Restoration of the skin barrier as the essence of management.
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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
[102][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
[102][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
[102][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
[103][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
[104][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
[102][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
[102][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
[105][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
[106][29]. These weakly defined “states” constitute a continuum of bound states and provide a perspective on the mobility of water molecules in the SC
[107][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
[107][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
[107][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
[108][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
[109][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
[110][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
[111][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
[111][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
[112][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
[112][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
[113][36]. Patients are also encouraged, during their spa course, to drink thermal spring water as part of the program
[95][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.