Atopic Dermatitis and Water

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1		Emilia Vassilopoulou	--	2504	2023-02-06 12:51:55	\|
2	format correct	Catherine Yang	Meta information modification	2504	2023-02-08 03:40:30	\|

This entry is adapted from the peer-reviewed paper 10.3390/children10020273

Water is a vital nutrient with innumerable functions for every living cell. The functions of human skin include protection against dehydration of the body. Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that presents with dry skin, erythematous and eczematous lesions, and lichenification.

atopic dermatitis atopic skin oral hydration water

1. Water for Life: Biological Functions of Water

Thales of Miletus, one of the seven Sages of Greece, referred to water as a fundamental element from which everything originated, and with which everything could be resolved ^[1] In the human body, water is an abundant component; in newborns, it constitutes approximately 75% of their body mass ^[2] During the first year of life, this proportion rapidly decreases to 60%, and remains relatively stable throughout childhood until adolescence ^[3]. Thereafter, hormonal changes dictate changes in the body’s composition, including a relative decrease in water content, especially in young women ^[4], to the range of 50–60%.

From a physiological aspect, water is a vital nutrient for every living cell, with innumerable functions. Firstly, it acts as a building material, as it constitutes approximately 76% of muscle mass ^[5]. It protects the maintenance of the shape and structure of human cells by creating pressure inside the cells and thus enabling them to oppose external forces. It contributes to the structure of the cell membrane by interacting with only the polar heads of phospholipids. Water adequacy ensures the structural stability of the cell membrane and ensures that the necessary molecules remain inside and the harmful molecules outside the cell. In addition, water is fundamental to the correct folding of the amino acids of proteins that function as structural elements, or as enzymes or catalysts of chemical reactions in the human body. In a similar way, water surrounds the DNA in an ordered fashion to support its characteristic double-helix configuration. In the event that this double-helix shape is lost, the DNA is unable to encode the appropriate functionality of the cells and, thus, growth, reproduction, and survival are abnormal, disrupted, or discontinued.

Water molecules interact with each other due to their polarity, forming strong bonds known as cohesion, important in the regulation of the body’s temperature. The polarity of water leads to its interaction with other biological molecules presenting electrical asymmetry; water surrounds both their positive and negative regions, penetrates them, and dissolves them. Because of this function, water is considered to be a universal solvent and is of vital importance for the transportation of oxygen and nutrients, the optimum functioning of drugs, and for the elimination of waste products.

2. Healthy Skin Hydration and Dietary Water Intake

Human skin, among other functions, protects the body against dehydration, with the outermost layer of the epidermis, unique to the skin, the stratum corneum (SC), providing a strong barrier against external, changeable, or dry environments, and controlling trans-epidermal water loss [TEWL] ^[6]. The SC is composed of flattened, non-nucleated keratinocytes (KCs), called corneocytes, surrounded by a complex lipid-enriched extracellular matrix ^[6]. Under normal skin conditions, the SC must only be impermeable enough to allow a small amount of water loss, in order to (a) hydrate the outer layers of the SC to maintain its flexibility and (b) provide water to enable the enzyme reactions that facilitate SC maturation activities. The SC uses three main mechanisms to retain water: (a) intercellular lamellar lipids, the physical conformation of which provides a tight and semi-permeable barrier to the passage of water through the tissue, (b) fully mature corneodesmosome-bound and ceramide hydrophobed corneocytes, which influence the tortuosity of the SC, and thereby the diffusion-path length of the water, and (c) intracellular and extracellular hydroscopic substances called natural moisturizing factors (NMFs) ^[7].

The regenerative capacity of skin, and maintenance of its protection against water loss among other functions, are determined by its components, the functions of which are interdependent. The water in the SC enables enzymatic activities for lipid processing, corneodesmolysis and desquamation, and the production of natural moisturizing factors (NMFs). In turn, corneodesmolysis drives the shedding of the outer layers, and the maintenance of an optimal hydration level is provided by the NMFs and permeability barrier constituted by intercellular lamellar lipids ^[8]. The skin’s surface contains approximately 30% of water in the SC, which increases to about 65% in the deeper layer of the epidermis, the stratum granulosum (SG) ^[9]. This proportion of water significantly decreases in dry skin ^[10], probably related to TEWL ^[11]. Significant for the degree of dryness is the change in the gradient of water content from the uppermost SC layer to the deeper SG ^[12]^[13]. Additionally, the sebum secreted acts together with the epidermal lipids, providing a lipid layer that enhances the maintenance of the hydration of the skin ^[14]. Skin barrier functionality, however, is influenced by several endogenous and environmental factors, including ethnicity, atmospheric humidity and temperature, and exposure to ultraviolet (UV) rays, chemicals, and mechanical damage ^[15].

