ARTICLE: Clinical Insights About the Role of pH in Atopic Dermatitis

December 2019 | Volume 18 | Issue 12 | Supplement Individual Articles | 215 | Copyright © December 2019

Charles Lynde MD FRCPC

American Board of Dermatology, Royal College of Physicians and Surgeons of Canada, Department of Medicine, University of Toronto, Toronto, ON, Canada, Lynderm Research, Markham, ON, Canada 

Jerry Tan MD FRCPC

Royal College of Physicians and Surgeons of Canada, Schulich School of Medicine and Dentistry, Department of Medicine, Western University, Windsor, ON, Canada, Windsor Clinical Research Inc., The Healthy Image Centre, Windsor, ON, Canada Sandra Skotnicki MD FRCPC

American Board of Dermatology, the Royal College of Physicians and Surgeons of Canada, Department of Medicine, Divisions of Dermatology, and Occupational and Environmental Health, University of Toronto, Toronto, ON, Canada, Bay Dermatology Centre, Toronto, ON, Canada Anneke Andriessen PhD

Radboud UMC, Nijmegen and Andriessen Consultants, Malden, The Netherlands 

Jennifer Beecker MD CCFP(EM) FRCPC DABD

Royal College of Physicians and Surgeons of Canada, American Board of Dermatology, University of Ottawa, Ottawa, ON, Canada, The Ottawa Hospital, Director of Research, The Ottawa Hospital Research Institute, Ottawa, ON, Canada 

Joël Claveau MD FRCPC

American Board of Dermatology, Royal College of Physicians and Surgeons of Canada, Department of Medicine, Laval University, Quebec City, QC, Canada; Melanoma and Skin Clinic, Le Centre Hospitalier Universitaire de Québec, Hôtel-Dieu de Québec, Quebec City, QC, Canada 

Monica K. Li MD FRCPC

Royal College of Physicians and Surgeons of Canada, Faculty of Medicine, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada, Enverus Medical, Surrey, BC, Canada and Cosmetic Dermatologist, City Medical Aesthetics Center, Vancouver, BC, Canada 

Jaggi Rao MD FRCPC

Royal College of Physicians and Surgeons of Canada, Division of Dermatology, University of Alberta, Edmonton, AB, Canada 

Jennifer Salsberg MD FRCP

Royal College of Physicians and Surgeons of Canada, University of Toronto, Women’s College Hospital, Toronto, ON, Canada, Bay Dermatology Centre, Toronto, ON, Canada Maxwell B. Sauder MD FRCPC FAAD

Royal College of Physicians and Surgeons of Canada, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA, Harvard Medical School, Boston, MA, Toronto Dermatology Centre, Toronto, ON, Canada 

Catherine Zip MD FRCPC

Royal College of Physicians and Surgeons of Canada, Department of Medicine, University of Calgary, Calgary, AB, Canada, Dermatologist, Dermatology Centre, Calgary, AB, Canada

Literature Review
A literature review explored clinical insights into the role of pH in AD and into the influence of cleansing and moisturizers. For this purpose searches were performed on PubMed and Google Scholar of the English-language literature (2010–2018) using the terms: Atopic eczema; Atopic dermatitis; Skin pH; AD pathogenesis; Filaggrin; Inflammation in AD; Risk factors for AD; Acid mantle; Immune response and epidermal skin barrier function; Skin barrier; Skin barrier deficiency; Immunity; Stratum corneum hydration and skin surface pH in AD; Prevention; Emollients; Cleansers; and Moisturizers.

The selected publications were manually reviewed for additional resources by a dermatologist and a clinical scientist with experience in this field (AA). The searches yielded forty-two publications. After exclusion of duplicates and papers not relevant for skin surface pH in AD, twenty-nine publications were included (Figure 1). The two reviewers prepared statements using the results of the literature reviews for discussion by the expert panel. The panel discussed at length the consensus statements, revised them, and voted.

