This leads to activation of epidermal inflammatory dendritic and innate lymphoid cells which subsequently attracts Th2 CD4+ helper T cells to the skin. This dysregulated Th2 inflammatory response is thought to lead to the eczematous lesions. The Th2 helper T cells become activated, leading to the release of inflammatory cytokines including IL-4, IL-13 and IL-31 which activate downstream Janus kinase (Jak) pathways. The active Jak pathways lead to inflammation and downstream activation of plasma cells and B lymphocytes which release antigen specific IgE contributing to further inflammation. Other CD4+ helper T-cell pathways thought to be involved in atopic dermatitis inflammation include the Th1, Th17, and Th22 pathways. Some specific CD4+ helper T-cell inflammatory pathways are more commonly activated in specific ethnic groups with AD (for example, the Th-2 and Th-17 pathways are commonly activated in Asian people) possibly explaining the differences in phenotypic presentation of atopic dermatitis in specific populations.Mutations in the filaggrin gene, FLG, also cause impairment in the skin barrier that contributes to the pathogenesis of AD. Filaggrin is produced by epidermal skin cells (keratinocytes) in the horny layer of the epidermis. Filaggrin stimulates skin cells to release moisturizing factors and lipid matrix material, which cause adhesion of adjacent keratinocytes and contributes to the skin barrier. A loss-of-function mutation of filaggrin causes loss of this lipid matrix and external moisturizing factors, subsequently leading to disruption of the skin barrier.
Another monoclonal antibody treatment, lebrikizumab, is in phase 3 trials in the US; the drug has been granted Fast Track Designation by the FDA, and Eli Lilly and Company is expected to apply for FDA approval of the drug in the second half of 2022.Some JAK inhibitors such as abrocitinib, trade name Cibinquo, and upadacitinib, trade name Rinvoq, have been approved in the US for the treatment of moderate-to-severe eczema as of January 2022. Tentative, low-quality evidence indicates that allergy immunotherapy is effective in AD. This treatment consists of a series of injections or drops under the tongue of a solution containing the allergen.Antibiotics, either by mouth or applied topically, are commonly used to target overgrowth of S. aureus in the skin of people with AD, but a 2019 meta-analysis found no clear evidence of benefit. Light
A more novel form of treatment involves exposure to broad- or narrow-band ultraviolet (UV) light. UV radiation exposure has been found to have a localized immunomodulatory effect on affected tissues and may be used to decrease the severity and frequency of flares. In particular, the usage of UVA1 is more effective in treating acute flares, whereas narrow-band UVB is more effective in long-term management scenarios. However, UV radiation has also been implicated in various types of skin cancer, and thus UV treatment is not without risk. UV phototherapy is not indicated in young adults and children due to this risk of skin cancer with prolonged use or exposure.