Adolescent Atopic Dermatitis

Atopic dermatitis (AD) is the most common inflammatory skin condition in pediatric patients, affecting 10% to 30% of patients worldwide.¹ Although it is primarily a disease of infancy and childhood, as many as 10% to 20% of children with AD have persistence of symptoms through adolescence.² Additionally, patients with apparent resolution of AD during childhood can have a reappearance of symptoms duing the adolescent years. Several risk factors associated with adolescent AD include a family history of allergic rhinitis, allergic sensitization during infancy, and female sex. Though AD is more common in boys during the childhood years, prevalence among girls is higher in adolescence and is possibly attributed to hormonal influences.² The typical clinical features of adolescent AD can be quite disruptive and include xerosis, pruritus, and lichenified plaques in flexor surfaces, especially the antecubital and popliteal fossae, and on the volar aspects of the wrists, ankles, and neck.³ Many activities in a teenager’s daily routine, such as heat and sweating with physical exertion during sports and other extracurricular activities, can exacerbate symptoms. Furthermore, as academic pressures increase during adolescence, anxieties and stress levels rise, worsening symptoms of AD.   

AD is associated with significant patient burden and is an especially challenging condition to endure during adolescence. Teenagers place a high value on self-image and strive to be accepted by their peers. The appearance of dry and inflamed skin can be embarrassing and socially isolating for teenagers and, thus, it is not surprising that adolescent AD is frequently associated with psychosocial consequences. The symptoms and visible physical manifestations of AD can negatively impact mood, self-esteem, and interpersonal relationships and can lead to difficulties at home, school, and in social settings. Pruritus is a major contributor to decreased quality of life and is associated with disrupted sleep, fatigue, and feelings of helplessness.⁴ The early-onset, chronicity, and relapsing course of this disease can serve as an additional nidus for anxieties and frustrations among patients and their families.²

For many years, the management of AD in adolescent patients has centered on gentle skin care measures and topical therapies such as corticosteroids, calcineurin inhibitors, or the newer crisaborole (Eucrisa), a topical phosphodiesterase-4 inhibitor. Topical treatment regimens often require multiple daily applications to large body surface areas for extended periods. The need for topical treatments of various strengths and vehicles in different areas of the body further adds to the complexity of the treatment regimen, making adherence challenging, especially for adolescents. Teenagers often struggle to incorporate chronic diseases into the development of their self-identity, which can lead to issues with treatment adherence.⁵ The adolescent years are a crucial period when teenagers transition into independence and are often less keen on taking commands from their parents, especially when made daily. To add to the burden, many teenagers with AD also suffer from other chronic allergic conditions, including asthma and seasonal allergies, that may require management with multiple other treatments.

Dupilumab (Dupixent), the first biologic therapy approved for treating adolescent AD, may help alleviate some of the burden associated with the disease. In March 2019, the FDA approved dupilumab for use in patients aged 12 to 17 years for moderate to severe AD refractory to topical treatments or when those therapies are not advisable. This biologic is now approved for both adolescent and adult AD as well as for the maintenance treatment of moderate to severe asthma in patients aged 12 years and older. In adolescent AD, the recommended dosing schedule is an initial subcutaneous injection using a prefilled syringe of 400 mg (two 200-mg injections) for patients weighing less than 60 kg or 600 mg (two 300-mg injections) for those over 60 kg. Maintenance dosing involves one 200-mg (weight <60 kg) or 300-mg (>60 kg) subcutaneous injection every other week.⁶ 

Dupilumab is a fully human monoclonal antibody targeting IL-4Ra, the common alpha chain of IL-4 and IL-13 receptors, which blocks signaling through these cytokines and ultimately downregulates type 2 immunity. In a pivotal phase 3 trial (AD-1526) evaluating dupilumab for use in adolescent patients with AD, investigators reported a significant reduction and extent of disease severity and itching, similar to results seen in adult studies.^7-9 At 16 weeks, the average improvement from baseline in Eczema Area and Severity Index (EASI) score was 66% in those receiving dupilumab compared with 24% for placebo (P<.0001). Additional findings of the trial showed that 42% and 38% of patients achieved EASI 75 and 24% and 18% achieved clear or almost clear skin in the intervention groups that received dupilumab every 2 weeks and every 4 weeks, respectively. By comparison, only 8% and 2% of patients in the placebo group achieved EASI 75 and clear and almost clear skin, respectively. Of the patients in the intervention arm, 37% of those who received dupilumab every 2 weeks and 27% who received it every 4 weeks achieved a clinically significant improvement in itch defined as a decrease by at least 4 points on the Peak Pruritus Numerical Rating Scale vs only 5% in the placebo group. Safety findings in adolescents were similar to those seen in adult trials with approximately 10% or less of patients on dupilumab experiencing injection site reactions and conjunctivitis compared with 5% on placebo. 

