Guidelines for management of atopic dermatitis

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease characterized by pruritus and inflammation and accompanied by cutaneous physiological dysfunction (dry and barrier-disrupted skin). Most of the patients have atopic diathesis. A standard guideline for the management (diagnosis, severity classification and therapy) of AD has been established. In our guideline, the necessity of dermatological training is emphasized in order to assure diagnostic skill and to enable evaluation of the severity of AD. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution; and (iii) chronic and chronically relapsing course. For the severity classification of AD, three elements of eruption (erythema/acute papules, exudation/crusts and chronic papules/nodules/lichenification) are evaluated in the most severely affected part of each of the five body regions (head/neck, anterior trunk, posterior trunk, upper limbs and lower limbs). The areas of eruption on the five body regions are also evaluated, and both scores are totaled (maximum 60 points). The present standard therapies for AD consist of the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation, topical application of emollients to treat the cutaneous physiological dysfunction, systemic antihistamines and anti-allergic drugs as adjunctive treatments for pruritus, avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. Tacrolimus ointment (0.1%) and its low-density ointment (0.03%) are available for adult patients and 2–15-year-old patients, respectively. The importance of the correct selection of topical corticosteroids according to the severity of the eruption is also emphasized. Furthermore, deliberate use of oral cyclosporine for severe recalcitrant adult AD is referred.     

Clinical practice guidelines for the management of atopic dermatitis 2018

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. 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.     

Importance of concomitant topical therapy in moderate‐to‐severe atopic dermatitis treated with cyclosporine

Cyclosporine (CS) is widely used in patients with refractory atopic dermatitis (AD). During CS treatment, many patients have a tendency to decrease their adherence to topical agents as their disease improves. Our aim was to compare the efficacy and relapse rate of CS treatment combined with topical therapy and CS monotherapy. This prospective, randomized, 6 month study involved 60 patients with moderate‐to‐severe AD who were randomly assigned to two groups, one receiving CS and topical agents and the other, CS only. Clinical outcomes were based on investigators’ global assessment (IGA) scores, eczema areas and severity index scores, and trans‐epidermal water loss. If a patient achieved treatment success (IGA score ≤2) during the study period, CS was stopped. Relapse rate and time to relapse were evaluated during the 3 months after discontinuation of CS. The treatment success rate was significantly higher in the combination group (p = 0.028). The combination group had a shorter median time to response (p = 0.040), a lower cumulative dose (p = 0.041), and a longer time to relapse (p < 0.01) than the monotherapy group. Although CS monotherapy is effective against AD, topical agents should be used concomitantly.     

保湿剂并用糖皮质激素治疗异位性皮炎的疗效观察

目的：研究保湿剂对外用糖皮质激素治疗异位性皮炎疗效的影响。方法：通过随机对照临床研究，采用湿疹面积及严重度指数评分法，对外用糖皮质激素和保湿剂治疗45例轻中度异位性皮炎患者的临床疗效进行评估。结果：与单独外用糖皮质激素或保湿剂相比，联合外用糖皮质激素加保湿剂治疗轻、中度异位性皮炎，较单用糖皮质激素疗效显著，单独外用保湿剂可明显减轻轻中度异位性皮炎患者的临床症状。结论：外用保湿剂能增强局部糖皮质激素的疗效，单独外用保湿剂治疗异位性皮炎可获得与糖皮质激素相近的疗效。     

Meta-analysis on the comparison between two topical calcineurin inhibitors in atopic dermatitis

Topical calcineurin inhibitors have proved to be suitable for the treatment of AD. We conducted a meta-analysis comparing efficacy and tolerance of tacrolimus with pimecrolimus in treatment of AD. According to our meta-analysis, tacrolimus 0.1% was more effective than pimecrolimus 1% in adult patients (week 3: risk ratio [RR] 0.55, 95% confidence interval [CI] 0.42-0.73), and tacrolimus (a combination of 0.03% and 0.1%) was also more effective than pimecrolimus 1% in pediatric patients (week 6/end of study: RR 0.76, 95% CI 0.63-0.92). Regardless of age or illness severity, tacrolimus 0.1% had higher efficacy than pimecrolimus 1% in the treatment of AD (week 3: RR 0.55, 95% CI 0.42-0.72). In adult patients, tacrolimus 0.1% had more adverse events than pimecrolimus 1% (RR 1.30, 95% CI 1.02-1.66), but the incidence of adverse events between tacrolimus 0.1% (or 0.03%) and pimecrolimus 1% was not significantly different in pediatric patients. No matter whether the patients were adult or pediatric, more pimecrolimus-treated patients withdrew from the trials because of a lack of efficacy. Regardless of age and illness severity, more pimecrolimus 1%-treated patients withdrew from the trials because of a lack of efficacy, compared with tacrolimus 0.1% (or 0.03%)-treated patients. More pimecrolimus-treated pediatric patients withdrew from the trials because of adverse events (RR 0.26, 95% CI 0.1-0.68). More pimecrolimus 1%-treated patients withdrew from the trials because of adverse events, compared with tacrolimus 0.03%-treated patients, regardless of age (RR 0.1, 95% CI 0.02-0.53). In conclusion, tacrolimus ointment has higher efficacy and better tolerance than pimecrolimus cream in treatment of AD.     

