Symptoms and exacerbating factors

It is now thought that high serum IgE levels and Th2 cells are the primary causal factors in many patients suffering from atopic dermatitis. Because of the high co-occurrence of asthma, the prevailing view is that atopic dermatitis is entirely triggered by Th2 immunopathy. However, about 20% of patients have normal IgE levels, and the skin conditions associated with atopic dermatitis are the same Th1-caused inflammatory reactions seen in contact dermatitis.

The so-called "hygiene hypothesis" has also been put forth to explain the outbreak of atopic dermatitis before age 30 or so ¹¹. The hypothesis is based on epidemiological studies that correlate the outbreak of atopic dermatitis with lower levels of pathogen exposure during childhood. Later reports showed epidemiological data indicating that infections and unsanitary conditions during infancy correlated with a lower incidence of allergies ¹². Research reports backing this hypothesis have suggested that higher concentrations of allergens stimulate the body’s protective mechanisms and activate immunosuppressive regulatory T cells (T-regs) ¹³. At the present moment, however, there is still no consensus on the role that T-regs play in the development of atopic dermatitis.

Furthermore, Palmer et al. recently discovered changes in the genetic structure of filaggrin, one of the key proteins that make up keratinocytes, in patients with atopic dermatitis (2006) ¹⁴. Their findings strongly support the idea that a breakdown in the skin’s barrier function is heavily involved in the development of the disease. However, although variants in filaggrin genes nearly triple a person’s risk of developing atopic dermatitis, many patients with the disease show no such genetic mutations, suggesting the possibility that epigenetic factors may translate to variations in the quality and/or quantity of filaggrin proteins. Variants in other proteins that are involved in the stratum corneum barrier function besides filaggrin, such as loricrin, involucrin, and the S100 proteins, have also been confirmed in patients with atopic dermatitis ¹⁵. There are two major hypotheses regarding the development of the disease, based on whether the pathogenic mechanism is exogenous or endogenous. The exogenous mechanism starts with a breakdown of the barrier function in the stratum corneum triggering an allergic reaction, while the endogenous mechanism often begins with a normal barrier function. Atopic dermatitis patients with exogenous causing factors usually has a relatively high Th2 cytokines level compared to the patients with endogenous pathomechanisms whose expression of Th1 cytokines is rather high. It has also been reported that the endogenous mechanism is triggered by metal allergies ¹⁶.

It has become clear in recent years that the penetration of transdermal allergens is a major factor in the development of atopic dermatitis. Particularly because this is related to a loss of barrier function in the stratum corneum (either genetic or acquired), we need to define it as a pathogenic or exacerbating factor. In other words, allergens are able to penetrate the skin due to a loss of barrier function, which causes a T2-type allergic reaction to predominate and triggers the production of IgE and IL-4. These in turn bring about inflammation.

Among the environmental factors known to trigger atopic dermatitis at present the most common are mites and house dust. Diet also plays a role. There are exacerbating factors like sweat, fabrics, and cosmetics, while soaps and shampoos can contribute to exfoliation of the outer skin layers.

Epidemiological studies have already concluded that even if pregnant or nursing mothers restrict their intake of food antigens like eggs and dairy, it does nothing to lower the prevalence of atopic dermatitis in the baby ¹⁷. After birth, using topical preparations to stimulate the skin’s barrier function as soon as possible not only successfully lowers the likelihood that the disease will develop, but has also been reported to reduce asthma and allergic rhinitis rates. This theory, known as the dual allergic exposure hypothesis, is rapidly gaining traction. The hypothesis states that the oral consumption of food protein allergens shortly after birth develops a tolerance to those allergens, while direct contact with the allergens via skin whose barrier function is compromised will trigger an allergic sensitivity ¹⁸.

Netherton syndrome (a form of ichthyosis) rare hereditary disease characterized by a loss of barrier function in the outer skin layers. It involves a mutation in the serine protease inhibitor Kazal-type 5 (SPINK5) gene that controls enzyme activity related to exfoliation of the stratum corneum. It therefore accelerates exfoliation of the outer skin layers, and is known to cause the symptoms of atopic dermatitis. This strongly suggests that the development of atopic dermatitis is related to a loss of barrier function in the stratum corneum ¹⁹.