|Year : 2020 | Volume
| Issue : 2 | Page : 84-87
Skin pH and its relationship with transepidermal water loss and disease severity in children with atopic dermatitis: A cross-sectional study
Choon S Lee1, Adawiyah Jamil2
1 Department of Dermatology, Hospital Tuanku Ja'afar, Seremban, Negeri Sembilan, Malaysia
2 Department of Medicine, Dermatology Unit, Universiti Kebangsaan Malaysia Medical Center, Cheras, Kuala Lumpur, Malaysia
|Date of Submission||02-Jun-2020|
|Date of Acceptance||05-Aug-2020|
|Date of Web Publication||10-Nov-2020|
Dr. Adawiyah Jamil
Department of Medicine, Dermatology Unit, Universiti Kebangsaan Malaysia Medical Center, Cheras, 56000 Kuala Lumpur
Source of Support: None, Conflict of Interest: None
Background: pH is increasingly a target in therapeutic strategies for skin barrier repair, but the relationship between pH, transepidermal water loss (TEWL), and atopic dermatitis (AD) severity is not well characterized. Purpose: The purpose of the study was to determine the relationship between skin pH with TEWL and their correlations with AD severity. Methods: A cross-sectional study enrolled children aged 4–12 years with AD. Measurements were made using HI 99181 and Tewameter TM 300 at two lesional sites and two nonlesional sites (left cubital fossa, left thigh, and forehead). Disease severity was evaluated using the Eczema Area and Severity Index (EASI) and pruritus score. Results: A total of 14 (58%) girls and 10 (42%) boys aged 7.3 ± 2.6 years with age of AD onset 3.0 ± 2.1 years participated. The mean EASI score was 8.9 ± 8.2, body surface area 13.1% ± 18.5%, pruritus score 5.9 ± 2.7, and Children Dermatology Life Quality Index 5.6 ± 4.9. pH and TEWL were higher at lesional compared to nonlesional skin, pH 5.2 ± 0.7 versus 4.6 ± 0.4, P < 0.01 and TEWL 31.1 ± 15.2 versus 16.0 ± 10.2, P < 0.01. Lesional pH positively correlated with TEWL (r = 0.59, P= 0.02 and r = 0.55, P = 0.01), while nonlesional pH was inversely correlated (r = −0.42,P = 0.04 and r = −0.40, P = 0.05). pH showed significant positive correlations with EASI and itch at one lesional site. Conclusion: pH and TEWL were higher at lesional skin. pH correlated positively with TEWL at lesional skin but inversely at nonlesional areas. Higher pH was associated with disease severity and itch. pH restoration may have therapeutic potential in AD.
Keywords: Atopic dermatitis, eczema, pH, transepidermal water loss
|How to cite this article:|
Lee CS, Jamil A. Skin pH and its relationship with transepidermal water loss and disease severity in children with atopic dermatitis: A cross-sectional study. J Dermatol Dermatol Surg 2020;24:84-7
|How to cite this URL:|
Lee CS, Jamil A. Skin pH and its relationship with transepidermal water loss and disease severity in children with atopic dermatitis: A cross-sectional study. J Dermatol Dermatol Surg [serial online] 2020 [cited 2020 Nov 25];24:84-7. Available from: https://www.jddsjournal.org/text.asp?2020/24/2/84/300391
| Introduction|| |
The pH of normal skin is naturally acidic. The value varies according to endogenous factors including age, gender, site, and sebum production,,, and exogenous factors such as hygiene, grooming, and cosmetic products. pH is regulated by the products of filaggrin degradation, urocanic acid, phospholipase A2, sodium-hydrogen exchanger 1, and melanin persistence and extrusion of cholesterol sulfate.,
The skin pH in patients with atopic dermatitis (AD) is higher than that of normal skin. Neutralization of the skin's acidic pH enhances serine proteases activity which inhibits key lipid processing enzymes in the synthesis of ceramide, a major component of the lipid lamellae matrix that cemented corneocytes., In addition, activated serine proteases degrade the adhesion proteins that bind the corneocytes together. Corneocyte dehiscence and defective extracellular matrix result in the breach of the epidermal barrier leaving the skin vulnerable to irritants, allergens, haptens, and microorganisms. The skin's natural antimicrobial defense, dermcidin, functions optimally at lower pH which could explain Staphylococcus aureus colonization in AD.,
Clinically, higher skin pH in AD is associated with worse itch. Its relationship with disease severity is unclear. We hypothesized that higher pH is associated with AD severity. We performed a cross-sectional study in children with AD to determine their skin pH and transepidermal water at both lesional and nonlesional areas. We investigated the relationship between pH and TEWL and the correlation between pH and AD severity.
