Atopic eczema treatment now and in the future:Targeting the skin barrier and key immune mechanisms in human skin

The skin facilitates a number of key roles but its functioning can be impaired by disease. Atopic eczema is a chronic inflammatory disease where the skin barrier has become leaky, and inflammation occurs. It affects up to 20% of children and 3% of adults worldwide, manifesting as red itchy patches of skin with varying severity. This review aims to investigate the leaky skin barrier and immune mechanisms from the perspective of potential novel treatments. The complexity of atopic eczema as a disease is what makes it difficult to treat. Genome-wide association studies have highlighted possible genetic variations associated with atopic eczema, however in some cases, individuals develop the disease without these genetic risk factors. Loss of function mutations in the filaggrin gene are one of these associations and this is plausible due to its key role in barrier function. The Th2 immune response is the link with regards to the immune mechanisms as atopic inflammation often occurs through increased levels of interleukin(IL)-4 and IL-13. Eczematous inflammation also creates susceptibility to colonisation and damage by bacteria such as Staphylococcus aureus. Potential novel treatments are becoming ever more specific, offering the hope of fewer side effects and better disease control. The best new treatments highlighted in this review target the immune response with human beta defensin 2, phosphodiesterase-4 inhibitors and monoclonal antibodies all showing promise.

From the outside-in: Epidermal targeting as a paradigm for atopic disease therapy

Atopic dermatitis(AD) is a chronic inflammatory skin disorder which can precede asthma and allergic rhinitis in a disease trajectory known as the atopic march. The pathophysiology of AD includes cutaneous inflammation, disrupted epidermal barrier function, xerosis and propensity to secondary infections. AD had previously been thought to arise from the systemic atopic immune response and therapies are therefore directed towards ameliorating Th2-mediated inflammation. However in recent years the focus has shifted towards primary defects in the skin barrier as an initiating event in AD. Links between loss-of-function variants in the gene encoding filaggrin and disrupted activity of epidermal serine proteases and AD have been reported. Based on these observations, a mechanism has been described by which epidermal barrier dysfunction may lead to inflammation and allergic sensitization. Exogenous and endogenous stressors can further exacerbate inherited barrier abnormalities to promote disease activity. Pathways underlying progression of the atopic march remain unclear, but recent findings implicate thymic stromal lymphopoietin as a factor linking AD to subsequent airway inflammation in asthma. This new appreciation of the epidermis in the development of AD should lead to deployment of more specific strategies to restore barrier function in atopic patients and potentially halt the atopic march.