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This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

This article covers the salient and updated themes of the Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL) 2020 published by the Japanese Society of Pediatric Allergy and Clinical Immunology. In the 2020 guidelines, five new clinical questions (CQs) have been added to address the 12 CQs regarding the treatment of childhood asthma. “Infant and preschool asthma” is diagnosed when young children (

Background: Adrenaline is the first-line medication for managing anaphylaxis. A better understanding of prescription trends for adrenaline auto-injectors (AAIs) is important to improving patient care as well as information on health education interventions and medical guidelines. However, it has been difficult to gather comprehensive data in a sustainable manner. Thus, we aimed to investigate trends in AAI prescriptions in Japan. Methods: We searched the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), a unique and comprehensive database of health insurance claims, and investigated prescriptions for AAIs for all ages (April 2017 to March 2018). We assessed the annual number of prescriptions per person as well as prescription rates per 100,000 population per year by age, sex, and geographic region. Results: A total of 88,039 subjects (56,109 males, 31,930 female) and 116,758 devices (1.33 AAIs per patient per year) were prescribed AAIs at least once a year for all ages. The prescription rate for AAIs was 69.5 per 100,000 population-years. Patients aged 0–9 years were prescribed AAIs at the rate of 278.9 per 100,000 population-years. Patients aged 0–19 years were 6.4 times more likely to be prescribed AAIs than those over 20 years of age. Males were more frequently prescribed AAIs than females in all age groups, except for those aged 20–24 years. We also evaluated differences in prescription rates by geographic region. Conclusions: This comprehensive evaluation revealed trends in AAI prescriptions, thus helping develop preventive strategies with respect to anaphylaxis in Japan.

Background: IgE-mediated egg allergy is a common food allergy worldwide. Patients with egg allergy are known to easily achieve tolerance compared to other allergens such as nuts. Oral food challenge (OFC) is often performed on patients diagnosed with or suspected of having IgE-mediated food allergy, but whether hen's egg OFC is useful in IgE-dependent egg allergy patients to avoid complete elimination remains unknown. Methods: We identified articles in which OFCs were performed in Japanese patients diagnosed with or suspected of having IgE-mediated egg allergy. We evaluated whether the OFCs were useful to avoid the complete elimination of eggs by assessing the following: (1) the number of patients who could avoid complete elimination; (2) the number of patients who experienced serious adverse events (SAEs); or (3) adverse events (AEs); (4) improvement in quality of life (QOL); and (5) immunological changes. Results: Fifty-nine articles were selected in the study; all the references were case series or case studies in which OFC was compared to pre-challenge conditions. The overall negative ratio against egg OFC was 62.7%, but an additional 71.9% of OFC-positive patients could take eggs when expanded to partial elimination. Of the 4182 cases, 1146 showed AEs in the OFC, and two cases reached an SAE. Two reports showed an improvement in QOL and immunological changes, although the evidence was weak. Conclusions: OFCs against eggs may be useful to avoid complete elimination, but medical professionals should proceed with the test safely and carefully.

Background: Cow's milk, along with hen's egg, are common causes of food allergies in children worldwide. Accidental ingestion of milk is common and often induces severe allergic reactions. Oral food challenge test (OFC) is usually performed in patients with or suspected of having a food allergy. However, the evidence of whether cow's milk OFC is useful in IgE-dependent cow's milk allergy patients to avoid total elimination is not known. Methods: After setting the clinical question and outcomes, we performed a systematic review for relevant articles published from January 1, 2000 to August 31, 2019 using PubMed® and Ichushi-Web databases. Each article was then evaluated for the level of evidence. All positive results of the OFC were defined as adverse events. Results: Forty articles were selected in this study. Our review revealed that cow's milk OFC was able to avoid the complete elimination of cow's milk in 66% of the patients with cow's milk allergy. We also found that adverse events occurred frequently (50.5%). Conclusions: This analysis supports the recommendation of conducting cow's milk OFC to avoid complete elimination of cow's milk, however the test should be conducted with careful consideration of the patient's safety. As the methods of OFC and subjects varied among the articles selected in this study, further studies are needed to obtain higher quality evidence.

