An Overview of Topical Therapies for Managing Pediatric AD

Atopic dermatitis (AD), or eczema, is a condition characterized by dysfunctional maintenance of the skin barrier, resulting in dry, itchy skin, frequent infections, and significant discomfort. Eczema affects approximately 15% to 30% of children and 2% to 10% of adults worldwide, making it one of the most common skin conditions.¹ Current topical management of AD includes emollients and moisturizers, topical steroids, and most recently, immune modulators. This review will serve to compare classic topical therapies with recently US Food and Drug Administration (FDA)-approved therapies for the treatment of pediatric AD. 

Moisturizers

While new prescription treatments for AD have become available over the last 5 years, topical treatment guidelines have not yet incorporated these products. Moisturization remains a mainstay in AD treatment, as it has been shown to reduce both inflammation and itch via reducing transepidermal water loss.² No specific moisturizer formulation has demonstrated superiority over another. Bleach baths have not shown statistical or clinical significance in the prophylaxis of infection and are only conditionally recommended.³ In recent guidelines,3 regular bathing was previously discouraged due to its association with net water loss. However, bathing with moisturization afterward allows liberal frequency of bathing consistent with cultural practices.⁴

Corticosteroids and Calcineurin

Among prescription treatments for AD, topical corticosteroids (TCS) remain mainstays due to their reliable results and low cost, and are the most commonly prescribed therapy for the treatment of AD due to their ability to target a variety of immune cells and inhibition of inflammatory cytokines; their efficacy has been well-established in more than 100 clinical trials.^2,5 Factors that should be considered when selecting the strength of steroid include the anatomical site of application (ie, lower potencies should be used on areas with thinner skin, such as the face and genitals), severity, and extent of disease (stronger formulations are required for more severe disease). Regimens for adequate treatment with minimization of adverse events may include treatment of flares with twice-daily or daily application and intermittent or proactive use to reduce additional flares in relapse-prone patients.⁶ Once-daily application is often sufficient for AD management.⁷

Pimecrolimus and Tacrolimus

Topical calcineurin inhibitors, such as pimecrolimus and tacrolimus, are well-established AD treatment options and are particularly beneficial in cases where there is concern for adverse events related to corticosteroid use. Treatments with calcineurin inhibitors have demonstrated a reduction in the number of days of topical corticosteroid use required to treat AD flares.⁸ When compared directly to each other, tacrolimus 0.1% ointment demonstrated significantly higher efficacy compared to pimecrolimus 1% cream based on Investigator’s Global Assessment (IGA) and Eczema Area and Severity Index (EASI) score reductions across several randomized controlled trials from 2005 to 2007.^9,10  Both tacrolimus and pimecrolimus are well-tolerated, though tacrolimus tends to have a stronger association with irritation (ie, burning) at the application site. The choice of calcineurin inhibitor for treatment of AD should ultimately be made based on the disease severity, with tacrolimus 0.1% or 0.03% ointment generally preferred to pimecrolimus 1% cream for mild-to-moderate cases. Patient age is also an important consideration, as pimecrolimus 1% cream and tacrolimus 0.03% ointment are FDA-approved for children 2 and older, while tacrolimus 0.1% ointment is only FDA-approved for patients 16 and older. 

