de Graaf, Marlies

Pasmans, Suzanne G M A

Ragamin, Aviël

Rustemeyer, Thomas

Schappin, Renske

Schuttelaar, Marie L A

Tupker, Ron A

Utrecht University Repository

Br J Dermatol 2023; 189:129–147https://doi.org/10.1093/bjd/ljad085Advance access publication date: 22 March 2023 Research LettersAccepted: 15 March 2023© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. This is an Open Access article distrib-uted under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Investigator Global Assessment for impetiginization in atopic dermatitis: development and initial reliability testingDear Editor, Secondary infections with Staphylococcus aureus (i.e. impetiginization) are common in patients with atopic dermatitis (AD).1 However, owing to a lack of defini-tion and standardized outcome measures, research investi-gating the prevalence and treatment of impetiginization in AD is lacking.We sought to develop an Investigator Global Assessment scale (IGA) for impetiginization in AD. To develop the scale, a team of five dermatologists (S.G.M.A.P., R.A.T., M.L.A.S., M.dG., T.R.), specialized in AD, from five hospitals reviewed the literature, consulted other dermatologists and further elucidated the concept of IGA for impetiginization over six online, structured, consensus-based meetings. The need for a simple IGA for impetiginization in which the degree of impetiginization relates to treatment intensity was expressed. Unanimous consensus was achieved for an IGA scale with three outcome options: absent impetig-inization; limited impetiginization; or extensive impetigini-zation (Figure 1). After development, we pilot tested the comprehensibility and relevance of the IGA for impetigini-zation among five clinicians, two of whom were involved in its development.We next developed online surveys to evaluate the inter- and intra-rater reliability of the IGA for impetiginization. Surveys contained an instruction section and 36 cases of AD. Case information included several photographs and the patients’ ages. All cases were selected by three AD experts (S.G.M.A.P., R.A.T., M.L.A.S.) from two existing academic hospital databases that contain images of patients with AD. Cases were selected to represent the full spectrum of both AD severity and degree of impetiginization across all age groups (58% paediatric cases) and skin types (81% Fitzpatrick skin type I–III). For analysis purposes, the three experts selected cases at an approximate ratio of 1 : 1 : 1 for absent, limited and extensive impetiginization, respectively. All cases were presented to dermatologists at two time points (survey 1 and survey 2). Cases from survey 1 were duplicated and randomized to develop survey 2. At least 6 weeks after the completion of survey 1, dermatologists assessed survey 2. Attending Dutch dermatologists were recruited using the contact lists of four academic hospitals and one public one. Dermatologists who developed the IGA did not participate in the surveys.We used intraclass correlation (ICC2.1), weighted kappa (linear) and the Kendall coefficient of concordance (W ) to assess reliability and agreement.2 We calculated the overall, positive and negative agreement for absent vs. any degree of impetiginization.3 Furthermore, we investigated specific agreement to evaluate the agreement between all possible outcomes.4 Based on our assumptions (expected reliability 0.65) a sample size of 36 cases and 20 dermatologists was deemed sufficient to reject the null hypotheses of poor reli-ability (ICC < 0.5).This study was exempt from the Dutch Medical Research Involving Human Subjects Act according to the institutional review board of Erasmus MC (MEC-2020-0369).Twenty-two and 14 dermatologists participated in the first and second surveys, respectively. The median years of experience of the dermatologists was 8.5 years (interquar-tile range 1–14) and the majority worked in public hospitals (59%). General dermatology (84%), inflammatory derma-tology (64%) and paediatric dermatology (46%) were the most common subspecialties. Overall reliability parame-ters indicated moderate reliability and agreement {ICC 0.68 [95% confidence interval (CI) 0.57–0.79]; Kendall W [0.75]; weighted kappa 0.59 [95% CI 0.57–0.61]}. Additionally, overall agreement was high (81%). Specific agreement was highest for absent vs. extensive impetiginization (91%) and lowest for limited vs. absent impetiginization (59%), suggesting that dermatologists may have disagreed more in distinguishing patients with mild-to-absent impetiginiza-tion. Furthermore, we found good intra-rater reliability [ICC 0.81 (95% CI 0.75–0.87); weighted kappa 0.74 (95% CI 