Sánchez, Sánchez, Macías-Weinmann, Barreto, Ensina, Uriarte-Obando, Castro-Almarales, Adorni, Lázaro, Callero-Viera, Ale, and Álvarez: Systematic review about 10 interventions in dermatitis. A document from the Latin American Society of Allergy, Asthma, and Immunology



Background

Atopic dermatitis (AD) affects a large portion of the population, particularly children under 5 years.1,2,3,4 It usually precedes the development of other allergic diseases such as food allergy, asthma, rhinitis, and/or conjunctivitis, therefore, it is considered as an important risk factor for these diseases.5,6

AD has a great impact on the quality of life of patients. The frequency of physiological or psychiatric problems in patients with moderate to severe dermatitis is higher than those in patients with diabetes mellitus.7 The economic cost of skin hydration, physician visits, and drug treatment has increased in the last years.8,9,10 Therefore, the evaluation and management of AD should be comprehensive and must include all the stakeholders: patients, relatives, and health care systems.

Although there are excellent guidelines offering an appropriate approach to manage this disease,11,12 transparent evidence-based guidelines following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach13 are needed.14 Since each patient must receive personalized treatment, the recommendations presented here may not be appropriate for all patients, nevertheless, they offer a kickoff for disease management based on current scientific evidence.

Methods

  • Update objectives: to evaluate some commonly used interventions in dermatitis and new practical interventions.

  • Target population: patients with AD regardless their age, but it is focused on under-6 children because they are the population with the highest AD incidence.15

  • Implementation place: these recommendations are to be implanted on outpatient clinical management.

  • Target users: general practitioners, family doctors, dermatologists, allergists, and pediatricians.

  • Clinical aspects covered: evaluation of topical and systemic dermatitis management interventions. Prevention and acute management. Outpatient management.

  • Clinical aspects not covered: management in hospitalization and/or emergencies.

Definitions

According to the recommendation of the WAO (World Allergy Organization),16 it is better to use the term “eczema” than “dermatitis”, while confirmatory immunological studies are done; also, WAO recommends limiting the use of the term “atopic eczema” when a mediation IgE is demonstrated in the pathophysiology of the disease, and “non-atopic eczema” when it is discarded. In many countries, the term “dermatitis” is used as an equivalent to “eczema”, so, in this guideline and in the bibliographic search we use both.17,18,19

Staff conformation

Since the first revision of the Dermatitis-SLAAI (Sociedad Latinoamericana de Asma, Alergia e Inmunología) Guidelines in 2015,20 new evidence has accumulated about some interventions in AD.

For this update, a stakeholder group with allergists, dermatologists, pediatricians, epidemiologists, and immunologists, developed the review protocol and made an open invitation to SLAAI members to participate.21 Subsequently, those members who correctly performed the protocol tasks and writing the guide were included in the staff.

Protocol to the guide update

This guideline update was focused on new information about some practical interventions in dermatitis. Characteristics of the epidemiology, classification, and pathogenesis of the disease are discussed in detail in the 2015 Consensus.20 ARIA (Allergic Rhinitis and its Impact on Asthma) report protocol was used as a model22 and the update protocol was based on PRISMA recommendations (see supplementary material).23

By using the Delphi process,24 the panel staff reached an agreement on the topics that required an update and on new topics that deserved to be included, and performed a systematic review of the literature to identify and summarize the evidence for each one of them (see supplementary material). Each topic is presented as a clinical question, and the answer to each question includes a conclusion with the strength of the recommendation according to the GRADE system.14 The AGREE Reporting Checklist was used to evaluate the completeness and transparency of the guideline recommendations.

For external validation and to assess the clarity of the concepts and their applicability, the manuscript was presented to allergists, dermatologists, general physicians from academic and external scientific institutions, and groups of patients. External recommendations were then discussed again by the staff and included in the manuscript.

Questions and outcomes of interest

The guideline panel deemed the following outcomes to be important to patients: cutaneous symptoms like pruritus and eczema, quality of life, work/school performance, and serious adverse effects. In general, these variables were considered critical for the decisions to be made, regarding the answer to each question. The questions chosen were:

  1. How should we classify atopic dermatitis in clinical practice?

  2. Can atopic dermatitis be prevented?

  3. Can we predict the duration of atopic dermatitis?

  4. Does the cutaneous microbiota influence the control of atopic dermatitis?

  5. Is the use of probiotics in atopic dermatitis useful?

  6. Can restriction diet help as a treatment of atopic dermatitis?

  7. Are non-pharmacological interventions useful in the treatment of dermatitis?

  8. Do antihistamines help in the treatment of atopic dermatitis?

  9. When and which immunomodulator should be used in atopic dermatitis?

  10. What new pharmacological treatments are available for atopic dermatitis?

Bibliographic search and evidence review

We systematically searched articles from December 2000 to December 2018 from the Medline and LILACs electronic databases. Titles and abstracts, and subsequently full-text articles were screened in duplicate to assess eligibility. Articles in English, Spanish and Portuguese were reviewed.

Studies were included if they provided empirical data related to the panel staff questions (clinical trials, cohort studies, case-control studies). We excluded narrative reviews and case reports. We shared the bibliography collected among the team members; in case any staff member considered it was necessary to include an additional reference, this was discussed.

Clinical recommendations

We prepared evidence summaries for each question according to the GRADE approach.14,25 The certainty of the evidence was categorized into four levels: strong, moderate, low, and very low. Specific criteria for evidence classification are presented in figure 1.

Figure 1

Classification of the evidence. The recommendation was classified based on the grade of evidence and the interpretation of the committee. We considered patient preferences and cost effectivity.

2448-9190-ram-66-04-426-gf1.jpg

For each question, we summarized all information including a concise description of desirable and undesirable health effects.26,27 The answer to each question was reviewed by the panel staff, who provided feedback by means of electronic communications. The answers were modified accordingly when it was necessary. Recommendations and their strength were decided by consensus.

Results

Limitations from the systematic review

The protocol for this systematic review was not previously registered in any database, which limits the reproducibility of the results. However, since in the guide we considered the patients’ opinions and the reality of the clinical practice in different countries, these variables, that influenced the recommendation, could not be reproduced only with the bibliographic search. In supplementary material 1 and 2, an approach of the search carried out for each question is presented. However, a standardized evaluation to avoid the risk of bias was not used.

Limitations from articles

There is a considerable heterogeneity among the studies, patients’ characteristics, evaluation of clinical control, and the safety of each intervention. Additionally, many studies indicated the response to treatment without clarifying the doses of the drug, the treatment length, measurement of treatment efficacy, the speed of the effect, and/or follow-up period. We provide the rationale for the recommendations and the consideration of some factors that influenced the recommendations.

1. How should we classify atopic dermatitis in clinical practice?

Recommendation. Severity classification is available to all physicians and it is useful to define interventions (high, 1a). Atopy-based classification (yes/no) seems to be useful for the prognostic of duration in children (moderate 1a).

Explanation. AD can be classified in several ways.20 Some classification proposals according to endotypes have been done,28,29 but their utility in clinical practice is unclear. The presence or not of atopy seems to be associated with the patient’s clinical characteristics and the probability of remission or not, thus, the classification of allergic or non-allergic eczema according to the skin prick test result or IgE serum can be useful in the clinical practice.

The classification of the severity is established with different scoring scales, such as: Severity Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index. These scores are defined according to three parameters: extension of the disease and type of injury; some scales also include pruritus and sleep disturbance as perceived by the patient. We recommend the use of these or any other validated clinical scale since they allow physicians to classify the severity of the patient, the degree of affectation and allow the decision making regarding the most appropriate medical intervention.

2. Can atopic dermatitis be prevented?

Recommendation. Primary prevention: early skin hydration (first six months of life) seems to decrease the risk of dermatitis (strong 1b). Secondary prevention: skin hydration and inflammation control improve the clinical control of dermatitis, and some evidence suggests that these interventions could modify the severity of eczema (moderate 2b).

Explanation. Primary prevention: the increase of IgA levels with breast milk30 and the use of milk hydrolyzed formulas in high-risk infants reduced the cumulative prevalence of eczema.31 Although these results are supported by some studies, other research studies do not reproduce these results, so their implementation cannot be widely recommended.

Two multicenter studies demonstrated that the daily use of emollients, with application on all the skin, significantly reduced the cumulative incidence of AD in children at 12 and 36 months, which corresponded to a relative risk reduction, between 30% and 50%.32,33 It is necessary to evaluate the cost-effectiveness of this intervention.34

Secondary prevention. The daily use of emollients in patients with mild-moderate disease prevents and delays exacerbations, as well as decreases the use of topical steroids and prolongs eczema-free time.35,36,37 Although there is controversial evidence,38 it seems that vitamin D supplementation during the winter season improves AD related to winter.39,40

3. Can we predict the duration of atopic dermatitis?

Recommendation. Maternal eczema, onset after two years old, severe onset, are associated with long duration of dermatitis periods (over 14 years old) (moderate 2a). Nevertheless, no single factor is enough to predict the duration of the disease (strong 2b). The creation of a prognostic model evaluating the magnitude of each individual factor could be useful.41

Explanation. Most childhood dermatitis remitted before puberty, nevertheless, from 1% to 25% of patients persist with symptoms even in adulthood.20,41 Findings from 14 systematic reviews published before 2016 observed that persistent atopic dermatitis is associated with more severe disease at the time of diagnosis, onset after the age of two years and being a female.42 A systematic review including 45 studies was considered and found that a later onset increased persistence.43 Some genetic factors have been associated with persistent dermatitis, but these factors are not easy to use in clinical practice.44

Some studies suggest that children with atopy from house dust mites or foods before their first year should be considered at risk of AD persistence;45,46 although it is not clear if atopy is a consequence of greater severity, it could be used as a duration predictor.

4. Does the cutaneous microbiota influence the control of atopic dermatitis?

Recommendation. The cutaneous microbiota influences the control of AD (strong 1b), however, heterogeneity in intervention strategies on bacterial overgrowth (topic or systemic antibiotics), makes comparative evaluations and the power of evidence difficult to extend and evaluate (moderate 2a).

Explanation. Microbial colonization of skin begins, more effectively, after birth and depends, in part, on the type of delivery; cesarean delivery children have a cutaneous microbiota profile that resembles maternal skin, while cutaneous microbiota of vaginal delivery children has a more diversified profile, similar to the maternal vaginal scenario.47 During puberty, new changes occur in skin microbiota.48 There are several mechanisms by which changes in microbial skin diversity (dysbiosis) affect the development of atopic dermatitis; the production, by these dysbiosis bacteria, of several enzymes, such as: proteases (which induce corneocyte desquamation); lipases (which break down lipids of skin barrier); ceramidases (which break down the ceramides present in the barrier structure).49,50 This bacterial overgrowth, with subsequent biofilm formation and mainly related to the pathogenic strains of Staphylococcus aureus (methicillin-resistant Staphylococcus aureus), would be directly related to changes in the cutaneous barrier.51,52,53

Cutaneous microbiota is associated with dermatitis severity, but it is less clear its effect in the pathogenesis; antibiotic interventions are also expected to be able to improve the dermatitis symptom scores. However, a systematic review,54 in 21 studies with different interventions (oral antibiotics, antibacterial soaps, topical steroids/antibiotics/antifungal, baths with antibacterial solutions) did not show differences statistically significant.

5. Is the use of probiotics in atopic dermatitis useful?

Recommendation. There is a potential effect of the use of probiotics in the prevention of atopic dermatitis (moderate 3a); however, methodological limitations, a wide variety of strains and the dosage schemes, lead to discordant and contradictory results and their routine use is not recommended.

