study included 20 patients (DM.Diagnosed on base of clinical, laboratory and histopathological findings. We excluded patients with hypertension or diabetes mellitus. The NFC performed using videocapillaroscope. A semiquantitative rating scale was used to score capillaroscopy changes. Myositis disease activity assessment tools were used to assess disease activity [Manual Muscle Testing (MMT), Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT), Health Assessment Questionnaire (HAQ), physician’s VAS, patient’s VAS, skin scoring, serum muscle enzymes levels] Result The median age of our patients was 36 (S.D.12) Mean disease duration was 24months (S.D.19).The results presented mean value 3,8 (S.D.3,3) for muscle disease activity score,2(S.D.3) for skin score and 3,92 (S.D.3,09) for global disease activity .Enlarged capillaries was found in12 patients (100%), avascular areas in 10 patients (83.3%), capillaries hemorrhage in 8 patients (66,7%), and branched capillaries in 6 patients (50%).Sixteen patient (80%) had scleroderma like pattern. We found that disease activity positively correlate with branched capillaries(p = 0,04), muscle disease activity correlate positively with capillaries density score(p = 0,002) while hemorrhage correlate positively with skin score(p = 0,024). In our study major capillaroscopic abnormalities appeared to be virtually confined to patients with DM while patients with PM had only minor changes. No signifcant correlations between NFC and other demographic, clinical and laboratory parameters were observed. Conclusion NFC may provide helpful information about patients with PM/DM by: (a) contributing to the diagnosis and (b) correlating with disease activity parameters. Additional investigations with larger series of patients and prospective studies may be useful to reinforce our data.

Effect of Coptischinensis, Glycyrrhiza uralensis, and Fermented Glycine max Extract as Proactive Therapy for Atopic Dermatitis

The aim of this study was to investigate the effect of the Coptis chinensis, Glycyrrhiza uralensis, and fermented Glycine max (3Hb) extract on lipid barrier recovery and the alleviation of atopic dermatitis (AD). The 3Hb extract was administered to lipid barrier-eliminated mice (3HbT) for 5 days. Subsequently, the effect of the 3Hb extract on general skin features and the regulation of filaggrin, inflammatory response, Th2 differentiation, and the skin micro-environment for defense, was evaluated. In the 3HbT, filaggrin was effectively recovered. The clinical skin score was significantly lower in the 3HbT compared with control groups. In addition, significant decreases in pH and TEWL as well as in the levels of kallikrein 7, PAR-2, TSLP, IL-4, Fc ε receptor, and phosphate-NF-κB p65 were observed in the 3HbT, compared with the other control groups. Further, compared with control groups, the 3HbT showed a significant increase in those of claudin, cathelicidin, TLR, and NHE-1. Our results indicated that the 3Hb extract effectively recovered filaggrin. Through the recovery of filaggrin, inflammation and the Th2 differentiation process can be regulated, and microenvironments for defense can be recovered. Therefore, we confirmed the potential of the 3Hb extract for use in the proactive therapy of AD.

The Relationship Between Modified Rodnan Skin Score (mRSS) With Pulmonal Hypertension and Lung Fibrosis in Systemic Sclerosis Patients

Background: Systemic sclerosis (SSc) is a connective tissue disease, which affects the skin, blood vessels, heart, lungs, kidneys, gastrointestinal tract and musculoskeletal system. The manifestations in blood vessels include pulmonary hypertension which can be seen from echocardiography, while the manifestations to the lungs in the form of pulmonary fibrosis are examined by high-resolution computed tomography (HRCT). Modified Rodnan Skin Score (mRSS) a method for measuring skin thickness in SSc patients. Objective: This study aims to determine the relationship between mRSS and pulmonary hypertension and pulmonary fibrosis in SSc patients. Methods and Materials: Research with a cross sectional approach at Dr Kariadi Hospital. There were 23 study subjects with SSc patients having their mRSS measured by a rheumatologist and an HRCT examination by a radiologist to see the percent of lung damage and echocardiographic examination by a cardiologist to measure the Tricuspid Regurgitation Velocity Maximum (TRV Max) as a marker of pulmonary hypertension. Normality test using Saphiro-Wilk. The Spearman rank correlation test was used to analyze the relationship between the mRSS score, pulmonary hypertension and pulmonary fibrosis. Results: The proportion of study subjects with a mean age of 40.39 years, women, and 4.43 years of illness. The mean mRSS score was 17.43. Examination of pulmonary hypertension from echocardiography found most of the light category 95.6%, heavy category 4.4%, while the HRCT examination found pulmonary fibrosis of 86.9%, normal 13.1%. There are significant relationship between mRSS and pulmonary fibrosis (r = 0.485, p = 0.019), and significant relationship between pulmonary hypertension (r = 0.63, p = 0.001) Conclusion: There is a significant relationship between mRSS, pulmonary fibrosis and pulmonary hypertension.

Validation of the Raynaud’s Condition Score in Argentina

Objective: the aim of our study was to adapt and validate the Raynaud’s Condition Score (RCS) in patients with Systemic Sclerosis (SSc) who attend a public hospital in Argentina. Materials and Methods: for adaptation, rheumatologists translated to Spanish the original version in English. To assess the construct validity we used: Health Assesment Questionnaire (HAQ), Duruöz´s Hand Index (DHI), spanish validation for Argentina, Raynaud Visual Analogue Scale (VAS) by an expert and Modified Rodnan skin score (mRSS).To assess reproducibility, a subgroup of patients was randomly evaluated with no changes in treatment or clinical condition ten days after the baseline evaluation. Results: A total of 35 patients with SSc were included. The correlation between RCS and Raynaud VAS by an expert was 0.89; RCS and HAQ 0.58; RCS and mRSS 0.61; RCS and DHI 0.57 indicating a very good correlation mainly between the studied Score and the Raynaud VAS and being all statistically significant. The reproducibility was 0.998. Conclusion: The results show that the RCS is a reliable and valid tool for this argentinian population with SSc.

Rheuma und Lunge

Was ist neu? Diagnostik Goldstandard in der Diagnostik einer ILD bei rheumatischen Erkrankungen bleibt weiterhin die hochauflösende, nicht kontrastmittelverstärkte HRCT. Verlässliche Biomarker für CTD-ILDs stehen für den klinischen Alltag noch nicht zur Verfügung. Die klinisch und apparativ erhobenen Befunde lassen fast immer eine belastbare Diagnose stellen. Eine histologische Sicherung ist nur bei unklaren Fällen nötig. Eine interessante diagnostische Option könnte in Zukunft die molekulare Diagnostik von Lungenparenchym sein. Therapie MTX gilt nicht länger als Risikofaktor für die Entwicklung einer chronischen ILD bzw. einer Lungenfibrose bei RA. Neuere Daten weisen darauf hin, dass MTX die Ausbildung einer ILD bei RA sogar verhindern oder zumindest verzögern kann. In Studien bei Patienten mit SSc zeigten sich Hinweise für einen positiven Einfluss von Tocilizumab auf den Verlauf einer ILD mit Stabilisierung der forcierten Vitalkapazität in der Lungenfunktionsprüfung. Allerdings wurde der primäre Endpunkt der Studien – Verbesserung im modifizierten Rodnan-Skin-Score – nicht erreicht. Nintedanib wurde jüngst zur Behandlung Erwachsener mit SSc-ILD sowie bei Patienten mit chronisch PF-ILD bei unterschiedlichen Grunderkrankungen (u. a. RA) zugelassen.