Applying the phenotype approach for rosacea to practice and research J. Tan,1 M. Berg,2 R.L. Gallo,3 J.Q. Del Rosso4 1. Department of Medicine, Western University, Windsor, Ontario, Canada; 2. Department of Dermatology, Uppsala University, Uppsala, Sweden; 3. Department of Dermatology, University of California-San Diego, La Jolla, CA; 4. Department of Dermatology, Touro University Nevada, Henderson, NV. British Journal of Dermatology 2018; doi: 10.1111/bjd.16815.

Jerry Tan

Introduction What’s already known? Rosacea diagnosis and classification have evolved from a subtype to a phenotype approach Adoption of the phenotype approach has begun, but more widespread adoption and support across the field is required to ensure a complete transition

Objective To identify challenges to implementation of a phenotype approach across clinical practice, interventional research, epidemiological research and basic science in rosacea To make practical recommendations to facilitate assessment, management and research progression inclusive of the individual experience of disease

Methods A panel of four dermatologists defined the framework for possible recommendation categories pertaining to clinical practice, interventional research, epidemiological research and basic science in rosacea A literature search was performed to assess the current approach to rosacea practice and research within these four areas Hits were limited to articles published between April 2015 and December 2017 to cover the period after publication of the most recent Cochrane systematic review on interventions for rosacea1 The authors then identified challenges to implementation of a phenotype approach based on the literature search results and their experience in the field They consolidated and refined their recommendations through discussion 1. Van Zuuren EJ, et al. Cochrane Database Syst Rev. 2015;(4):CD003262

Summary of recommendations (1 of 2) Clinical practice Interventional research Update language on diagnosis and classification Support core stakeholder meeting to develop international communications plan Educate patients and Health Care Professionals to improve awareness and understanding Demonstrate proven clinical value of phenotyping; reinforce the shortcomings of subtyping Develop simple clinical tools for physician– patient use* Establish standardised clinical and patient- reported measures Produce best-practice examples of phenotype use **applicable to all skin pigment types.

Summary of recommendations (2 of 2) Epidemiological research Basic science Facilitate longitudinal epidemiology studies on the potential for fluctuation of features Include regional groups from all continents in studies for representation of all skin pigment types Highlight the need for national initiatives to support research Extend clinical practice updates to basic science Reinforce the idea of phenotype variation over time Interrogate existing data to identify: Specific pathophysiological factors The treatments with largest/fastest impact on disease

Supplementary info: Clinical checklist for use with patients This checklist is intended to be an ongoing record of a patient’s rosacea phenotype, to help monitor changes in disease features and their response to treatment It is free to download via the supporting information and should be completed together with the patient at each consult Available at: http://s3.amazonaws.com/objects.readcube.com/publishers/ wiley/original_supplements/6e80396a5b0691a350c1e441661545f94577de132736a4d1d398c77bd40dee4c/bjd16815-sup-0001-SupInfo.docx

Discussion The authors support the phenotype approach in rosacea across clinical practice, interventional and epidemiological research, and basic science Several of these strategies span multiple areas, which reflects the need for an integrated approach to ensure consistent and comprehensive uptake Since audit and feedback lead to small but potentially important improvements in professional practice,1 it is important to measure effectiveness of the phenotype approach as it becomes more widely used, to: Enable sharing of successes to promote a virtuous circle of uptake Identify areas for improvement, which could include:2 Medical record audit Computerised databases Health practitioner questionnaire/interview Ivers N, et al. Cochrane Database Syst Rev. 2012:CD000259. Hakkennes S, Green S. Implement Sci 2006;1(1):29.

Limitations This is an evolving field of inquiry, so future advances may inform both modification of signs and symptoms, and subsequent adjustment to suggested tools and language updates Even given an objective tool, the severity of some signs can be subjective E.g. Some cultures may consider persistent mild centrofacial erythema presenting as ‘rosy cheeks’ to be a normal or healthy variation Persistent centrofacial erythema can be of limited use as a definitive diagnostic feature in dark skin phototypes, which will require specific guidance from future work to ensure consistent diagnosis and classification across the patient spectrum

The transition to a phenotype approach in rosacea is underway; however, there is still significant work to be done to ensure a comprehensive uptake These practical recommendations are intended to indicate the next steps in this process, with the goals of: Improving our understanding of the disease Facilitating treatment developments Ultimately improving care for patients with rosacea Conclusions

Conclusions What does this study add? This study offers practical guidance for clinical practice, interventional and epidemiological research, and basic science, to help overcome challenges and facilitate comprehensive uptake of the phenotype approach in rosacea Conclusions What does this study add?

Co-authors M. Berg (left), R. L. Gallo (right), J. Q Co-authors M. Berg (left), R. L. Gallo (right), J. Q. del Rosso (not shown)

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