Explanation. Probiotics could help dermatitis through restoration in the function of the intestinal barrier, degrading food antigens, regulating the Th1 and Th2 response, regulating the composition and activity of the intestinal microbiota and stimulating the production of IgA.55 The WAO in a systematic review indicates that is likely net benefit from using probiotics the primary prevention of eczema.56 The use of Lactobacillus rhamnosus, Lactobacillus salivarius, Bifidobacterium lactis and others, in several small studies has shown relief of symptoms, which results in an improvement of SCORAD,57,58 being more effective during the first two years of life.

Although probiotics are safe and are used as a reasonable option of dermatitis preventive treatment in under-6-month children or high-risk pregnant women, their impact on active treatment appears to be reduced.59,60

However, in order to apply this recommendation, solving several practical questions that currently do not have an answer is necessary, for instance: Does the type of microbiota affect the impact of probiotics? What dosage? For how long? What strains should be used?.61 The lack of control of these variables in the different clinical trials limits the ability to implement this intervention.

6. Can restriction diet help as a treatment of atopic dermatitis?

Recommendation. In patients with an objective demonstration of exacerbation of dermatitis by a food, dietary restriction is indicated (moderate 3a). Atopy to food allergens is not enough to initiate a dietary restriction (strong 1a).

Explanation. Frequently, patients associate food consumption with the onset or worsening of their disease.62,63,64 The sensitization to foods in children with AD is very prevalent, being the majority of cases asymptomatic (without clinical relevance).65,66 The subgroup of moderate to severe AD have a higher risk of sensitization to food allergens and this is translated into a high risk of true food allergy.65,67,68 The clinical history, along with an allergology evaluation, can help to identify suspect foods, but it is necessary to verify with restriction diets for 3 to 4 weeks or controlled oral challenges.

The avoidance of foods previously tolerated or never ingested due to a positive skin test without clinical confirmation of hypersensitivity reactions, is associated with an increased risk of severe reactions, after their reintroduction into the regular diet.69,70,71,72 Therefore, the avoidance of food should only occur in cases of AD with clinical impact confirmation.73 In cases in which negative results in oral challenges or food restrictions did not improve AD, foods must be reintroduced.74

7. Are non-pharmacological interventions useful in the treatment of dermatitis?

Recommendation. The hydration of the skin is a non-pharmacological intervention with adequate evidence for the treatment and prevention of eczema exacerbation in dermatitis (moderate 2a). Although the evidence is weak and the magnitude of this measure is not known, we recommend the use of hypochlorite, loose and preferably cotton-made clothing in patients with AD (low 3a-4). We discourage the use of products with perfume or clothing that may increase sweating (low 3b).

Explanation. The treatment of AD is a challenge because it is a chronic disease, which occurs with periods of outbreak and remission. The therapeutic approach of dermatitis includes two aspects: the management of active eczema and the prevention of new exacerbations.

The emollient preparation should be chosen according to the skin dryness degree, the areas of application, and the patient’s acceptance.75,76 Using tight or rough clothes, personal care products with alcohol or perfume, exposing oneself to heat or carrying out activities inducing heavy sweating, among others, should be avoided as far as possible.77,78 Some recommendations with low evidence but cost-effective are usually done: baths should be tempered and brief, no more than five minutes. Skin hygiene and cleaning should be smooth, scabs should be removed; avoid perfumes. Using hypochlorite during bath could reduce colonization of some bacteria.79,80,81 Using comfortable, loose and preferably cotton-made clothing seems to prevent skin exacerbation.

8. Do antihistamines help in the treatment of atopic dermatitis?

Recommendation. Some studies support the use of second-generation antihistamines to decrease pruritus in dermatitis (low 4). However, due to the lack of high-level evidence, we cannot make a recommendation in favor of or against the use of H1-antihistamines in the treatment of dermatitis-associated pruritus.

Explanation. Pruritus is usually the most distressing feature of AD.82 Histamine is one of the multiple mediators of itching in dermatitis. However, it is not clear if it has a key role.83 There are no large, randomized, double-blind, and placebo-controlled studies with precise endpoints on the efficacy of antihistamines in AD. Antihistamines (especially first generation) have been used in dermatitis to reduce scratching, however, these drugs, in most of the studies, are not more effective than placebo.84,85,86,87 Nevertheless, some studies, especially those with second-generation antihistamines, suggest a possible positive effect in pruritus and repair of the cutaneous tissue;88,89,90,91 these effects increased with a topical steroid.92

First generation sedating antihistamines have been used in dermatitis to promote sleep84,85 but sedating antihistamines reduce the rapid-eye-movement (REM)-sleep, affecting the quality of sleep and directly interfering with work efficiency in adults and learning skills in children.93

9. When and what immunomodulator should be used in atopic dermatitis?

Recommendation. The decision to start systemic therapy should be based on the severity of the symptoms, but also on the impact on the patient’s quality of life, as well as on the consideration of the risks and benefits of systemic therapies for each individual patient (strong 1b). Many randomized controlled trials (RCTs) with immunomodulator interventions for dermatitis have not used standardized efficacy outcome measures, which makes interpretation of results difficult. In addition, comparative studies between the existent systemic treatments in dermatitis are rare.

Explanation. Most patients with AD respond satisfactorily to conventional topical management. However, 10% to 50% of patients may not achieve adequate disease control with these regimens and require systemic immunomodulatory/immunosuppressive therapies. Before considering a systemic therapy, it should be determined whether the failure of conventional therapies is due to the severity of the disease, comorbidities, or lack of adherence to the treatment. The action mechanism of each one of these interventions is explained in detail in the previous dermatitis-SLAAI guideline.20 In table 1, we present some details of each one of some of these therapies. It is important to note that most of these therapies are not approved by the FDA or EMA for dermatitis.

Table 1

Immunomodulator interventions

Systemic drug

intervention

Doses

Do not use in…*

Efficacy-

effectivity**

GRADE

recommendations

Dupilumab

Serious eosinophilic conditions

50%-70%

Strong 1a

Phototherapy

40-120 sessions

Do not use in pregnancy and children under

6-year-old

40%-70%

Moderate 2b

Cyclosporine A

2.5-5 mg/kg/day

Renal failure, pregnancy

30%-90% after

4 months

Moderate 2b

Methotrexate

5-25 mg once a week (the use of MTX must be complemented with folic acid)

Pregnancy, breastfeeding, liver dysfunction

30%- 80%

Moderate 2b

Azathioprine

1-2.5 mg/kg/day

Pregnancy,

mielosupression

30%- 70%

Moderate 2b

Mycophenolate (oral)

1-3 g/day

Pregnancy, breastfeeding,

20%-80%

Weak 3b

Omalizumab

150 mg/4 weeks to 450/2 weeks

Patients without IgE demonstration

30%- 50%

Weak 4, expert opinion based in case reports

[i] The selection of the systemic drug for dermatitis, more than a selection step by step, should be based in individual safety profile, availability and access. The use of immunosuppressants can facilitate the onset of respiratory or skin infections.

[ii] *These medications may have other contraindications, the most frequently described are presented in the table.

[iii] **Different scales have been used to evaluated efficacy-effectivity, we present the effect size in percent as standard unit. The safety and efficacy of dupilumab in children have not been established.

  • Dupilumab. It was approved in early 2017 for moderate-to-severe adult dermatitis.94,95 Dupilumab is a fully human monoclonal antibody that blocks the alpha subunit of the receptor interleukin (IL) 4 and IL-13. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)-mediated inflammation help in the treatment of AD. Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of AD disease activity; Dupilumab also reduces the need for systemic steroids (NCT01259323, NCT01385657, NCT01639040, and NCT01548404.).95,96,97,98

  • Phototherapy or photochemotherapy. It is one of the alternatives with the highest number of articles and some RCT supporting its effectiveness. However, the need of attendance to the center of execution between 2 to 4 times per week limits its access and use.99,100,101,102 Different forms of light therapy are available, and have proved efficacy: narrowband (NB)-UVB, broadband (BB)-UVB, UVA, UVA1, cold-light UVA1, UVA and UVB (UVAB), full-spectrum light (including UVA, infrared and visible light), psoralen plus UVA, and other forms of phototherapy. One of the principal limitations for phototherapy is the requirement to attend several times per week for its application. However, some new home-applied modalities are being developed.103

  • Systemic corticosteroids (SCSs). They are not recommended as a control intervention for the treatment of dermatitis. Their use should be limited to very short terms (up to 1 week) during acute flares in need of immediate relief and as a transition to steroid-sparing therapies because of their adverse-effect potential.104,105,106

  • Cyclosporine A (CSA). It is an approved drug for severe dermatitis in some countries and numerous studies showed improvement of the skin symptoms by at least 50% after six to eight weeks of therapy.107,108,109,110,111 Once the drug is stopped the symptoms reappear quickly, eventually reaching pretreatment values approximately after 8 weeks from the end of treatment.109,110,111 CSA has been shown to be effective and relatively safe in adults who received up to 1 year of continuous treatment,112,113,114,115,116 but some of these studies had high dropout rates.116 The staff recommended choosing the regimen on an individual basis; it could be reasonable to start with a dose of 2.5 mg/kg/day,114,117 unless a rapid improvement is considered necessary, when a dose of up to 5 mg/kg/day may be used.116,118,119

  • Methotrexate (MTX). Patients receiving MTX should be monitored for hepatic and pulmonary toxicity, and myelosuppression.120 Different studies have shown good efficacy for MTX.121,122 MTX has some advantages and disadvantages compared to CSA but it seems to have a similar effectivity;122,123,124 The onset of control seems to be faster with ciclosporin, but relapse after stopping the medication seems to be less frequent with MTX

  • Azathioprine (AZA). Efficacy of AZA (2.5 mg/kg/day) was tested in some RCT, especially in adults,107,125 with efficacy (30 to 70%) in the severity of eczema and skin pruritus. In an RCT comparing MTX (10-22.5 mg/week) with AZA (1.5-2.5 mg/kg/day), at week 12, no statistically significant differences were found in the clinical impact (MTX SCORAD of 42% (standard deviation [SD], 18%) vs AZA 39% [SD, 25%]),126 but abnormalities in blood count (mostly lymphocytopenia) were statistically and significantly more frequent in the AZA group (p = 0.002).

  • Mycophenolate (MMF). Some case reports or uncontrolled clinical trial data from adults indicate that MMF could be effective in dermatitis.127,128,129,130,131 In an observer-blinded randomized controlled trial in 55 patients, a lower dose CSA (3 mg/kg/d) was found to be equally effective to oral MMF (EC-MPS, 1440 mg/d) as a maintenance therapy for severe dermatitis during a maintenance phase of 30 weeks and a 12-week follow-up period.112 The MMF group had a slower onset of action with 29% of the MMF patients requiring short courses of systemic glucocorticoids compared to none in the CSA group.132

Therapies like omalizumab, interferon gamma, and others, have been used in atopic dermatitis and may be useful for some patients but there are only case reports and case series supporting this recommendation. Some clinical trials are being conducted with omalizumab, but no results have been reported (Clinicaltrials.gov NCT01678092, NCT01179529).

10. What new pharmacological treatments are available for dermatitis?

Recommendation. Dupilumab is recommended in severe AD (strong 1a). Crisaborole is recommended in mild and moderate AD, but a safety-efficacy comparison to other topical interventions is needed (strong 1a).

From the dermatitis-SLAAI guideline in 2015 to these days, two molecules were released to the market and approved by the Food and Drugs Administration (FDA): crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, became available in late 2016 in the United States and Europe for mild-to-moderate dermatitis. It can be used topically. Clinical trials have demonstrated its efficacy in treating patients with mild to moderate atopic dermatitis (children > 2 years) (AD-301: NCT02118766; AD-302: NCT02118792).133,134 The potency of crisaborole seems to be equivalent to the one of a moderate-potency steroid , but the frequency of adverse effects seems to be lower; as of now, there is no evidence of atrophy, telangiectasia, or hypopigmentation, resulting from its use.135 However, there are few equivalence or superiority studies comparing this molecule to topical steroids, therefore, at the moment, crisaborole is recommended at the same level as the use of steroids or calcineurin inhibitors.