Infantile wheezing and eczema are associated with the subsequent onset of asthma and other atopic diseases. However, there are no large population-based surveys on infantile allergic symptoms in Japan. The objective of the study was to determine the prevalence of wheezing and asthma in infants in Nagoya, Japan. This population-based cross-sectional study was performed in the metropolitan city of Nagoya, Japan. We surveyed parents to ascertain the prevalence of wheezing and eczema in infants who attended group health checkups at 3, 18, and 36 months of age. Their parents completed modified questionnaires from the International Study of Asthma and Allergies in Childhood. More than 90% of the approximately 40,000 children in each study group living in the target area were included in the survey. The prevalence of wheezing was 8%, 17%, and 13% at 3, 18, and 36 months, respectively, and was characterized by birth season. The prevalence of eczema was 24%, 30%, and 31%, at 3, 18, and 36 months, respectively. Participants born in autumn and winter had a higher incidence of eczema in each age group. Three-quarters of the children had a parental history of allergic conditions. Parental allergic diseases and male gender are risk factors for wheezing and eczema in children. This survey had a high response rate and covered almost the entire population of the target age groups in a large city. We believe that the results of this study, therefore, provide a much higher level of confidence regarding the prevalence of allergies in infants in Japan than that in previous studies with limited cohorts.

The Japanese Guideline for Childhood Asthma (JGCA) 2020 is a translation of the Japanese Pediatric Guideline for the Treatment and Management of Asthma (JPGL) 2017 into English, which was published by the Japanese Society of Pediatric Allergy and Clinical Immunology. It makes recommendations for best practices in the management of childhood asthma, including management of acute exacerbations and non-pharmacological and pharmacological management. These guidelines will be of interest to non-specialist physicians involved in the care of children with asthma. In JPGL, JPGL2017 is the first evidence-based guidelines updated according to the GRADE system and Minds approach, and it addresses eight clinical questions about the treatment of childhood asthma. In children aged ≤5 years, infant and preschool asthma is diagnosed according to the response to short acting beta2 agonists or the effect of a therapeutic trial during 1 month with controller treatment and worsening after treatment cessation. Long-term management both promotes pharmacological therapy and measures against risk factors that induce exacerbation, better patient education and a partnership with trinity. In addition, long-term management should not be carried out without review but rather be based on a cycle of evaluation, adjustment and treatment. In JPGL2017, the transdermal patch and oral beta2 agonists are positioned as drugs within the concept of “short-term additional treatment” to be used until the symptoms are stabilized when the control state transiently deteriorates.

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.

Background: Atopic dermatitis (AD) influences a child's emotional and social well-being, as well as his or her physical health. The influence of AD on the daily lives of parents and caregivers has also been documented. This study examined how parenting stress is affected by demographic background, characteristics of children's AD, and their family systems. Methods: The participants were mothers of children, aged 2–6 years old, who had been diagnosed with AD. The predictive power of a model of parenting stress was examined using multiple regression analysis (stepwise), with parenting stress (PSI-SF) as the dependent variable, and children's demographics, including characteristics of AD; parents' demographics; QoL of families of children with AD (JCMV-CADIS); and family functioning (FAI) as independent variables. We handled missing values using a multiple imputation method. Results: The pooled coefficients obtained from the multiple regression analysis after multiple imputation indicated that “family cohesion,” “family system flexibility,” “emotions related to social factors” and “occupation of mother” determined parenting stress. Lower family cohesion and family system flexibility predicted higher parenting stress. The high impact of “emotions related to social factors” on families’ QoL predicted higher parenting stress. Full-time work by mothers predicted lower parenting stress. Conclusions: The current results reveal that “family cohesion,” “family system flexibility,” “emotions related to social factors” and “full-time work by mothers” predicted parenting stress of mothers who had children with AD. Keywords: Atopic dermatitis, Family, Multiple imputation, Multiple regression, Stress

BackgroundCow's milk allergy (CMA) and egg allergy (EA) are common and can reduce quality of life in children. Infantile eczema is a well-established risk factor for the onset of food allergy via transdermal sensitization; however, various types of infantile eczema have not yet been evaluated. Therefore, we assessed the association between CMA and EA and the sites and the severity of infantile eczema.MethodsThis retrospective study was based on data from patients aged 2-19 years with atopic disease who were treated between July 2015 and March 2019 in a pediatric allergy clinic in Japan. Data regarding the history of IgE-mediated symptoms, eczema in the first year of life, parental history of atopic diseases, and infantile nutrition were collected.ResultsA total of 289 patients were included in the study, of which 81 and 111 children had IgE-mediated CMA and EA, respectively. The rates of CMA and EA were higher in the children with infantile eczema than in those without (30% vs. 9% and 42% vs. 21%). The rate of CMA was also higher in children with eczema on the face. Significant differences were noted in the rate of CMA among children with facial eczema of exudation (adjusted odds ratio 2.398; P = 0.017) and papules (adjusted odds ratio 2.787; P = 0.008), using multivariate analysis.ConclusionThe rate of IgE-mediated CMA was high among children with atopic disease having severe facial eczema during infancy.

