Interleukin 4 inhibition as a potential therapeutic in pemphigus

•The cytokine interleukin-4 has an important role in pemphigus disease.•Inhibition of interleukin-4 may be a possible treatment in pemphigus disease.•Dupilumab is a possible adjuvant treatment in pemphigus.•Interferon injection should improve pemphigus in relapse phase.

Pemphigus is an autoimmune bullous skin disease that results from desmosomal protein desmoglein 3 and 1 loss in pemphigus vulgaris and foliaceus, respectively. It can be considered as a Th2-dominant disease over-expressed by Th2 cell cytokines. Interleukin (IL)-4 is a key cytokine which can exacerbate Th2 over-expression in addition to isotype switching to immunoglobin (Ig)G1 and IgG4 that are responsible for desmoglein loss. Elevation of IL-4 level has also been reported in various studies. Considering the important role of IL-4 in severe phase of pemphigus and lack of effective and safeness therapy for this potentially fatal disease, anti-IL-4 therapy was introduced as a potential curative for pemphigus disease. This study reviewed all studies about any roles of IL-4 that can directly and indirectly be played in the development of pemphigus and IL-4 inhibition with interferons and dupilumab therapy were introduced as a novel pemphigus treatment for patients who are in relapse phase of the disease. Dupilumab was also introduced as a possible treatment for patients with severe pemphigus. It can directly inhibit IL-4 by targeting IL-4 α-chain receptor. IL-4 inhibition can lead to the creation of Th1:Th2 balance by various pathways, discussed in this study.