Dupilumab has been shown to be effective in adult patients refractory to topical steroids and also in patients who did not respond to CSA.136 Among the adverse effects that have been described are the increase of eosinophils in the blood (without apparent clinical impact, but it requires more studies) and a high frequency of conjunctivitis.137 The high cost of dupilumab and the lack of studies in children are the main limitations for its use.

Conclusions

For this update, we covered a small number of topics. However, these were systematically reviewed. Many interventions have been proven in patients with dermatitis, but due to the lack of studies with an adequate design, most of these interventions have a weak or moderate recommendation. Further studies are needed in order to predict the duration and severity of the disease, as well as which interventions are the most appropriate for each patient.

Funding

This article was supported by the Group of Clinical and Experimental Allergy, from the Clinic IPS Universitaria of the University of Antioquia (Medellín, Colombia).

Acknowledgment

Special thanks to the scientific societies that participated as external reviewers of the guide: Mauricio Sarrazola and Eizabeth García (Asociación Colombiana de Alergia Asma e Inmunología); Mirta Álvarez Castelló, and Olaine Gray (Sociedad Cubana de Alergia, Asma e Inmunología Clínica); Natalia Hernández (Asociación Colombiana de Dermatología); Dirceu Solé (Associação Brasileira de Alergia e Imunologia); and Diana Gavazza (Academia Colombiana de Pediatría y Puericultura).

References

1. Odhiambo JA, Williams HC, Clayton TO, Robertson CF, Asher MI, ISAAC Phase Three Study Group. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol. 2009;124(6):1251-1258. DOI: 10.1016/j.jaci.2009.10.009

JA Odhiambo HC Williams TO Clayton CF Robertson MI Asher ISAAC Phase Three Study Group Global variations in prevalence of eczema symptoms in children from ISAAC Phase ThreeJ Allergy Clin Immunol200912461251125810.1016/j.jaci.2009.10.009

2. Grize L, Gassner M, Wüthrich B, Bringolf-Isler B, Takken-Sahli K, Sennhauser FH, et al. Trends in prevalence of asthma, allergic rhinitis and atopic dermatitis in 5-7-year old Swiss children from 1992 to 2001. Allergy. 2006;61(5):556-562. DOI: 10.1111/j.1398-9995.2006.01030.x

L Grize M Gassner B Wüthrich B Bringolf-Isler K Takken-Sahli FH Sennhauser Trends in prevalence of asthma, allergic rhinitis and atopic dermatitis in 5-7-year old Swiss children from 1992 to 2001Allergy200661555656210.1111/j.1398-9995.2006.01030.x

3. Weber AS, Haidinger G. The prevalence of atopic dermatitis in children is influenced by their parents’ education: results of two cross-sectional studies conducted in Upper Austria. Pediatr Allergy Immunol. 2010;21(7):1028-1035. DOI: 10.1111/j.1399-3038.2010.01030.x

AS Weber G Haidinger The prevalence of atopic dermatitis in children is influenced by their parents’ education: results of two cross-sectional studies conducted in Upper AustriaPediatr Allergy Immunol20102171028103510.1111/j.1399-3038.2010.01030.x

4. Solé D, Mallol J, Wandalsen GF, Aguirre V, Latin American ISAAC Phase 3 Study Group. Prevalence of symptoms of eczema in Latin America: results of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3. J Investig Allergol Clin Immunol. 2010;20(4):311-323. Available at: http://www.jiaci.org/issues/vol20issue4/6.pdf

D Solé J Mallol GF Wandalsen V Aguirre Latin American ISAAC Phase 3 Study Group Prevalence of symptoms of eczema in Latin America: results of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3J Investig Allergol Clin Immunol2010204311323http://www.jiaci.org/issues/vol20issue4/6.pdf

5. Barnetson RS, Rogers M. Childhood atopic eczema. BMJ. 2002;324(7350):1376-1379. DOI: 10.1136/bmj.324.7350.1376

RS Barnetson M Rogers Childhood atopic eczemaBMJ200232473501376137910.1136/bmj.324.7350.1376

6. Gustafsson D, Sjöberg O, Foucard T. Development of allergies and asthma in infants and young children with atopic dermatitis: a prospective follow-up to 7 years of age. Allergy. 2000;55(3):240-245. DOI: 10.1034/j.1398-9995.2000.00391.x

D Gustafsson O Sjöberg T Foucard Development of allergies and asthma in infants and young children with atopic dermatitis: a prospective follow-up to 7 years of ageAllergy200055324024510.1034/j.1398-9995.2000.00391.x

7. Kemp AS. Cost of illness of atopic dermatitis in children: a societal perspective. Pharmacoeconomics. 2003;21(2):105-113. DOI: 10.2165/00019053-200321020-00003

AS Kemp Cost of illness of atopic dermatitis in children: a societal perspectivePharmacoeconomics200321210511310.2165/00019053-200321020-00003

8. Lapidus CS, Schwarz DF, Honig PJ. Atopic dermatitis in children: who cares? Who pays? J Am Acad Dermatol. 1993;28(5 Pt 1):699-703.

CS Lapidus DF Schwarz PJ Honig Atopic dermatitis in children: who cares? Who pays?J Am Acad Dermatol1993285Pt 1699703

9. Lawson V, Lewis-Jones MS, Finlay AY, Reid P, Owens RG. The family impact of childhood atopic dermatitis: the Dermatitis Family Impact Questionnaire. Br J Dermatol. 1998;138(1):107-113. DOI: 10.1046/j.1365-2133.1998.02034.x

V Lawson MS Lewis-Jones AY Finlay P Reid RG Owens The family impact of childhood atopic dermatitis: the Dermatitis Family Impact QuestionnaireBr J Dermatol1998138110711310.1046/j.1365-2133.1998.02034.x

10. Adamson AS. The economics burden of atopic dermatitis. Adv Exp Med Biol. 2017;1027:79-92. DOI: 10.1007/978-3-319-64804-0_8

AS Adamson economics burden of atopic dermatitisAdv Exp Med Biol20171027799210.1007/978-3-319-64804-0_8

11. Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. 2018;32(5):657-682. DOI: 10.1111/jdv.14891

A Wollenberg S Barbarot T Bieber S Christen-Zaech M Deleuran A Fink-Wagner Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part IJ Eur Acad Dermatol Venereol201832565768210.1111/jdv.14891

12. Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. J Eur Acad Dermatol Venereol. 2018;32(6):850-878. DOI: 10.1111/jdv.14888

A Wollenberg S Barbarot T Bieber S Christen-Zaech M Deleuran A Fink-Wagner Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part IIJ Eur Acad Dermatol Venereol201832685087810.1111/jdv.14888

13. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926. DOI: 10.1136/bmj.39489.470347.AD

GH Guyatt AD Oxman GE Vist R Kunz Y Falck-Ytter P Alonso-Coello GRADE: an emerging consensus on rating quality of evidence and strength of recommendationsBMJ2008336765092492610.1136/bmj.39489.470347.AD

14. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383-394. DOI: 10.1016/j.jclinepi.2010.04.026

G Guyatt AD Oxman EA Akl R Kunz G Vist J Brozek GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tablesJ Clin Epidemiol201164438339410.1016/j.jclinepi.2010.04.026

15. Davies E, Rogers NK, Lloyd-Lavery A, Grindlay DJC, Thomas KS. What’s new in atopic eczema? An analysis of systematic reviews published in 2015. Part 1: epidemiology and methodology. Clin Exp Dermatol. 2018;43(4):375-379. DOI: 10.1111/ced.13377

E Davies NK Rogers A Lloyd-Lavery DJC Grindlay KS Thomas What’s new in atopic eczema? An analysis of systematic reviews published in 2015. Part 1: epidemiology and methodologyClin Exp Dermatol201843437537910.1111/ced.13377

16. Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832-826. DOI: 10.1016/j.jaci.2003.12.591

SG Johansson T Bieber R Dahl PS Friedmann BQ Lanier RF Lockey Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003J Allergy Clin Immunol2004113583282610.1016/j.jaci.2003.12.591

17. Schäfer T, Krämer U, Vieluf D, Abeck D, Behrendt H, Ring J. The excess of atopic eczema in East Germany is related to the intrinsic type. Br J Dermatol. 2000;143(5):992-998. DOI: 10.1046/j.1365-2133.2000.03832.x

T Schäfer U Krämer D Vieluf D Abeck H Behrendt J Ring The excess of atopic eczema in East Germany is related to the intrinsic typeBr J Dermatol2000143599299810.1046/j.1365-2133.2000.03832.x

18. Böhme M, Wickman M, Lennart-Nordvall S, Svartengren M, Wahlgren CF. Family history and risk of atopic dermatitis in children up to 4 years. Clin Exp Allergy. 2003;33(9):1226-1231. DOI: 10.1046/j.1365-2222.2003.01749.x

M Böhme M Wickman S Lennart-Nordvall M Svartengren CF Wahlgren Family history and risk of atopic dermatitis in children up to 4 yearsClin Exp Allergy20033391226123110.1046/j.1365-2222.2003.01749.x

19. Schmid-Grendelmeier P, Flückiger S, Disch R, Trautmann A, Wüthrich B, Blaser K, et al. IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. J Allergy Clin Immunol. 2005;115(5):1068-1075. DOI: 10.1016/j.jaci.2005.01.065

P Schmid-Grendelmeier S Flückiger R Disch A Trautmann B Wüthrich K Blaser gE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitisJ Allergy Clin Immunol200511551068107510.1016/j.jaci.2005.01.065

20. Sánchez J, Páez B, Macías A, Olmos C, de Falco A. Atopic dermatitis guideline. Position paper from the Latin American Society of Allergy, Asthma and Immunology. Rev Alerg Mex. 2014;61(3):178-211.

J Sánchez B Páez A Macías C Olmos A de Falco Atopic dermatitis guideline. Position paper from the Latin American Society of Allergy, Asthma and ImmunologyRev Alerg Mex2014613178211

21. Mizrahi M. Arguments from expert opinion and persists bias. Argumentation. 2018;32(2):175-95. DOI: 10.1007/s10503-017-9434-x

M Mizrahi Arguments from expert opinion and persists biasArgumentation201832217519510.1007/s10503-017-9434-x

22. Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017;140(4):950-958. DOI: 10.1016/j.jaci.2017.03.050

JL Brożek J Bousquet I Agache A Agarwal C Bachert S Bosnic-Anticevich Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revisionJ Allergy Clin Immunol2017140495095810.1016/j.jaci.2017.03.050

23. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 350: g7647. DOI: 10.1136/bmj.g7647

L Shamseer D Moher M Clarke D Ghersi A Liberati M Petticrew Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanationBMJ2015350g764710.1136/bmj.g7647

24. Okoli C, Pawlowski SD. The Delphi method as a research tool: an example, design considerations and applications. 2004;42(1):15-29. DOI: 10.1016/j.im.2003.11.002

C Okoli SD Pawlowski The Delphi method as a research tool: an example, design considerations and applications2004421152910.1016/j.im.2003.11.002

25. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401-406. DOI: 10.1016/j.jclinepi.2010.07.015

H Balshem M Helfand HJ Schünemann AD Oxman R Kunz J Brozek GRADE guidelines: 3. Rating the quality of evidenceJ Clin Epidemiol201164440140610.1016/j.jclinepi.2010.07.015

26. Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, et al. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: clinical practice guidelines. BMJ. 2016;353:i2089. DOI: 10.1136/bmj.i2089

P Alonso-Coello AD Oxman J Moberg R Brignardello-Petersen EA Akl M Davoli GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: clinical practice guidelinesBMJ2016353i208910.1136/bmj.i2089

27. Schünemann HJ, Mustafa R, Brozek J, Santesso N, Alonso-Coello P, Guyatt G, et al. GRADE Guidelines: 16. GRADE evidence to decision frameworks for tests in clinical practice and public health. J Clin Epidemiol. 2016;76:89-98. DOI: 10.1016/j.jclinepi.2016.01.032

