By Anthony Calabro
April 3, 2025

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition affecting up to 20% of children and approximately 10% of adults in developed countries, with a notably high prevalence among young children. Characterized by intense pruritus, xerosis, and recurrent eczematous lesions, AD's distribution often varies with age.

Beyond its cutaneous manifestations, AD is recognized as a systemic disease with immunologic underpinnings and frequent comorbidities, including food allergies, allergic rhinitis, and asthma, often referred to as the "atopic march."​ This concept describes the interconnectedness of these well-known allergic conditions and their progression over time. Generally, the sequence of disorders begins with atopic dermatitis (at infancy), progresses to food allergies (between 1 and 3 years old) moves to allergic rhinitis (4 to 6 years old), and finally, asthma, which can develop at any time in a person's life, but often advances following allergic rhinitis.¹

AD can lead to disrupted sleep, impaired psychosocial functioning, and diminished quality of life. The disease course is heterogeneous; some individuals achieve remission, while others progress to more severe, treatment-resistant forms. Despite this continued variability, significant strides have been made in understanding the immunopathogenesis of AD in the last 5 years, particularly concerning specific cytokine pathways, skin microbiome alterations, and genetic predispositions. This evolving landscape necessitates continuous updates in clinical practice to ensure optimal patient outcomes.

The pathogenesis of AD involves a complex interplay between genetic susceptibility, skin barrier dysfunction, immune dysregulation, and environmental triggers. Central to this process is the filaggrin gene (FLG), which encodes a protein critical to skin barrier function. Loss-of-function mutations in FLG have been associated with early-onset, severe, and persistent AD.²

Moreover, disruption of the skin barrier increases transepidermal water loss and allows for penetration of allergens and microbes, which subsequently provoke immune responses. Staphylococcus aureus also plays a role, as it colonizes more than 90% of AD lesions, producing exotoxins that act as superantigens and exacerbate inflammation.³

In addition, environmental factors such as urban pollution and climate extremes have emerged as contributors to disease flares. A 2020 longitudinal cohort study in urban areas of Europe and North America found significant associations between air pollution exposure and increased AD severity in pediatric patients.⁴

Early diagnosis remains essential to minimize long-term morbidity. AD is primarily diagnosed clinically based on morphology, distribution of lesions, and chronicity. The updated 2021 American Academy of Dermatology guidelines emphasize distinguishing AD from mimicking conditions such as contact dermatitis, psoriasis, and seborrheic dermatitis.⁵

In the last 5 years, diagnostic tools have expanded to include noninvasive biomarkers, such as serum thymus and activation-regulated chemokine and periostin, which correlate with disease severity.⁶ Additionally, tape stripping—a minimally invasive skin sampling method—has been used to analyze mRNA expression in stratum corneum and may soon play a larger role in diagnostics and treatment monitoring.⁷

Novel, non-invasive imaging modalities, such as reflectance confocal microscopy provide a real-time, high resolution view of the skin's cellular structure without the need of cutting or biopsies.⁸ Another non-invasive imaging technique, line-field confocal optical coherence tomography, uses light to visualize skin structures in real-time, providing dermatologists with noted changes in epidermal thickness, stratum corneum thickness, and the dermo-epidermal junction in AD lesions versus healthy skin.⁹

Topical corticosteroids remain the first-line therapy for mild-to-moderate AD. However, long-term use is associated with side effects including skin atrophy and hypothalamic-pituitary-adrenal axis suppression. Topical calcineurin inhibitors such as tacrolimus and pimecrolimus serve as steroid-sparing agents, particularly useful in sensitive areas like the face and intertriginous zones.⁵

Recent therapeutic advances include crisaborole, a topical phosphodiesterase-4 inhibitor. Published studies have shown that crisaborole improved pruritus and disease severity scores with a favorable safety profile.¹⁰ In 2021, the FDA approved ruxolitinib cream, a topical Janus kinase (JAK) 1/2 inhibitor. A phase 3 trial showed ruxolitinib resulted in significant improvement in Eczema Area and Severity Index (EASI) scores within 2 weeks of treatment, offering rapid relief.¹¹

For moderate-to-severe cases, systemic treatment is often required. Dupilumab, a monoclonal antibody targeting the interleukin-4 receptor alpha (IL-4Rα), was the first biologic approved for AD and remains a cornerstone of systemic therapy. In long-term trials, dupilumab significantly reduced EASI scores and improved quality of life, with sustained efficacy and a favorable safety profile.¹²

In December 2021, the FDA approved the interleukin-13 antagonist, tralokinumab, for adults after demonstrating robust reductions in both lesion severity and pruritus in two 52-week phase 3 trials.¹³ This indication was expanded to include pediatric patients aged 12 and older in December 2023. The FDA approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis in adults and children 12 years of age and older in September 2024.