Crisaborole and Roflumilast 

Topical phosphodiesterase-4 (PDE-4) inhibitors (crisaborole and roflumilast) are prescription therapies that have been FDA-approved within the last decade for AD treatment. Crisaborole 2% ointment was approved in 2016 as an alternative to TCS or calcineurin inhibitors for treatment of mild-to-moderate cases of AD. Crisaborole has demonstrated safety and efficacy in children 3 months and older and has also proven to be a useful maintenance therapy suitable for long-term use, in addition to reducing the frequency of flares.^11,12 In a 2020 phase IV study investigating the tolerability of crisaborole ointment, treatment-related adverse effects included only erythema and pain or discomfort at the application site.¹³ Compared to effects associated with TCS, crisaborole ointment is significantly less likely to cause serious or permanent skin damage. Roflumilast 0.05% cream is approved for use in children 2 to 5 years old, and 0.015% cream for use in patients 6 and older. Roflumilast demonstrated efficacy in the treatment of pediatric AD based on significant improvement in EASI and vIGA scores in a phase 3 randomized-controlled trial. Once-daily application of roflumilast 0.05% cream resulted in 25.4% of patients achieving vIGA-AD success, 39.4% achieving EASI-75, and 35.3% achieving Worst Itch-Numeric Rating Scale (WI-NRS) success (defined as a reduction of at least 4 points on the 10-point scale), compared to vehicle-treated patients with 10.7%, 20.6%, and 18.0%, respectively.¹⁴ Additionally, roflumilast was associated with minimal treatment-related adverse events, which were limited to self-resolving mild diarrhea and vomiting, headaches, and skin irritation localized to the application site. It also requires only once-daily application and does not have a maximum body surface area limitation of application. In a 1-year open-label extension study of roflumilast 0.05% and 0.15%, proactive treatment twice weekly to normal-appearing flare-prone sites showed maintenance of minimal signs and symptoms of AD.¹³

One new PDE-4 inhitibor to watch is diflamilast, showing strong potential for the treatment of pediatric AD with minimal adverse effects. While it is currently approved in Japan (not the US) for patients ages 3 months and older, phase 3 trials in the United States are ongoing.¹⁵

JAK Inhibitors

JAK inhibitors are another recently FDA-approved topical treatment option for AD. Ruxolitinib is a JAK-1/2 inhibitor that recently gained expanded approval for use in patients 2 and older (a change from the original age of 12 and older). In a 2025 phase 3 study, pediatric patients treated with ruxolitinib had improvement of at least 2 points in Investigator’s Global Assessment–Treatment Score (IGA-TS), and it was superior to vehicle cream.¹⁶ Most ruxolitinib treatment-related adverse events are minimal and self-resolving, including minor upper respiratory infections and application site burning/pain. However, despite being a topical cream, JAK inhibitors as a drug class carry an FDA box warning due to their association with an increased risk of severe infection, thrombolysis, cardiovascular effects, and malignancies. Ruxolitinib application is limited to a total BSA of 20% and 60 grams per week/100 grams per 2 weeks for patients 12 years and older, and 60 grams per 2 weeks for ages 2 through 11 to mitigate these risks.¹⁷ Delgocitinib is a topical JAK-1, -2, and -3 inhibitor and an inhibitor of tyrosine kinase 2. It is currently FDA approved for the treatment of chronic hand eczema in adults and demonstrated superiority to vehicle cream in a 2024 randomized-controlled, double-blind phase 3 trial.¹⁸ FDA approval for treatment of AD with delgocitinib in teenagers is pending ongoing phase 3 trial review.

Tapinarof

A very recent addition to FDA-approved topical AD treatment is tapinarof, an aryl hydrocarbon receptor modulator approved for children 2 and older. Its activation of aryl hydrocarbon receptors is postulated to be efficacious for eczema patients via several downstream effects, including the induction of keratinocyte barrier genes (filaggrin, hornerin, and involucrin), downregulation of IL-17 and other pro-inflammatory cytokines, and promotion of antioxidant effects.¹⁹ Tapinarof demonstrated promising clinical results in the phase 3 ADORING 1 and 2 trials, which were randomized, double-blind, multicenter, placebo-controlled trials completed in 2023.¹⁹ After 8 weeks of treatment, 45.4% of patients treated with tapinarof in ADORING 1 and 46.4% of patients treated with tapinarof in ADORING 2 achieved a vIGA-AD response (defined as a score of 0 or 1 and at least a 2-point improvement from baseline) compared to 13.9% and 18.0% treated with vehicle cream, respectively. Additionally, patients treated with tapinarof demonstrated superior EASI-75 responses with 55.8% vs 22.9% in ADORING 1 and 59.1% vs 21.2% in ADORING 2. Treatment-related adverse events associated with tapinarof were minimal, occurring in 8.1% of treated patients in each ADORING group, and included folliculitis, headache, and nasopharyngitis. Of note, more treatment-related adverse effects resulting in discontinuation of treatment occurred with placebo cream treatment than with tapinarof cream (3.6% with placebo and 1.9% with tapinarof in ADORING 1; 3.0% with placebo and 1.5% with tapinarof in ADORING 2).²⁰

