A heterogenous, chronic and relapsing skin disease, fluid in expression and capricious in its course, atopic dermatitis underlying mechansisms are not fully understood and recent studies cast more doubt on established treatment protocols which long reined medical literature. Nevertheless, unrelenting efforts have continued to reveal certain aspects of the disease, still not incorporated in the current treatment guidelines, and accounted genetics, inflammation, dysbiosis in skin’s microbiota and change in skin barrier function in its pathogenesis.
Atopic dermatitis is heterogenous for its broad presentation which varies by age, ethnicity and severity of the disease. Most common manifesatations include erythema, oedema, xerosis, scaling, exudation, lichenifications, excoriations and pruritus, most pervasive symptom of the disease.
Loss of function mutation in the gene filaggrin accounts for the genetic factors contribution to the disease, seen in about one fourth of the patients. A cardinal structural protein, filaggrin reconciles and aggregates keratin bundles in stratum corneum, providing cutaneous strength and enhances moisture retaining capacity of the epidermal barrier.
In association with staphylococcus aureus colonization, there exists a less diversity of skin’s natural microbiome, a phenomenon which warrants attention in treatment of atopic dermatitis. The two concurrent sequence of atopic dermatitis predisopose the skin to more bacterial (staph aureus superinfections), fungal (tinea or yeast colonization) and viral infections (higher risk of eczema herpeticum).
Synthesized by keratinocytes within the skin, antimicrobial peptides, AMPs, cathelicidins (LL37) and beta-defensins, with a cardinal purpose in host defense, are reduced in expression as Th2 cytokines upregulated in atopic dermatitis. With AMPs decline, staphylococcus aureus colonization can occurs and withal dwindling of inflammatory response of monocytes, neutrophils and lymphocytes as AMPs function as chemoattractants for them.
Malfunction of immune system and inflammatory response is a principal aspect of the disease, with IL-4 and IL-13 most notable to incur skin barrier dysfunction, inhibition of anti-microbial peptides and chemokine and allergic incitement. In addition, IL-17 appears to reduce expression of filaggrin and involucrin, two major epidermal structrual proteins. Transition from Th2 response to Th1 has also been observed in transformation of the disease from acute to a chronic state.
Downregulation of epidermal barrier proteins, fillagrin, loricrin, keratin, involucrin and cell adhesion molecules is a culprit in atopic dermatitis as a result of activity of inflammatory cytokines, IL-4 and IL-14. Less expression of genes encoding filagrrin appears to be another aspect of the disease and withal increases permeability of skin barrier allowing more intrusion of allergens and foreign insults which further instigates immune system response.
These barrier proteins are competent in effective control of transepidermal water loss, sustain epidermal barrier as well as maintenance of skin’s pH, amplified in skin’s eczema and should be meaningfully addressed through an atopic dermatitis treatment cream.
Tight junctions, glue adjacent cells and provide intercellular passages which allow transfer of water, ions and solutes, are also affected in atopic dermatitis. Within the epidermis, tight juctions are primarily localized to granular layer and contribute to differentiation and keratinization. Reduced expression of genes encoding claudins leads to exaggerated epidermal water loss and facilitated penetration of microbes and allergens within the skin, a trigger for inflammatory response.
Akin to psoriatic skin disease, skin’s lipid barrier dysfunction is hallmark of atopic dermatitis. During differentiation, corneocytes release their content of lamellar bodies which consists of free fatty acids, cholesterol and ceramides which sustain skin barrier function. Under further enzymatic cleavage these molecules turn into the major lipids found on the surface of the skin. Th2 cytokines deplete levels of long chain fatty acids and ceramides over the surface of the skin of patients with atopic dermatitis.
Alteration in sebaceous activity plagued with inflammation is another aspect of pathogenesis of atopic dermatitis which stokes sebum changes and further distortion in skin lipids in areas of the body where sebaceous glands reside with greater density, mainly face and trunk.
On the other hand, sebaceous glands are active immune modulators as they produce and degrade endocannabinoids, which perform in the skin as anti inflammatory and may be targeted in production of an atopic dermatitis cream. Inhibiting IL-33 in keratinocytes, propionate, a product of sebaceous glands, has been found to be reduced in this skin disease, stirring inflammation.
Furthermore, sebaceous lipids permeates into the dermis, affect the stromal cells and implicate in skin’s homeostasis by changing skin’s microbiome and perifollicular immunology. In sebum of affected patients proinflammatory lipids show an increase while squalene and propionic acid with inhibitory effect on IL-33 in kderatinocytes are depleted.