Background: The Childhood Atopic Dermatitis Impact Scale (CADIS) was developed to measure the impact of AD on QoL in both affected children and their families. However, no scale of this kind exists in Japan. The aims of this study were to validate the Japanese Culturally Modified Version of the CADIS (JCMV-CADIS) and to describe the family impact of children with AD in a Japanese context. Methods: Participants included primary-caregivers for children with AD between 2 and 6 years of age. Interviews were conducted, and new items for the Japanese version were drafted. Reliability and validity were evaluated and compared with the original CADIS, and unique features of the Japanese version were analyzed. Results: Exploratory factor analysis revealed the following factors: “Symptoms” and “Activity Limitations and Behavior” in the Child domain, and “Emotions Related to Social Factors,” “Emotions Related to the Child's Condition,” “Family and Social Function,” “Complexity of Care,” and “Approaches to Management of AD in Daily Life” in the Parent domain. The latter two factors were unique to the JCMV-CADIS and were not derived from the Original. “Emotion” was split into two independent factors. All factors showed good reliability (internal consistency and stability) and validity (concurrent validity and discriminant validity), except for the concurrent validity of “Approaches to Management of AD in Daily Life.” This factor seemed to reflect characteristics similar to the family-related function. Conclusions: The JCMV-CADIS is a QoL scale developed for Japanese children with AD and their families. Further evaluation of clinical applicability is needed.

Background: The prevalence of maternal oral contraceptive pills (OCP) use and that of childhood asthma are high in western countries. The aim of this study is to examine the association of OCP use with childhood wheeze and allergic diseases in Japan. Methods: Relevant data were extracted from a hospital based birth cohort study named as Tokyo-Children's Health, Illness and Development Study (T-CHILD) of which questionnaire conducted during pregnancy included maternal history and duration of OCP use. To identify wheeze and allergic diseases in the children, the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) was used. Logistic regression models were applied to estimate those association and adjustments were made for maternal history of allergy, maternal education level, maternal age at pregnancy, maternal BMI, maternal smoking during pregnancy, mode of delivery, gestational age at delivery, daycare attendance, number of previous live births, and gender of child. Results: OCP use was associated with ever wheeze (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.10–2.40), current wheeze (aOR, 1.59; 95% CI, 1.01–2.50), ever asthma (aOR, 1.65; 95% CI, 1.02–2.65), and ever rhinitis (aOR, 1.90; 95% CI, 1.30–2.80). Compared with no prior OCP use, using OCP for more than three months statistically increased the odds of ever wheeze (P = 0.012), current wheeze (P = 0.035), and ever rhinitis (P = 0.002). Conclusions: Our findings suggest that maternal OCP use has a role in the development of wheeze, asthma and rhinitis in children. Extended use of OCP is likely to increase the risk of wheeze and rhinitis.

Background: The International Study of Asthma and Allergies in Childhood (ISAAC) has reported the prevalence of asthma and allergic diseases in many countries. Methods: We used the ISAAC core written questionnaire to examine the prevalence of asthma and allergic diseases in 6- to 14-year old schoolchildren in Tokyo. In 2005, we conducted a cross-sectional survey of all schoolchildren in all public schools located in the Setagaya area of Tokyo. Results: Data were collected from 27,196 children in 95 schools. Prevalence ranged from 10.5% to 18.2% for asthma symptoms and from 10.9% to 19.6% for atopic dermatitis, with both conditions tending to decrease with age. As has been previously reported for all age groups, significantly higher rates of current asthma are observed in boys than in girls. The prevalence of allergic rhinoconjunctivitis exhibited a different pattern from that of asthma and atopic dermatitis, peaking at the age of 10 (34.8%). Prevalence of allergic rhinoconjunctivitis was 1.5 to 2-fold higher than the previous ISAAC studies that were performed in Tochigi and Fukuoka. In all age groups, symptoms of allergic conjunctivitis were more frequent from February to May, which coincides with the Japanese cedar pollen season, and were less frequent between June to September. Conclusions: The prevalence of asthma and atopic dermatitis was higher in younger schoolchildren. Tokyo schoolchildren appear to have extremely high prevalence rates of seasonal allergic rhinoconjunctivitis.

