Topical Gentamicin 0.1% Promotes Collagen 7 Expression in Recessive Dystrophic Epidermolysis Bullosa.

Background: Currently, there is no cure for epidermolysis bullosa (EB) but few studies have explored the role of aminoglycosides in promoting collagen 7 expression in recessive dystrophic EB (RDEB). Materials and Methods: Consecutive patients aged >1 year with a confirmed diagnosis of dystrophic EB (DEB) were advised to apply 0.1% w/w gentamicin cream in a collagen base (Derbriment G™) twice daily on a representative area on right lower limb (RLL) and paraffin gauze dressings on the corresponding opposite side on the left lower limb (LLL). Skin lesions were evaluated clinically during the 12-week treatment period at the end of which a repeat skin biopsy was sent for immunofluorescence antigen mapping (IFM). Results: Twelve patients with DEB were recruited but only eight completed the study and were analyzed. The mean fluorescence intensity (MFI) of the study cohort increased from 2765 ± 1732.07 (263-4845) at baseline to 5412.75 ± 3937.64 (2100-13536) at 12 weeks; a 95.75% (range 5.34%-775.14%) increase in the MFI of collagen 7 from baseline (P = 0.06). Among patients with a known termination codon mutation (n = 3), the percentage increase in MFI was greater among patients with known premature termination codon (PTC) mutations compared to those with unknown mutations. The clinical severity did not change significantly in terms of the mean number of blisters, erosions, and scarring during the study period. None of the parents reported any adverse effect. Conclusions: Topical gentamicin 0.1% w/w is a safe and effective way to promote the expression of COL7A1 in DEB patients, especially those carrying PTC mutations.

Correlating clinical and laboratory diagnostic modalities in the diagnosis of epidermolysis bullosa in a resource-poor setting.

BACKGROUND: Mutational analysis and immunofluorescence antigen mapping (IFM) are recommended as the laboratory tools of choice for diagnosing EB. In the past, transmission electron microscopy (TEM) was considered the gold standard, and more recently, clinical diagnostic matrix (CDM) has shown good concordance with next-generation sequencing (NGS). METHODS: In this prospective diagnostic study, a skin biopsy was taken for TEM and IFM in consecutive patients with EB (aged >6 months) diagnosed clinically with CDM. Wherever possible, mutational analysis was done using targeted NGS. RESULTS: Of the 80 patients diagnosed with CDM, skin biopsy specimens of 42 patients were assessed using TEM, and of 59 patients using IFM. NGS was done in 39 patients. Taking NGS as the gold standard for diagnosing EB (n = 39 patients), the concordance with CDM, TEM, and IFM were estimated at 84.6% (33/39), 78.5% (11/14), and 76% (19/25) respectively. CDM showed a substantial agreement with NGS (k = 0.69, p < 0.001). CONCLUSIONS: In comparison to NGS, the highest concordance was seen with CDM followed by TEM and IFM in diagnosing major subtypes of EB.

Hindi translation and validation of quality of life score in Indian patients with epidermolysis bullosa; and its correlation with the clinical severity assessment scores: A cross-sectional study.

BACKGROUND: Quality of life (QoL) has not been evaluated in Indian patients having epidermolysis bullosa (EB). AIMS: The aims of the study were to measure health-related QoL in Indian patients having EB using the quality of life in epidermolysis bullosa (QoLEB) questionnaire, and to find its correlation with clinically measured disease severity. METHODS: In this observational cross-sectional study, the QoLEB questionnaire was translated from English to Hindi (QoLEB-Hin) and culturally adapted without a change in concept following standard guidelines. QoLEB-Hin and three clinical scores that have been independently validated in EB, that is, Birmingham Epidermolysis Bullosa severity score (BEBs), Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) and Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI), were administered to EB patients/their parents in the presence of an expert. This was followed by validity and correlation studies. RESULTS: Fifty-four patients were recruited (19-females, 35-males; median age 5 years, range 0.025-36 years and 12 patients with an age >13 years). The parents answered the questions for 42 patients (age <13 years). Dystrophic epidermolysis bullosa was diagnosed in 32 (59.2%) patients (dominant dystrophic epidermolysis bullosa [DDEB]-19 [35.2%] and recessive dystrophic epidermolysis bullosa [RDEB]-13 [24.1%]). Junctional epidermolysis bullosa (JEB) and epidermolysis bullosa simplex (EBS) were each diagnosed in 11 (20.4%) patients. The mean ± standard deviation (SD) of QoLEB-Hin score of all epidermolysis bullosa patients was 11.3 ± 7.6 (range 0-28; median and interquartile range [IQR], 10, 10) and reflected an overall moderate degree of affliction on QoL of patients. Mean ± SD of QoLEB-Hin scores for EBS, JEB, DDEB and RDEB were 5.4 ± 3.7 (range, 1-13; median and IQR, 6, 6), 11 ± 6.2 (range, 1-22; median and IQR, 10, 6), 9 ± 5.7 (range, 0-19; median and IQR, 10, 10) and 20.1 ± 6.4 (range, 12-28; median and IQR, 19, 12.5), respectively (P < 0.001, Kruskal-Wallis analysis of variance). Cronbach's alpha coefficient of 0.946 was obtained for all items indicating excellent internal consistency and reliability. Mean sample adequacy was 0.91; absolute fit based off diagonal values was 0.99; indices root mean square error of approximation and root mean square residual were 0.04 and 0.05, respectively, and Tucker Lewis index was >1 indicating overfit. The mean time taken to complete the questionnaire was 6.1 min (range, 6-8 min). QoLEB-Hin correlated significantly (P < 0.001) with BEBs (ρ = 0.79), iscorEB (ρ= 0.63) and EBDASI (ρ = 0.77). Three multiple linear regression models were used to ascertain the strength of relationship between QoL-Hin, and BEBs, iSCOREB and EBDASI, respectively, after adjusting for age, gender and disease subtype. The EBDASI clinical score accounted for approximately 74% (R2 = 0.736, P < 0.001) of the variability in QOL-Hin, as compared to 73% and 55% by BEBs (R2 = 0.731, P < 0.001) and iscorEB (R2 = 0.545, P < 0.001), respectively. LIMITATIONS: Parents filled out the questionnaires for many patients and probably led to an overall moderate degree of affliction of QoL. Comparison with Dermatology Life Quality Index and other QoL scores were not done in this study. Furthermore, the scoring was done at one point in time, and test-retest measurements could not be performed. CONCLUSION: This study validated QoLEB-Hin in an Indian population finding an overall moderate reduction in QoL due to EB. Maximally affected QoL was seen in patients with RDEB. Furthermore, QoLEB-Hin had a variable positive correlation and association with all clinical severity assessment scores.

