Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing prevalence regionally and globally. With the increase in the availability of treatment options for healthcare practitioners and patients, new challenges arise for treatment selection and approach. The current guideline was developed to provide updated evidence and evidence-based recommendations to guide dermatologists and healthcare professionals managing patients with AD in Saudi Arabia.
The task force voted on all consensus content, including diagnostic criteria, assessment of AD severity, comorbidities, and therapeutic options for AD. Clinical practice guidelines are based on the best information available at the time of writing and should be updated regularly. They are not fixed protocols and strict treatment guidelines that should be followed, but are merely tools to help manage AD patients.
Decisions regarding treatment should be made on a case-by-case basis, with the treatment regimen tailored to the patient's personal circumstances and medical history. The current guidelines will be periodically reviewed and updates will be provided as necessary to incorporate new data or therapeutic agents.
INTRODUCTION
- Background and Definition
- Purpose and Aim
- Scope
- Methodology
- Target Population
- Targeted Audience/End-Users
A multidisciplinary working group of 11 experts, including six dermatologists and five pharmacists, was selected based on their experience in the treatment of AD. During the first meeting, the working group defined the objectives, scope, target population and target audience of the guidelines. The working group identified 4 main topics of interest, which would serve as the sections for review: (1) diagnostic criteria, (2) AD severity assessment, (3) evaluation and treatment of comorbidities, (4) management of AD and treatment options.
Working group members were assigned to one of these four work streams, depending on their interest and expertise, and developed the content for the document within their respective sections. The task force identified seven international guidelines for the management of AD that served as the basis for generating the current guidelines: the European Guidelines 2017 and 2020, the Japanese Guidelines 2017 and 2020, the US Guidelines 2014 and 2017, and the Indian Guidelines 2019. The draft of the developed content was shared between group members before the second and third meetings.
All the approved recommendations were shared with MOH and working group experts for further input. A final workshop of the working group was then held in March 2021 to discuss the additional inputs for further agreement.
DIAGNOSTIC CRITERIA
Intended audience/end users are general dermatologists and other health care providers who encounter patients with AD in secondary and tertiary care settings.
ATOPIC DERMATITIS SEVERITY ASSESSMENT
COMORBIDITIES OF ATOPIC DERMATITIS
Atopic Comorbidities
Other comorbidities
Development of various atopic comorbidities in younger children with AD was found to be associated with disease severity, age at onset, parental atopic history, filaggrin (FLG) mutations, polysensitization and non-rural environment [27]. AD is also associated with a higher risk of extracutaneous infections, such as upper respiratory tract infections, pneumonia, recurrent ear infections, sinus infections, gastroenteritis, urinary tract infections, and higher antibiotic use in children with AD compared to healthy controls [42, 43]. Consider infection risk in clinical decision making for patients with AD.
Cardio-metabolic Comorbidities
MANAGEMENT OF ATOPIC DERMATITIS
ELIGIBILITY CRITERIA FOR ANTI JAK/BIOLOGIC TREATMENT AT SAUDI MOH
ATOPIC DERMATITIS TREATMENT GOALS
PATIENT EDUCATION
However, this should be done with mildly irritating, non-allergenic formulas with a minimum of additives such as pigments and perfumes, and should be washed off thoroughly to protect the skin from irritation [7, 15]. In a small randomized study, frequency of showering showed no difference between twice weekly or daily when skin hydration was controlled after bathing [61]. The water temperature should be set between 37 °C and 38 °C, as this is the optimal temperature for the restoration of the skin barrier, and higher temperatures cause itching [63-65].
For example, sweat and saliva should be washed or wiped away, non-irritating clothing should be chosen (clothes with rough textures such as wool should be avoided), and hair should be tied to reduce itching [15]. Suspicion of contact allergy should be raised in cases where the onset and exacerbation of AD has occurred recently with limited response to treatment or with atypical distribution of eczema [37]. Food elimination should only be undertaken when there is clear evidence of food allergy as this may affect the child's development.
Aeroallergen avoidance should be based on careful evaluation of any changes in exposure characteristics or environmental factors. Due consideration should be given to the individual's medical history and the results of the elimination and challenge tests [15].
