Palmoplantar Pustulosis as an Immune-Mediated Inflammatory Disease with a Possible Relevance of Th17 Cell Plasticity:...

Palmoplantar pustulosis (PPP) is an immune-mediated inflammatory disease (IMID) of the skin that causes the formation of sterile pustules on the palms and soles. The clinical course of PPP is variable, with some patients having persistent skin lesions and others having lesions that wax and wane repeatedly. PPP has been treated with drugs such as those used for plaque psoriasis. The efficacy of biologics targeting the interleukin (IL)-23-helper T (Th)17 axis is not as conspicuous in PPP as in plaque psoriasis. Traditionally, CD4⁺ Th cell subsets have been defined by the expression of a small number of cytokines; however, recent advances in immunology have shown that some Th cell subsets can express cytokines of other Th subsets in response to changes in the environment. Recent studies have suggested the involvement of unique Th17 cells with Th2 cell characteristics in the pathogenesis of PPP. Thus, the insufficient efficacy of biologics targeting the IL-23-Th17 axis in PPP raises the question of whether Th17 cell plasticity is involved in the pathogenesis of PPP. In this review, we discuss the complexity of PPP pathogenesis with some speculation, compare the new knowledge obtained by other IMIDs or their mouse models with that of PPP elucidated thus far, and contribute to the development of future research.