HJ Schünemann R Mustafa J Brozek N Santesso P Alonso-Coello G Guyatt GRADE Guidelines: 16. GRADE evidence to decision frameworks for tests in clinical practice and public healthJ Clin Epidemiol201676899810.1016/j.jclinepi.2016.01.032

28. Thijs JL, Strickland I, Bruijnzeel-Koomen CAFM, Nierkens S, Giovannone B, Csomor E, et al. Moving toward endotypes in atopic dermatitis: identification of patient clusters based on serum biomarker analysis. J Allergy Clin Immunol. 2017;140(3):730-737. DOI: 10.1016/j.jaci.2017.03.023

JL Thijs I Strickland CAFM Bruijnzeel-Koomen S Nierkens B Giovannone E Csomor Moving toward endotypes in atopic dermatitis: identification of patient clusters based on serum biomarker analysisJ Allergy Clin Immunol2017140373073710.1016/j.jaci.2017.03.023

29. Muraro A, Lemanske RF, Hellings PW, Akdis CA, Bieber T, Casale TB, et al. Precision medicine in patients with allergic diseases: airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2016;137(5):1347-1358. DOI: 10.1016/j.jaci.2016.03.010

A Muraro RF Lemanske PW Hellings CA Akdis T Bieber TB Casale Precision medicine in patients with allergic diseases: airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & ImmunologyJ Allergy Clin Immunol201613751347135810.1016/j.jaci.2016.03.010

30. Orivuori L, Mustonen K, Roduit C, Braun-Fahrländer C, Dalphin JC, Genuneit J, et al. Immunoglobulin A and immunoglobulin G antibodies against β-lactoglobulin and gliadin at age 1 associate with immunoglobulin E sensitization at age 6. Pediatr Allergy Immunol. 2014;25(4):329-337. DOI: 10.1111/pai.12246

L Orivuori K Mustonen C Roduit C Braun-Fahrländer JC Dalphin J Genuneit Immunoglobulin A and immunoglobulin G antibodies against β-lactoglobulin and gliadin at age 1 associate with immunoglobulin E sensitization at age 6Pediatr Allergy Immunol201425432933710.1111/pai.12246

31. von Berg A, Filipiak-Pittroff B, Schulz H, Hoffmann U, Link E, Sußmann M, et al. Allergic manifestation 15 years after early intervention with hydrolyzed formulas-the GINI Study. Allergy. 2016;71(2):210-219. DOI: 10.1111/all.12790

A von Berg B Filipiak-Pittroff H Schulz U Hoffmann E Link M Sußmann Allergic manifestation 15 years after early intervention with hydrolyzed formulas-the GINI StudyAllergy201671221021910.1111/all.12790

32. Simpson EL, Chalmers JR, Hanifin JM, Thomas KS, Cork MJ, McLean WH, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol. 2014;134(4):818-823. DOI: 10.1016/j.jaci.2014.08.005

EL Simpson JR Chalmers JM Hanifin KS Thomas MJ Cork WH McLean Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis preventionJ Allergy Clin Immunol2014134481882310.1016/j.jaci.2014.08.005

33. Horimukai K, Morita K, Narita M, Kondo M, Kitazawa H, Nozaki M, et al. Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol. 2014;134(4):824-830. DOI: 10.1016/j.jaci.2014.07.060

K Horimukai K Morita M Narita M Kondo H Kitazawa M Nozaki Application of moisturizer to neonates prevents development of atopic dermatitisJ Allergy Clin Immunol2014134482483010.1016/j.jaci.2014.07.060

34. Chalmers JR, Haines RH, Mitchell EJ, Thomas KS, Brown SJ, Ridd M, et al. Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomised controlled trial. Trials. 2017;18(1):343. DOI: 10.1186/s13063-017-2031-3

JR Chalmers RH Haines EJ Mitchell KS Thomas SJ Brown M Ridd Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomised controlled trialTrials201718134334310.1186/s13063-017-2031-3

35. Tiplica GS, Kaszuba A, Malinauskienė L, Konno P, Boralevi F, Garrigue E, et al. Prevention of flares in children with atopic dermatitis with regular use of an emollient containing glycerol and paraffin: a randomized controlled study. Pediatr Dermatol. 2017;34(3):282-289. DOI: 10.1111/pde.13113

GS Tiplica A Kaszuba L Malinauskienė P Konno F Boralevi E Garrigue Prevention of flares in children with atopic dermatitis with regular use of an emollient containing glycerol and paraffin: a randomized controlled studyPediatr Dermatol201734328228910.1111/pde.13113

36. Åkerström U, Reitamo S, Langeland T, Berg M, Rustad L, Korhonen L, et al. Comparison of moisturizing creams for the prevention of atopic dermatitis relapse: a randomized double-blind controlled multicentre clinical trial. Acta Derm Venereol. 2015;95(5):587-592. DOI: 10.2340/00015555-2051

U Åkerström S Reitamo T Langeland M Berg L Rustad L Korhonen Comparison of moisturizing creams for the prevention of atopic dermatitis relapse: a randomized double-blind controlled multicentre clinical trialActa Derm Venereol201595558759210.2340/00015555-2051

37. Fukuie T, Hirakawa S, Narita M, Nomura I, Matsumoto K, Tokura Y, et al. Potential preventive effects of proactive therapy on sensitization in moderate to severe childhood atopic dermatitis: a randomized, investigator-blinded, controlled study. J Dermatol. 2016;43(11):1283-1292. DOI: 10.1111/1346-8138.13408

T Fukuie S Hirakawa M Narita I Nomura K Matsumoto Y Tokura Potential preventive effects of proactive therapy on sensitization in moderate to severe childhood atopic dermatitis: a randomized, investigator-blinded, controlled studyJ Dermatol201643111283129210.1111/1346-8138.13408

38. Muehleisen B, Gallo RL. Vitamin D in allergic disease: shedding light on a complex problem. J Allergy Clin Immunol. 2013;131(2):324-329. DOI: 10.1016/j.jaci.2012.12.1562

B Muehleisen RL Gallo Vitamin D in allergic disease: shedding light on a complex problemJ Allergy Clin Immunol2013131232432910.1016/j.jaci.2012.12.1562

39. Camargo CA, Ganmaa D, Sidbury R, Erdenedelger K, Radnaakhand N, Khandsuren B. Randomized trial of vitamin D supplementation for winter-related atopic dermatitis in children. J Allergy Clin Immunol. 2014;134(4):831-835. DOI: 10.1016/j.jaci.2014.08.002

CA Camargo D Ganmaa R Sidbury K Erdenedelger N Radnaakhand B Khandsuren Randomized trial of vitamin D supplementation for winter-related atopic dermatitis in childrenJ Allergy Clin Immunol2014134483183510.1016/j.jaci.2014.08.002

40. Sidbury R, Sullivan AF, Thadhani RI, Camargo CA. Randomized controlled trial of vitamin D supplementation for winter-related atopic dermatitis in Boston: a pilot study. Br J Dermatol. 2008;159(1):245-247. DOI: 10.1111/j.1365-2133.2008.08601.x

R Sidbury AF Sullivan RI Thadhani CA Camargo Randomized controlled trial of vitamin D supplementation for winter-related atopic dermatitis in Boston: a pilot studyBr J Dermatol2008159124524710.1111/j.1365-2133.2008.08601.x

41. Sánchez J, Sánchez A, Cardona R. Particular characteristics of atopic eczema in tropical environments. The Tropical Environment Control for Chronic Eczema and Molecular Assessment (TECCEMA) cohort study. An Bras Dermatol. 2017;92(2):177-183. DOI: 10.1590/abd1806-4841.20175140

J Sánchez A Sánchez R Cardona Particular characteristics of atopic eczema in tropical environments. The Tropical Environment Control for Chronic Eczema and Molecular Assessment (TECCEMA) cohort studyAn Bras Dermatol201792217718310.1590/abd1806-4841.20175140

42. Solman L, Lloyd-Lavery A, Grindlay DJC, Rogers NK, Thomas KS, Harman KE. What’s new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and prevention. Clin Exp Dermatol. 2019;44(4):363-369. DOI: 10.1111/ced.13885

L Solman A Lloyd-Lavery DJC Grindlay NK Rogers KS Thomas KE Harman What’s new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and preventionClin Exp Dermatol201944436336910.1111/ced.13885

43. Kim JP, Chao LX, Simpson EL, Silverberg JI. Persistence of atopic dermatitis (AD): a systematic review and meta-analysis. J Am Acad Dermatol. 2016;75(4):681-687. DOI: 10.1016/j.jaad.2016.05.028

JP Kim LX Chao EL Simpson JI Silverberg Persistence of atopic dermatitis (AD): a systematic review and meta-analysisJ Am Acad Dermatol201675468168710.1016/j.jaad.2016.05.028

44. Thorsteinsdottir S, Stokholm J, Thyssen JP, Nørgaard S, Thorsen J, Chawes BL, et al. Genetic, clinical, and environmental factors associated with persistent atopic dermatitis in childhood. JAMA Dermatol. 2018;155(1):50-57. DOI: 10.1001/jamadermatol.2018.4061

S Thorsteinsdottir J Stokholm JP Thyssen S Nørgaard J Thorsen BL Chawes Genetic, clinical, and environmental factors associated with persistent atopic dermatitis in childhoodJAMA Dermatol20181551505710.1001/jamadermatol.2018.4061

45. Pajno GB, Peroni DG, Barberio G, Pietrobelli A, Boner AL. Predictive features for persistence of atopic dermatitis in children. Pediatr Allergy Immunol. 2003;14(4):292-295. DOI: 10.1034/j.1399-3038.2003.00060.x

GB Pajno DG Peroni G Barberio A Pietrobelli AL Boner Predictive features for persistence of atopic dermatitis in childrenPediatr Allergy Immunol200314429229510.1034/j.1399-3038.2003.00060.x

46. Guo MM, Tseng WN, Ou CY, Hsu TY, Kuo HC, Yang KD. Predictive factors of persistent infantile atopic dermatitis up to 6 years old in Taiwan: a prospective birth cohort study. Allergy. 2015;70(11):1477-1484. DOI: 10.1111/all.12706

MM Guo WN Tseng CY Ou TY Hsu HC Kuo KD Yang Predictive factors of persistent infantile atopic dermatitis up to 6 years old in Taiwan: a prospective birth cohort studyAllergy201570111477148410.1111/all.12706

47. Domínguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971-11975. DOI: 10.1073/pnas.1002601107

MG Domínguez-Bello EK Costello M Contreras M Magris G Hidalgo N Fierer Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newbornsProc Natl Acad Sci U S A201010726119711197510.1073/pnas.1002601107

48. Park YJ, Lee HK. The role of skin and orogenital microbiota in protective immunity and chronic immune-mediated inflammatory disease. Front Immunol. 2017;8:1955. DOI: 10.3389/fimmu.2017.01955

YJ Park HK Lee The role of skin and orogenital microbiota in protective immunity and chronic immune-mediated inflammatory diseaseFront Immunol20178195510.3389/fimmu.2017.01955

49. Baldwin HE, Bhatia ND, Friedman A, Eng RM, Seite S. The Role of cutaneous microbiota harmony in maintaining a functional skin barrier. J Drugs Dermatol. 2017;16(1):12-18. DOI: 10.25251/skin.1.supp.138

HE Baldwin ND Bhatia A Friedman RM Eng S Seite The Role of cutaneous microbiota harmony in maintaining a functional skin barrierJ Drugs Dermatol2017161121810.25251/skin.1.supp.138

50. Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T, et al. Antimicrobials from human skin commensal bacteria protect against. Sci Transl Med. 2017;9(378). DOI: 10.1126/scitranslmed.aah4680