Background: Asthma is the most common chronic diseases in school-aged children in Japan. It is important to consider health-related quality of life (QoL) among children with chronic diseases when treatment decisions are made. Methods: A school-based survey was conducted in randomly selected public schools in Tokyo by using a KINDL® questionnaire for evaluating QoL and the international study of asthma and allergy on childhood (ISAAC) questionnaire, which is designed for comparing the asthma prevalence in various countries, from May to June in 2005. We recruited approximately 10% of the total children 6–7-years-old and 13–14-years-old living in Tokyo for sampling. Results: Response rate of this questionnaire was 86% (22,645 children) in the 6–7-year-old group and 64% (12,879 children) in the 13–14-year-old group. Comparing asthmatics with non-asthmatics in the same age, QoL of children with asthma was significantly impaired. The severity of QoL of children with asthma was significantly impaired. QoL of children with exercise-induced asthma (EIA) were more significantly impaired than ones without EIA and showed lower scores in the categories of physical functioning, emotional and school activities than those without EIA. Of note, QoL was more impaired in the EIA-positive group among severe asthmatics, suggesting that QoL of children with even severe asthma could be improved when EIA is appropriately controlled. Conclusions: Existence of EIA among asthmatic children most strongly impairs their QoL. We should be more cautious about the management of EIA.

The hygiene hypothesis implies, in immunological terms, that microbial stimulation in early life skews the immune system towards the development of a T helper type 1 (Th1)-type lymphocyte population, and away from a T helper type 2 (Th2)-type development that is associated with atopy. The hygiene hypothesis originally theorized that increased infections protected against atopy. This theory has evolved since harmful infections may not be as critical as exposure to microbial burden because exposure to microbes can occur in the absence of infections. Despite substantial public hygiene measures in modern metropolitan communities, an atopy-protective effect of endotoxin in these metropolitan environments still occurs. This article is a review of clinical and experimental studies concerning the protective effect of endotoxin exposure on the susceptibility to atopic responses. The discussion includes : (1) factors influencing household endotoxin levels ; (2) recent developments in the potential use of endotoxin for the prevention of atopy and asthma ; (3) association of endotoxin and pets with atopic sensitization and diseases ; (4) animal studies on the protective effects of timing of endotoxin exposure on atopy and asthma and (5) animal studies on the protective effects of endotoxin dose on atopy and asthma.

Many research studies have been published on atopic eczema and these are often summarised in systematic reviews (SRs). Identifying SRs can be time-consuming for health professionals, and researchers. In order to facilitate the identification of important research, we have compiled an on-line resource that includes all relevant eczema reviews published since 2000.SRs were searched for in MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Database of Systematic Reviews, DARE and NHS Evidence. Selected SRs were assessed against the pre-defined eligibility criteria and relevant articles were grouped by treatment category for the included interventions. All identified systematic reviews are included in the Global Resource of EczemA Trials (GREAT) database (www.greatdatabase.org.uk) and key clinical messages are summarised here.A total of 128 SRs reviews were identified, including three clinical guidelines. Of these, 46 (36%) were found in the Cochrane Library. No single database contained all of the SRs found. The number of SRs published per year has increased substantially over the last thirteen years, and reviews were published in a variety of clinical journals. Of the 128 SRs, 1 (1%) was on mechanism, 37 (29%) were on epidemiology, 40 (31%) were on eczema prevention, 29 (23%) were on topical treatments, 31 (24%) were on systemic treatments, and 24 (19%) were on other treatments. All SRs included searches of MEDLINE in their search methods. One hundred six SRs (83%) searched more than one electronic database. There were no language restrictions reported in the search methods of 52 of the SRs (41%).This mapping of atopic eczema reviews is a valuable resource. It will help healthcare practitioners, guideline writers, information specialists, and researchers to quickly identify relevant up-to-date evidence in the field for improving patient care.