Japanese Guideline for Atopic Dermatitis

Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is a inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level.The basics of treatment discussed in this guideline are based on the “Guidelines for the Treatment of Atopic Dermatitis 2008” prepared by the Health and Labour Sciences Research and the “Guidelines for the Management of Atopic Dermatitis 2009 (ADGL2009)” prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle.     

Japanese Guideline for Atopic Dermatitis 2014

Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and coun- termeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is a inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level.The basics of treatment discussed in this guideline are based on the "Guidelines for the Treatment of Atopic Dermatitis 2008" prepared by the Health and Labour Sciences Research and the "Guidelines for the Management of Atopic Dermatitis 2012 (ADGL2012)" prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the "Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2013" together with those for other allergic diseases.     

A novel atopic dermatitis model induced by topical application with dermatophagoides farinae extract in NC/Nga mice.

BACKGROUND: Atopic dermatitis is a chronically relapsing inflammatory skin disease. Animal models induced by relevant allergens play a very important role in the elucidation of the disease. The patients with atopic dermatitis are highly sensitized with mite allergens such as Dermatophagoides farinae (Df). Therefore, in the present study, we tried to develop a novel model for atopic dermatitis by repeated application with Df extract ointment. METHODS: Df extract ointment was repeatedly applied to the back of NC/Nga mice together with barrier disruption. Atopic dermatitis-like skin lesions were evaluated by dermatitis scores, skin histology and immunological parameters. The effect of corticosteroid and calcineurin inhibitor was also examined. RESULTS: Repeated application of Df extract ointment caused rapid increase in dermatitis scores. Clinical (skin dryness, erythema, edema and erosion) and histological symptoms (dermal and epidermal thickening, hyperkeratosis, parakeratosis and inflammatory cell infiltration) in this model were very similar to those in human atopic dermatitis. Serum total and Df-specific IgE levels were elevated in this model compared with normal mice, and draining lymph node cells isolated from the mice that exhibited dermatitis produced significant amounts of interleukin-5, interleukin-13 and interferon-gamma after re-stimulation with Df. Furthermore, current first-line drugs for the treatment of human atopic dermatitis, corticosteroid and tacrolimus ointments, were effective against the clinical and histological symptoms in this model. CONCLUSIONS: These results suggest that the model we have established is useful for not only elucidating the pathogenesis of atopic dermatitis but also for evaluating therapeutic agents.     

Recurrent prosthetic valve endocarditis caused by Staphylococcus aureus colonizing skin lesions in severe atopic dermatitis

Infective endocarditis, a serious infection most commonly affecting rheumatic or prosthetic valves, generally occurs after bacteremia. Atopic dermatitis, a very common disease, carries a high prevalence of skin infections, particularly with Staphylococcus aureus. While cutaneous colonization by S. aureus represents an important source of bacteremia, few cases of infective endocarditis arising from the skin lesions of atopic dermatitis have been reported. We describe a patient with recurrent S. aureus prosthetic valve endocarditis developing in this manner.     

Update on atopic dermatitis: insights into pathogenesis and new treatment paradigms.

Atopic dermatitis (AD) is a common skin disorder whose prevalence has increased, similarly to other atopic diseases. The immunopathogenesis of AD is complex, although Staphylococcus aureus may play an important role in cutaneous inflammation, possibly resulting from a deficiency in antimicrobial peptide secretion in the skin. Although more than 50% of patients will go on to develop asthma and allergies, atopic dermatitis is often the start of the "atopic march." Studies with topical fluticasone provide a rationale for maintenance therapy, whereas studies with the topical nonsteroidal immunomodulator pimecrolimus in patients as young as 3 months of age suggest that early intervention may be an effective strategy in treating this chronic, relapsing skin disease.     

Skin Biomes

The cutaneous microbiome has been investigated broadly in recent years and some traditional perspectives are beginning to change. A diverse microbiome exists on human skin and has a potential to influence pathogenic microbes and modulate the course of skin disorders, e.g. atopic dermatitis. In addition to the known dysfunctions in barrier function of the skin and immunologic disturbances, evidence is rising that frequent skin disorders, e.g. atopic dermatitis, might be connected to a dysbiosis of the microbial community and changes in the skin microbiome. As a future perspective, examining the skin microbiome could be seen as a potential new diagnostic and therapeutic target in inflammatory skin disorders.     