T Nakatsuji TH Chen S Narala KA Chun AM Two T Yun Antimicrobials from human skin commensal bacteria protect againstSci Transl Med2017937810.1126/scitranslmed.aah4680

51. Di Domenico EG, Cavallo I, Bordignon V, Prignano G, Sperduti I, Gurtner A, et al. Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: a pivotal interplay in the pathogenesis of atopic dermatitis. Sci Rep. 2018;8(1):9573. DOI: 10.1038/s41598-018-27421-1

EG Di Domenico I Cavallo V Bordignon G Prignano I Sperduti A Gurtner Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: a pivotal interplay in the pathogenesis of atopic dermatitisSci Rep2018819573957310.1038/s41598-018-27421-1

52. Jinnestål CL, Belfrage E, Bäck O, Schmidtchen A, Sonesson A. Skin barrier impairment correlates with cutaneous Staphylococcus aureus colonization and sensitization to skin-associated microbial antigens in adult patients with atopic dermatitis. Int J Dermatol. 2014;53(1):27-33. DOI: 10.1111/ijd.12198

CL Jinnestål E Belfrage O Bäck A Schmidtchen A Sonesson Skin barrier impairment correlates with cutaneous Staphylococcus aureus colonization and sensitization to skin-associated microbial antigens in adult patients with atopic dermatitisInt J Dermatol2014531273310.1111/ijd.12198

53. Cavalcante FS, Abad ED, Lyra YC, Saintive SB, Ribeiro M, Ferreira DC, et al. High prevalence of methicillin resistance and PVL genes among Staphylococcus aureus isolates from the nares and skin lesions of pediatric patients with atopic dermatitis. Braz J Med Biol Res. 2015;48(7):588-594. DOI: 10.1590/1414-431X20154221

FS Cavalcante ED Abad YC Lyra SB Saintive M Ribeiro DC Ferreira High prevalence of methicillin resistance and PVL genes among Staphylococcus aureus isolates from the nares and skin lesions of pediatric patients with atopic dermatitisBraz J Med Biol Res201548758859410.1590/1414-431X20154221

54. Birnie AJ, Bath-Hextall FJ, Ravenscroft JC, Williams HC. Interventions to reduce Staphylococcus aureus in the management of atopic eczema. Cochrane Database Syst Rev. 2008(3):CD003871. DOI: 10.1002/14651858.CD003871.pub3

AJ Birnie FJ Bath-Hextall JC Ravenscroft HC Williams Interventions to reduce Staphylococcus aureus in the management of atopic eczemaCochrane Database Syst Rev20083CD00387110.1002/14651858.CD003871.pub3

55. Yeşilova Y, Çalka Ö, Akdeniz N, Berktaş M. Effect of probiotics on the treatment of children with atopic dermatitis. Ann Dermatol. 2012;24(2):189-193. DOI: 10.5021/ad.2012.24.2.189

Y Yeşilova Ö Çalka N Akdeniz M Berktaş Effect of probiotics on the treatment of children with atopic dermatitisAnn Dermatol201224218919310.5021/ad.2012.24.2.189

56. Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2015;8(1):4. DOI: 10.1186/s40413-015-0055-2

A Fiocchi R Pawankar C Cuello-Garcia K Ahn S Al-Hammadi A Agarwal World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): ProbioticsWorld Allergy Organ J2015814410.1186/s40413-015-0055-2

57. Niccoli AA, Artesi AL, Candio F, Ceccarelli S, Cozzali R, Ferraro L, et al. Preliminary results on clinical effects of probiotic Lactobacillus salivarius LS01 in children affected by atopic dermatitis. J Clin Gastroenterol. 2014;48(Suppl 1):S34-S36. DOI: 10.1097/MCG.0000000000000233

AA Niccoli AL Artesi F Candio S Ceccarelli R Cozzali L Ferraro Preliminary results on clinical effects of probiotic Lactobacillus salivarius LS01 in children affected by atopic dermatitisJ Clin Gastroenterol201448Suppl 1S34S3610.1097/MCG.0000000000000233

58. Huang R, Ning H, Shen M, Li J, Zhang J, Chen X. Probiotics for the treatment of atopic dermatitis in children: a systematic review and meta-analysis of randomized controlled trials. Front Cell Infect Microbiol. 2017;7:392. DOI: 10.3389/fcimb.2017.00392

R Huang H Ning M Shen J Li J Zhang X Chen Probiotics for the treatment of atopic dermatitis in children: a systematic review and meta-analysis of randomized controlled trialsFront Cell Infect Microbiol2017739210.3389/fcimb.2017.00392

59. Wickens K, Barthow C, Mitchell EA, Stanley TV, Purdie G, Rowden J, et al. Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczema. Pediatr Allergy Immunol. 2018;29(3):296-302. DOI: 10.1111/pai.12874

K Wickens C Barthow EA Mitchell TV Stanley G Purdie J Rowden Maternal supplementation alone with Lactobacillus rhamnosus HN001 during pregnancy and breastfeeding does not reduce infant eczemaPediatr Allergy Immunol201829329630210.1111/pai.12874

60. Boyle RJ, Bath-Hextall FJ, Leonardi-Bee J, Murrell DF, Tang ML. Probiotics for treating eczema. Cochrane Database Syst Rev. 2008(4):CD006135. DOI: 10.1002/14651858.CD006135.pub3

RJ Boyle FJ Bath-Hextall J Leonardi-Bee DF Murrell ML Tang Probiotics for treating eczemaCochrane Database Syst Rev20084CD00613510.1002/14651858.CD006135.pub3

61. Yang HJ, Min TK, Lee HW, Pyun BY. Efficacy of probiotic therapy on atopic dermatitis in children: a randomized, double-blind, placebo-controlled trial. Allergy Asthma Immunol Res. 2014;6(3):208-215. DOI: 10.4168/aair.2014.6.3.208

HJ Yang TK Min HW Lee BY Pyun Efficacy of probiotic therapy on atopic dermatitis in children: a randomized, double-blind, placebo-controlled trialAllergy Asthma Immunol Res20146320821510.4168/aair.2014.6.3.208

62. Sánchez J, Sánchez A. Epidemiology of food allergy in Latin America. Allergol Immunopathol (Madr). 2015;43(2):185-195. DOI: 10.1016/j.aller.2013.07.001

J Sánchez A Sánchez Epidemiology of food allergy in Latin AmericaAllergol Immunopathol (Madr)201543218519510.1016/j.aller.2013.07.001

63. Sánchez J, Sánchez A. Epidemiologic studies about food allergy and food sensitization in tropical countries. Results and limitations. Allergol Immunopathol (Madr). 2019;47(4):401-408. DOI: 10.1016/j.aller.2018.11.001

J Sánchez A Sánchez Epidemiologic studies about food allergy and food sensitization in tropical countries. Results and limitationsAllergol Immunopathol (Madr)201947440140810.1016/j.aller.2018.11.001

64. Estrada-Reyes E, Pardo-Castañeda MG, Toledo-Bahena ME, Lerma-Ortiz ML, Del Río-Navarro B, Nava-Ocampo AA. A case-control study of food hyper-sensitivity, timing of weaning and family history of allergies in young children with atopic dermatitis. Allergol Immunopathol (Madr). 2007;35(3):101-104. DOI: 10.1157/13106777

E Estrada-Reyes MG Pardo-Castañeda ME Toledo-Bahena ML Lerma-Ortiz B Del Río-Navarro AA Nava-Ocampo A case-control study of food hyper-sensitivity, timing of weaning and family history of allergies in young children with atopic dermatitisAllergol Immunopathol (Madr)200735310110410.1157/13106777

65. Jøhnke H, Norberg LA, Vach W, Høst A, Andersen KE. Patterns of sensitization in infants and its relation to atopic dermatitis. Pediatr Allergy Immunol. 2006;17(8):591-600. DOI: 10.1111/j.1399-3038.2006.00453.x

H Jøhnke LA Norberg W Vach A Høst KE Andersen Patterns of sensitization in infants and its relation to atopic dermatitisPediatr Allergy Immunol200617859160010.1111/j.1399-3038.2006.00453.x

66. Roerdink EM, Flokstra-de Blok BM, Blok JL, Schuttelaar ML, Niggemann B, Werfel T, et al. Association of food allergy and atopic dermatitis exacerbations. Ann Allergy Asthma Immunol. 2016;116(4):334-338. DOI: 10.1016/j.anai.2016.01.022

EM Roerdink BM Flokstra-de Blok JL Blok ML Schuttelaar B Niggemann T Werfel Association of food allergy and atopic dermatitis exacerbationsAnn Allergy Asthma Immunol2016116433433810.1016/j.anai.2016.01.022

67. Rennick GJ, Moore E, Orchard DC. Skin prick testing to food allergens in breast-fed young infants with moderate to severe atopic dermatitis. Australas J Dermatol. 2006;47(1):41-45. DOI: 10.1111/j.1440-0960.2006.00221.x

GJ Rennick E Moore DC. Orchard Skin prick testing to food allergens in breast-fed young infants with moderate to severe atopic dermatitisAustralas J Dermatol2006471414510.1111/j.1440-0960.2006.00221.x

68. Levy SA, Dortas Junior SD, Pires AH, Abe AT, Valle SO, Coelho VP, et al. Atopy patch test (APT) in the diagnosis of food allergy in children with atopic dermatitis. An Bras Dermatol. 2012;87(5):724-728. DOI: 10.1590/s0365-05962012000500009

SA Levy SD Dortas Junior AH Pires AT Abe SO Valle VP Coelho Atopy patch test (APT) in the diagnosis of food allergy in children with atopic dermatitisAn Bras Dermatol201287572472810.1590/s0365-05962012000500009

69. David TJ. Anaphylactic shock during elimination diets for severe atopic eczema. Arch Dis Child. 1984;59(10):983-986. DOI: 10.1136/adc.59.10.983

TJ David Anaphylactic shock during elimination diets for severe atopic eczemaArch Dis Child1984591098398610.1136/adc.59.10.983

70. Barbi E, Gerarduzzi T, Longo G, Ventura A. Fatal allergy as a possible consequence of long-term elimination diet. Allergy. 2004;59(6):668-669. DOI: 10.1111/j.1398-9995.2004.00398.x

E Barbi T Gerarduzzi G Longo A Ventura Fatal allergy as a possible consequence of long-term elimination dietAllergy200459666866910.1111/j.1398-9995.2004.00398.x

71. Flinterman AE, Knulst AC, Meijer Y, Bruijnzeel-Koomen CA, Pasmans SG. Acute allergic reactions in children with AEDS after prolonged cow’s milk elimination diets. Allergy. 2006;61(3):370-374. DOI: 10.1111/j.1398-9995.2006.01018.x

AE Flinterman AC Knulst Y Meijer CA Bruijnzeel-Koomen SG Pasmans Acute allergic reactions in children with AEDS after prolonged cow’s milk elimination dietsAllergy200661337037410.1111/j.1398-9995.2006.01018.x

72. Chang A, Robison R, Cai M, Singh AM. Natural history of food-triggered atopic dermatitis and development of immediate reactions in children. J Allergy Clin Immunol Pract. 2016;4(2):229-236. DOI: 10.1016/j.jaip.2015.08.006

A Chang R Robison M Cai AM Singh Natural history of food-triggered atopic dermatitis and development of immediate reactions in childrenJ Allergy Clin Immunol Pract20164222923610.1016/j.jaip.2015.08.006

73. Fleischer DM, Bock SA, Spears GC, Wilson CG, Miyazawa NK, Gleason MC, et al. Oral food challenges in children with a diagnosis of food allergy. J Pediatr. 2011;158(4):578-583. DOI: 10.1016/j.jpeds.2010.09.027

DM Fleischer SA Bock GC Spears CG Wilson NK Miyazawa MC Gleason Oral food challenges in children with a diagnosis of food allergyJ Pediatr2011158457858310.1016/j.jpeds.2010.09.027

74. Eapen AA, Kloepfer KM, Leickly FE, Slaven JE, Vitalpur G. Oral food challenge failures among foods restricted because of atopic dermatitis. Ann Allergy Asthma Immunol. 2019;122(2):193-197. DOI: 10.1016/j.anai.2018.10.012

AA Eapen KM Kloepfer FE Leickly JE Slaven G Vitalpur Oral food challenge failures among foods restricted because of atopic dermatitisAnn Allergy Asthma Immunol2019122219319710.1016/j.anai.2018.10.012

75. Santer M, Rumsby K, Ridd MJ, Francis NA, Stuart B, Chorozoglou M, et al. Adding emollient bath additives to standard eczema management for children with eczema: the BATHE RCT. Health Technol Assess. 2018;22(57):1-116.

