Atopic dermatitis revisited
Authors: S. Weidinger, N. Novak
Journal: Allergy (2014)

At the beginning of this new year, we would like to wrap up current knowledge on atopic dermatitis (AD) and highlight key advances of the past few years. Therefore, both front-line researchers and clinicians have provided original research and review articles on this important disease for the current issue of Allergy. Together, these articles allow state-of-the art insights into the field. Beyond that, they impressively demonstrate how heterogeneous and complex the disease is in terms of clinical picture, course, pathophysiological mechanisms and therapy. Although it is quite obvious from epidemiological studies that the global prevalence of AD has considerably increased over the past decades and constitutes a major public health problem 1, accurate estimates and cross-data source comparisons of prevalence are challenging because of different designs, assessment instruments and outcome definitions. Flohr and Mann 2 provide a comprehensive review on the epidemiology of childhood AD, showing that over 20% of children in most developed countries are affected by AD, that AD continues to increase in prevalence in particular in low-income countries, and that epidemiology has identified a number of well-established risk factors as well as protective factors. Based on the frequent co-occurrence of atopic diseases and the well-known association of early AD with later asthma and/or rhinitis 3, 4, the concept of the ‘atopic march’ has been developed, which, however, is a highly and controversially debated theory. In this issue, Dharmage and colleagues 5 present a critical reflection of the available data in favour of and against the atopic march hypothesis and the possible explanations thereof. Deckert et al. 6 shed some light on comorbidities of AD apart from asthma and rhinitis. Their overview of systematic reviews on this topic indicates that AD might affect the risk of different types of cancer, auto-inflammatory conditions and psychiatric diseases, and demonstrates the need for further studies on AD comorbidities. Recently published results from a US population-based study of almost 100 000 children in addition indicate an increased susceptibility for epilepsy 7. AD is among the complex diseases with the highest heritability estimates, and the discovery of filaggrin (FLG) null mutations as major risk factors constituted a major breakthrough in allergy genetics. Findings from molecular genetics support the notion that a primary skin barrier deficiency is central for the initiation and progress of AD at least in subgroups of patients. The renewed interest in the epidermal barrier has stimulated fresh approaches of prevention, which so far have been mostly focused on allergen avoidance, dietary measures and immunoregulation 8-10. However, the results have not produced consistently effective interventions, as reviewed by Flohr and Mann 11. The accumulating knowledge on the genetic architecture of AD is also increasingly being translated into clinical questions, e.g. AD subclassification and stratified therapy 12-14. However, it is unlikely that single factors and markers will be sufficient to achieve this, since multiple genetic and environmental factors are involved in the complex AD pathogenesis. These factors affect both the epidermal 15, 16 and immunological phenotype 17, 18, to which also Th17 cells contribute, as shown by Simon et al. 19. Of note, epidermal and immunological mechanisms are closely entangled, as e.g. demonstrated by in vitro studies showing the impact of immune cell mediators such as histamine on keratinocyte differentiation 20. It is thus conceivable that the individual predisposition and environmental exposures in combination affect multiple different pathophysiological pathways with varying degrees of skin barrier failure and immune dysregulation 21, opening out in rather uniform, yet distinguishable clinical presentations if closely looked at as shown by Garmhausen and colleagues for AD 22, and Amelink and colleagues for asthma 23. It is likely that the results of molecular studies will be of great nosological significance, enabling a classification of AD based on the underlying mechanisms rather than on hypothetical concepts and clinical symptoms as is the case today. They will also help to identify biomarkers from different molecular levels and sources for different purposes, e.g. gene variants like FLG mutations 24 and STAT6 polymorphisms 25, vitamin D pathway genes 26, protein profiles in vernix 27 or vitamin levels in serum 28, 29 for risk prediction, and to allocate available approved and off-label therapies in a more targeted fashion 14, 30, 31. All of these recent advances in biomedical research have contributed to an altered view of how AD is initiated, triggered and maintained. A major challenge of the next years, including this year, will be to translate more of this knowledge into the clinic and to achieve improved diagnosis, preventive measures and therapeutic approaches. None.