PHARMACOLOGIC THERAPIES
Proactive, intermittent therapy with tacrolimus twice weekly for up to 52 weeks is effective in preventing, delaying, and reducing the occurrence of flares, thereby improving quality of life for patients with AD [ 78 , 79 ]. Crisaborole is indicated for the treatment of mild to moderate AD in adults and pediatric patients 3 months or older [80]. Phototherapy is an adjuvant skin-directed therapy, thus reducing sleep disturbances in patients with AD [83].
It, together with concurrent topical anti-inflammatory therapies, is considered an acceptable treatment choice for moderate to severe AD when available. It can also be used as monotherapy for patients in whom local anti-inflammatory therapies are not suitable (i.e. side effect, contraindication) [84]. Concomitant treatment with topical anti-inflammatory drugs, emollients and phototherapy are suitable options to reduce the frequency of flares.
It is useful in patients who usually require powerful TCS for large body areas over long periods of time. It is licensed for the treatment of AD in adults in many European countries and can be used off-label in children and adolescent patients with refractory or severe disease. MTX is an immunosuppressive drug frequently used off-label to treat moderate to severe AD [ 14 , 90 ].
In 2017, the US Food and Drug Administration (USFDA) and the Saudi Food and Drug Authority (SFDA) approved dupilumab as the first biologic drug for patients with moderate to severe AD. Dupilumab should be combined with daily emollients with or without topical anti-inflammatory drugs as needed. Combining dupilumab with a conventional drug or phototherapy is an appropriate and safe treatment option that allows patients recalcitrant to dupilumab monotherapy [99].
On the other hand, USFDA and SFDA approved upadacitinib for the treatment of moderate to severe AD in pediatric patients at least 12 years of age and adults, and abrocitinib only for adults (Table 6). Tralokinumab is another fully human monoclonal anti-IL-13 antibody recently approved by the USFDA and EMA for the treatment of moderate to severe AD not adequately controlled with topical prescription therapies for adults. New Treatment in the Pipeline Monoclonal antibodies that inhibit the effects of several interleukins (i.e. IL-4, IL13, IL-5, IL-17, IL-22, IL-31, IL-33) show therapeutic promise for the treatment of AD such as Nemolizumab, Lebrikizumab, fezakinumab [108].
TREATMENT ALGORITHM
REFERRAL OF PATIENTS WITH ATOPIC DERMATITIS
AD responds to optimal management, but with non-improving QoL and psychological well-being should be referred for psychological counseling. Moderate or severe AD with suspected food allergy should be referred for specialized investigations and management of AD and allergy. As reflected by local growth charts, children with AD who exemplify failure to thrive at normal growth rates should be referred to specialists.
SPECIAL PATIENT POPULATIONS
Due to practical challenges, long-term concerns, and limited data on its use in pediatric AD, phototherapy may be considered in children [7]. Several systemic therapies are used to treat moderate to severe pediatric AD refractory to topical therapy and/or phototherapy. They include MTX, CsA, AZA, MMF, systemic corticosteroids (SCS), and dupilumab as the only biologic approved for use in patients 6 years of age or older.
We recommend that physicians exercise careful caution regarding safety, tolerability, and allergenic profiles when treating children under 2 years of age. The first-line pharmacological treatment of AD during pregnancy and lactation is TCSs, as they are considered safe. Although long-term use of high doses of higher-ranked topical steroids (300 g or more) has been reported to be associated with low birth weight in a few cases, this is unlikely with appropriate use.
In moderate to severe AD during pregnancy that is refractory to local therapy and/or phototherapy, the benefit of using systemic therapies should be considered in light of patient characteristics and any potential or actual risks. The decision to start systemic therapies for pregnant or lactating women should be made in collaboration with obstetricians. Both male and female patients with AD who want to pursue a family life require special considerations to ensure the safety and efficacy of treatment.
VACCINATION
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Berth-Jones, J., et al., Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial. Gori, N., et al., Successful combination of systemic agents for the treatment of atopic dermatitis resistant to dupilumab therapy. Nezamololama, N., et al., Emerging systemic JAK inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib.