M Santer K Rumsby MJ Ridd NA Francis B Stuart M Chorozoglou Adding emollient bath additives to standard eczema management for children with eczema: the BATHE RCTHealth Technol Assess201822571116

76. Antonijević MD, Novac O, O’Hagan BM. Can emollients of similar composition be assumed to be therapeutically equivalent: a comparison of skin occlusivity and emulsion microstructure. Clin Cosmet Investig Dermatol. 2018;11:461-465. DOI: 10.2147/CCID.S176943

MD Antonijević O Novac BM O’Hagan Can emollients of similar composition be assumed to be therapeutically equivalent: a comparison of skin occlusivity and emulsion microstructureClin Cosmet Investig Dermatol20181146146510.2147/CCID.S176943

77. Jung HJ, Bae JY, Kim JE, Na CH, Park GH, Bae YI, et al. Survey of disease awareness, treatment behavior and treatment satisfaction in patients with atopic dermatitis in Korea: a multicenter study. J Dermatol. 2018;45(10):1172-1180. DOI: 10.1111/1346-8138.14540

HJ Jung JY Bae JE Kim CH Na GH Park YI Bae Survey of disease awareness, treatment behavior and treatment satisfaction in patients with atopic dermatitis in Korea: a multicenter studyJ Dermatol201845101172118010.1111/1346-8138.14540

78. Sala-Cunill A, Lazaro M, Herráez L, Quiñones MD, Moro-Moro M, Sánchez I, et al. Basic skin care and topical therapies for atopic dermatitis: essential approaches and beyond. J Investig Allergol Clin Immunol. 2018;28(6):379-391. DOI: 10.18176/jiaci.0293

A Sala-Cunill M Lazaro L Herráez MD Quiñones M Moro-Moro I Sánchez Basic skin care and topical therapies for atopic dermatitis: essential approaches and beyondJ Investig Allergol Clin Immunol201828637939110.18176/jiaci.0293

79. Eriksson S, van der Plas MJA, Mörgelin M, Sonesson A. Antibacterial and antibiofilm effects of sodium hypochlorite against Staphylococcus aureus isolates derived from patients with atopic dermatitis. Br J Dermatol. 2017;177(2):513-521. DOI: 10.1111/bjd.15410

S Eriksson MJA van der Plas M Mörgelin A Sonesson Antibacterial and antibiofilm effects of sodium hypochlorite against Staphylococcus aureus isolates derived from patients with atopic dermatitisBr J Dermatol2017177251352110.1111/bjd.15410

80. Harris V, Smith SD. Lifting the biofilm lid on the antibacterial and antibiofilm effects of sodium hypochlorite against Staphylococcus aureus in atopic dermatitis. Br J Dermatol. 2017;177(2):347-348. DOI: 10.1111/bjd.15692

V Harris SD Smith Lifting the biofilm lid on the antibacterial and antibiofilm effects of sodium hypochlorite against Staphylococcus aureus in atopic dermatitisBr J Dermatol2017177234734810.1111/bjd.15692

81. Asch S, Vork DL, Joseph J, Major-Elechi B, Tollefson MM. Comparison of bleach, acetic acid, and other topical anti-infective treatments in pediatric atopic dermatitis: a retrospective cohort study on antibiotic exposure. Pediatr Dermatol. 2019;36(1):115-120. DOI: 10.1111/pde.13663

S Asch DL Vork J Joseph B Major-Elechi MM Tollefson Comparison of bleach, acetic acid, and other topical anti-infective treatments in pediatric atopic dermatitis: a retrospective cohort study on antibiotic exposurePediatr Dermatol201936111512010.1111/pde.13663

82. Church MK, Maurer M. H1-antihistamines and itch in atopic dermatitis. Exp Dermatol. 2015;24(5):332-333.

MK Church M Maurer H1-antihistamines and itch in atopic dermatitisExp Dermatol2015245332333

83. Ohsawa Y, Hirasawa N. The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study. Allergol Int. 2014;63(4):533-542. DOI: 10.2332/allergolint.13-RA-0675

Y Ohsawa N Hirasawa The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical studyAllergol Int201463453354210.2332/allergolint.13-RA-0675

84. Munday J, Bloomfield R, Goldman M, Robey H, Kitowska GJ, Gwiezdziski Z, et al. Chlorpheniramine is no more effective than placebo in relieving the symptoms of childhood atopic dermatitis with a nocturnal itching and scratching component. Dermatology. 2002;205(1):40-45. DOI: 10.1159/000063138

J Munday R Bloomfield M Goldman H Robey GJ Kitowska Z Gwiezdziski Chlorpheniramine is no more effective than placebo in relieving the symptoms of childhood atopic dermatitis with a nocturnal itching and scratching componentDermatology20022051404510.1159/000063138

85. Wahlgren CF, Hägermark O, Bergström R. The antipruritic effect of a sedative and a non-sedative antihistamine in atopic dermatitis. Br J Dermatol . 1990;122(4):545-551. DOI: 10.1111/j.1365-2133.1990.tb14732.x

CF Wahlgren O Hägermark R Bergström The antipruritic effect of a sedative and a non-sedative antihistamine in atopic dermatitisBr J Dermatol1990122454555110.1111/j.1365-2133.1990.tb14732.x

86. Frosch PJ, Schwanitz HJ, Macher E. A double blind trial of H1 and H2 receptor antagonists in the treatment of atopic dermatitis. Arch Dermatol Res. 1984;276(1):36-40. DOI: 10.1007/bf00412560

PJ Frosch HJ Schwanitz E Macher A double blind trial of H1 and H2 receptor antagonists in the treatment of atopic dermatitisArch Dermatol Res19842761364010.1007/bf00412560

87. Savin JA, Dow R, Harlow BJ, Massey H, Yee KF. The effect of a new non-sedative H1-receptor antagonist (LN2974) on the itching and scratching of patients with atopic eczema. Clin Exp Dermatol . 1986;11(6):600-602. DOI: 10.1111/j.1365-2230.1986.tb00515.x

JA Savin R Dow BJ Harlow H Massey KF Yee The effect of a new non-sedative H1-receptor antagonist (LN2974) on the itching and scratching of patients with atopic eczemaClin Exp Dermatol198611660060210.1111/j.1365-2230.1986.tb00515.x

88. Hannuksela M, Kalimo K, Lammintausta K, Mattila T, Turjanmaa K, Varjonen E, et al. Dose ranging study: cetirizine in the treatment of atopic dermatitis in adults. Ann Allergy. 1993;70(2):127-133.

M Hannuksela K Kalimo K Lammintausta T Mattila K Turjanmaa E Varjonen Dose ranging study: cetirizine in the treatment of atopic dermatitis in adultsAnn Allergy1993702127133

89. Langeland T, Fagertun HE, Larsen S. Therapeutic effect of loratadine on pruritus in patients with atopic dermatitis. A multi-crossover-designed study. Allergy. 1994;49(1):22-26. DOI: 10.1111/j.1398-9995.1994.tb00768.x

T Langeland HE Fagertun S Larsen Therapeutic effect of loratadine on pruritus in patients with atopic dermatitis. A multi-crossover-designed studyAllergy1994491222610.1111/j.1398-9995.1994.tb00768.x

90. La Rosa M, Ranno C, Musarra I, Guglielmo F, Corrias A, Bellanti JA. Double-blind study of cetirizine in atopic eczema in children. Ann Allergy . 1994;73(2):117-122.

M La Rosa C Ranno I Musarra F Guglielmo A Corrias JA Bellanti Double-blind study of cetirizine in atopic eczema in childrenAnn Allergy1994732117122

91. Yamanaka K, Motomura E, Noro Y, Umeda K, Morikawa T, Umeda-Togami K, et al. Olopatadine, a non-sedating H1 antihistamine, decreases the nocturnal scratching without affecting sleep quality in atopic dermatitis. Exp Dermatol . 2015;24(3):227-229. DOI: 10.1111/exd.12630

K Yamanaka E Motomura Y Noro K Umeda T Morikawa K Umeda-Togami Olopatadine, a non-sedating H1 antihistamine, decreases the nocturnal scratching without affecting sleep quality in atopic dermatitisExp Dermatol201524322722910.1111/exd.12630

92. Kawashima M, Tango T, Noguchi T, Inagi M, Nakagawa H, Harada S. Addition of fexofenadine to a topical corticosteroid reduces the pruritus associated with atopic dermatitis in a 1-week randomized, multicentre, double-blind, placebo-controlled, parallel-group study. Br J Dermatol . 2003;148(6):1212-1221. DOI: 10.1046/j.1365-2133.2003.05293.x

M Kawashima T Tango T Noguchi M Inagi H Nakagawa S Harada Addition of fexofenadine to a topical corticosteroid reduces the pruritus associated with atopic dermatitis in a 1-week randomized, multicentre, double-blind, placebo-controlled, parallel-group studyBr J Dermatol200314861212122110.1046/j.1365-2133.2003.05293.x

93. Church MK, Maurer M, Simons FE, Bindslev-Jensen C, van Cauwenberge P, Bousquet J, et al. Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper. Allergy . 2010;65(4):459-466. DOI: 10.1111/j.1398-9995.2009.02325.x

MK Church M Maurer FE Simons C Bindslev-Jensen P van Cauwenberge J Bousquet Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paperAllergy201065445946610.1111/j.1398-9995.2009.02325.x

94. Hamilton JD, Suárez-Fariñas M, Dhingra N, Cardinale I, Li X, Kostic A, et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014;134(6):1293-1300. DOI: 10.1016/j.jaci.2014.10.013

JD Hamilton M Suárez-Fariñas N Dhingra I Cardinale X Li A Kostic Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitisJ Allergy Clin Immunol201413461293130010.1016/j.jaci.2014.10.013

95. Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130-139. DOI: 10.1056/NEJMoa1314768

LA Beck D Thaçi JD Hamilton NM Graham T Bieber R Rocklin Dupilumab treatment in adults with moderate-to-severe atopic dermatitisN Engl J Med2014371213013910.1056/NEJMoa1314768

96. Silverberg JI, Simpson EL, Ardeleanu M, Thaçi D, Barbarot S, Bagel J, et al. Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator’s Global Assessment: a pooled analysis of data from 2 phase III trials. Br J Dermatol . 2019;181(1):80-87. DOI: 10.1111/bjd.17791

JI Silverberg EL Simpson M Ardeleanu D Thaçi S Barbarot J Bagel Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator’s Global Assessment: a pooled analysis of data from 2 phase III trialsBr J Dermatol20191811808710.1111/bjd.17791

97. Storan ER, Woolf RT, Smith CH, Pink AE. Clearance of molluscum contagiosum virus infection in patients with atopic eczema treated with dupilumab. Br J Dermatol . 2019;181(2):385-386. DOI: 10.1111/bjd.17712

ER Storan RT Woolf CH Smith AE Pink Clearance of molluscum contagiosum virus infection in patients with atopic eczema treated with dupilumabBr J Dermatol2019181238538610.1111/bjd.17712