| Methods|| |
A cross-sectional study was performed on children with AD attending a dermatology clinic in a tertiary health facility. Children aged 4–12-year old diagnosed with AD based on the Hanifin-Rajka criteria were included in the study. Patients with cutaneous infection and on antibiotic and systemic corticosteroid or other immunosuppressants were excluded from the study. Consent was obtained from the children's parents or guardians. Skin pH was measured using the HI 99181 skin pH meter at two sites which clinically has obvious eczematous patches (lesional sites A and B) and two sites with clinically normal-looking skin (nonlesional sites C and D). Measurements were made at the left cubital fossa (site E), left thigh (site F) and the face (site G) regardless of the presence or absence of lesions. Transepidermal water loss (TEWL) was measured at the same sites using Tewameter TM 300. Disease severity was evaluated using the Eczema Area and Severity Index (EASI). Total body surface area (BSA) affected with AD, pruritus score, and Children Dermatology Life Quality Index (cDLQI) were assessed as other parameters that reflect AD disease severity. Pruritus was scored using a visual analog where 0 means no itch at all, 5 moderately severe itch, and 10 denotes worst itch. The sample size was calculated with the formula (1/q1 + 1/q0) (Zα+Zβ) 2/(E/S) 2 based on the results of a previous study, the effect size was 0.2 and outcome standard deviation 0.18. The sample size was 33 considering a 10% dropout rate where two-tailed α level was 0.05 and β level 0.2. Statistical analysis was performed using Statistical analysis was performed using IBM SPSS Statistics, New York, United States. Exploratory data analysis showed most continuous variables were normally distributed; therefore, variables are expressed in mean ± standard deviation and parametric test was used. Pearson correlation coefficient tests were performed to determine the relationship between pH and TEWL, and pH with AD severity.
The study was approved by the Medical Research and Ethics Committee, Ministry of Health Malaysia, research code NMRR-17-1054-35621.
| Results|| |
A total of 14 (58%) girls and 10 (42%) boys participated in the study. Their mean age was 7.3 ± 2.6 years, while the mean age of AD onset was 3.0 ± 2.1 years. The mean EASI score of 8.9 ± 8.2 falls into moderate disease severity with a mean BSA of 13 ± 18%. The pruritus score was 5.9 ± 2.7. However, the mean cDLQI score was 5.6 ± 4.9, which showed a small effect of AD on the children's life [Table 1].
|Table 1: Demography and clinical characteristics of the study population|
Click here to view
Skin pH is higher at lesional skin compared to nonlesional skin with values consistently above 5.0 at lesional skin, ranging from 5.1 ± 0.7 to 5.1 ± 0.6. At nonlesional skin, the pH ranges from 4.4 ± 0.3 to 4.8 ± 0.4. A similar pattern in the TEWL values was observed. The TEWL at lesional skin ranges from 17 ± 6.9 to 32 ± 16, while the values at nonlesional skin range from 15 ± 10 to 22 ± 12. The TEWL values at each site were consistently higher at lesional versus nonlesional areas [Table 2]. pH at lesional A and B and F was significantly higher at nonlesional sites, 5.2 ± 0.7 versus 4.6 ± 0.4, P < 0.01 for A and B and 5.1 ± 0.6 versus 4.6 ± 0.4, P = 0.02 for F. The difference at site G was approaching significance with pH 5.1 ± 0.7 at lesional areas and 4.8 ± 0.4 at nonlesional areas, P = 0.05. TEWL at lesional A and B and G was significantly higher at nonlesional sites, 31 ± 15 versus 16 ± 10, P < 0.01 for A and B and 28 ± 22 versus 15 ± 9.0, P = 0.02 for G [Table 3].