Etiologic implication of foods in atopic dermatitis: evidence against

Atopic dermatitis is a typical chronic inflammatory skin disease that usually occurs in individuals with a personal or family history of atopy. Children with atopic dermatitis frequently present IgE-mediated food sensitization, the most commonly involved foods being egg and cow's milk. However, controversy currently surrounds whether food allergy is an etiological factor in atopic dermatitis or whether it is simply an associated factor, accompanying this disease as one more expression of the patient's atopic predisposition. Approximately 40 % of neonates and small children with moderate-to-severe atopic dermatitis present food allergy confirmed by double-blind provocation tests but this allergy does not seem to be the cause of dermatitis since in many cases onset occurs before the food responsible for allergic sensitization is introduced into the newborn's diet.Studies of double-blind provocation tests with food in patients with atopic dermatitis demonstrate mainly immediate reactions compatible with an IgE-mediated allergy. These reactions occur between 5 minutes and 2 hours and present mainly cutaneous symptoms (pruritus, erythema, morbilliform exanthema, wheals) and to a lesser extent, digestive manifestations (nausea, vomiting, abdominal pain, diarrhea), as well as respiratory symptoms (wheezing, nasal congestion, sneezing, coughing). However, these reactions do not indicate the development of dermatitis.Some authors believe that responses to the food in provocation tests may also be delayed, appearing mainly in the following 48 hours, and clinically manifested as exacerbation of dermatitis. However, delayed symptoms are difficult to diagnose and attributing these symptoms to a particular foodstuff may not be possible.Delayed reactions have been attributed to a non-IgE-mediated immunological mechanism and patch tests with food have been proposed for their diagnosis. In our experience and in that of other authors, the results of patch tests with cow's milk do not seem very specific and could be due, at least in part, to the irritant effect of these patches on the reactive skin of children with atopic dermatitis.The involvement of foods in atopic dermatitis will always be difficult to demonstrate given that an exclusion diet is not usually required for its resolution. Food is just one among several possible exacerbating factors and consequently identification of its precise role in the course of the disease is difficult. Further double-blind prospective studies are required to demonstrate the effectiveness of exclusion diets in the treatment of atopic dermatitis.Apart from the controversy surrounding the etiological role of foods, the most important point in atopic dermatitis is to understand that the child is atopic, that is, predisposed to developing sensitivity to environmental allergens; in the first few years of life to foods and subsequently to aeroallergens. Consequently, possible allergic sensitization to foods should be evaluated in children with atopic dermatitis to avoid allergic reactions and to prevent the possible development of allergic respiratory disease later in life.     

High doses intravenous immunoglobulin versus oral cyclosporine in the treatment of severe atopic dermatitis

Atopic dermatitis is one of the most common allergic diseases that almost always respond to conventional therapies with topical emollient, topical corticosteroids, systemic antihistamines and allergic abstinence. However few cases of atopic dermatitis with severe course do not respond to conventional therapies and high dose of intravenous immunoglobulin or cyclosporine are recommended for them. This clinical trial study has been done to compare the last two regimens in patients with severe atopic dermatitis, Scoring Atopic Dermatitis (SCORAD) greater than 70. We included 14 patients in two groups. In group 1, eight patients were randomly selected and received 4mg/kg cyclosporine daily for 3 months and in group 2, six patients received 2g/kg Intravenous Immunoglobulin (IVIG) as stat infusion. All patients were followed on days 15, 30, 60 and 90 after starting the therapy. About 75% and 62.5% of patients had positive skin tests to egg and to milk respectively. Six patients out of 14 patients did not have skin test, so specific IgE by Radioallergosobent tests (RAST) was used for them. All of these patients had positive RAST to egg and 66.6% against cow's milk. There was a significant difference in the clinical outcomes of these two groups with a marked reduction in SCORAD of day 90th in group 1 in comparison to group 2 (P-value = 0.005). No significant adverse drug reaction was seen in these two groups.     

Severe atopic dermatitis: Dupilumab is not just safer,but more efficient

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsing eczema and pruritus. Until the development of Dupilumab, a new monoclonal antibody targeting IL-4 and IL-13 receptors, the current treatment of severe cases was based on immunosuppressant agents. Our main goal was to build a case series of five patients with severe atopic dermatitis, who were using immunosuppressive drugs with significant adverse effects and only partially controlled AD, and compare their symptoms, SCORAD index, treatment regimens, total and specific IgE, and blood cell count before and after the introduction of Dupilumab. SCORAD index and topical corticosteroids used on a daily basis had a significant decrease after 16 weeks of Dupilumab. Adverse effects were mild: conjunctivitis, local reaction and regional dermatosis. All patients with severe atopic dermatitis achieved better control of AD with Dupilumab than with immunosuppressive drugs. Adverse effects, secondary infections, total and specific IgE levels were greatly reduced.     

Assessment of IL-31 levels and disease severity in children with atopic dermatitis

Introduction and objectives

Atopic dermatitis is a chronic, relapsing, highly pruritic, inflammatory skin disease characterized by typical localization with increasing prevalence of 10–20% in children. Pruritus is one of the major diagnostic criteria of atopic dermatitis and also the main complaint altering quality-of-life of affected patients, inducing and aggravating inflammation. Although pruritus is the absolute symptom of AD, the etiology has not been fully explained yet and current antihistamine therapies are ineffective.The aim of the study was to assess the correlation between IL-31 level and disease severity in patients with atopic dermatitis through Severity SCORing of Atopic Dermatitis (SCORAD) index and the degree of itching assessed subjectively.