A useful resource for adolescents with AD is the National Eczema Association,¹⁰ through which teenagers can connect to an online support group or on Instagram, Twitter, YouTube, and Facebook to share their stories and find common ground with others. The American Academy of Dermatology has an online resource center geared for patients with AD that includes general information, skin care tips, and a video library where adolescents can learn more about managing AD as well as hear inspiring stories from others.¹¹ 

The advent of dupilumab in adolescent AD has the potential to improve quality of life, adherence, and health outcomes in this patient population. The proven efficacy of this biologic can serve to help teenagers feel more confident about the appearance of their skin and decrease repercussions associated with itching and loss of sleep. Every other week dosing schedule cuts down on the need for daily application of topical treatments, allowing teenagers to feel less isolated from their peers. Additionally, for adolescents with comorbid asthma, dupilumab improves symptoms of both chronic conditions and streamlines therapy. The continued emergence of therapies that are both safe and effective as well as decrease the time spent managing symptoms will further improve quality of life and health outcomes in adolescents with AD.

Ms Payne is a medical student and research associate at the Center for Dermatology Research in the department of dermatology at Wake Forest School of Medicine in Winston-Salem, NC. Ms Ghamrawi is a medical student and research associate at the Center for Dermatology Research in the department of dermatology at Wake Forest School of Medicine. Dr Strowd is an assistant professor at the Wake Forest School of Medicine, department of dermatology.

Disclosure: Dr Strowd has received research, speaking, and/or consulting support from Galderma, Pfizer, Regeneron, Sanofi, and Actelion. The remaining authors report no relevant financial relationships.

References
1. Maliyar K, Sibbald C, Pope E, Sibbald GR. Diagnosis and management of atopic dermatitis: a review. Adv Skin Wound Care. 2018;31(12)L538-550. doi:10.1097/01.ASW.0000547414.38888.8d

2. Ricci G, Bellini F, Dondi A, Patrizi A, Pession A. Atopic dermatitis in adolescence. Dermatol Reports. 2012;4(1):e1. doi: 10.4081/dr.2012.e1

3. Rudikoff D, Lebwohl M. Atopic dermatitis. Lancet. 1998;351(9117):1715-1721. doi:10.1016/S0140-6736(97)12082-7

4. Sibbald C, Drucker AM. Patient burden of atopic dermatitis. Dermatol Clin. 2017;35(3):303-316. doi:10.1016/j.det.2017.02.004

5. Taddeo D, Egedy M, Frappier JY. Adherence to treatment in adolescents. Paediatr Child Health. 2008;13(1):19-24. doi:10.1093/pch/13.1.19

6. Dupixent. Package insert. Regeneron Pharmeceuticals Inc; 2019. Accessed May 1, 2020. https://www.regeneron.comhttps://s3.amazonaws.com/HMP/hmp_ln/imported/Dupixent_FPI.pdf

7. Dupixent^® (dupilumab) showed positive phase 3 results in adolescents with inadequately controlled moderate-to-severe atopic dermatitis. News release. Sanofi; May 16, 2018. Accessed May 1, 2020. https://www.news.sanofi.us/2018-05-16-Dupixent-R-dupilumab-showed-positive-Phase-3-results-in-adolescents-with-inadequately-controlled-moderate-to-severe-atopic-dermatitis

8. Efficacy and Safety of dupilumab in participants ≥12 to <18 years of age, with moderate-to-severe atopic dermatitis. ClinicalTrials.gov identifier: NCT03054428. Updated July 23, 2015. Accessed May 1, 2020. https://clinicaltrials.gov/ct2/show/NCT03054428?id=NCT03054428

9. Fishbein AB, Silverberg JI, Wilson EJ, Ong PY. Update on atopic dermatitis: diagnosis, severity assessment, and treatment selection. J Allergy Clin Immunol Pract. 2020;8(1):91-101. doi:10.1016/j.jaip.2019.06.044

10. Get support. National Eczema Association. Accessed May 1, 2020. https://nationaleczema.org/get-support/

11. Atopic dermatitis: overview. American Academy of Dermatology. Accessed May 1, 2020. https://www.aad.org/public/diseases/eczema/types/atopic-dermatitis