Development, reliability, and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI).

BACKGROUND: There is a lack of validated standardized outcome measures for epidermolysis bullosa (EB) that can separate activity from damage. OBJECTIVE: We sought to develop and validate an instrument for inherited EB of all ages and subtypes, the EB Disease Activity and Scarring Index (EBDASI), which scores activity responsive to therapy separately from scarring. METHODS: The EBDASI was validated by comparing its reliability and validity against the Birmingham EB Severity (BEBS) score (partially validated with activity mixed with scarring), using the Physician Global Assessment (PGA) scale as a reference measurement. Sixteen patients with EB (7 EB simplex, 5 dominant dystrophic EB [DDEB], 2 junctional EB, and 2 recessive dystrophic EB) were assessed by 5 EB experts using the EBDASI, BEBS, and PGA, and data from 9 additional patients assessed on an ad hoc basis during routine patient clinic were also included. RESULTS: For interrater reliability, the overall total score intraclass correlation coefficients (95% confidence intervals) were: EBDASI 0.964 (0.929-0.986), BEBS 0.852 (0.730-0.937), and PGA 0.873 (0.765-0.946). For intrarater reliability, the intraclass correlation coefficients were: EBDASI 0.994 (0.976-0.998), BEBS 0.926 (0.748-0.981), and PGA 0.932 (0.764-0.982). The EBDASI had a higher correlation with PGA (ρ = 0.871) than BEBS with PGA (ρ = 0.852). Intraclass correlation coefficients scatterplots showed the EBDASI was better at distinguishing milder forms of EB, with better correlations at higher severity scores than the BEBS. LIMITATIONS: A limited number of patients were recruited for this study. An independent study will be required to demonstrate the responsiveness of the EBDASI. CONCLUSION: The EBDASI demonstrated excellent reliability and validity, as compared with 2 other outcome measures.

A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa.

BACKGROUND: Chronic wounds are a major source of morbidity and mortality in generalized severe recessive dystrophic epidermolysis bullosa (RDEB-GS). OBJECTIVE: This was a phase II double-blinded randomized controlled trial of intralesional allogeneic cultured fibroblasts in suspension solution versus suspension solution alone for wound healing in RDEB-GS. METHODS: Adult patients with RDEB-GS were screened for chronic ulcers and reduced collagen VII expression. Up to 6 pairs of symmetric wounds were measured and biopsied at baseline, then randomized to cultured allogeneic fibroblasts in a crystalloid suspension solution with 2% albumin or suspension solution alone. Ulcer size, collagen VII protein and messenger RNA expression, anchoring fibril numbers, morphology, and inflammatory markers were measured at 2 weeks and at 3, 6, and 12 months. RESULTS: All wounds healed significantly more rapidly with fibroblasts and vehicle injections, with an area decrease of 50% by 12 weeks, compared with noninjected wounds. Collagen VII expression increased to a similar degree in both study arms in wounds from 3 of 5 patients. LIMITATIONS: The number of patients with RDEB-GS who met inclusion criteria was a limitation, as was 1 trial center rather than multicenter. CONCLUSIONS: The injection of both allogeneic fibroblasts and suspension solution alone improved wound healing in chronic nonhealing RDEB-GS wounds independently of collagen VII regeneration. This may provide feasible therapy for wound healing in patients with RDEB-GS.

Retrospective evidence on outcomes and experiences of pregnancy and childbirth in epidermolysis bullosa in Australia and New Zealand.

BACKGROUND: Pregnancy in epidermolysis bullosa (EB) has not been comprehensively studied. OBJECTIVE: We aimed to develop a foundational database, which could provide peri-obstetric advice in EB. METHODS: Survey questionnaires were sent to obstetricians, unaffected mothers of EB babies, and mothers with EB. Results were analyzed using chi-square, Fisher exact, and t-tests. RESULTS: Out of 1346 obstetricians surveyed, 195 responded, and only 14 had encountered EB. All recommended normal vaginal delivery (NVD), except for one elective Caesarean section (CS). We received responses from 75 unaffected mothers who had delivered EB babies. They had significantly more complications in their EB pregnancies compared to their non-EB pregnancies. A further 44 women with various types of EB who had given birth responded. Most delivered via NVD and had no significant increase in complications in both their EB and non-EB pregnancies. In both groups, there were no significant differences in blistering at birth in babies delivered via NVD and CS. CONCLUSION: In conclusion, most patients with EB who are capable of giving birth do not have an increased risk for pregnancy-related complications and NVD appears to be safe. Awareness of this data amongst obstetricians and dermatologists should lead to improved quality of care for mothers and babies affected with EB.

Retrospective evidence on outcomes and experiences of pregnancy and childbirth in epidermolysis bullosa in Australia and New Zealand.