A systematic review of the safety of topical therapies for atopic dermatitis

BACKGROUND: The safety of topical therapies for atopic dermatitis (AD), a common and morbid disease, has recently been the focus of increased scrutiny, adding confusion as how best to manage these patients. OBJECTIVES: The objective of these systematic reviews was to determine the safety of topical therapies for AD. METHODS: Databases searched included: OVID Medline, Medline In-Process and Other Non-Indexed Citations, Embase, and the Cochrane Central Register of Controlled Trials. In addition to the articles identified by this search, investigators were also referred to a list of links (most recently updated 25 September 2005) to recent Food and Drug Administration (FDA) studies, reports and meetings regarding the topical calcineurin inhibitors for further potential references. Only fully published papers available in English and data obtained from FDA sites were included. Furthermore, the criteria for inclusion and exclusion for each systematic review were further evaluated at a meeting of all of the content and evidence-based medicine experts participating in this process and alteration of the inclusion criteria was done at that time when it was felt necessary to avoid inclusion of lower-quality data in the review. Qualitative review of the abstracted data was performed and reviewed at a meeting of all of the content and evidence-based medicine experts. RESULTS: While systemic exposure to these topical agents does occur, physiological changes appear to be uncommon and systemic complications rare and have only been found with use of topical corticosteroids. CONCLUSIONS: Based on the data that are available the overall safety of AD therapies appears to be good with the only documented systemic side-effects of therapy those occasionally seen with use of topical corticosteroids.     

Dosage and adverse effects of topical tacrolimus and steroids in daily management of atopic dermatitis

Since 1999, combination therapy with tacrolimus and topical steroids has been widely used for the treatment of adolescent/adult-type atopic dermatitis. In order to determine the clinical doses of topical tacrolimus and steroids for daily treatment of atopic dermatitis and to elucidate their beneficial and adverse effects, we analyzed the clinical data from 215 patients with atopic dermatitis who were more than 16 years old. Less than 70 g of tacrolimus and less than 15 g of steroids were applied to 90% of the patients on the face and neck, and less than 75.8 g of tacrolimus and less than 322 g of steroids were applied to 90% of the patients on the trunk and extremities during the six-month treatment period. Topical tacrolimus is much more frequently used on face and neck lesions (99.1%); in only 39.5% of cases was it used on the trunk and extremities. The majority of patients improved after six months of the combination topical therapy; however, atopic dermatitis was not controlled in 6% of the patients. The combination therapy did not seem to increase the risk of cutaneous infections; however, the incidence of herpes simplex infection on the face and neck was 2.8% at pre-treatment and slightly increased to 4.7% during the therapy. The incidence of all steroid-induced adverse effects was reduced both in frequency and intensity with a decrease in the dose of topical steroids through simultaneous tacrolimus application. Combination therapy with topical tacrolimus and steroids is useful for treating atopic dermatitis, but a small percentage of the patients still cannot be satisfactorily treated. For such patients, adjustments of the dose and rank of topical steroids and tacrolimus and other therapeutic adjuncts are necessary.     

Clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis

BACKGROUND: Topical steroids are used as the first-line therapy for atopic dermatitis. OBJECTIVES: To determine the clinical doses of topical steroids for the daily treatment of atopic dermatitis in clinics and to elucidate their adverse effects. PATIENTS AND METHODS: A multicentre retrospective analysis of a series of 1271 patients (210 infants, 546 children, and 515 adolescents and adults) with atopic dermatitis. RESULTS: Less than 89.5 g, 135 g and 304 g of topical steroid were applied in 90% of the patients in the infant, childhood, and adolescent and adult AD groups, respectively, on the entire body during the 6-month treatment period. The majority of patients were controlled well; however, 7% of infant, 10% of childhood and 19% of adolescent and adult patients remained in a very severe or severe state or experienced exacerbation even though they applied larger amounts of topical steroids. With regard to adverse effects, the incidence of telangiectasia on cheeks tended to increase in patients who had a longer duration of disease and who applied more than 20 g to the face during the 6-month treatment period. The steroid-induced atrophy of the antecubital and popliteal fossae was more frequently observed in males than in females. CONCLUSIONS: Topical steroids are useful for treating atopic dermatitis, but a substantial percentage of patients cannot be satisfactorily treated with topical steroids. For such patients, adjustments of dose and rank of topical steroids and other therapeutic adjuncts are necessary.     