It is of note that skin surface lipids are released from two major sources, one is sebum and the other is keratinocytes lipids. It is sebaceous glands density in each area of the body which determines the composition of the actual skin lipids and in areas of high density such as forehead, skin surface lipids is almost similar to sebum. Although skin xerosis is the hallmark of the disease, similar to oily skin, change in surface skin lipids prominently related to a decline in proportion of sebaceous lipids with an increase in epidermal fraction such as cholesterol.
| Epithelial Elements | Underlying mechanisms | Outcomes | Effect of Atopic Dermatitis Cream |
|---|---|---|---|
| Cornified envelope proteins | ↓ Expression of filaggrin, keratins, loricrin, involucrin, transglutaminases | ↓ Water-retaining capacity of the skin, ↑ skin pH, ↑ infiltration of external allergens and microbes into the skin | ↑ Skin hydration, ↑ epidermal barrier strength |
| Tight junctions | ↓ Claudins | ↓ Skin hydration, ↑ TEWL | ↑ Skin hydration, ↓ TEWL |
| Antimicrobial peptides | ↓ Cathelicidins (LL-37), ↓ human β-defensins | ↑ Inflammatory response, ↑ vulnerability to skin infections | Contain inflammation, re-balances skin's microbiome |
| Sebum and skin surface lipids | ↓ Ceramides, ↓ long-chain fatty acids | ↑ TEWL, ↑ susceptibility to cutaneous infections | Prevents skin's infections, ↓ TEWL |
| Natural moisturizing factor (NMF) | Filaggrin degradation | ↓ Pyrrolidone carboxylic acid (PCA), ↓ amino acids | ↓ Moisture retention function, ↓ skin barrier function, xerosis |
Corticosteroids have been mainstay of treatment in mild to moderate disease and their pervasive use has prevailed within medical community for their brisk result, found satisfactory to patients expectations. Nevertheless, frequent adverse effects of streroid creams especially with long term use has sown concerns and the challenge to seek alternative topical creams has been lingering toward a palpable progress with findings which primarily rely on non-pharmacologicals.
Repeated use of emollients in mild disease and as a preventive method in moderate to severe disease has been found effective and incorporated in guidelines of treatment. It appears that best atopic dermatitis cream should address the basic mechanisms involved in pathogenesis of the disease stated above. An atopic dermatitis cream which can help to maintain skin barrier function and provide the skin with essential sebaceous lipids depleted under inflammatory and allergic command presents a judicial approach.
Use of atopic dermatitis skin care in mild to moderate disease is grounded in restoring skin barrier function to dwindle transepidermal water loss, TEWL, to dismantle cutaneous bacteria dysbiosis and to regulate cytokine incites. Atopic dermatitis skin care is warranted in severe disease between the relapses to prevent recurrences by sustaining epidermal barrier competence and in exacerbations of the disease as an adjunctive treatment.
Inflammatory response, known in several dermatological diseases such as acne vulgaris, is another aspect of the disease which should be attended to in an atopic dermatitis cream. While multitude of anti inflammatory agents in botanical extracts have been examined and researched over the past two decades, none proved promising results. Two recent studies report artocalpus altilis extract and shotokuseki extract which help restore epidermal barrier function yet further reassuring research is called to get the results established.
While inflammation is the culprit of the disease and is ensued following epidermal impairment, prolonged cytokine activity as in oxidation can by itself escalate failure of cutaneous adequacy and in one additional axis impart to development of atopic dermatitis. This gives us sufficient rational to utilize skin care agents which challenge oxidative processes the skin sustains while exposed to environmental rigors.
Centerpiece to our research is to explore most efficient routes to deliver provisions to the skin affected by atopic dermatitis. Although, serums are more concentrated vehicles and in certain dermatological diseases and skin conditions confer a more versatile instrument and provably more accomplished apparatus to dispense ingredients within the cutaneous layers, more conventional means such as cream preparations may offer alternatives found more functional and effective in other skin conditions.
Atopy is the hallmark of the disease in atpoic dermatitis and a major fraction of the patients report history of allergy such as asthamtic disease and allergic rhinitis. In atopic dermatitis the skin is very susceptible to allergens and the competence of the epithelial barrier is compromised. Once allergens are introduced to the cutaneous layers, Th1, in chronic disease, and Th2, in acute phase, cells infiltration incite cytokine activity and promote sebum changes. Skin care for sensitive skin aims to restore sebaceous components alterations and reconstitute stratum corneum barrier effect.
While atopic dermatitis is a dermatological disorder, sensitive skin, characterized by thinning of epidermal layer and impaired barrier function, is a subjective syndrome and majority of those who have perception of having sensitive skin are not clinically diagnosed with sensitive skin. Most common symptoms are skin’s redness and tautness, dry skin and lichenification. Atopy is not a common finding with sensitive skin diagnosis. Atopic dermatitis cream is exclusively development for management of this skin condition of any severity regardless of skin type.
Whether individuals with either sensitive skin or very dry skin type are more prone to development of atopic dermatitis is subject of investigation and clinical trials. Nevertheless, coexistence of thinner stratum corneum and some breadth of impaired epidermal barrier present in these skin types provide a rationale for a predilection for progression toward atopic dermatitis.
