If topical corticosteroids and moisturisers fail, short-term treatment with topical calcineurin inhibitors such as tacrolimus or pimecrolimus may be tried, although their use is controversial, as some studies indicate that they increase the risk of developing skin cancer or lymphoma. A 2007 meta-analysis showed that topical pimecrolimus is not as effective as corticosteroids and tacrolimus. A 2015 meta-analysis, though, indicated that topical tacrolimus and pimecrolimus are more effective than low-dose topical corticosteroids, and found no evidence for increased risk of malignancy or skin atrophy. In 2016, crisaborole, an inhibitor of PDE-4, was approved as a topical treatment for mild-to-moderate eczema.Other medications used for AD include systemic immunosuppressants such as ciclosporin, methotrexate, interferon gamma-1b, mycophenolate mofetil, and azathioprine. Antidepressants and naltrexone may be used to control pruritus (itchiness). Leukotriene inhibitors such as monteleukast are of unclear benefit as of 2018.In 2017, the monoclonal antibody(mAb) dupilumab under the trade name Dupixent was approved to treat moderate-to-severe eczema. In 2021, an additional monoclonal antibody, tralokinumab, was approved in the EU & UK with the trade name Adtralza then later in the US as Adbry for similarly severe cases.
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.