The severity of malnutrition in children with epidermolysis bullosa correlates with disease severity.

WHO defines malnutrition as severe if the z-scores are less than - 3 Standard deviation (SD), moderate if between - 2 and - 3 SD and mild if between - 2 SD to - 1 SD. This study was aimed to assess nutritional aspects of Indian children suffering from EB and to evaluate the effect of severity of EB on the severity of malnutrition. In this study, pediatric EB patients were evaluated prospectively for baseline nutritional status using anthropometric parameters and WHO growth charts, and its correlation with disease severity using instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa-iscorEB. In second phase, an individualized diet chart was given to meet the energy, protein and micronutrients needs and its effects were observed after 6 months. The median age of participants was 3 years (IQR-9). Of 57 patients, malnutrition was seen in 40.35% patients (22.81%-moderate and 17.54%-severe), and significantly correlated with iscorEB (r = 0.45, p < 0.0001). On bivariate regression analysis, iscorEB was independently associated with moderate-to-severe malnutrition (p = 0.047; OR 1.038, CI 1.011-1.066). iscorEB enabled the identification of patients with moderate-to-severe malnutrition with an Area Under Receiver Operating Curve (AUROC) of 0.72 (95%CI 0.58-0.85; p < 0.005). In phase 2, there was significant improvement in nutritional status in children with recessive dystrophic EB (RDEB) and dominant dystrophic EB (DDEB) subtype (p < 0.0001). The severity of malnutrition in EB children significantly correlates with disease severity, and is an independent predictor of moderate-to-severe malnutrition.

A comparative study on the turnaround time of article processing in dermatology journals: A need for improvement of this aspect in Indian journals.

INTRODUCTION: Submission and publishing of research articles in scientific journals is a multistep process that should be efficient and swift. OBJECTIVE: To compare the editorial, peer review and publication time between Indian dermatology journals and international dermatology journals. METHODS: Three Indian (Indian Journal of Dermatology, Venereology and Leprology; Indian Journal of Dermatology and Indian Dermatology Online Journal) and three international (International Journal of Dermatology; the Australasian Journal of Dermatology and Dermatology [Karger]) dermatology journals were identified for this study. Information pertaining to time to acceptance, time to publication and the total time to publication were extracted for original articles, case reports and letters to the editor published in issues from January 2017 to December 2017. RESULTS: The mean total time to publication in the order for Indian Journal of Dermatology, Venereology and Leprology, Indian Dermatology Online Journal, Indian Journal of Dermatology, International Journal of Dermatology, Dermatology and Australasian Journal of Dermatology were 12.61, 12.50, 9.14, 7.92, 7.13 and 6.52 months respectively. While time to acceptance and time to publication were the longest in Indian Journal of Dermatology (7.01 months) and Indian Dermatology Online Journal (8.99 months), respectively, Indian Journal of Dermatology, Venereology and Leprology was found to have the maximum overall total time for publication i.e. 12.61 months. The differences among the journals were found to be significant for all three time measures (P < 0.0001, ANOVA). On comparison of Indian and international journals, all three time measures were found to be higher in Indian journals (5.81 vs 4.96 months, 6.75 vs 3.59 months and 11.53 vs 7.51 months, respectively) with the differences being significant (P < 0.0001, independent samples t-test). LIMITATION: This data does not represent the performance status of rejected manuscripts, the information of which was not available in the public domain. CONCLUSION: An effective editorial screening, fast-tracked editorial and peer review process and regulation on turnover time of submissions by Indian dermatology journals are imperative in improving the impact of research publication.