T Helper Cell-Mediated Immunity and IgE Responses in Extrinsic vs Intrinsic Atopic Dermatitis: A Systematic Review
Mariella T. Hafalla
The Godolphin and Latymer School, London, United Kingdom
Publication date: November 20, 2025
The Godolphin and Latymer School, London, United Kingdom
Publication date: November 20, 2025
DOI: http://doi.org/10.34614/JIYRC2025II62
ABSTRACT
Atopic dermatitis (AD) is a heterogeneous inflammatory skin condition affecting approximately 200 million individuals globally. AD can be categorised into extrinsic (IgE high) atopic dermatitis (EAD) and intrinsic (IgE normal) atopic dermatitis (IAD) subtypes. Whilst these subtypes share clinical features, their immunological profiles differ. Clarifying the immunological differences between these subtypes, particularly their T helper cell cytokine and IgE levels, may improve diagnosis and development of subtype-specific treatments. The objective of this systematic review was to compare the immunological biomarkers (IgE, eosinophils and cytokine profiles) in EAD and IAD. Following PRISMA guidelines, PubMed was searched using the terms (atopic dermatitis) AND (Intrinsic) AND (IgE); eight articles met the inclusion criteria. All studies found that EAD patients had significantly higher total serum IgE levels and eosinophil counts than IAD patients, suggesting that EAD is driven by Th2 pathways. However, cytokine findings were heterogeneous. IL-4 levels showed no difference between the groups, but IL-4R was generally higher in EAD patients. IFN-γ was elevated in IAD. IL-5 and IL-13 had variable results, although some papers reported higher IL-5 expression and higher IL-13 levels in EAD than IAD. IL-17 findings were also variable. Different IgE thresholds were used for classification and different methods of biomarker identification were applied. Standardised thresholds and larger sample sizes would be required in the future to better define the immunological basis. Although this review focused on biomarkers, the findings have treatment relevance, indicating that Th2 pathways remain clinically important in both EAD and IAD and may inform future treatment strategies.
Atopic dermatitis (AD) is a heterogeneous inflammatory skin condition affecting approximately 200 million individuals globally. AD can be categorised into extrinsic (IgE high) atopic dermatitis (EAD) and intrinsic (IgE normal) atopic dermatitis (IAD) subtypes. Whilst these subtypes share clinical features, their immunological profiles differ. Clarifying the immunological differences between these subtypes, particularly their T helper cell cytokine and IgE levels, may improve diagnosis and development of subtype-specific treatments. The objective of this systematic review was to compare the immunological biomarkers (IgE, eosinophils and cytokine profiles) in EAD and IAD. Following PRISMA guidelines, PubMed was searched using the terms (atopic dermatitis) AND (Intrinsic) AND (IgE); eight articles met the inclusion criteria. All studies found that EAD patients had significantly higher total serum IgE levels and eosinophil counts than IAD patients, suggesting that EAD is driven by Th2 pathways. However, cytokine findings were heterogeneous. IL-4 levels showed no difference between the groups, but IL-4R was generally higher in EAD patients. IFN-γ was elevated in IAD. IL-5 and IL-13 had variable results, although some papers reported higher IL-5 expression and higher IL-13 levels in EAD than IAD. IL-17 findings were also variable. Different IgE thresholds were used for classification and different methods of biomarker identification were applied. Standardised thresholds and larger sample sizes would be required in the future to better define the immunological basis. Although this review focused on biomarkers, the findings have treatment relevance, indicating that Th2 pathways remain clinically important in both EAD and IAD and may inform future treatment strategies.