In children, the skin is a dynamic tissue in a continuous process of maturation up to the fourth year of life, and even longer for some of its elements. This can be viewed as a period of optimization, leading to adult-like characteristics and functions ^[16]. The inherent physical characteristics vital for barrier function determine the length of this period and the optimum levels for everyone. This might explain, in part, why children’s skin is more vulnerable. Skin structure in children comprises smaller corneocytes, smaller keratinocytes that are more densely packed, a denser microrelief network, and more homogeneous dermal papillae, all of these constituting an epidermis that is 20% and an SC 30% thinner in relation to adult skin. Children’s skin is characterized by its lower water content, a lower concentration of NMF and surface lipids, and by higher cell proliferation and turnover; it has a low water-holding capacity, with higher absorption and desorption rates, and low TEWL. All the above mentioned factors lead to a weaker skin barrier function more prone to dryness, which under genetic and environmental influences are predisposed to diaper rash and atopic dermatitis ^[8].

Treatment of dry skin requires topical leave-on products’ application as the first-line action to improve the skin’s hydration and barrier function ^[17]^[18]. The effectiveness of adequate water intake as a measure to treat dry skin is still under debate ^[19]. In a systematic review of adult population studies conducted to explore the effect of healthy skin hydration in relation to fluid intake, despite the paucity of high-quality studies, the authors concluded that an additional intake of water may increase SC hydration, especially in individuals with lower prior water consumption ^[20]. Increasing the fluid intake increases the water content in the dermis, as the dermal layer can store water ^[21]. An effect on water content in the epidermis is also speculated, although the water content of the SC is largely determined by natural moisturizing factors, the structure of the corneocytes, and SC intercellular lipids ^[22].

Even less data are available on the differences in effectiveness between tap, mineral, and thermal spring water. Mac-Mary and colleagues reported that the long-term intake of mineral water improved the clinical signs of dryness and roughness in healthy subjects ^[23], in contrast to Williams and colleagues, who observed no significant differences in the skin’s surface morphology between the long-term drinking of mineral or tap water ^[24]. However, increasing one’s water intake might increase the skin’s hydration and the biomechanics by means of extensibility and the ability of the skin to return to its original state ^[24].

Considering children, to the best of our knowledge, no data have been published on the exploration of the effect of fluid intake on healthy skin’s SC hydration, at any age.

3. Treatment of Atopic Dermatitis

The management of AD focuses on three main targets:

(a): Avoidance of aggravating factors;
(b): Treatment of the underlying inflammation;
(c): Restoration of the skin barrier as the essence of management.

The avoidance of aggravating factors should improve the patient’s quality of life. This requires a detailed diary of everyday activities and environments to reveal the factors that can be avoided or managed to significantly improve the patient’s life with the disease ^[25].

The treatment of underlying inflammation, both topically and systemically, is entering a new era of targeted and stratified medicine, with new and advanced therapeutic choices for all ages. The successful control of the inflammation will provide definitive control of AD and of a major part of skin barrier impairment ^[25].

However, the restoration of the skin’s barrier, focused on the restoration of the SC, will continue to be the essence of management of AD, because (a) most cases are of mild-to-moderate severity, and will require reactive, intermittent, anti-inflammatory treatment; (b) most of the cases of AD occur in infants and toddlers with mild-to-moderate disease, and there are certain restrictions to the use of anti-inflammatory treatment; and, mainly, (c) the initiating step of the disease is the genetically determined SC defect that will necessitate its own individual treatment ^[25].

It is known that the prolonged application of a water-holding substance on healthy skin increases the water content throughout the SC. This water is then gradually released from the upper SC after the discontinuation of the hydration procedure. This indicates an important role of applicable water-holding substances, such as certain moisturizers, in the regulation of SC water content, but also the restricted time of their action ^[26]. Additionally, in blinded, randomized trials on healthy skin, it can be observed that certain emollients could improve water gradients and SC hydration. Those emollients include ingredients that can substitute or increase epidermal lipogenesis and SC barrier function ^[27]. Various emollients, with different hydration capacities, are used for the treatment of AD, each with a different, but restricted, duration of action, after which reapplication is needed. Based on such data, the guidelines recommend that the hydration of the skin is usually maintained by the application, at least twice daily, of emollients with a hydrophilic base, such as glycerol or urea ^[25].