An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases.

Background: Atopic dermatitis is a chronic or chronically relapsing, pruritic inflammatory skin disease. The incidence of atopic dermatitis has dramatically increased during the past three decades in industrialized countries. We attempted to develop an improved method to induce an animal model of atopic dermatitis and to use it to evaluate the efficacy of a Tec family kinase inhibitor. Methods: We treated dermatitis-prone inbred mice, NC/Nga, by repetitive epicutaneous applications of a house dust mite allergen and staphylococcal enterotoxin B to induce atopic dermatitis-like skin lesions. Results: We established a highly efficient protocol to induce skin lesions in NC/Nga mice, which were histologically and immunologically similar to human atopic dermatitis. Similar to human patients, serum IgE levels were increased in dermatitis-induced mice. Consistent with the proposed roles of infiltrated immune cells in the pathogenesis of human atopic dermatitis, skin lesions were treatable with terreic acid, an inhibitor of Tec family kinases, as well as dexamethasone. Conclusions: We established a highly efficient, highly reproducible protocol to induce skin lesions in NC/Nga mice and successfully applied it to show the efficacy of terreic acid in treating skin lesions. This mouse model of atopic dermatitis will be useful to study the pathogenetic processes of atopic dermatitis and to evaluate the efficacy of drug candidates.     

Cutaneous manifestations of Hyper IgE syndrome

Hyper-IgE syndrome (HIES) is a primary immunodeficiency disorder characterized by atopic manifestations and susceptibility to infections with extracellular bacteria and fungi. Atopic manifestations include atopic dermatitis-like skin lesion and extremely high serum IgE levels. Most of the extracellular bacterial infections are caused by Staphylococcus aureus, which is associated with milder inflammation compared to normal. Recent studies have revealed that the most cases of the HIES are caused by dominant negative mutations in STAT3 gene. Cutaneous manifestations of HIES includes newborn rash, eczematoid dermatitis, cold abscesses, mucocutaneous candidiasis, and coarse texture of the facial skin. Impaired Th17 cell development due to the defective IL-6 signaling in T cells and impaired induced regulatory T (iTreg) cell generation due to defective IL-10 signaling in dendritic cells may, at least in part, account for the cutaneous pathology of HIES.     

Does atopic dermatitis cause food allergy? A systematic review

Background

Atopic dermatitis is the commonest chronic inflammatory disorder of the skin, affecting more than 20% of children in industrialised countries and up to 5% of adults. This condition is often associated with other atopic diseases, such as IgE-mediated food allergy (FA). Food allergen recognition via antigen-presenting cells in eczematous skin has been suggested to act as an important mediator of food sensitisation and FA. This would have important implications for prevention and treatment. We aimed to review the association between atopic dermatitis and FA; the effect of FA on atopic dermatitis severity, chronicity, and age of onset; and whether there was a temporal association between atopic dermatitis and FA.

Contact haptens in emollients marketed in two European countries (Poland and Spain)

Introduction and objectivesAtopic dermatitis (AD) is the most common skin disease among pediatric patients, which affects up to 20% of children worldwide. Characterized by pruritus and eczema, it is also associated with improper skin barrier function and allergen sensitization. Here, we aimed to assess the presence of haptens in emollients marketed in two European countries: in Poland and Spain, as, firstly, these products are considered to be AD's basic therapy, and, secondly, frequent application of potent sensitizers on atopic skin may result in contact dermatitis.Materials and methodsWe systematically searched for moisturizers explicitly described as “Atopic skin care” products in the most frequently visited online pharmacies in Poland and Spain.Subsequently, we created a database of all products and compared their composition with 139 contact haptens listed in the European Baseline Series (EBS), Fragrance and Cosmetic Series.ResultsAs of December 2018, our list comprised 159 and 111 emollients available on the Polish and Spanish markets, respectively. There were no ingredients listed in 28 (17.5%) products in Poland and 24 (21.6%) in Spain. Only 23 (17.5%) and 13 (14.8%) products were hapten free. The pattern of most common haptens was similar in both countries, including phenoxyethanol, tocopherol and tocopheryl acetate, undefined parfum in Poland and tocopherol, phenoxyethanol, tocopheryl acetate and undefined parfum in Spain.ConclusionsThis study shows that a vast majority of products taken into consideration contain at least one potential contact hapten. These findings indicate a need for patient education about potentially allergenic ingredients and stronger cooperation between academia and cosmetic manufacturers.     

