The presentation of atopic dermatitis varies by

• Age of onset
• Duration of symptoms
• Location of lesions
• Severity
• Likelihood of allergic sensitization
• Comorbidities

One prospective, 6-year, longitudinal study of 1,038 children delineated subtypes of atopic dermatitis that may assist in identifying the children who are more at risk for specific comorbidities. This study outlined some potential risk factors for specific phenotypes.

Pathogenesis: Alterations in Skin Barrier

• The passive barrier formed by the skin has 2 chief components, the stratum corneum and tight junctions.
• Filaggrin is an important protein in the epidermal barrier formation.
• Filaggrin is crucial for keratinization. The thickened insoluble matrix surrounded by lipids forms a barrier against water loss and ingress of allergens, irritants, and microbes.
• Filaggrin is a precursor for natural moisturizing factor, which is responsible for maintaining skin pH and skin hydration.
• Loss-of-function mutations in the FLG gene are strongly associated with moderate-to-severe atopic dermatitis with early onset of disease; however, about 8% of the population carries mutations in filaggrin but do not develop atopic dermatitis.

Pathogenesis of Atopic Dermatitis

The microbiome of the skin may also be important in the pathogenesis of atopic dermatitis. Some evidence shows that altering the microbiota of the skin by transplanting specific bacteria to the skin of those with atopic dermatitis improves the clinical course of the disease and reduces colonization with Staphylococcus aureus (Source: JCI Insight, The Journal of Biotechnology).

If the skin barrier is broached, then the immune system is faced with responding to various antigens. An immune response can include:

• Components of the adaptive immune system (T-cell subsets)
• Components of the innate immune system
• Phagocytes
• Mast cells
• Basophils
• Eosinophils

Pathogenesis: Alterations in Adaptive Immunity

The inflammatory response in patients with atopic dermatitis is associated with the activation of specific T-cell subsets.

• Active lesions of atopic dermatitis have high levels of helper T cells (TH), specifically TH2 lymphocytes, which secrete interleukin (IL) 4, IL-5, IL-13, IL-31, and others. 
• These T-cell lymphokines downregulate the expression of proteins in the stratum corneum and tight junctions, particularly filaggrin and claudins.
• The alterations in T_H2 expression of IL-4 and IL-13 (among other cytokines) predispose those with atopic dermatitis to skin infections.
  • The increased risk of skin infections occurs in part because IL-4 and IL-13 further downregulate the expression of antimicrobial peptides that protect the skin from bacterial and viral infections.
  • IL-4 and IL-13 also inhibit the antimicrobial effects of other cytokines (eg, interferon gamma and IL-17).

After atopic dermatitis lesions form, the expression and complex interplay of inflammatory cytokines changes and evolves as chronic atopic dermatitis develops.

• Different T-cell subsets (T_H17, T_H1, and T_H22) are active in chronic lesions compared with newly formed lesions.
• This shift results in a clinically apparent thickening of the epidermis and abnormal keratinocyte formation.