|Table 2: Skin pH and transepidermal water loss measured at lesional and nonlesional sites A to G|
Click here to view
|Table 3: Comparison of skin pH and transepidermal water loss between lesional and nonlesional sites|
Click here to view
Lesional skin pH was positively correlated with TEWL. However, nonlesional skin pH showed inverse correlations at site C and a trend approaching statistical significance at site D. Skin pH was not significantly correlated with EASI score except for lesional skin at site B; however, there were positive correlations between pH and EASI at all sites. Similarly, pH correlated significantly with itch at skin site B and pH was positively correlated with itch at all sites [Table 4]. Sites E, F, and G were not included in the analyses as each site consists of either lesional or nonlesional skin.
|Table 4: Correlations between pH with transepidermal water loss, Eczema Area and Severity Index, and itch|
Click here to view
| Discussion|| |
Skin pH differs between AD and normal, healthy individuals.,,, Implications of higher pH on AD disease severity are still unclear. Restoring the skin pH to normal may have therapeutic potential in AD. Normal skin pH varies below 5.0, with an estimated average of 4.7. pH ranged from 4.4 to 5.2 in our AD patients; skin clinically unaffected by eczema, i.e., nonlesional areas, has lower pH. The lowest pH was at nonlesional areas of the cubital fossae. pH values in AD vary according to the anatomical site. The highest pH is at lesional areas followed by perilesional and clinically unaffected skin.,, pH of clinically normal-looking skin in AD is higher than the normal skin of healthy individuals.,
The severity of epidermal barrier disruption in AD is reflected by TEWL. TEWL of lesional areas is higher than nonlesional areas., Data on the relationship between skin pH and TEWL vary.,, Most studies did not show a significant relationship between pH and TEWL.,,, Differences in the measurement sites – normal appearing skin in AD patients,, sites with lesional skin only, sites involving either lesional and nonlesional skin – may explain these inconsistencies. pH of lesional skin was higher and had a positive correlation with TEWL in our patients. Unexpectedly, nonlesional skin pH was inversely correlated with TEWL. We postulate that this was due to the effect of applying moisturizer all over and topical corticosteroid (TCS) at lesional areas only. pH of moisturizers and TCS used by our patients was between 6 and 7. Regular moisturizer use without TCS over 28 days resulted in increased pH with no change in TEWL. Most moisturizers improved hydration, while TEWL remained unchanged. Meanwhile, TCS use reduces TEWL. AD patients may benefit from using topical formulations with physiologically compatible pH.
Higher skin pH was associated with higher EASI scores; however, our results were nonsignificant except at lesional skin site B. pH had a nonsignificant positive correlation with diseases severity in AD patients evaluated in the use of immunoglobulin E, β-endorphin, and vasoactive intestinal peptide as objective parameters of itch. pH correlated with the individual components of SCORAD (area, erythema, and lichenification) but not with total SCORAD. The role of pH in the pathophysiology of itch is poorly understood and has not been adequately explored. AD children with moderately severe itch had higher pH at both lesional and nonlesional areas compared to those with mild itch. Higher pH at clinically normal skin was associated with higher itch scores. Alkalinization of the skin pH enhances the activity of serine proteases that serve as pruritogens., We found higher itch scores correlated with higher pH, especially at lesional areas. Higher pH is associated with AD severity; this further justifies skin pH normalization approaches in AD management.
| Conclusion|| |
Skin pH ranged from 4.43 to 5.24 in our AD patients. pH was lowest at nonlesional areas of the cubital fossae. pH and TEWL at lesional skin were higher than nonlesional skin. Lesional skin pH correlated positively with TEWL, while nonlesional skin pH showed inverse correlations. Skin pH showed a nonsignificant positive correlation with AD severity. Therapeutic strategies in AD management could include the restoration of physiological pH and avoidance of high pH topical formulations.