A randomized controlled trial of pimecrolimus cream 1% in adolescents and adults with head and neck atopic dermatitis and intolerant of, or dependent on, topical corticosteroids

BACKGROUND: There is a need for alternative treatments for atopic dermatitis (AD) of the face and neck as long-term use of topical corticosteroids (TCS) is associated with skin atrophy and telangiectasia and some patients develop allergy, intolerance or other side-effects. OBJECTIVES: This study was designed to assess the efficacy and safety of pimecrolimus cream 1% in patients with AD of the face and neck who are either dependent on, or intolerant of, TCS. METHODS: A 12-week study comprising a 6-week, double-blind, randomized, vehicle-controlled phase was conducted, followed by a 6-week, open-label phase. Two hundred patients aged 12 years or over with mild to moderate head and neck AD, intolerant of, or dependent on, TCS were randomized to either pimecrolimus cream or vehicle cream. The primary efficacy criterion was the facial investigator's global assessment score at 6 weeks. Secondary efficacy criteria were head and neck Eczema Area and Severity Index (EASI), pruritus score and eyelid dermatitis. Facial skin atrophy and telangiectasia were assessed with dermatoscopy. RESULTS: A significantly higher percentage of patients treated with pimecrolimus was cleared or almost cleared of facial AD compared with vehicle (47% vs. 16%, respectively). A statistically significant difference was also seen on head and neck EASI and pruritus score. Significantly more pimecrolimus-treated patients than vehicle-treated patients achieved clearance of eyelid dermatitis (45% vs. 19%, respectively). Among the 77 patients with skin atrophy at baseline, treatment with pimecrolimus was associated with a reversal in skin thinning. Of the 112 patients with telangiectasia at baseline, no statistically significant difference was seen between treatment groups. Adverse events occurred with similar frequency in both groups. CONCLUSION: Pimecrolimus cream 1% is effective in patients with head and neck dermatitis intolerant of, or dependent on, TCS. Reversion of skin atrophy may occur during TCS-free intervals.     

Comparison of psoriasis and atopic dermatitis guidelines—an argument for aggressive atopic dermatitis management

The development of effective systemic treatments has revolutionized the treatment of inflammatory skin diseases. The availability of safe new treatments and the understanding of psoriasis as a systemic disease with comorbidities and effects on quality of life have driven the current aggressive treatment paradigm of psoriasis. Historically the morbidity of atopic dermatitis (AD) has been dismissed, given the perception of AD as “just” a rash. Differences in the guidelines for psoriasis and AD management may suggest variations in the current conceptualization of disease severity and effects on quality of life. Published guidelines from the American Academy of Dermatology for the management of psoriasis and AD were reviewed. We recorded the similarities and differences in disease assessment and therapy. The threshold to use biologic agents for moderate to severe psoriasis highlights the aggressive nature of modern psoriasis treatment. AD guidelines include an assessment of quality of life but do not designate a disease severity threshold for systemic treatment. AD and psoriasis have a tremendous effect on quality of life. The AD guidelines have a less aggressive approach to disease management than the psoriasis guidelines. We should think critically about rapid advancement to systemic agents in AD management, especially now that more and better agents are being developed.     

Italian guidelines for therapy of atopic dermatitis—Adapted from consensus‐based European guidelines for treatment of atopic eczema (atopic dermatitis)

Atopic dermatitis (AD) therapeutic approach calls for a long‐term treatment. Treatment options for AD have recently undergone a revolutionary change by the introduction of the first biologic drug. Availability in daily practice of the last version of international AD guidelines, taking peculiarities of the country into account, can contribute to good clinical practice in Italy. To adapt European Dermatology Forum (EDF) guidelines for AD to the Italian medical–legal context, the EDF guidelines were assessed independently by two independent Italian renowned experts in the field and further integrated with articles published and systematically reviewed before May 2019. The first draft was collegially corrected and updated by the members of the SIDEMAST, ADOI, and SIDAPA. Recommendation levels (A; B; C; D) were graded based on the evidence levels (1–4). The adapted guidelines presented here focus on topical and systemic therapies in AD patients, both children and adults. As opposed to previous Italian guidelines, they include indications about biologics. New relevant evidence available from very recent literature and peculiarities of the Italian medical and legal context have been integrated in the revision process. If compared to general guidelines for AD not adapted to a specific national and cultural context, a revision for specific Italian needs is now available: It comprises the option of implementing the new biologic treatments and is likely to provide an important contribution to the improvement of clinical practice in Italy. Cooperation between patients, dermatologists, allergologists, and pediatricians remains mandatory in AD management. The authors of the present revision recommend an update of the Italian guidelines to be performed at least every second year.     

