Are Topical Steroids Enough in Early Childhood Atopic Dermatitis?

Since their introduction in the 1950s, topical corticosteroids (TCS) have remained the mainstay of therapy for atopic dermatitis (AD), particularly in infants and young children. Decades of clinical experience confirm their efficacy in reducing erythema, pruritus, and acute inflammation. However, evolving insights into early-life immunology and type 2 inflammation are prompting renewed scrutiny of whether TCS sufficiently address the underlying immune pathways that link infant AD to later atopic comorbidities, including food allergy (FA), asthma, and allergic rhinitis.¹

A recent narrative review synthesizes emerging data on innate and adaptive immune drivers of type 2 inflammation in early childhood AD, the concept of “remote priming,” and the immunomodulatory effects of established and emerging therapies.² The findings suggest that although TCS improve clinical disease and reduce selected biomarkers, they may only partially modulate the immune circuits implicated in atopic progression.

Type 2 Inflammation: ILC2 and Th2 in Early Life

Type 2 inflammation in AD is sustained by a dynamic interplay between innate lymphoid cells type 2 (ILC2) and memory T helper 2 (Th2) cells. Epithelial-derived alarmins—including thymic stromal lymphopoietin, IL-25, and IL-33—activate tissue-resident immune cells, leading to production of IL-4, IL-5, and IL-13. These cytokines promote eosinophil recruitment, IgE class switching, and neuronal activation associated with itch.

In infancy, innate immunity predominates. ILC2s are relatively abundant at barrier surfaces, and neonatal immune responses are skewed toward Th2-type cytokine production. In the context of epidermal barrier dysfunction, this environment may favor epicutaneous sensitization. Food antigens penetrating inflamed skin can induce IgE responses locally, with downstream effects at distant mucosal sites—a process termed “remote priming.” IL-33–driven activation of ILC2s has been implicated in facilitating antigen-specific responses in gut-associated lymphoid tissue, potentially linking early AD to subsequent FA.

Systemic and Epidermal Effects of TCS

The immunologic effects of TCS in infants were evaluated in a 6-week study by McAleer and colleagues involving 74 infants with AD. Treatment was associated with significant reductions in circulating type 2–related biomarkers, including CCL17 (TARC), IL-13, CCL22, IL-5, and CCL26, as well as soluble adhesion molecules. These findings suggest that short-term TCS therapy can dampen systemic markers of type 2 inflammation.

At the epidermal level, transepidermal water loss (TEWL) decreased, along with IL-18, IL-8, and vascular markers such as VEGF-A. However, IL-13 remained elevated in the stratum corneum, and IL-5 levels increased locally despite systemic reductions. Natural moisturizing factor levels did not improve, irrespective of filaggrin mutation status.

These findings raise important mechanistic questions. Persistent epidermal IL-13 and increased IL-5 may indicate continued local type 2 activity, potentially involving ILC2s or eosinophils. In parallel, increases in certain chemokines and growth factors associated with tissue repair and immune cell recruitment were observed. Although TCS effectively reduces visible inflammation and TEWL, the data suggest that some components of innate type 2 signaling may remain active in treated skin.

FA Risk and Treatment Strategy

Epidemiologic data reinforce the strong association between early AD severity and FA. In a large cohort study, infants with eczema were substantially more likely to develop peanut and egg allergy, with FA prevalence exceeding 50% among those with early-onset, corticosteroid-treated disease. Meta-analytic data similarly demonstrate increasing FA prevalence with greater AD severity.

Whether TCS modify FA risk remains unclear. A trial comparing proactive vs reactive TCS application in infants with mild AD showed a lower proportion of FA in the proactive group at 28 weeks (31.4% vs 41.0%). However, rates of egg-specific IgE sensitization increased in both groups, and proactive therapy was associated with reduced gains in weight and height. The study did not include an untreated severity-matched comparator, limiting conclusions regarding causality.

Barrier enhancement alone may also be insufficient. The Barrier Enhancement for Eczema Prevention trial found that daily emollient use in high-risk newborns did not reduce AD incidence by age 2 years, suggesting that inflammation, rather than barrier dysfunction alone, is central to disease pathogenesis.

Similarly, in the Study of the Atopic March, early treatment with topical pimecrolimus controlled AD symptoms but did not reduce the development of atopic comorbidities over nearly 3 years of follow-up. These findings align with the hypothesis that targeting T-cell activation alone may not adequately modulate upstream innate drivers such as ILC2.

Biologic and Targeted Therapies: Broader Immunomodulation

The IL-4 receptor α (IL-4Rα) antagonist dupilumab has demonstrated broader immunologic effects in pediatric AD. In infants and young children treated with dupilumab plus TCS, serum IgE decreased by approximately 70% over 16 weeks, whereas IgE increased in those receiving TCS alone. Additional studies have shown reductions in food allergen–specific IgE and decreases in circulating and epidermal biomarkers, including TARC/CCL17 and CCL22.

By blocking IL-4 and IL-13 signaling, dupilumab appears to modulate both innate and adaptive type 2 pathways, with potential implications for atopic comorbidity risk. In contrast, other targeted therapies—including IL-13–specific monoclonal antibodies, PDE4 inhibitors, AhR agonists, and Janus kinase inhibitors—have shown variable or limited effects on IgE and type 2 biomarkers in available studies, most of which derive from adult populations.

Mechanistic data further suggest that early interruption of IL-4Rα signaling may prevent the establishment of long-lived IgE-secreting plasma cells, which become resistant to conventional therapy once established.

Clinical Implications

AD is diagnosed in up to 60% of affected children by age 1 year, during a critical window of immune development. Current evidence supports the continued use of TCS for short-term disease control and reduction of systemic inflammatory markers. However, available data indicate that TCS may not fully suppress innate type 2 drivers implicated in IgE sensitization and remote priming.

Emerging biologic therapies that target shared cytokine pathways across innate and adaptive immunity may offer broader immunomodulation. Whether very early intervention can meaningfully alter the trajectory of FA and other atopic comorbidities remains an open question. Longitudinal, severity-matched comparative studies will be essential to define optimal early treatment strategies and to clarify whether modifying type 2 inflammation in infancy can interrupt the atopic march.

References

1. Das A, Panda S. Use of topical corticosteroids in dermatology: an evidence-based approach. Indian J Dermatol. 2017;62(3):237-250. doi:10.4103/ijd.IJD_169_17
2. Chau CA, Cyr SL, Gupta R, Lio P. Atopic comorbidities and topical steroids in early childhood atopic dermatitis: are we missing a piece of the puzzle? Clin Rev Allergy Immunol. 2026;69(1):3. doi:10.1007/s12016-025-09131-5