T. Bieber

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Guidelines for treatment of atopic eczema (atopic dermatitis) Part I.

The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti‐inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune‐suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen‐specific immunotherapy to aeroallergens may be useful in selected cases. Stress‐induced exacerbations may make psychosomatic counselling recommendable. ‘Eczema school’ educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.

Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment

Background:  Long‐term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti‐inflammatory agents may control acute disease and prevent relapses. This 12‐month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE).

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper

 Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE‐dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co‐morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto‐immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis.

Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine.

Atopic dermatitis (AD) is a paradigmatic inflammatory chronic skin disease. As for other chronic skin diseases, (i) the spectrum of the clinical phenotype and severity as well as (ii) the genetic background and (iii) the underlying mechanisms strongly suggest a high degree of pathophysiological heterogeneity yet leading to a similar clinical pattern, that is, the eczematous skin lesion, but showing distinct progression patterns. This review suggests to exploit the recent knowledge about AD for a novel approach proposing a tentative first molecular taxonomy of this disease based on the genotype and endophenotype. The consequences in terms of personalized prevention and management are delineated.

Characterization of different courses of atopic dermatitis in adolescent and adult patients

Atopic dermatitis (AD) starts most often during the first years of life and goes into remission in a high proportion of cases during childhood. However, in severe cases, AD persists until adulthood or starts and relapses later in life. So far, studies investigating the natural course of AD during adolescence and adulthood are rare. The aim of our study was to classify different courses of AD and to correlate these with specific risk factors for severe variants of AD.

A multicentre, randomized, double‐blind, controlled study of long‐term treatment with 0·1% tacrolimus ointment in adults with moderate to severe atopic dermatitis

Background  Atopic dermatis (AD) is a chronic disease that often requires long‐term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side‐effects.

Atopic dermatitis: a candidate for disease‐modifying strategy

The concept of disease modification has been introduced to define the therapeutic strategies aimed to break, stop, or reverse the natural course of a chronic invalidating disease. This strategy is tightly related to the biomarker‐based stratification of affected patients using genetic and other biological markers. With regard to the progress in understanding the genetic background of atopic dermatitis (AD), its natural history and its pivotal role in the emergence of allergic asthma, the time is mature to foster the research field of biomarkers in AD and to consider the elaboration of disease‐modifying strategies in the management of AD with the goal to stop or even reverse the atopic march.

Proactive therapy of atopic dermatitis – an emerging concept

Atopic dermatitis (AD) is a chronic and highly pruritic skin disease with a broad spectrum of clinical manifestations. Atopic dermatitis has clearly increased by twoto threefold (prevalence of 15–30% in children and 2–10% in adults) during the past three decades in industrialized countries. As it is one of the most common of the skin diseases in developed countries, it has an increasing socioeconomical impact. The direct cost is estimated almost 1 billion dollar in the United States alone (1). Pruritus, sleep loss, dietary restrictions and psychosocial affectations significantly lower the quality of life of AD patients (2). The common long-term treatment concept for AD is based on daily application of emollients with or without antibacterial ingredients accompanied with symptomatic anti-inflammatory therapy consisting of topical glucocorticosteroids (TCS) or topical calcineurin inhibitors (TCI) on an as needed basis (3, 4). This reactive treatment approach is well established, widely accepted and the legal basis for all licensed TCS and TCI. Experienced physicians tailor this approach to every patient by choosing the optimal emollient and antiinflammatory compounds eventually combined with UV-light, antihistamines and other treatment options. Recently, an alternative treatment approach has been evaluated in clinical trials. This proactive approach starts with an intensive topical anti-inflammatory therapy until all lesions have mostly cleared, followed by longterm, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin together with daily application of emollients to unaffected areas. On the one hand, identification of the most suitable treatment approach for AD as such calls for general evidence from basic science and immunobiology. On the other hand, clinical efficacy and safety studies, quality of life assessments and pharmaco-economic data can only be produced by comparing specific, well-defined treatment strategies in clinical trials. As a long-term clinical trial comparing the proactive and reactive approach has been published in a recent issue of Allergy (5), this editorial covers general evidence from basic science and immunobiology as well as recent trial data supporting long-term proactive treatment strategies. Defects of epidermal barrier function in AD lesions are mirrored by less pronounced, but clearly detectable similar defects in nonlesional AD skin, as recently reviewed by Proksch et al. (6). This barrier dysfunction results in an increased outside-in permeability of the stratum corneum for allergens in AD skin (7), corresponding to an increased inside-out permeability that may be assessed by measuring the transepidermal water loss in both lesional and nonlesional AD skin (8). The barrier dysfunction of nonlesional skin in close proximity to AD lesions is more pronounced than in regions distant from the florid lesions (9). The increased permeability of nonlesional AD skin for large protein allergens is an important factor for the atopy patch test (10). Thus, protein allergens dissolved in petrolatum penetrate the epidermal barrier and elicit an eczematous skin reaction to the respective proteins (11). Atopic dermatitis skin has been investigated by profilometric examination, showing intermediate smoothness levels for nonlesional AD skin, which are below normal skin but better than lesional AD (12). An analysis of the epidermal lipids essential for skin barrier function showed lower results for extractable long-chain fatty acids not just in lesional AD skin (75%) but also in nonlesional AD skin (60%) (13). Finally, several loss of function mutations of the Filaggrin gene have recently been detected in high association with AD (14, 15), leading to a barrier A. Wollenberg, T. Bieber Department of Dermatology and Allergy, Ludwig-Maximilian-University of Munich, Munich; Department of Dermatology and Allergy, University of Bonn, Bonn, Germany

Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7.

Background  Adhesion molecules and chemokine receptors are involved in tissue‐specific homing of T cells to the skin and play an important role in the pathophysiology of cutaneous lymphoma. It has recently been reported that the chemokine CCL27 expressed by keratinocytes attracts lymphocytes bearing the chemokine receptor CCR10.