Corticosteroid phobia and other confounders in the treatment of childhood atopic dermatitis explored using parent focus groups

Background/Objectives: Anxieties associated with corticosteroid treatment and preference for ‘safer natural therapy’ are common in parents of children with atopic dermatitis. We used focus groups to explore the source of these attitudes. Methods: The study involved 16 parents. Parents expressed difficulties with living with and treating atopic dermatitis which were categorized into themes using qualitative data analysis software. Results: Themes identified include: emotional impact of atopic dermatitis; difficulty in accepting ‘control’ verses ‘cure’; topical corticosteroid negative perceptions; anxiety and confusion with treatment; preference for ‘natural’ therapy; and attitude‐changing positive experiences. Conclusions: Our findings illustrate the emotional impact of atopic dermatitis and the frustration with the lack of potential cure. ‘Corticosteroid phobia’ was universal among parents in our cohort and is a fear generated by doctors, pharmacists, close acquaintances and information from the internet. Participants expressed high levels of parental guilt linked to a desire for an eradicable ‘cause’ for atopic dermatitis, despite intellectually understanding this is a genetically determined condition. Parents were willing to change attitudes with accurate information from perceived reliable sources, positive hospitalization experiences and a relationship with a trusted dermatologist. Parents' suggestions to improve confidence included the provision of readily available information and better access to doctor‐ and nurse‐led paediatric dermatology services.     

特应性皮炎的全程管理共识

【摘要】 特应性皮炎是常见的瘙痒性、慢性炎症性皮肤病,近20年来患病率迅速增加,在非致命性皮肤疾病负担中排名第一。临床上迫切需要开展行之有效的特应性皮炎全程管理。本共识根据特应性皮炎在预防、治疗、康复、照护等方面的特性,遵循既往指南和临床共识,制定了一整套管理方案,有望为我国特应性皮炎的全程管理提供科学参考。     

Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in atopic dermatitis

Background There is a lack of studies on the effect of tacrolimus on eosinophils and related molecules including eotaxin, CCR3, RANTES and interleukin (IL)‐5. Objectives To investigate the effects of tacrolimus on in vivo eosinophil counts and on the related molecules eotaxin, CCR3, RANTES and IL‐5 in patients with atopic dermatitis (AD). Methods Lesional skin specimens and sera were obtained from 15 patients with AD and from 15 normal controls. For 8 weeks, the patients with AD applied 0·03% tacrolimus ointment to all affected areas twice daily. Blood sampling and skin biopsies were then repeated. We evaluated serum eotaxin and IL‐5 levels, and tissue eotaxin, CCR3, RANTES and IL‐5 levels. Additionally, tissue levels of eotaxin and CCR3 mRNA were measured. Results After treatment with topical tacrolimus twice daily for 8 weeks, significant decreases were found in serum IL‐5 levels, immunoreactive cell counts of eotaxin, IL‐5, CCR3 and RANTES in AD skin, and tissue eosinophil counts. However, the change in the serum eosinophil count was not statistically significant, and mRNA levels of eotaxin and CCR3 were not decreased significantly after treatment. Conclusions Topical tacrolimus reduces the number of eosinophils in tissue and suppresses the expression of eotaxin, CCR3, RANTES and IL‐5 related to proliferation, recruitment, activation and survival of eosinophils.     

Non‐corticosteroid adherence and itch severity influence perception of itch in atopic dermatitis

Topical corticosteroid phobia is an important problem in the treatment of atopic dermatitis as it can affect the ability to control disease severity and itch by reducing treatment adherence. Topical corticosteroid phobia often ends up even non‐corticosteroid adherence. As such, non‐corticosteroid adherence, disease severity and itch are likely to be associated with each other, but their relationship has yet to be thoroughly investigated. Thus, the purpose of this study is to investigate it in atopic dermatitis. Using data from 1190 participants in an Internet survey, we identified 255 non‐corticosteroid users and 225 with moderate to severe itch who were defined as non‐corticosteroid adherents. Corticosteroid users with the same itch categories (n = 878) served as controls. We also examined how itch severity affects the perception of itch in atopic dermatitis. Unexpectedly, non‐corticosteroid adherents were less sensitive to the conditions to elicit itch such as perspiring, commuting homeward, drinking alcohol and wearing woolen clothes compared with the control. We also found that patients with severer itch were more sensitive to itch during/after bathing, when lying in bed, commuting homeward, studying/working, drinking alcohol, undressing, getting up in the morning, after a meal, ingesting piquant foods and when they were unoccupied, angry, busy, nervous, sad or enjoying themselves. In conclusion, we found that non‐corticosteroid adherence and itch severity influence perception of itch in atopic dermatitis and discuss possible mechanisms underlying these results. The information obtained in this study may be useful for communication with and education of atopic dermatitis patients and their treatment in outpatient clinics.