Roberto Takaoka

Thymopentin therapy reduces the clinical severity of atopic dermatitis

One hundred patients with moderate to severe atopic dermatitis were entered into a two-center, double-blind trial. Patients were randomized to receive either thymopentin (Timunox, n = 48) or placebo (n = 52), administered as daily subcutaneous injections for 6 weeks. Clinical extent of disease and severity parameters were measured at baseline and at regular time intervals during the study. Both the placebo- and thymopentin-treated groups demonstrated a progressive and statistically significant (p less than 0.001) decline in the overall severity of their disease, but reduction in the clinical severity score was higher in the thymopentin-treated group and statistically significant (p = 0.04) in comparison with the placebo-treated group after 6 weeks of treatment. Of the individual symptoms comprising the total severity score, pruritus (p = 0.02) and erythema (p = 0.04) were reduced significantly when thymopentin therapy was compared to placebo therapy. In addition, both the extent of body involvement and severity index (a combined severity/extent index) were significantly reduced after 6 weeks in the thymopentin-treated group in comparison to the placebo-treated group (p = 0.04). There were no serious adverse experiences in either treatment group. We conclude that treatment with thymopentin is safe and offers significant therapeutic promise for atopic dermatitis.

Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence‐based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence‐based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long‐term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23–24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient‐reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient‐reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient‐reported symptoms were discussed [including the Patient‐Oriented SCOring Atopic Dermatitis index, Patient‐Oriented Eczema Measure (POEM), Self‐Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient‐reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME)

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6–7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient‐reported symptoms, long‐term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long‐term control is needed before progress can be made towards recommending a core outcome measure.

Therapeutic Patient Education in Atopic Dermatitis: Worldwide Experiences

Therapeutic patient education (TPE) has proven effective in increasing treatment adherence and improving quality of life (QoL) for patients with numerous chronic diseases, especially atopic dermatitis (AD). This study was undertaken to identify worldwide TPE experiences in AD treatment. Experts from 23 hospitals, located in 11 countries, responded to a questionnaire on 10 major items. Patients in TPE programs were mainly children and adolescents with moderate to severe AD or markedly affected QoL. Individual and collective approaches were used. Depending on the center, the number of sessions varied from one to six (corresponding to 2 to 12 hours of education), and 20 to 200 patients were followed each year. Each centers education team comprised multidisciplinary professionals (e.g., doctors, nurses, psychologists). Evaluations were based on clinical assessment, QoL, a satisfaction index, or some combination of the three. When funding was obtained, it came from regional health authorities (France), insurance companies (Germany), donations (United States), or pharmaceutical firms (Japan, Italy). The role of patient associations was always highlighted, but their involvement in the TPE process varied from one country to another. Despite the nonexhaustive approach, our findings demonstrate the increasing interest in TPE for managing individuals with AD. In spite of the cultural and financial differences between countries, there is a consensus among experts to integrate education into the treatment of eczema.

Atopic dermatitis: correlation between non‐damaged skin barrier function and disease activity

Background  Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous‐type lesions with xerosis as the prominent clinical sign.

Global Allergy Forum and 3rd Davos Declaration 2015: Atopic dermatitis/Eczema: Challenges and opportunities toward precision medicine

Atopic dermatitis/eczema (AD) is a highly complex disease showing a clear increase in its incidence across all continents during the last decades 1, 2. It is the most common skin disease and has, almost other allergic diseases, a substantial socioeconomic impact 3. The complexity of the underlying mechanisms explains the wide spectrum of the clinical phenotype such as the age of onset, natural history, range of sensitization, provocation factors, clinical appearance, severity, and therapeutic response. Moreover, progress in the last years 4 has also highlighted the potential role of the skin microbiome, neuro‐immunological signals, and epigenetic regulation in the modulation of the disease, adding another level of complexity. This situation calls for a more differentiated approach in our efforts to understand the pathophysiology and to develop new preventative and therapeutic strategies better tailored for the subsets of this complex phenotype. This is particularly true when we consider the infantile and childhood onsets of AD, which are currently regarded as the first step of the feared atopic march including allergic rhinitis and/or asthma 5, 6. Thus, AD should more be considered as a systemic disease with a number of relevant comorbidities 7, 8, which will greatly benefit from new developments in the era of precision medicine 9. In July 2015, a group of 63 scientists and clinicians from 13 countries gathered under the auspices of the Christine Kuhne – Center for Allergy Research and Education (CK‐CARE) for the 3rd Global Allergy Forum in Davos, Switzerland. As in the past, the scientists intensely discussed key issues relevant in the field of allergy and AD 10, 11. The aim of the Think Tank meeting in 2015 was to define and discuss new strategies in research and education in AD, which will pave the way for the precision medicine pathways in AD. This document is not meant to be a comprehensive list of research areas but rather summarizes the main results of the working groups in charge of the six most important fields considered for this meeting.

Global Allergy Forum and 3rd Davos Declaration 2015: Atopic dermatitis/Eczema: Challenges and opportunities toward precision medicine Global Allergy Forum and 3rd Davos Declaration 2015: Atopic dermatitis/Eczema: Challenges and opportunities toward precision medicine

Atopic dermatitis/eczema (AD) is a highly complex disease showing a clear increase in its incidence across all continents during the last decades 1, 2. It is the most common skin disease and has, almost other allergic diseases, a substantial socioeconomic impact 3. The complexity of the underlying mechanisms explains the wide spectrum of the clinical phenotype such as the age of onset, natural history, range of sensitization, provocation factors, clinical appearance, severity, and therapeutic response. Moreover, progress in the last years 4 has also highlighted the potential role of the skin microbiome, neuro‐immunological signals, and epigenetic regulation in the modulation of the disease, adding another level of complexity. This situation calls for a more differentiated approach in our efforts to understand the pathophysiology and to develop new preventative and therapeutic strategies better tailored for the subsets of this complex phenotype. This is particularly true when we consider the infantile and childhood onsets of AD, which are currently regarded as the first step of the feared atopic march including allergic rhinitis and/or asthma 5, 6. Thus, AD should more be considered as a systemic disease with a number of relevant comorbidities 7, 8, which will greatly benefit from new developments in the era of precision medicine 9. In July 2015, a group of 63 scientists and clinicians from 13 countries gathered under the auspices of the Christine Kuhne – Center for Allergy Research and Education (CK‐CARE) for the 3rd Global Allergy Forum in Davos, Switzerland. As in the past, the scientists intensely discussed key issues relevant in the field of allergy and AD 10, 11. The aim of the Think Tank meeting in 2015 was to define and discuss new strategies in research and education in AD, which will pave the way for the precision medicine pathways in AD. This document is not meant to be a comprehensive list of research areas but rather summarizes the main results of the working groups in charge of the six most important fields considered for this meeting.

Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion.

Background:  Atopic dermatitis (AD) is a chronic, inflammatory skin disease with a high prevalence and complex pathogenesis. The skin of AD patients is usually colonized by Staphylococcus aureus (S. aureus); its exotoxins may trigger or enhance the cutaneous inflammation. Several mediators are related to the AD immune imbalance and interleukin‐18 (IL‐18), an inflammatory cytokine, may play a role in the atopic skin inflammation.

When does atopic dermatitis warrant systemic therapy?: Recommendations from an expert panel of the International Eczema Council

Background: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. Objective: To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. Methods: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic‐specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. Results: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. Limitations: Our work is a consensus statement, not a systematic review. Conclusion: The decision to start systemic medication should include assessment of severity and quality of life while considering the individuals general health status, psychologic needs, and personal attitudes toward systemic therapies.