Determining the Appropriate Regimen

Given the availability of topical agents available for AD treatment, it can be difficult to decide which regimen is most appropriate for each patient. Most of the reports detailing efficacy and safety of specific treatments only compare the treatment of interest to vehicle rather than directly against other established treatment options. A Cochrane network meta-analysis attempted to reconcile this, but inconsistencies between underlying study methodologies, populations studied, and outcome measures make it difficult to trust comparisons that did not necessarily correlate with clinical experiences. Overall, ruxolitinib is the most efficacious of all non-steroids and is equivalent to, if not stronger than, triamcinolone 0.1% cream.²³ Tacrolimus and pimecrolimus rarely produce the same results as ruxolitinib.

Determining the optimal amount of treatment per application has historically proven challenging. Utilization of the AD topical medication volume calculator (TMVC), developed by pediatric dermatologists at Rady Children’s Hospital, can provide guidance. The TMVC is a tool that can be integrated into electronic health records to provide an estimate of the necessary volume of topical therapy, in grams, to be applied over a given period based on the age of the patient and their body surface area (BSA) involvement.²² It utilizes a cubic regression model in accordance with the understanding that a palm-sized area of skin involvement is roughly equal to 1% of BSA. This calculator also specifies how much medication should be applied for flares, how and when to taper therapy, and what is appropriate for maintenance therapy. An additional purpose of this calculator is to discourage underutilization of topical treatments by providing the total expected amount for use per a given month. Personalized treatment instructions can then be generated from these data and given to patients and their families/caregivers, streamlining the treatment process for both physician and patient. 

Summary

Topical AD treatments are numerous and continually evolving as more therapies receive FDA approval. The choice of treatment should ultimately depend on a variety of factors, including extent of disease, severity of disease, patient age, and lifestyle (ie, how much time is the patient and/or their family willing to devote to the treatment regimen), recognizing the importance of drug access and total cost of treatment. It is also important to consider the associated side effects of a given therapy and educate the patient accordingly to facilitate maximum treatment compliance and minimize adverse events.  It is crucial to keep up with the approval and mechanisms of novel treatments to ensure you are offering patients the best possible treatment. n

1. Nemeth V, Syed HA, Evans J. Eczema. In: StatPearls [Internet]. StatPearls Publishing; updated March 1, 2024. Accessed December 3, 2025. https://www.ncbi.nlm.nih.gov/books/NBK538209/

2. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-132. https://doi.org/10.1016/j.jaad.2014.03.023

3. Sidbury R, Alikhan A, Bercovitch L, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. J Am Acad Dermatol. 2023;89(1):e1-e20. https://doi.org/10.1016/j.jaad.2022.12.029

4. Visscher MO, Chatterjee R, Ebel JP, LaRuffa AA, Hoath SB. Biomedical assessment and instrumental evaluation of healthy infant skin. Pediatr Dermatol. 2002;19(6):473-481. https://doi.org/10.1046/j.1525-1470.2002.00214.x

5. Canadian Agency for Drugs and Technologies in Health. Pharmacoeconomic report: dupilumab (Dupixent). CADTH; June 2020. Accessed December 3, 2025. https://www.ncbi.nlm.nih.gov/books/NBK566136/

6. Williams HC. Established corticosteroid creams should be applied only once daily in patients with atopic eczema. BMJ. 2007;334(7606):1272. 

7. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-132. https://doi.org/10.1016/j.jaad.2014.03.023

8. Gollnick H, Kaufmann R, Stough D, et al; Pimecrolimus Cream 1% Investigator Study Group. Pimecrolimus cream 1% in the long-term management of adult atopic dermatitis: prevention of flare progression. Br J Dermatol. 2008;158(5):1083-1093. https://doi.org/10.1111/j.1365-2133.2008.08484.x

9. Fleischer AB Jr, Abramovits W, Breneman D, et al; US/Canada Tacrolimus Ointment Study Group. Tacrolimus ointment is more effective than pimecrolimus cream in adult patients with moderate to very severe atopic dermatitis. J Dermatolog Treat. 2007;18(3):151-157. https://doi.org/10.1080/09546630701287332

10. Paller AS, Lebwohl M, Fleischer AB Jr, et al; US/Canada Tacrolimus Ointment Study Group. Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis. J Am Acad Dermatol. 2005;52(5):810-822. https://doi.org/10.1016/j.jaad.2004.12.038

11. Su JC, Spelman LJ, Eichenfield LF, et al. Crisaborole ointment, 2%, in patients 3 months of age and older with mild-to-moderate atopic dermatitis. Australas J Dermatol. 2021;62(Suppl 1):123-124.