Consequently, basic, topical emollient therapy constitutes the essence of every treatment regimen of AD. Emollients should, and usually do, contain (a) an occludent (to reduce evaporation), such as lipids, which, ideally, will replace in part defective skin lipid function, and (b) a humectant or moisturizer to promote the hydration of the SC, such as glycerol or urea. This, ideally, will replace in part the defective NMF’s function, restore the water-holding capacity, and reduce skin dryness ^[25]. A Cochrane review comparing emollients containing moisturizers with those containing no moisturizers determined that the former was better at reducing investigator-reported severity and was associated with fewer flares and less topical corticosteroid use ^[28]. These results highlight the importance of preserving hydration in the SC in the management of AD. How does the water in the SC plays a critical role in skin homeostasis? Depending on their mobility that is determined by their hydrogen bonds and space limitations, SC water molecules “move” into three levels: (a) “bound” (least mobile) molecules that are directly bonded with SC molecules, (b) intermediately mobile molecules that form hydrogen bonds with “bound” water molecules, forming a “loose cloud” around the binding site, and (c) the most mobile molecules that can diffuse freely, constantly forming and breaking bonds with surrounding water molecules ^[29]. These weakly defined “states” constitute a continuum of bound states and provide a perspective on the mobility of water molecules in the SC ^[30]. The bound and most mobile water molecules decrease toward the skin’s surface, while the intermediate group increases. These changes are subtle but statistically significant, and are constant at different adult ages and body sites, implying a controlled mechanism to define them ^[30]. They appear to be in accordance with: (a) a gradual increase in NMF concentrations toward the SC surface, indicative of proteolytic processes along the SC exposing pockets of bound water molecules, increasing their mobility, and (b) a decrease in lipids toward the outer SC, indicative of diminished processes along the lipid headgroups bound in water, increasing their mobility. These observations provide important information for the dynamic equilibrium of water molecules in the SC of healthy skin and their contribution to skin hydration. More importantly, they present the question of how these patterns differ in children and in deficit disorders of barrier elements (i.e., NMFs and lipids), such as AD ^[30]. Is there an increase in most mobile water molecules in the SC in AD, instead of the intermediate group, due to deficits in lipids and NMFs, and consequently increased water loss and skin dryness? Additionally, if so, would an increase in water intake result in an increase in “bound” and intermediate water molecules that would counterbalance, in part, the loss of mobile water molecules, and thus improve the skin’s dryness?

4. Dietary Water Intake and Atopic Dermatitis

The data on the overall water intake, quality of water, and hydration status in patients with AD are limited. Three studies analyzed the relationship between water hardness and chlorine levels, and the prevalence of AD. First McNally and colleagues showed a correlation between water hardness and chlorine levels, and an increased prevalence of AD in primary-school children ^[31]. These results were later confirmed by Miyake and colleagues in a cohort study involving children aged 6–7 years, and they speculated that water rich in calcium and magnesium might be involved in the pathophysiological mechanisms of AD ^[32]. These results were replicated in a Spanish cohort of 6–7- and 13–14-year-old children by Arnedo-Pena and colleagues; however, a significant relationship was observed only in the younger age group ^[33]. None of these studies investigated the effect of consuming this type of water on AD incidence or exacerbation.

Kimata and colleagues reported that patients with AD presented an improvement in skin symptoms, with the control of the production of inflammatory/atopy cytokines when they drank mineral deep-sea water rich in calcium and other minerals, while distilled water failed to provide any benefits ^[34]; moreover, a 100 mL increase in overall fluid intake was associated with a slight decrease in the sebum content, but had no effect on hydration ^[34]. Hataguchi and colleagues conducted an intervention program on a group of 33 adult patients with AD. The patients drank 500 mL of deep-sea water with a high-magnesium and low-sodium chloride (NaCl) content for 6 months, and an evaluation of the clinical symptoms was performed using different scoring systems for inflammation, lichenification, and cracking, at different body sites. Additionally, the researchers measured the levels of various essential and toxic minerals ^[35]. They reported an improvement in skin symptoms in 27/33 patients with AD, and concluded that the deep-sea water, which facilitated the elimination of toxic metals, specifically mercury and lead, and increased the levels of the antioxidant selenium, may play a role in the treatment of AD ^[35].

Considering thermal spring water, it is known that there are certain differences in the mineral compositions in different springs, which is considered important for the treatment of normal skin and certain dermatoses ^[36]. Patients are also encouraged, during their spa course, to drink thermal spring water as part of the program ^[37]. However, in contrast to the documentation of the curative effects of certain thermal spring waters on the skin’s structure and function after bathing, there are no data on any possible benefits, qualitative or quantitative, to the skin after drinking the same thermal spring waters.

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