Consensus Recommendations on Adjunctive Topical Management of Atopic Dermatitis

October 2018 | Volume 17 | Issue 10 | Original Article | 1070 | Copyright © October 2018

James Q. Del Rosso DO,a Julie Harper MD,b Leon Kircik MD,c Glynis Albon MD,d Diane Berson MD,e Adelaide Hebert MD,f Doris Day MDg

aJDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; Touro University Nevada, Henderson, NV bThe Dermatology and Skin Care Center of Birmingham, Birmingham, AL cIcahn School of Medicine at Mount Sinai NY; Indiana Medical Center, Indianapolis, IN; Physicians Skin Care, PLLC; DermResearch, PLLC, Louisville, KY dUniversity of California, Los Angeles, CA; Albon Skin Institute & Research Center, Manhattan Beach, CA eWeill Medical College of Cornell University, New York, NY; New York-Presbyterian Hospital, New York, NY fMcGovern Medical School, The University of Texas Health Science Center at Houston, TX gDay Dermatology and Aesthetics, New York, NY

SeverityThe severity of AD encompasses three major areas: (1) symptomatology, which includes pruritus and interference with sleep; (2) skin lesion findings such as erythema, scaling, crusting, lichenification, and excoriations; and (3) the body surface area affected.5 Importantly, these characteristics require both subjective reporting and professional objective evaluation. A large population-based study of AD from the United Kingdom (UK) that incorporated dermatologist evaluation showed severity rates of 84% with mild disease, 14% with moderate disease, and 2% with severe disease.6 Despite variability among different states, population-based US survey data on severity of childhood AD from 2007-2008 noted mild disease in 67%, moderate disease in 26%, and severe disease in 7%, encompassing an estimate of 2.98 million children with moderate-severe AD.5,7 Notably, severity of AD tends to be greater in the African-American/black population.5Course of DiseaseA systematic review and meta-analysis inclusive of 45 studies from 15 countries (N=110,651; 434,992 patient-years) evaluated persistence of AD.8 From the time of diagnosis, 80% of childhood AD did not persist by 8 years and <5% persisted by 20 years. Children with onset of AD by age 2 years were less likely to exhibit persistent disease. This large-scale analysis showed that most childhood AD remitted by adulthood, although children with already persistent disease, later onset of AD, and/or AD of marked severity are more likely to experience greater AD persistence.8 The early onset of AD, severe early AD, family history of atopy, female gender, black race, low income, and presence of filaggrin gene mutations have all been correlated with higher disease activity and greater likelihood of a more prolonged course.9 Persistence of AD into adulthood often reflects cases of greater severity, with added clinical presentations such as hand eczema and/or lichenified nummular dermatitis.10Progression of DiseaseThe recurrent nature of AD places patients on an unfortunate ‘roller coaster pattern’ characterized by periods of flare and remission; unfortunately, there is a relative lack of data on definitive patterns and time-courses of AD recurrence.9 However, what is evident is that intermittent flares do occur, and that fluctuations in AD intensity and clinical presentations emerge over time.9 In a given individual with AD, their inherent pathophysiologic makeup, the timing and nature of environmental conditions and exposures, and both when and how they have specifically utilized skin care products and medical therapies all can impact directly on the frequency, intensity, and duration of their AD flares over time. Regardless of whether AD is primarily a disease of the epidermal barrier (outside in theory), or is a primary systemic process with epidermal barrier dysfunction occurring as a secondary phenomenon (inside out theory), there are several inherent abnormalities present within normal-appearing skin of people with AD that characterize their chronic predisposition to develop both xerosis and eczematousflares.9,11-19 These abnormalities, referred to collectively as atopic skin, include differences in stratum corneum (SC) lipid composition and content, reduction in epidermal antimicrobial peptides, changes in SC enzyme function, decreased epidermal humectancy (filaggrin gene mutations), altered cutaneous microflora with increased staphylococcal colonization, changes in the dendritic cell population, and increased presence of cutaneous T lymphocytes (T cells).2,9,11-25 This supports the concept of subclinical inflammation in AD that is present between flares, with transition to an active flare occurring when atopic skin is triggered by a variety of potential exacerbating factors (ie, allergens, irritants, bacterial toxins, psychosocial stimuli, climatic changes). Atopic skin is not able to elicit effective repair mechanisms to correct epidermal barrier impairments that lead to flares of AD.11-14,17,18 Therefore, in order to reduce the frequency of AD flares, it is important to incorporate long term management approaches that serve to maintain physiologic SC  function in atopic skin and support the diversity and relative stability of the cutaneous microbiome that is present in  normalappearing skin.9,12,25-30 Interestingly, there are data to support that early intervention of topical skin barrier therapy during the neonatal period may delay or prevent the emergence of clinical signs of AD.9Newer Data on Disease Course/ProgressionMore recently, there are data to suggest that maintaining diversity of the cutaneous microbiome is important in the acute and long term management of AD.23,26,29,30 For some time, it has been well-recognized that flares of AD correlate with an increased density of S. aureus at eczematous skin sites.23 However, it is now apparent that flares of AD are also associated with a decrease in the diversity of skin bacteria and other microbialorganisms, reflecting the importance of trying to sustain stability and diversity as a component of managing AD.29,30 Data supporting this concept is reviewed in more detail below.Pathophysiologic MechanismsAlthough a complete discussion of AD pathophysiology is beyond the scope of this article, a review of contributory pathogenic mechanisms serves to better understand both the acute and long-term management of AD. Several components contribute to the complex pathophysiology of AD including genetic and environmental factors, epidermal barrier dysfunction, dysregulation of innate and adaptive immune responses, decreased antimicrobial peptides (AMPs), aberrant activation and homing of T lymphocytes, role of specific dendritic cells, effects of certain cytokines and chemokines, overexpression of phosphodiesterase-4 (PDE4), augmented itch-scratch cycle, neuroimmunologic factors, and shifting of the cutaneous