Financial support and sponsorship
The study was financially supported by an educational grant from the Dermatological Society of Malaysia.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Man MQ, Xin SJ, Song SP, Cho SY, Zhang XJ, Tu CX, et al
. Variation of skin surface pH, sebum content and stratum corneum hydration with age and gender in a large Chinese population. Skin Pharmacol Physiol 2009;22:190-9.
Luebberding S, Krueger N, Kerscher M. Skin physiology in men and women:In vivo
evaluation of 300 people including TEWL, SC hydration, sebum content and skin surface pH. Int J Cosmet Sci 2013;35:477-83.
Stefaniak AB, Plessis Jd, John SM, Eloff F, Agner T, Chou TC, et al
. International guidelines for the in vivo
assessment of skin properties in non-clinical settings: Part 1. pH. Skin Res Technol 2013;19:59-68.
Lambers H, Piessens S, Bloem A, Pronk H, Finkel P. Natural skin surface pH is on average below 5, which is beneficial for its resident flora. Int J Cosmet Sci 2006;28:359-70.
Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M, et al
. Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol 2009;129:1892-908.
Jang H, Matsuda A, Jung K, Karasawa K, Matsuda K, Oida K, et al
. Skin pH Is the master switch of Kallikrein 5-mediated skin barrier destruction in a murine atopic dermatitis model. J Invest Dermatol 2016;136:127-35.
Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown BE, Rogiers V, et al
. Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. J Invest Dermatol 2005;125:510-20.
Rippke F, Schreiner V, Schwanitz HJ. The acidic milieu of the horny layer: New findings on the physiology and pathophysiology of skin pH. Am J Clin Dermatol 2002;3:261-72.
Burian M, Schittek B. The secrets of dermcidin action. Int J Med Microbiol 2015;305:283-6.
Sparavigna A, Setarol M, Gualandri V. Cutaneous pH in children affected by atopic dermatitis and in healthy children: A multicenter study. Skin Res Technol 1999;5:221-7.
Danby SG, Chalmers J, Brown K, Williams HC, Cork MJ. A functional mechanistic study of the effect of emollients on the structure and function of the skin barrier. Br J Dermatol 2016;175:1011-9.
Knor T, Meholjić-Fetahović A, Mehmedagić A. Stratum corneum hydration and skin surface pH in patients with atopic dermatitis. Acta Dermatovenerol Croat 2011;19:242-7.
Choi SJ, Song MG, Sung WT, Lee DY, Lee JH, Lee ES, et al
. Comparison of transepidermal water loss, capacitance and pH values in the skin between intrinsic and extrinsic atopic dermatitis patients. J Korean Med Sci 2003;18:93-6.
Seidenari S, Giusti G. Objective assessment of the skin of children affected by atopic dermatitis: A study of pH, capacitance and TEWL in eczematous and clinically uninvolved skin. Acta Derm Venereol 1995;75:429-33.
Lee CH, Chuang HY, Shih CC, Jong SB, Chang CH, Yu HS. Transepidermal water loss, serum IgE and beta-endorphin as important and independent biological markers for development of itch intensity in atopic dermatitis. Br J Dermatol 2006;154:1100-7.
Zainal H, Jamil A, Md Nor N, Tang MM. Skin pH mapping and its relationship with transepidermal water loss, hydration and disease severity in adult patients with atopic dermatitis. Skin Res Technol 2020;26:91-8.
Hon KL, Kung J, Ng WG, Tsang K, Cheng NS, Leung TF. Are skin equipment for assessing childhood eczema any good? J Dermatolog Treat. 2018;1-15. doi:10.1080/09546634.2018.1442551
Hon KL, Kung JSC, Ng WG, Leung TF. Emollient treatment of atopic dermatitis: Latest evidence and clinical considerations. Drugs Context 2018;7:212530.
Jensen JM, Pfeiffer S, Witt M, Bräutigam M, Neumann C, Weichenthal M, et al
. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol 2009;123:1124-33.
Furue M, Yamamura K, Kido-Nakahara M, Nakahara T, Fukui Y. Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis. Allergy 2018;73:29-36.
Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: Getting the itch out? Clin Rev Allergy Immunol 2016;51:263-92.
[Table 1], [Table 2], [Table 3], [Table 4]