BACKGROUND: Pregnancy in epidermolysis bullosa (EB) has not been comprehensively studied. OBJECTIVE: We aimed to develop a foundational database, which could provide peri-obstetric advice in EB. METHODS: Survey questionnaires were sent to obstetricians, unaffected mothers of EB babies, and mothers with EB. Results were analyzed using chi-square, Fisher exact, and t-tests. RESULTS: Out of 1346 obstetricians surveyed, 195 responded, and only 14 had encountered EB. All recommended normal vaginal delivery (NVD), except for one elective Caesarean section (CS). We received responses from 75 unaffected mothers who had delivered EB babies. They had significantly more complications in their EB pregnancies compared to their non-EB pregnancies. A further 44 women with various types of EB who had given birth responded. Most delivered via NVD and had no significant increase in complications in both their EB and non-EB pregnancies. In both groups, there were no significant differences in blistering at birth in babies delivered via NVD and CS. CONCLUSION: In conclusion, most patients with EB who are capable of giving birth do not have an increased risk for pregnancy-related complications and NVD appears to be safe. Awareness of this data amongst obstetricians and dermatologists should lead to improved quality of care for mothers and babies affected with EB.

Development of a quality-of-life instrument for autoimmune bullous disease: the Autoimmune Bullous Disease Quality of Life questionnaire.

IMPORTANCE: Quality-of-life (QOL) evaluation is an increasingly important outcome measure in dermatology, with disease-specific QOL instruments being the most sensitive to changes in disease status. OBJECTIVE: To develop a QOL instrument specific to autoimmune bullous disease (AIBD). DESIGN: A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL before factor analysis was performed to yield the final ABQOL questionnaire of 17 questions. We evaluated validity and reliability across a range of indices. SETTING: Australian dermatology outpatient clinics and private dermatology practices. PATIENTS AND EXPOSURE: Patients with a histological diagnosis of AIBD. MAIN OUTCOMES AND MEASURES: The development of an AIBD-specific QOL instrument. RESULTS: Face and content validity were established through the comprehensive patient interview process and expert review. In terms of convergent validity, the ABQOL was found to have a moderate correlation with scores on the Dermatology Life Quality Index (R = 0.63) and the General Health subscale of the 36-Item Short Form Health Survey (R = 0.69; P = .009) and low correlation with the Pemphigus Disease Area Index (R = 0.42) and Autoimmune Bullous Disease Skin Disorder Intensity Score (R = 0.48). In terms of discriminant validity, the ABQOL was found to be more sensitive than the Dermatology Life Quality Index (P = .02). The ABQOL was also found to be a reliable instrument evaluated by internal consistency (Cronbach α coefficient, 0.84) and test-retest reliability (mean percentage variation, 0.92). CONCLUSIONS AND RELEVANCE: The ABQOL has been shown to be a valid and reliable instrument that may serve as an end point in clinical trials. Future work should include incorporating patient weighting on questions to further increase content validity and translation of the measure to other languages. CLINICAL TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12612000750886.

Epidemiology of epidermolysis bullosa in the antipodes: the Australasian Epidermolysis Bullosa Registry with a focus on Herlitz junctional epidermolysis bullosa.

OBJECTIVE: To present epidemiologic and clinical data from the Australasian Epidermolysis Bullosa (EB) Registry, the first orphan disease registry in Australia. DESIGN: Observational study (cross-sectional and longitudinal). SETTING: Australian private dermatology practice, inpatient ward, and outpatient clinic. PATIENTS: Systematic case finding of patients with EB simplex, junctional EB (JEB), and dystrophic EB and data collection were performed throughout Australia and New Zealand from January 1, 2006, through December 31, 2008. Patients were consecutively enrolled in the study after clinical assessment and laboratory diagnosis. Medical records were retrospectively examined, and physicians involved in EB care were contacted to obtain patient history. A Herlitz JEB case series was prepared from registry data. MAIN OUTCOME MEASURES: Demographics and prognosis of patients with Herlitz JEB. RESULTS: A total of 259 patients were enrolled in the study: 139 with EBS, 91 with dystrophic EB, 28 with JEB, and 1 with Kindler syndrome. Most enrollees were Australian citizens (n = 243), with an Australian prevalence rate of 10.3 cases per million. The age range in the registry was birth to 99 years, with a mean and median age of 24.1 and 18.0 years, respectively. Ages were similar in patients with EBS and dominant dystrophic EB but were markedly lower in patients with JEB. Patients with Herlitz JEB (n = 10) had the highest morbidity and mortality rates, with a mean age at death of 6.8 months. Sepsis, failure to thrive, and tracheolaryngeal complications were the leading causes of death. CONCLUSIONS: The Australasian EB registry is the first registry in Australia and New Zealand to provide original data on age, sex, ethnicity, and geographical and disease subtype distribution. The Australasian Herlitz JEB cohort witnessed a high infant mortality rate and poor prognosis overall.