98. Blauvelt A, Rosmarin D, Bieber T, Simpson EL, Bagel J, Worm M, et al. Improvement of atopic dermatitis with dupilumab occurs equally well across different anatomic regions: data from phase 3 clinical trials. Br J Dermatol . 2019;181(1):196-197. DOI: 10.1111/bjd.17703

A Blauvelt D Rosmarin T Bieber EL Simpson J Bagel M Worm Improvement of atopic dermatitis with dupilumab occurs equally well across different anatomic regions: data from phase 3 clinical trialsBr J Dermatol2019181119619710.1111/bjd.17703

99. Tintle S, Shemer A, Suárez-Fariñas M, Fujita H, Gilleaudeau P, Sullivan-Whalen M, et al. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response. J Allergy Clin Immunol. 2011;128(3):583-593. DOI: 10.1016/j.jaci.2011.05.042

S Tintle A Shemer M Suárez-Fariñas H Fujita P Gilleaudeau M Sullivan-Whalen Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic responseJ Allergy Clin Immunol2011128358359310.1016/j.jaci.2011.05.042

100. Clayton TH, Clark SM, Turner D, Goulden V. The treatment of severe atopic dermatitis in childhood with narrowband ultraviolet B phototherapy. ClinExp Dermatol . 2007;32(1):28-33. DOI: 10.1111/j.1365-2230.2006.02292.x

TH Clayton SM Clark D Turner V Goulden The treatment of severe atopic dermatitis in childhood with narrowband ultraviolet B phototherapyClinExp Dermatol2007321283310.1111/j.1365-2230.2006.02292.x

101. Meduri NB, Vandergriff T, Rasmussen H, Jacobe H. Phototherapy in the management of atopic dermatitis: a systematic review. Photodermatol Photoimmunol Photomed. 2007;23(4):106-112. DOI: 10.1111/j.1600-0781.2007.00291.x

NB Meduri T Vandergriff H Rasmussen H Jacobe Phototherapy in the management of atopic dermatitis: a systematic reviewPhotodermatol Photoimmunol Photomed200723410611210.1111/j.1600-0781.2007.00291.x

102. Brownell J, Wang S, Tsoukas MM. Compliance and phototherapy. Clin Dermatol. 2016;34(5):582-586. DOI: 10.1016/j.clindermatol.2016.05.007

J Brownell S Wang MM Tsoukas Compliance and phototherapyClin Dermatol201634558258610.1016/j.clindermatol.2016.05.007

103. Cline A, Unrue EL, Collins A, Feldman SR. Adherence to a novel home phototherapy system with integrated features. Dermatol Online J. 2019;25(3). Available at: https://www.clarifymed.com/wp-content/uploads/DOJ-Adherence-Publication-March-2019.pdf

A Cline EL Unrue A Collins SR Feldman Adherence to a novel home phototherapy system with integrated featuresDermatol Online J2019253https://www.clarifymed.com/wp-content/uploads/DOJ-Adherence-Publication-March-2019.pdf

104. Drucker AM, Eyerich K, de Bruin-Weller MS, Thyssen JP, Spuls PI, Irvine AD, et al. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol . 2018;178(3):768-775. DOI: 10.1111/bjd.15928

AM Drucker K Eyerich MS de Bruin-Weller JP Thyssen PI Spuls AD Irvine Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statementBr J Dermatol2018178376877510.1111/bjd.15928

105. Roekevisch E, Spuls PI, Kuester D, Limpens J, Schmitt J. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014;133(2):429-438. DOI: 10.1016/j.jaci.2013.07.049

E Roekevisch PI Spuls D Kuester J Limpens J Schmitt Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic reviewJ Allergy Clin Immunol2014133242943810.1016/j.jaci.2013.07.049

106. Yu SH, Drucker AM, Lebwohl M, Silverberg JI. A systematic review of the safety and efficacy of systemic corticosteroids in atopic dermatitis. J Am Acad Dermatol. 2018;78(4):733-740. DOI: 10.1016/j.jaad.2017.09.074

SH Yu AM Drucker M Lebwohl JI Silverberg A systematic review of the safety and efficacy of systemic corticosteroids in atopic dermatitisJ Am Acad Dermatol201878473374010.1016/j.jaad.2017.09.074

107. Berth-Jones J, Takwale A, Tan E, Barclay G, Agarwal S, Ahmed I, et al. Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial. Br J Dermatol . 2002;147(2):324-330. DOI: 10.1046/j.1365-2133.2002.04989.x

J Berth-Jones A Takwale E Tan G Barclay S Agarwal I Ahmed Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trialBr J Dermatol2002147232433010.1046/j.1365-2133.2002.04989.x

108. Berth-Jones J, Graham-Brown RA, Marks R, Camp RD, English JS, Freeman K, et al. Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis. Br J Dermatol . 1997;136(1):76-81. DOI: 10.1046/j.1365-2133.1997.d01-1146.x

J Berth-Jones RA Graham-Brown R Marks RD Camp JS English K Freeman Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitisBr J Dermatol19971361768110.1046/j.1365-2133.1997.d01-1146.x

109. Salek MS, Finlay AY, Luscombe DK, Allen BR, Berth-Jones J, Camp RD, et al. Cyclosporin greatly improves the quality of life of adults with severe atopic dermatitis. A randomized, double-blind, placebo-controlled trial. Br J Dermatol . 1993;129(4):422-430. DOI: 10.1111/j.1365-2133.1993.tb03170.x

MS Salek AY Finlay DK Luscombe BR Allen J Berth-Jones RD Camp Cyclosporin greatly improves the quality of life of adults with severe atopic dermatitis. A randomized, double-blind, placebo-controlled trialBr J Dermatol1993129442243010.1111/j.1365-2133.1993.tb03170.x

110. van Joost T, Heule F, Korstanje M, van den Broek MJ, Stenveld HJ, van Vloten WA. Cyclosporin in atopic dermatitis: a multicentre placebo-controlled study. Br J Dermatol . 1994;130(5):634-640. DOI: 10.1111/j.1365-2133.1994.tb13111.x

T van Joost F Heule M Korstanje MJ van den Broek HJ Stenveld WA van Vloten Cyclosporin in atopic dermatitis: a multicentre placebo-controlled studyBr J Dermatol1994130563464010.1111/j.1365-2133.1994.tb13111.x

111. Sowden JM, Berth-Jones J, Ross JS, Motley RJ, Marks R, Finlay AY, et al. Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis. Lancet. 1991;338(8760):137-140. DOI: 10.1016/0140-6736(91)90134-b

JM Sowden J Berth-Jones JS Ross RJ Motley R Marks AY Finlay Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitisLancet1991338876013714010.1016/0140-6736(91)90134-b

112. Haeck IM, Knol MJ, Ten Berge O, van Velsen SG, de Bruin-Weller MS, Bruijnzeel-Koomen CA. Enteric-coated mycophenolate sodium versus cyclosporin A as long-term treatment in adult patients with severe atopic dermatitis: a randomized controlled trial. J Am Acad Dermatol. 2011;64(6):1074-84. DOI: 10.1016/j.jaad.2010.04.027

IM Haeck MJ Knol O Ten Berge SG van Velsen MS de Bruin-Weller CA Bruijnzeel-Koomen Enteric-coated mycophenolate sodium versus cyclosporin A as long-term treatment in adult patients with severe atopic dermatitis: a randomized controlled trialJ Am Acad Dermatol20116461074108410.1016/j.jaad.2010.04.027

113. Koppelhus U, Poulsen J, Grunnet N, Deleuran MS, Obitz E. Cyclosporine and extracorporeal photopheresis are equipotent in treating severe atopic dermatitis: a randomized cross-over study comparing two efficient treatment modalities. Front Med (Lausanne). 2014;1:33. DOI: 10.3389/fmed.2014.00033

U Koppelhus J Poulsen N Grunnet MS Deleuran E Obitz Cyclosporine and extracorporeal photopheresis are equipotent in treating severe atopic dermatitis: a randomized cross-over study comparing two efficient treatment modalitiesFront Med (Lausanne)201413310.3389/fmed.2014.00033

114. Zonneveld IM, De Rie MA, Beljaards RC, Van Der Rhee HJ, Wuite J, Zeegelaar J, et al. The long-term safety and efficacy of cyclosporin in severe refractory atopic dermatitis: a comparison of two dosage regimens. Br J Dermatol . 1996;135(Suppl 48):15-20. DOI: 10.1111/j.1365-2133.1996.tb00704.x

IM Zonneveld MA De Rie RC Beljaards HJ Van Der Rhee J Wuite J Zeegelaar The long-term safety and efficacy of cyclosporin in severe refractory atopic dermatitis: a comparison of two dosage regimensBr J Dermatol1996135Suppl 48152010.1111/j.1365-2133.1996.tb00704.x

115. Granlund H, Erkko P, Remitz A, Langeland T, Helsing P, Nuutinen M, et al. Comparison of cyclosporin and UVAB phototherapy for intermittent one-year treatment of atopic dermatitis. Acta Derm Venereol. 2001;81(1):22-27. DOI: 10.1080/00015550120235

H Granlund P Erkko A Remitz T Langeland P Helsing M Nuutinen Comparison of cyclosporin and UVAB phototherapy for intermittent one-year treatment of atopic dermatitisActa Derm Venereol2001811222710.1080/00015550120235

116. Harper JI, Ahmed I, Barclay G, Lacour M, Hoeger P, Cork MJ, et al. Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy. Br J Dermatol . 2000;142(1):52-58. DOI: 10.1046/j.1365-2133.2000.03241.x

JI Harper I Ahmed G Barclay M Lacour P Hoeger MJ Cork Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapyBr J Dermatol20001421525810.1046/j.1365-2133.2000.03241.x

117. Czech W, Bräutigam M, Weidinger G, Schöpf E. A body-weight-independent dosing regimen of cyclosporine microemulsion is effective in severe atopic dermatitis and improves the quality of life. J Am Acad Dermatol. 2000;42(4):653-659. DOI: 10.1067/mjd.2000.103815

W Czech M Bräutigam G Weidinger E Schöpf A body-weight-independent dosing regimen of cyclosporine microemulsion is effective in severe atopic dermatitis and improves the quality of lifeJ Am Acad Dermatol200042465365910.1067/mjd.2000.103815

118. Bunikowski R, Gerhold K, Bräutigam M, Hamelmann E, Renz H, Wahn U. Effect of low-dose cyclosporin a microemulsion on disease severity, IL-6, IL-8 and tumor necrosis factor alpha production in severe pediatric atopic dermatitis. Int Arch Allergy Immunol. 2001;125(4):344-348. DOI: 10.1159/000053836

R Bunikowski K Gerhold M Bräutigam E Hamelmann H Renz U Wahn Effect of low-dose cyclosporin a microemulsion on disease severity, IL-6, IL-8 and tumor necrosis factor alpha production in severe pediatric atopic dermatitisInt Arch Allergy Immunol2001125434434810.1159/000053836

119. Bunikowski R, Staab D, Kussebi F, Bräutigam M, Weidinger G, Renz H, et al. Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: clinical and immunological effects. Pediatr Allergy Immunol. 2001;12(4):216-223. DOI: 10.1034/j.1399-3038.2001.012004216.x

R Bunikowski D Staab F Kussebi M Bräutigam G Weidinger H Renz Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: clinical and immunological effectsPediatr Allergy Immunol200112421622310.1034/j.1399-3038.2001.012004216.x

120. Totri CR, Eichenfield LF, Logan K, Proudfoot L, Schmitt J, Lara-Corrales I, et al. Prescribing practices for systemic agents in the treatment of severe pediatric atopic dermatitis in the US and Canada: the PeDRA TREAT survey. J Am Acad Dermatol. 2017;76(2):281-285. DOI: 10.1016/j.jaad.2016.09.021