Statements Defined by the Panel
The defined statements were based on the expert panel’s clinical experience and opinion coupled with support from the literature selected during the literature searches. The ten panel members reached consensus on eight statements on the role of pH in AD and the influence of cleansing and moisturizer use. Seven statements were accepted with a unanimous vote; statement number seven was passed with 8/10 panel members (80%) in agreement.

Statement 1: AD is a common chronic, relapsing skin disease, where there is interplay between the skin barrier, the immune system, and the skin microbiome.

The Skin Barrier
The epidermal barrier is composed of corneocytes, held together with corneodesmosomes.8 Skin barrier function is dependent on the complex interplay of SC pH including filaggrin production into natural moisturizing factor (NMF) components pyrrolidone, carboxylic acid, and trans-urocanic acid, all of which acidify the SC.6,8-11

The Immune System
When there is protease hyperactivity within the epidermis and an overrepresentation of pathogens (eg, Staphylococcus aureus [S. aureus]), the cleavage of the corneodesmosome junctions is enhanced. This increase in cleavage leads to a defective skin barrier, which is open to water loss and to an invasion of irritants and allergens, leading to inflammation.8 Skin lesions in AD affected skin are characterized by upregulations of T-helper cells (Th2), (Interleukin (IL) -4, IL-5, IL-13, IL-31), cytokines, and
chemokines.12,13 Th2 cytokines, IL-4, and IL-13, all play a major role in the disease pathogenesis leading to the dysfunctional epidermal barrier in AD.13 Finally, IL-4 and IL-13 promote S. aureus binding and inhibit antimicrobial peptides, predisposing AD-affected skin to S. aureus colonization and infection.13

The Skin Microbiome
Antimicrobial peptides produced from keratinocytes, neutrophils, and mast cells are regulated by pH6 while skin commensal organisms contribute to the skin’s acidic pH. Moreover, pathogenic organisms S. aureus and Streptococcus pyogenes (S. pyogenes) are inhibited by acid skin surface pH.6 When less filaggrin is produced in the skin, the surface pH increases, activating serine proteases, which, in turn, enhances cell degradation and decreases lipid synthesis.6,11 Serine proteases are pH dependent and break down corneodesmosomes, leading to barrier disruption and an unbalanced microbiome.6,8,13 A physiological skin surface pH acts as an antimicrobial defense mechanism limiting bacterial colonization6,11; moreover, acidic filaggrin breakdown products decrease S. aureus growth rates.6 If in healthy skin the surface pH increases, filaggrin proteolysis supports restoring the slightly acidic pH.6,11

Statement 2: Genetic and environmental factors can influence the pathogenesis of AD, including impaired skin barrier and lipid metabolism, activation of multiple immunologic and inflammatory pathways, skin microbial imbalance, and changes in the skin pH.

The skin barrier function includes physical, chemical, and immunological aspects.6 The acid mantle refers to the slightly acidic pH of the skin which affords protection against exogenous insults. The acid mantle contains amino acid, lactic acid, fatty acid, and other compounds (eg, ceramides), which play an important role in skin barrier homeostasis. Furthermore, the mantle provides a defense against pathogens and other factors such as frequent bathing, regular use of alkaline soaps increasing skin pH, dry air (eg, due to air conditioning), and physical stress.6,14 Ceramides are synthesized from keratinocyte lamellar structures via pH-dependent enzymes (ie, sphingomyelinase, B-glucocerebrosidase), which require an acidic environment to function.8 Lower levels of ceramides 1 and 3 as well as a lower ceramide/cholesterol ratio were noted in non-lesional AD-affected skin.8

The protective buffer capacity protects the skin against acid or alkaline assaults, and is influenced by keratinocyte-produced free fatty acids and components of NMF, including urocanic acid, carbonic acid, and keratins.6,13 The buffer capacity is decreased in babies and elderly patients15; skin pH at birth is near neutral (6.5), and takes several weeks to reach the physiological