Peripheral itch sensitization in atopic dermatitis

Atopic dermatitis is a skin disorder caused by skin dryness and barrier dysfunction, resulting in skin inflammation and chronic itch (or pruritus). The pathogenesis of atopic dermatitis is thought to be initiated by a lowering of the itch threshold due to dry skin. This lowering of the itch threshold is at least partially due to the increase in intraepidermal nerve fibers and sensitization of sensory nerves by interleukin (IL)-33 produced and secreted by keratinocytes. Such skin is easily prone to itch due to mechanical stimuli, such as rubbing of clothing and chemical stimuli from itch mediators. In patients with atopic dermatitis, once itch occurs, further itch is induced by scratching, and the associated scratching breaks down the skin barrier. Disruption of the skin barrier allows entry into the epidermis of external foreign substances, such as allergens derived from house dust mites, leading to an increased induction of type 2 inflammatory responses. As a result, type 2 cytokines IL-4, IL-13, and IL-31 are mainly secreted by Th2 cells, and their action on sensory nerve fibers causes further itch sensitization. These sequences of events are thought to occur simultaneously in patients with atopic dermatitis, leading to a vicious itch-scratch cycle. This vicious cycle becomes a negative spiral that leads to disease burden. Therefore, controlling itch is essential for the treatment of atopic dermatitis. In this review, we summarize and discuss advances in the mechanisms of peripheral itch sensitization in atopic dermatitis, focusing on skin barrier-neuro-immune triadic connectivity.     

Specific IgE to Common Food Allergens in Children with Atopic Dermatitis

Background: Atopic dermatitis is a major public health problem, often starting in early childhood and sometimes followed by other allergic diseases. Although hypersensitivity to foods is assumed to play an essential role in the development of atopic dermatitis in some patients, little is known about common food allergens in Iranian children with atopic dermatitis. Objectives: This study was designed to identify probable food allergens in Iranian children with atopic dermatitis and find the relationship between food sensitization and the severity of atopic dermatitis. Methods: This study included 90 children aged 2-48 months with atopic dermatitis. Skin prick tests for cow's milk, hen's egg, almond, potato and soybean were done. Serum specific IgE to 20 food allergens was also screened. Results: Among children with atopic dermatitis, the frequency of food sensitization was 40% by skin prick test and 51% by food-specific IgE. Children with atopic dermatitis were most commonly sensitized to cow's milk (31%), hen's egg (17.7%), tree nuts (17.7%), wheat (12.2%), potato (11.1%), tomato (8.8%) and peanut (8.8%). In 42 children with moderate to severe eczema, sensitivity to food allergens was 78.5% by skin prick test and 88% by serum specific IgE evaluation. Conclusion: Our results showed that cow's milk, hen's egg and tree nuts were the most common food allergens in Iranian children with atopic dermatitis. Sensitization to foods was much higher in patients with moderate to severe atopic dermatitis. Determining specific IgE in children with atopic dermatitis can be helpful in managing these patients.     

Contact sensitization in children with atopic dermatitis

Background

Atopic dermatitis is a common illness in childhood. Children with atopic dermatitis are prone to develop cutaneous sensitization due to skin barrier dysfunction.

Atopic dermatitis as a risk factor for acute native valve endocarditis

Colonization of Staphylococcus aureus is commonly observed in skin lesions of atopic dermatitis (AD) patients, and scratching of the pruritic lesions may lead to reiterative bacteremia. It is possible that acute native valve endocarditis may develop in a patient with uncontrolled AD; the latter condition may be a risk factor for the former. We report two cases of acute aortic and/or mitral valve endocarditis complicated with recurrent cutaneous infections caused by severe AD. The patients underwent successful surgical treatment of the heart lesions, plus intensive postoperative antibiotics and skin treatment for AD.     

Urinary eosinophil-derived neurotoxin concentrations in patients with atopic dermatitis: a useful clinical marker for disease activity.

BACKGROUND: It has been reported that measurements of eosinophil-derived neurotoxin (EDN) may be useful for identifying eosinophil activities in allergic diseases including atopic dermatitis. METHODS: EDN concentrations in the urine were measured by enzyme-linked immunosorbent assay, and the number of eosinophils in the peripheral blood was counted in 30 patients with atopic dermatitis. The severity of atopic dermatitis was graded on the criteria proposed by Rajka and Langeland. The disease activity was assessed by each patient on a visual analogue scale (VAS). RESULTS: Urinary concentrations of EDN in patients with atopic dermatitis showed a significant positive correlation with disease severity. Urine EDN concentrations also correlated with VAS scores for itching, skin condition, overall skin symptoms and total VAS score, but not with the VAS score for skin dryness. Urinary EDN concentrations did not correlate with the number of eosinophils in the peripheral blood. CONCLUSIONS: The urinary EDN concentration in patients with atopic dermatitis is a useful clinical marker for monitoring disease activity.