CR Totri LF Eichenfield K Logan L Proudfoot J Schmitt I Lara-Corrales Prescribing practices for systemic agents in the treatment of severe pediatric atopic dermatitis in the US and Canada: the PeDRA TREAT surveyJ Am Acad Dermatol201776228128510.1016/j.jaad.2016.09.021

121. Weatherhead SC, Wahie S, Reynolds NJ, Meggitt SJ. An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema. Br J Dermatol . 2007;156(2):346-351. DOI: 10.1111/j.1365-2133.2006.07686.x

SC Weatherhead S Wahie NJ Reynolds SJ Meggitt An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczemaBr J Dermatol2007156234635110.1111/j.1365-2133.2006.07686.x

122. Goujon C, Viguier M, Staumont-Sallé D, Bernier C, Guillet G, Lahfa M, et al. Methotrexate versus cyclosporine in adults with moderate-to-severe atopic dermatitis: a phase III randomized noninferiority trial. J Allergy Clin Immunol Pract. 2018;6(2):562-569. DOI: 10.1016/j.jaip.2017.07.007

C Goujon M Viguier D Staumont-Sallé C Bernier G Guillet M Lahfa Methotrexate versus cyclosporine in adults with moderate-to-severe atopic dermatitis: a phase III randomized noninferiority trialJ Allergy Clin Immunol Pract20186256256910.1016/j.jaip.2017.07.007

123. Law Ping Man S, Bouzillé G, Beneton N, Safa G, Dupuy A, Droitcourt C. Drug survival and postdrug survival of first-line immunosuppressive treatments for atopic dermatitis: comparison between methotrexate and cyclosporine. J Eur Acad Dermatol Venereol. 2018;32(8):1327-1335. DOI: 10.1111/jdv.14880

S Law Ping Man G Bouzillé N Beneton G Safa A Dupuy C Droitcourt Drug survival and postdrug survival of first-line immunosuppressive treatments for atopic dermatitis: comparison between methotrexate and cyclosporineJ Eur Acad Dermatol Venereol20183281327133510.1111/jdv.14880

124. El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. Eur J Pediatr. 2013;172(3):351-356. DOI: 10.1007/s00431-012-1893-3

MA El-Khalawany H Hassan D Shaaban N Ghonaim B Eassa Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from EgyptEur J Pediatr2013172335135610.1007/s00431-012-1893-3

125. Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet. 2006;367(9513):839-846. DOI: 10.1016/S0140-6736(06)68340-2

SJ Meggitt JC Gray NJ Reynolds Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trialLancet20063679513839846

126. Schram ME, Roekevisch E, Leeflang MM, Bos JD, Schmitt J, Spuls PI. A randomized trial of methotrexate versus azathioprine for severe atopic eczema. J Allergy Clin Immunol. 2011;128(2):353-359. DOI: 10.1016/j.jaci.2011.03.024

ME Schram E Roekevisch MM Leeflang JD Bos J Schmitt PI Spuls A randomized trial of methotrexate versus azathioprine for severe atopic eczemaJ Allergy Clin Immunol2011128235335910.1016/j.jaci.2011.03.024

127. Ballester I, Silvestre JF, Pérez-Crespo M, Lucas A. Severe adult atopic dermatitis: treatment with mycophenolate mofetil in 8 patients. Actas Dermosifiliogr. 2009;100(10):883-887. DOI: 10.1016/S1578-2190(09)70559-1

I Ballester JF Silvestre M Pérez-Crespo A Lucas Severe adult atopic dermatitis: treatment with mycophenolate mofetil in 8 patientsActas Dermosifiliogr20091001088388710.1016/S1578-2190(09)70559-1

128. Fallah Arani S, Waalboer-Spuij R, Nijsten T, Neumann HA, Thio B. Enteric-coated mycophenolate sodium in psoriasis vulgaris: an open pilot study. J Dermatolog Treat. 2014;25(1):46-49. DOI: 10.3109/09546634.2012.723124

S Fallah Arani R Waalboer-Spuij T Nijsten HA Neumann B Thio Enteric-coated mycophenolate sodium in psoriasis vulgaris: an open pilot studyJ Dermatolog Treat2014251464910.3109/09546634.2012.723124

129. Grundmann-Kollmann M, Podda M, Ochsendorf F, Boehncke WH, Kaufmann R, Zollner TM. Mycophenolate mofetil is effective in the treatment of atopic dermatitis. Arch Dermatol. 2001;137(7):870-873. DOI: 10-1001/pubs.Arch Dermatol.-ISSN-0003-987x-137-7-dst10044

M Grundmann-Kollmann M Podda F Ochsendorf WH Boehncke R Kaufmann TM Zollner Mycophenolate mofetil is effective in the treatment of atopic dermatitisArch Dermatol2001137787087310-1001/pubs.Arch DermatolISSN-0003-987x-137-7-dst10044

130. Murray ML, Cohen JB. Mycophenolate mofetil therapy for moderate to severe atopic dermatitis. ClinExp Dermatol. 2007;32(1):23-27. DOI: 10.1111/j.1365-2230.2006.02290.x

ML Murray JB Cohen Mycophenolate mofetil therapy for moderate to severe atopic dermatitisClinExp Dermatol2007321232710.1111/j.1365-2230.2006.02290.x

131. Dias-Polak D, Bergman R, Avitan-Hersh E. Mycophenolate mofetil therapy in adult patients with recalcitrant atopic dermatitis. J Dermatolog Treat. 2019;30(1):49-51. DOI: 10.1080/09546634.2018.1468068

D Dias-Polak R Bergman E Avitan-Hersh Mycophenolate mofetil therapy in adult patients with recalcitrant atopic dermatitisJ Dermatolog Treat2019301495110.1080/09546634.2018.1468068

132. Heller M, Shin HT, Orlow SJ, Schaffer JV. Mycophenolate mofetil for severe childhood atopic dermatitis: experience in 14 patients. Br J Dermatol . 2007;157(1):127-132. DOI: 10.1111/j.1365-2133.2007.07947.x

M Heller HT Shin SJ Orlow JV Schaffer Mycophenolate mofetil for severe childhood atopic dermatitis: experience in 14 patientsBr J Dermatol2007157112713210.1111/j.1365-2133.2007.07947.x

133. Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494-503. DOI: 10.1016/j.jaad.2016.05.046

AS Paller WL Tom MG Lebwohl RL Blumenthal M Boguniewicz RS Call Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adultsJ Am Acad Dermatol201675349450310.1016/j.jaad.2016.05.046

134. Draelos ZD, Stein Gold LF, Murrell DF, Hughes MH, Zane LT. Post hoc analyses of the effect of crisaborole topical ointment, 2% on atopic dermatitis: associated pruritus from phase 1 and 2 clinical studies. J Drugs Dermatol. 2016;15(2):172-176.

ZD Draelos LF Stein Gold DF Murrell MH Hughes LT Zane Post hoc analyses of the effect of crisaborole topical ointment, 2% on atopic dermatitis: associated pruritus from phase 1 and 2 clinical studiesJ Drugs Dermatol2016152172176

135. Zane LT, Hughes MH, Shakib S. Tolerability of crisaborole ointment for application on sensitive skin areas: a randomized, double-blind, vehicle-controlled study in healthy volunteers. Am J Clin Dermatol. 2016;17(5):519-526. DOI: 10.1007/s40257-016-0204-6

LT Zane MH Hughes S Shakib Tolerability of crisaborole ointment for application on sensitive skin areas: a randomized, double-blind, vehicle-controlled study in healthy volunteersAm J Clin Dermatol201617551952610.1007/s40257-016-0204-6

136. de Bruin-Weller M, Thaçi D, Smith CH, Reich K, Cork MJ, Radin A, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol . 2018;178(5):1083-1101. DOI: 10.1111/bjd.16156

M de Bruin-Weller D Thaçi CH Smith K Reich MJ Cork A Radin Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ)Br J Dermatol201817851083110110.1111/bjd.16156

137. Fukuda K, Ishida W, Kishimoto T, Fukushima A. Development of conjunctivitis with a conjunctival proliferative lesion in a patient treated with dupilumab for atopic dermatitis. Allergol Int . 2019;68(3):383-384. DOI: 10.1016/j.alit.2018.12.012

K Fukuda W Ishida T Kishimoto A Fukushima Development of conjunctivitis with a conjunctival proliferative lesion in a patient treated with dupilumab for atopic dermatitisAllergol Int201968338338410.1016/j.alit.2018.12.012

Notes

[4] How to cite this article: Sánchez J, Sánchez MR, Macías-Weinmann A, Barreto B, Ensina LF, Uriarte-Obando SA, et al. Systematic review about 10 interventions in dermatitis. A document from the Latin American Society of Allergy, Asthma, and Immunology. Rev Alerg Mex. 2019;66(4):426-455

Glossary

Abbreviations and acronyms

AD

atopic dermatitis

AZA

azathioprine

CSA

cyclosporine A

FDA

Food and Drugs Administration

GRADE

Grading of Recommendations, Assessment, Development, and Evaluation

IL

interleukin

MTX

methotrexate

RCT

randomized controlled trial

SCORAD

Severity Scoring Atopic Dermatitis

SCSs

systemic corticosteroids

SLAAI

Sociedad Latinoamericana de Asma, Alergia e Inmunología

WAO

World Allergy Organization

Appendices

Supplementary material 1.

Systematic review Check List from the PRISMA statement for the dermatitis-SLAAI guideline review of 10 interventions

Table present, is kindly offered freely for the PRISMA Group (2009) (for more information, visit http://www.prisma-statement.org). We highlight those recommendations that we did not make with red.

Section/topic

#

PRISMA Checklist item

Reported on page #

TITLE

Title

1

Identify the report as a systematic review, meta-analysis, or both.

1

ABSTRACT

Structured summary

2

Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.

1

INTRODUCTION

Rationale

3

Describe the rationale for the review in the context of what is already known.

2

Objectives

4

Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

3 and 4 Suppl 2

METHODS

Protocol and registration

5

Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.

No register

Eligibility criteria

6

Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

3 and 4

Information sources

7

Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

4

Search

8

Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

4*

Study selection

9

State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

4

Data collection process

10

Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

4

Data items

11

List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

4**

Risk of bias in individual studies

12

Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

4 and 5***

Summary measures

13

State the principal summary measures (e.g., risk ratio, difference in means).

Synthesis of results

14

Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.

Risk of bias across studies

15

Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

Suppl 1***

Additional analyses

16

Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

No apply

RESULTS

Study selection

17

Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

Suppl 2

Study characteristics

18

For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

Suppl 2

Risk of bias within studies

19

Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

4 and 5***

Results of individual studies

20

For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

Suppl 2*

Synthesis of results

21

Present results of each meta-analysis done, including confidence intervals and measures of consistency.

No apply

Risk of bias across studies

22

Present results of any assessment of risk of bias across studies (see Item 15).

0

Additional analysis

23

Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).

No apply

DISCUSSION

Summary of evidence

24

Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., health care providers, users, and policy makers).

5 to 14

Limitations

25

Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

5

Conclusions

26

Provide a general interpretation of the results in the context of other evidence, and implications for future research.

5 to 14

FUNDING

Funding

27

Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.

14

[i] Topic 2 and 5: the protocol for this systematic review was no register in any database.

[ii] Topic 12, 19, 22: see ***

[iii] * We summarize the search strategy using the flowchart proposed by PRISMA (see supplemental material 2). Additional information could be asked to the staff by email to the corresponding author.

[iv] ** In supplement material 2, PICO strategy for each question is presented.

[v] *** Lack of information to do the correct analysis of an article (e.g.: no clarity control group or measuring parameter), was identified by the reviewers (two for each question), and this was withdrawn if it did not allow to obtain a specific evaluation, however, a standardized evaluation to avoid risk of bias was not used. When a research group or center presented two or more results of an intervention in the same research, we only considered that which included more patients or had a better design.

Appendices

Supplementary material 2

PRISMA flow diagram and PIC strategy

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and

Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097. For more information, visit http://www.prisma-statement.org

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