0.66–0.81)].Based on these results, we assumed moderate-to-sub-stantial inter-rater reliability and good intra-rater reliability for the IGA for impetiginization.Compared to other clinical outcome measures for AD such as the Eczema Area and Severity Index (EASI), similar inter- and intra-rater reliabilities were found.5 Keeping in mind that the EASI is one of the most reliable outcome measures in AD assessment, this adds support to the IGA for assess-ing impetiginization in AD. However, ideally, the reliability of both the EASI and IGA impetiginization should be higher. For the IGA impetiginization, discrepancy between raters was largely due to differences in the judgement of limited impe-tiginization. Agreement on extensive impetiginization was high, which is more important for clinical decision-making. More training could help increase reliability. Although we have conducted the initial validation of the IGA for impetig-inization, more research is needed to further validate the IGA for impetiginization among other dermatologists and in real-life settings. Furthermore, the IGA for impetiginization could be compared to definitive measures (i.e. cultures).Use of the IGA for impetiginization in AD will help us to investigate the prevalence of impetiginization in AD and the effects of treatment. In turn, this will help with the devel-opment of treatment guidelines for impetiginization in AD.Downloaded from https://academic.oup.com/bjd/article/189/1/129/7083386 by Universiteitsbibliotheek Utrecht user on 04 December 2023130 Research LettersAviël Ragamin ,1,2 Ron A. Tupker ,3  Marlies de Graaf ,4 Thomas Rustemeyer ,5  Suzanne G.M.A. Pasmans ,1,2 Renske Schappin 1,2 and  Marie L.A. Schuttelaar 61Department of Dermatology, Erasmus MC, University Medical Center, Rotterdam; 2Department of Dermatology, Center of Pediatric Dermatology, Sophia Children’s Hospital, Erasmus MC University Medical Center Rotterdam-Sophia Children’s Hospital, Rotterdam; 3Department of Dermatology, Sint Antonius Hospital, Nieuwegein; 4Department of Dermatology and Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht; 5Department of Dermatology, Amsterdam University Medical Centers, Amsterdam; and 6Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsCorrespondence: Marie L.A. Schuttelaar. Email: m.l.a.schuttelaar@umcg.nlR.A.T. and M.dG. contributed equallyAcknowledgments:We would like to thank Dirk-Jan Hijnen, Elodie Mendels and Claire van Eijsden, in particular, for providing their views on the concept on an Investigator Global Assessment for impetiginization in atopic dermatitis. Additionally, we thank Karin Fieten for her contribution to the realization of the ABC project (ZonMw: 843004017) of which this study is a part. Finally, we thank all the dermatologists who participated in the study.Funding sources: ZonMw (Netherlands Organisation for Health Research and Development), grant number 843004017.Conflicts of interest: the authors declare they have no conflicts of interest.References 1 Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet 2020; 396:345–60. 2 Hallgren KA. Computing inter-rater reliability for observational data: an overview and tutorial. Tutor Quant Methods Psychol 2012; 8:23–34. 3 de Vet HCW, Dikmans RE, Eekhout I. Specific agreement on dichotomous outcomes can be calculated for more than two raters. J Clin Epidemiol 2017; 83:85–9. 4 de Vet HCW, Mullender MG, Eekhout I. Specific agreement on ordinal and multiple nominal outcomes can be calculated for more than two raters. J Clin Epidemiol 2018; 96:47–53. 5 Bożek A, Reich A. Assessment of intra- and inter-rater reliability of three methods for measuring atopic dermatitis severity: EASI, Objective SCORAD, and IGA. Dermatology 2017; 233:16–22.Figure 1 The Investigator Global Assessment for impetiginization in atopic dermatitis. Expert consensus was achieved using a 3-point scale based on morphological features and extent of impetiginization. © Copyright 2022. All rights reserved by authors. Users are free to use the IGA impetiginization on the condition that this article is cited accordingly. Modifications to this IGA scale are not permitted without consulting the developers.Downloaded from https://academic.oup.com/bjd/article/189/1/129/7083386 by Universiteitsbibliotheek Utrecht user on 04 December 2023

Investigator Global Assessment for impetiginization in atopic dermatitis: Development and initial reliability testing

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Investigator Global Assessment for impetiginization in atopic dermatitis: Development and initial reliability testing

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