Author(s): Claire Felmingham, Resident Medical Officer, NT, Australia. Rosemary Nixon, Associate Professor, Occupational Dermatology Research and Education Centre, Skin and Cancer Foundation Inc., Carlton, Victoria, Australia. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. October 2018.
Atopic dermatitis, or eczema, is a chronic, itchy skin condition that is associated with dry skin. It typically begins in infancy or childhood, and is often associated with other atopic conditions, such as asthma and allergic rhinoconjunctivitis (hayfever) .
Atopic dermatitis affects up to 20–30% of children and 2–10% of adults. People with a personal or family history of atopy (the tendency to develop allergic conditions) are more likely to get atopic dermatitis .
The cause of AD is incompletely understood. The underlying cause of atopic dermatitis is thought to be a result of a weakened skin barrier and a predisposition towards allergic inflammation . Environmental triggers provoke an allergic reaction, which exacerbates the symptoms of atopic dermatitis.
The immunological disturbance arises from T lymphocytes, specifically Type 2 helper cells (Th2) in the acute phase, and Type 1 helper cells (Th1), T helper 17 cells (Th17) and Th22 in chronic lesions. Th2 produces IL4 and IL13, which upregulates the production of IgE .
One theory of the pathogenesis of atopic dermatitis is the “Inside-Outside Theory”, where the primary issue is thought to be with the immune system, and the skin barrier becomes dysfunctional secondary to the IgE sensitization .
Another theory is the “Outside-Inside Theory”, where the original defect is thought to be in the skin barrier, leading to increased allergen exposure and subsequent IgE sensitization .
The skin barrier provides protection from external threats such as pathogens, chemicals, irritants, and allergens, which might cause an immune response if permitted to pass to deeper epidermal or dermal layers.
The skin barrier also protects the body from epidermal water loss, and skin barrier function can be measured by the rate of trans-epidermal water loss (TEWL). Increased TEWL corresponds with increased skin permeability. Skin barrier function can sometimes also be measured by surface pH, permeability of tracer compounds, and stratum corneum cohesion and hydration .
The stratum corneum is the uppermost layer of the epidermis. The stratum corneum is comprised of a highly organised intercellular lipid matrix, and corneocytes, which are flattened cells that have no nucleus and are filled with keratin filaments. This is often referred to as the ‘brick and mortar’ of the skin, with corneocytes representing ‘bricks’ and the lipids representing ‘mortar’ .
There is altered stratum corneum homeostasis in both the lesional and non-lesional skin of patients with atopic dermatitis. This leads to increased water loss and increased penetration of allergens .
In atopic dermatitis, the structure and composition of both the corneocytes and the intercellular lipid matrix of the stratum corneum can be affected in the following ways:
Filaggrin protein (FLG) is important for the structural integrity of the stratum corneum. FLG aggregates keratin filaments inside corneocytes, and then helps to form a cornified cell envelope surrounding the corneocytes. The degradation products of FLG further contribute to the water-holding capacity and acidic pH of the stratum corneum. Maintaining the acidic pH is important to regulate the enzyme activity that leads to desquamation, lipid synthesis, and inflammation [2,5].
A loss-of-function mutation in FLG is the strongest genetic risk factor for atopic dermatitis. FLG mutations are associated with an earlier onset of atopic dermatitis, greater disease severity, and persistence of disease. Approximately 50% of moderate to severe AD cases can be attributed to FLG mutations .
The activity of the serine proteases, such as kallikrein 5 and 7 (KLK5/7), is regulated by the pH of the stratum corneum. KLK5/7 cleaves the extracellular corneodesmosomal proteins that link the corneocytes together. Their increased activity leads to increased corneocyte dysadhesion and desquamation .
Normal skin pH is acidic and restricts the activity of these proteases, which are more active in alkaline environments. In atopic dermatitis, the pH of the skin is elevated, and subsequently so is the serine protease activity .
The stratum corneum lipid matrix is composed of three lipids — cholesterol, free fatty acids, and ceramides. They form a highly ordered structure of densely packed lipid layers. This intercellular lipid matrix is the main pathway for substances travelling across the skin barrier .
In atopic dermatitis, there is a reduction in the amount of total lipids, significant deficits of certain types of lipids, and changes in lipid composition. In combination, this leads to impaired skin barrier function and increased permeability of the stratum corneum .
A defect in the skin barrier can facilitate transport of allergens or haptens into the skin, inducing the release of proinflammatory cytokines causing inflammation of the skin .
At the same time, the Th2 cytokines IL4 and IL13, and the Th2 cytokine IL22 downregulate the expression of FLG, causing further damage to the skin barrier [2,8].
The cutaneous microbiome is the pathogenic and commensal bacteria, fungi and viruses that are resident on our skin and help maintain epidermal homeostasis .
More than 90% of patients with atopic dermatitis have skin colonized with Staphylococcus aureus .
When the stratum corneum is structurally competent, with an acidic pH, and a well-organised lipid matrix, it prevents colonization of pathogens such as S. aureus, a bacteria that can detrimentally affect the barrier function. S. aureus surface proteins reduce free fatty acid production in the epidermis, leading to increased skin permeability. In patients with atopic dermatitis, S. aureus exotoxins with super-antigenic properties stimulate production of IgE and pruritus. Subsequent excoriations create further defects in the skin barrier .
The understanding that skin barrier dysfunction drives disease activity in atopic dermatitis has resulted in an increased interest and emphasis on treatments that improve barrier function.
Moisturisers are the main treatment for atopic dermatitis. Moisturisers which improve barrier function have been shown to reduce relapse rates in atopic dermatitis with regular use .
Restoring skin barrier function may proactively prevent atopic dermatitis from developing or progressing, as has been shown in randomized control trials of neonates at risk of atopic dermatitis treated with daily moisturiser [9,10].
Moisturiser ingredients that are helpful in atopic dermatitis include [2,12]:
Bathing with water can remove irritants, allergens and squama (scales) in atopic dermatitis, allowing for repair of the skin barrier. Application of moisturiser soon after bathing is recommended. Non-soap cleansers, which are low in pH and hypoallergenic, are recommended as soap substitutes, causing less disruption to the stratum corneum structure and acid mantle . The “soak and smear” technique increases effectiveness of topical medicines. Application of topical corticosteroids to wet skin immediately after bathing traps water in the stratum corneum and increases the amount of medication delivered by 10–100 times .
Bleach baths have proven helpful in decreasing clinical severity of atopic dermatitis, as a result of their antibacterial and antifungal properties . While sodium hypochlorite (bleach) is typically alkaline (pH 11–13), it produces hypochlorous acid (pH 2–7.5) when dissolved in water . It is possible that this acidity helps maintain normal skin barrier function, in addition to acting as an antiseptic.
Other treatments sometimes required in atopic dermatitis include other topical anti-inflammatories such as:
In cases of severe atopic dermatitis, recommended treatments include:
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