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#### *2.1. pH Values on Skin Surfaces*

The skin pH of newborns is weakly alkaline (pH of 7.4) as a result of being encapsulated within the amniotic fluid and the vernix caseosa. Hans, et al., determined and described skin pH characteristics from 209 newborn infants [17]. However, after birth, the weakly alkaline skin becomes acidic in its quest to form the acid mantle [18,19] and the functional maturation of stratum corneum is accelerated within 2 to 8 weeks [20]. During this period, infant skin remains highly prone to damage.

During sexual maturation, the pH of skin in the axillary vault climbs from around 5.0 to near 7.0, and then returns to a lower pH during sexual involution [21,22]. A. Zlotogorski [23] measured the pH distribution on the surface of the skin (forehead and cheek) of 574 men and women aged 18 to 95, and found that those over the age of 80 had higher skin surface pH values compared to the other groups, which displayed skin surface pH values between 4.0 and 5.5 on the forehead and between 4.2 and 5.9 on the cheek. There was no significant pH di fference based on gender. Irvin H. Blank [24] obtained skin surface pH values (forearm, antecubital, elbow, upper arm, forehead, and back of neck) from 100 males and 100 females aged 19–27 and found pH values varying from 4.0 to 7.0, with the most frequent readings being between 4.2 and 5.6, and evidence suggesting that females have a slightly higher skin pH (0.5 higher) than males. C. Ehlers and coworkers [25] found that there was a statistically significant di fference in skin pH (arm) between men and woman. Notably, measurements could not be conducted close to the wrist because most people wash their hands several times each day, and soaps can make the skin more alkaline. Another study conducted by S. Luebberding and coworkers [26] followed strict criteria and found pH di fferences between males and females in TEWL, SC hydration, sebum content, and at the skin surface (forehead, forearm, hand and cheek). Table 1 (adapted from [26]) displays gender-related data showing that the pH values from five skin sites and across all age groups were higher in females compared to males. This data also shows that the mean evaporimetry and corneometry values were higher for the females of this group, while the mean sebumetry values were higher for the males.

It is common to obtain inconsistent pH measurements from men and women, but additional research could provide data to support a pattern of pH value di fferences between genders.

#### *2.2. Factors That A*ff*ects Skin pH*

Regulating skin surface pH is critical to physiological defense mechanisms, but skin is a ffected by a number of endogenous and exogenous factors [27], including age, ethnicity, sebum, sweat, detergents, cosmetic products, soaps, occlusive dressing, and more. These factors and their influence are displayed in Table 2 [23,26–47].

Elizabeth A. and coworkers [48] analyzed the distribution of the human skin microbiome via examination of 16S ribosomal RNA gene sequences, and found that bacteria in sebaceous sites where *Propionibacterium acnes* predominated were less diverse, less even, and less rich than the bacterial milieu in moist and dry sites, which were predominantly associated with Firmicutes and Proteobacteria. Multiple factors such as sweat, sebum secretion, and pH could have correlation with predominant microbiota. This study revealed a pattern of bacterial distribution on human skin that may have implications for the future treatment of pH-relevant skin disorders, a topic that we will explore further.


Soaps and detergents The use of soaps, synthetic detergents and even tap water will raise skin pH in a short-term effect. [27,31–35] Cosmetic products Skin pH values drop after the application of cosmetic products, which can buffer the impact of tap water washing. [36,37]

Occlusive dressings Under occlusion, skin pH increases, but after removing occlusive dressings, the pH milieu drops back to an acidic nature. The

application of occlusion has a short period effect on skin pH values. [38–40]

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#### *2.3. Skin Diseases and pH Values*

Beneath the acid mantle and lipid barrier, the various strata of skin have relatively static and regulated physiological pH values, but when disruptions in the protective barriers occur, or when normal skin pH is disrupted, the risk for specific skin diseases increases. Many studies have suggested a relationship between skin surface pH and disease.

