Development, reliability, and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI)  Clement C.H. Loh, BSc Med (Hons I), Jaehwan Kim, MD, PhD, John C. Su, MBBS, M Epi, FRACP, FACD, FAAD, Benjamin S. Daniel, BA, BCom, MBBS, MMed (Clin Epi), Supriya S. Venugopal, MBBS, MMed (Clin Epi), Lesley M. Rhodes, RN, RM, ACN, Lizbeth R.A. Intong, MD, DPDS, Matthew G. Law, MA, MSc, PhD, Dedee F. Murrell, MA (Cambridge), BMBCh (Oxford), FAAD, MD, FACD  Journal of the American Academy of Dermatology  Volume 70, Issue 1, Pages 89-97.e13 (January 2014) DOI: 10.1016/j.jaad.2013.09.041 Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Fig 1 The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). First page for skin assessment. (Refer to Supplementary Fig 1 for full EBDASI score sheet.) Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Fig 2 Epidermolysis bullosa (EB) intraclass correlation coefficient scatterplots. These graphs illustrate the spread of scores for all 3 outcome instruments. EB Disease Activity and Scarring Index (EBDASI) (A), Birmingham EB Severity (BEBS) (B), and Physician Global Assessment (PGA) (C) overall total score against mean rank order. The y axis gives the raw scores and the x axis gives the mean rank order for that patient. For each patient, the mean overall total score was calculated for each instrument and ranked in ascending order of the mean overall total scores (mean rank order). The overall total scores were plotted against the mean rank order for each instrument. These graphs demonstrate that the EBDASI is more capable than the BEBS in distinguishing difference on disease severities toward the lower end of the spectrum. For example, the EBDASI is able to discriminate between patients 1 to 5 in terms of disease severity, but not the BEBS or PGA scales. Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 1 The 4-page colored epidermolysis bullosa (EB) Disease Activity and Scarring Index scoring system contains 5 different sections to quantify disease severity. For section I (skin), the severity of disease is measured at 12 different skin sites. Sections II and III measure activity and disease on the scalp and mucous membranes, respectively, whereas section IV quantifies nail disease. Section V quantifies the presence of disease on other epithelized surfaces encountered in EB and aggressiveness of squamous cell carcinoma (SCC). The total activity score is calculated by adding up the respective total activity scores from all 5 sections. Similarly, the total damage score is derived from adding up the total damage scores from all 5 sections. Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 1 The 4-page colored epidermolysis bullosa (EB) Disease Activity and Scarring Index scoring system contains 5 different sections to quantify disease severity. For section I (skin), the severity of disease is measured at 12 different skin sites. Sections II and III measure activity and disease on the scalp and mucous membranes, respectively, whereas section IV quantifies nail disease. Section V quantifies the presence of disease on other epithelized surfaces encountered in EB and aggressiveness of squamous cell carcinoma (SCC). The total activity score is calculated by adding up the respective total activity scores from all 5 sections. Similarly, the total damage score is derived from adding up the total damage scores from all 5 sections. Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 1 The 4-page colored epidermolysis bullosa (EB) Disease Activity and Scarring Index scoring system contains 5 different sections to quantify disease severity. For section I (skin), the severity of disease is measured at 12 different skin sites. Sections II and III measure activity and disease on the scalp and mucous membranes, respectively, whereas section IV quantifies nail disease. Section V quantifies the presence of disease on other epithelized surfaces encountered in EB and aggressiveness of squamous cell carcinoma (SCC). The total activity score is calculated by adding up the respective total activity scores from all 5 sections. Similarly, the total damage score is derived from adding up the total damage scores from all 5 sections. Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 1 The 4-page colored epidermolysis bullosa (EB) Disease Activity and Scarring Index scoring system contains 5 different sections to quantify disease severity. For section I (skin), the severity of disease is measured at 12 different skin sites. Sections II and III measure activity and disease on the scalp and mucous membranes, respectively, whereas section IV quantifies nail disease. Section V quantifies the presence of disease on other epithelized surfaces encountered in EB and aggressiveness of squamous cell carcinoma (SCC). The total activity score is calculated by adding up the respective total activity scores from all 5 sections. Similarly, the total damage score is derived from adding up the total damage scores from all 5 sections. Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 2 Correlation of epidermolysis bullosa (EB) Disease Activity and Scarring Index (EBDASI) overall total scores against age for different EB subtypes. The color-coded symbols and lines represent different EB subtypes: red for recessive dystrophic EB (RDEB), orange for junctional EB (JEB), green for dominant dystrophic epidermolysis bullosa, and blue for EB simplex (EBS). Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 3 Mean epidermolysis bullosa (EB) Disease Activity and Scarring Index (EBDASI) total (A), activity (B), and damage (C) scores against EB types. A, On the y-axis is the mean EBDASI overall total score, whereas displayed on the x axis are different disease subtypes. This scatterplot shows increasing EBDASI scores for increasing severity of EB subtypes. The range of scores includes raw scores from the EB scoring exercise and ad hoc scores from individual visits in other patients. B, Mean EBDASI total activity scores against different EB subtypes. The trend of EBDASI activity scores is consistent with the clinical severity of EB subtype, in which the more severe subtypes such as recessive dystrophic EB (RDEB) have higher activity EBDASI scores than EB simplex (EBS), which are less clinically severe. C, Mean EBDASI total damage scores against different EB subtypes. The circle number 6 denotes an outlier score by patient 6 (Supplementary Table I). The trend of EBDASI damage scores is consistent with the clinical severity of EB subtype, in which the more severe subtypes such as RDEB have higher damage EBDASI scores than EBS, which are less clinically severe as these EBS have milder disease and experience much less of the permanent effects of disease and have a much better quality of life. JEB, Junctional EB. Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 4 Photographs demonstrated that erythema caused by previous inflammatory lesions on the back of this patient with recessive dystrophic epidermolysis bullosa (EB) persisted for more than 6 months, hence justifying the need to include erythema as a damage score item in the EB Disease Activity and Scarring Index. Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 5 Bland-Altman plots demonstrating the variation in patient scores, which is a measure of the intrarater reliability for Epidermolysis Bullosa (EB) Disease Activity and Scarring Index (EBDASI), Birmingham EB Severity (BEBS), and Physician Global Assessment (PGA), respectively. The scores given by different assessors are represented by different colored-coded diamonds on the scatterplots. The EBDASI is demonstrated in this figure to have the least variability of scores as compared with the other 2 instruments, as proven by the distribution of the scores close to the x-axis. This implies that the EBDASI has the better intrarater variability as compared with the other 2 instruments. Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions

Supplementary Fig 6 Based on linear regression analysis, the Epidermolysis Bullosa (EB) Disease Activity and Scarring Index (EBDASI) has a higher linear correlation than the Physician Global Assessment (PGA) (R2 = 0.828) as compared with Birmingham EB Severity (BEBS) with PGA (R2 = 0.649). Journal of the American Academy of Dermatology 2014 70, 89-97.e13DOI: (10.1016/j.jaad.2013.09.041) Copyright © 2013 American Academy of Dermatology, Inc. Terms and Conditions