12. Eichenfield LF, Gower RG, Xu J, et al. Once-daily crisaborole ointment, 2%, as a long-term maintenance treatment in patients aged ≥3 months with mild-to-moderate atopic dermatitis. Am J Clin Dermatol. 2023;24(4):623-635. https://doi.org/10.1007/s40257-023-00780-w

13. Schlessinger J, Shepard JS, Gower R, et al; CARE 1 Investigators. Safety, effectiveness, and pharmacokinetics of crisaborole in infants aged 3 to <24 months with mild-to-moderate atopic dermatitis. Am J Clin Dermatol. 2020;21(2):275-284. https://doi.org/10.1007/s40257-020-00510-6

14. Eichenfield LF, Serrao R, Prajapati VH, et al. Efficacy and safety of once-daily roflumilast cream 0.05% in pediatric patients aged 2-5 years with mild-to-moderate atopic dermatitis. Pediatr Dermatol. 2025;42(2):296-304. https://doi.org/10.1111/pde.15840

15. Saeki H, Ohya Y, Baba N, et al. A phase 3, long-term, open-label study of difamilast ointment in Japanese infants with atopic dermatitis. Dermatol Ther (Heidelb). Published online October 31, 2025. https://doi.org/10.1007/s13555-025-01581-1

16. Eichenfield LF, Stein Gold LF, Simpson EL, et al. Efficacy and safety of ruxolitinib cream in children aged 2 to 11 years with atopic dermatitis. J Am Acad Dermatol. 2025;93(3):689-698. https://doi.org/10.1016/j.jaad.2025.05.1385

17. Issa NT, Kwong P, Bunick CG, Kircik L. Ruxolitinib 1.5% cream and the boxed warning paradox. J Drugs Dermatol. 2025;24(2):S16-S22. https://doi.org/10.36849/JDD.49143

18. Bissonnette R, Warren RB, Pinter A, et al. Efficacy and safety of delgocitinib cream in adults with chronic hand eczema. Lancet. 2024;404(10451):461-473. https://doi.org/10.1016/S0140-6736(24)01027-4

19. Smith SH, Jayawickreme C, Rickard DJ, et al. Tapinarof is a natural AhR agonist that resolves skin inflammation. J Invest Dermatol. 2017;137(10):2110-2119. https://doi.org/10.1016/j.jid.2017.05.004

20. Silverberg JI, Eichenfield LF, Hebert AA, et al. Tapinarof cream 1% once daily in moderate to severe atopic dermatitis. J Am Acad Dermatol. 2024;91(3):457-465. https://doi.org/10.1016/j.jaad.2024.05.023

21. Lax SJ, Van Vogt E, Candy B, et al. Topical anti-inflammatory treatments for eczema: network meta-analysis. Cochrane Database Syst Rev. 2024;(8):CD015064. https://doi.org/10.1002/14651858.CD015064.pub2

22. Lee SS, Kaushik A, Natsis N, et al. A multimodal initiative improves pediatric provider management of atopic dermatitis. J Am Acad Dermatol. 2023;89(5):1041-1044. https://doi.org/10.1016/j.jaad.2023.02.065

23. Kircik L, Sturm D, Kallender H, Xue Z, Nasir A. Ruxolitinib cream versus triamcinolone cream in adults with mild to moderate atopic dermatitis. J Drugs Dermatol. 2025 Oct 1;24(10):1036-1039. htpps://doi.org/10.36849/JDD.8920.

Savannah Bush

Medical student, Tulane University School of Medicine

Pediatric Dermatology Research Associate, University of California San Diego and Rady Children’s Hospital - San Diego

Lena Chu, MD

Dermatology resident, University of California San Diego

David Schairer, MD

Department of Dermatology, University of California San Diego