It has been reported that grea<sup>t</sup> numbers of *Staphylococcus aureus* exist on the skin of patients with eczema can exacerbate the disease [49]. *Staphylococcus aureus* has a capacity for adhering to atopic corneocytes; this adherence phenomenon is partially attributable to the presence of protein A in its wall [50]. The pH range for optimal growth of *Staphylococcus aureus* is between 7.0 and 7.5, ye<sup>t</sup> the bacteria are able to reproduce at pH values from 4.5 to 9.0. The pH value of the normal skin surface, 4.5–6.0, is consequently insu fficient to kill the bacteria completely. However, the staphylococcal enterotoxin C2 (SEC2) can be destroyed in strongly acidic pH. Zinc ion, present in the crystalline structure of SEC2, may be removed completely in this process, which distorts SEC2 from its normal configuration [51].

pH on the skin surface increases in patients with seborrheic dermatitis [52–54]. *Pityrosporum ovule* prosper in scale of patients with dandru ff, since higher pH values also promote the growth of yeast. Its colonization in less acidic areas of the skin result in declining activity of calf thymus histones, parotid saliva, lysozyme, and proteins obtained from human neutrophil granulocyte, which are cationic substances critically related to bacterial activity [55–58].

Diaper dermatitis is frequently diagnosed in infants, and wearing diapers is associated with increases in wetness and skin pH value. Ronald and coworkers [59] carried out a study involving 1601 infants. Their results sugges<sup>t</sup> that diapered skin has approximately twice the TEWL of undiapered skin. Diapered skin has a higher pH value (5.9) while undiapered skin (pH 5.3) remains related to the acid mantle pH. Skin wetness could disturb the integrity of skin by increasing its permeability to irritants, frictional coe fficient, and promoting microbial growth [60]. Elevated pH can increase the activity of fecal proteolytic enzymes that can degrade the extracellular matrix of the skin and eventually destroy tissues [61].

Skin pH is believed to be one of possible factors that promote candida infection, which diabetics are particularly prone to su ffer from. Dimorphism of *Candida albicans* exists, as the blastospore form is related to acidic pH and the mycelial form is associated with alkaline pH [62,63]. The mycelial form of *Candida albicans* has been verified in clinical studies via its pathogenicity [64–66]. Gil Yosopovitch and coworkers [67] found that diabetic patients had significantly higher skin pH than that of normal control skin. Moreover, the skin pH values of diabetic patients with candidiasis was higher than that of diabetic patients without candidiasis. This suggests a possible correlation between skin pH and candida infection.

#### *2.4. Skin Care*

There are several structural di fferences between the skin of newborns and that of adults. Because newborn skin has a poorly functional skin barrier, and because newborns have fragile skin that can be easily damaged, proper and adequate steps must be taken to provide protection. S. Dhar [68] suggested that newborn bathing should not last longer than 5 min, or it could increase the hydration of the skin and decrease the friction threshold. Moreover, soaps and cleansers should be minimally used in the first few weeks of life for newborns, because any attempt intended to raise the skin pH would promote the number of bacteria and increase the TEWL [69]. There is not enough evidence that soaps have long-term impact on infants, but in the short term, it could disturb their acid mantles [31,33,34]. Synthetic detergents such as cocoyl isethionate, and sodium lauryl sulphate are soap substitutes that have pH values similar to skin and are more moderate than soaps. They do not alter skin pH and microflora, but they disintegrate rapidly and can cause skin dryness [70].

The spread of lesions in infantile seborrheic dermatitis can be limited by mineral oil or vegetable oil and minimizing the use of shampoos for cleaning the hair. Sarkar et al. [71] recommended the use of coconut oil as an emollient for application to neonatal skin due to its easy availability and economy. Skin irritation can also be avoided by using fragrance-free baby products.

For adult skin care, Y.C. Jung and coworkers [72] suggested that low skin pH could be maintained by increasing hydration, the presence of low skin pH induced higher sebum excretion rate, and the combined e ffects could suppress skin aging by reducing wrinkle length and depth. In work by S. H. Youn et al. [73], they found it helpful to control acne in the T-zone by increasing skin pH to 5.5–6 for female acne patients, and by decreasing skin pH to approximately 5.5 for male patients. Saba et al. [74] recommended that the ideal pH for body wash, soap, or cleanser would be in the range of 4.5–6.5, which is similar to that of the skin's acid mantle. Moreover, syndets, synthetic detergents, are less irritating and preferred. Nix and coworkers [75] suggested that the selection of skin cleaning products should take multiple factors into consideration, namely formulation, ingredients, skin compatibility, pH, and related infection control issues. Skin cleaning products with a pH value higher than 7 can disrupt skin barrier function. It is particularly important for elderly patients to select products with a pH value of 4–7 because the skin of the elderly is dryer, more prone to cracking, and recovers more slowly from damage caused by alkalinity.