Small-molecule JAK inhibitors have gained traction due to their ability to block multiple pro-inflammatory pathways. Abrocitinib and upadacitinib, both oral JAK1 inhibitors, have been approved for moderate-to-severe AD in adolescents and adults. In randomized controlled trials, both agents showed superior efficacy to placebo and dupilumab in some secondary endpoints, with rapid onset of action and significant pruritus relief.^14,15 However, long-term safety monitoring is warranted due to risks of infections, thrombosis, and laboratory abnormalities. Delgocitinib, a topical JAK inhibitor, received FDA approval for the treatment of moderate-to-severe chronic hand eczema in adults in September 2024.¹⁶

In December 2024, the FDA approved nemolizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in adolescents and adults. Nemolizumab is a monoclonal antibody that specifically blocks the IL-31 receptor, which is involved in itch and inflammation.¹⁷

AD is more than a skin disease—it affects emotional, psychological, and social well-being. Patients with moderate-to-severe AD experience higher rates of anxiety, depression, and sleep disturbances. Thus, a multidisciplinary approach is essential. Collaboration among dermatologists, allergists, pediatricians, psychologists, and dietitians can improve outcomes.

Psychodermatology services have been shown to improve treatment adherence and reduce psychological distress. In pediatric populations, behavioral therapy and parent-focused interventions are effective adjuncts to medical management.¹⁸ Furthermore, dietary interventions may play a role in some patients, particularly those with confirmed food allergies or sensitivities. However, routine elimination diets are not recommended unless medically indicated.

Patient and caregiver education remains central to management. Structured education programs have been shown to improve self-management and reduce disease flares. Digital tools, including mobile apps and teledermatology platforms, have expanded patient engagement and monitoring, especially in remote or underserved areas.¹⁹

The past 5 years have ushered in a new era of precision medicine in AD. Advances in molecular understanding have led to targeted therapies that offer improved efficacy and tolerability. With the emergence of new biologics, JAK inhibitors, and advanced diagnostics, clinicians are better equipped to deliver personalized care. Yet, challenges remain. Long-term safety data for new agents are still evolving, and disparities in access to care persist. A patient-centered, multidisciplinary approach, combined with continued research and innovation, will be key to improving outcomes for individuals living with this complex disease.

1. American Academy of Allergy, Asthma & Immunology. Atopic March Defined. AAAAI. Updated 2024. Accessed April 7, 2025. https://www.aaaai.org/tools-for-the-public/allergy,-asthma-immunology-glossary/atopic-march-defined
2. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-351.
3. Nakatsuji T, Chen TH, Butcher AM, et al. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Sci Adv. 2018;4(2):eaao4502.
4. Park KY, Seo SJ, Kim MN, et al. Impact of air pollution on atopic dermatitis. J Allergy Clin Immunol Pract. 2020;8(3):1133-1141.e5.
5. Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: Part 4. Prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol. 2021;85(1):83-99.
6. Brunner PM, Pavel AB, Khattri S, et al. Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to dupilumab. J Allergy Clin Immunol. 2019;143(1):142-154.
7. Dyjack N, Goleva E, Rios C, et al. Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of disease and treatment in atopic dermatitis. J Allergy Clin Immunol. 2018;141(4):1298-1309.
8. Atak MF, Farabi B, Navarrete-Dechent C, Rubinstein G, Rajadhyaksha M, Jain M. Confocal Microscopy for Diagnosis and Management of Cutaneous Malignancies: Clinical Impacts and Innovation. Diagnostics (Basel). 2023;13(5):854. Published 2023 Feb 23. doi:10.3390/diagnostics13050854.
9. Razi S, Kuo YH, Pathak G, et al. Line-Field Confocal Optical Coherence Tomography for the Diagnosis of Skin Tumors: A Systematic Review and Meta-Analysis. Diagnostics (Basel). 2024;14(14):1522. Published 2024 Jul 15. doi:10.3390/diagnostics14141522
10. Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 inhibitor for the topical treatment of atopic dermatitis (AD-301 and AD-302). J Am Acad Dermatol. 2016;75(3):494-503.e6.
11. Kim BS, Howell MD, Sun K, et al. Safety and efficacy of ruxolitinib cream for the treatment of atopic dermatitis: 52-week results from a phase 3 study. J Am Acad Dermatol. 2022;86(5):990-997.
12. Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab vs placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.
13. Wollenberg A, Blauvelt A, Guttman-Yassky E, et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week phase III trials. Br J Dermatol. 2021;184(3):437-449.
14. Silverberg JI, Simpson EL, Thyssen JP, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(8):863-873.
15. Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Upadacitinib efficacy and safety in atopic dermatitis: a 16-week randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;145(3):877-884.
16. Nakagawa H, Nemoto O, Igarashi A, et al. Delgocitinib cream, a pan-Janus kinase inhibitor, in adult patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase III study. Br J Dermatol. 2020;182(6):1497-1506.
17. Kabashima K, Matsumura T, Komazaki H, et al. Trial of nemolizumab and topical agents for atopic dermatitis with pruritus. N Engl J Med. 2020;383(2):141-150.
18. Evers AW, Verhoeven EW, van Middendorp H, et al. How stress gets under the skin: towards a psychobiological understanding of stress-related skin disorders. Acta Derm Venereol. 2010;90(3):232-238.
19. Rojahn TB, Lapidus CS, Duan L, et al. Use of digital health technology in pediatric eczema management: a scoping review. Pediatr Dermatol. 2022;39(3):383-392.
20. Guttman-Yassky E, Blauvelt A, Eichenfield LF, et al. Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: Results from two randomized phase 3 trials (ADvocate 1 and 2). Lancet. 2023;401(10375):951-964.