Cellular and molecular immunologic mechanisms in patients with atopic dermatitis

Atopic dermatitis is one of the most common chronic skin diseases among both adults and children.  Although it is often thought of as a skin disease, it also affects many organ systems. There remain a lot of gaps in our knowledge of atopic dermatitis, but researchers are developing a greater appreciation for its complexity of atopic dermatitis and introducing new treatments for this frustrating disease.

From an immunologic point of view, atopic dermatitis appears to be a collection of many different variants.  These endotypes are just recently beginning to be described, but involve the various arms of the immune system.  Defects in the innate immune system skew the skin towards inflammation; polarization of T-cells (Th2, Th17, and Th22) lead to further inflammation.  Other cell types, like dendritic cells, eosinophils, and mast cells, play important roles in the development of atopic dermatitis.  The interplay between immune cells and skin barrier proteins, like filaggrin, is also being explored.  Filaggrin influences cell differentiation, prevents water loss, and maintains the integrity of the skin barrier.  With defects in filaggrin, allergens penetrate deeper into the skin and bacteria like staphylococcus aureus are more likely to colonize the skin.

To make things even more complicated, as time progresses, so too does the disease, and patients can have an “atopic march” towards asthma, allergic rhinitis, and other allergic diseases.  Additionally, patients with atopic dermatitis have changes in the bacteria that colonize their skin and gut.  They have less microbial diversity, particularly when there is greater inflammation.  The role of these bacteria are being increasingly fleshed out with basic science and clinical research.

These insights are helping to guide new therapies.  In particular, dupilumab, an antagonist of the IL-4 receptor alpha chain, is showing promise in the treatment of atopic dermatitis.  And in those that don’t respond to dupilumab, there’s interest in other therapies like the IL-6 receptor antagonist tocilizumab.  As Werfel and colleagues note, it is difficult to find the best treatment for atopic dermatitis without knowing the pathophysiology behind the disease and its various endotypes (J Allergy Clin Immunol 2016; 138(2): 336-349).  In the future, with better knowledge, it may be possible to personalize appropriate treatment by identifying the correct endotype for each patient.