Pathogenic role of palatine tonsils in palmoplantar pustulosis: A review

Abstract Palmoplantar pustulosis (PPP) is characterized by symmetrical, erythematous, scaly plaques, with numerous, sterile, non‐bacterial, pinpoint pustules, which are restricted to the palms and soles. Because several reports have described the efficacy of tonsillectomy for improvement in PPP skin lesions, we consider that PPP is tonsil‐induced autoimmune/inflammatory syndrome (TIAS) while other factors are also involved in the pathogenesis of PPP. Here, the association between PPP pathogenesis and TIAS was examined, with a focus on results of previous studies. PPP patients show a hyperimmune response to indigenous bacteria such as α‐streptococci, due to impaired immunological tolerance towards such organisms. Such a novel immune response leads to T‐cell activation through the abnormal expression of secondary stimulation molecules, including cytotoxic T‐lymphocyte‐associated antigen 4, inducible T‐cell co‐stimulator and Smad7, in the tonsils of PPP patients. Activated tonsillar T cells express cutaneous lymphocyte antigen (CLA), CCR6 and β1‐integrin, enter the blood circulation and are recruited to PPP skin lesions. Within lesions, T cells roll onto endothelial cells through the interaction between CLA and E‐selectin, migrate into the extravascular area through β1‐integrin–vascular cell adhesion molecule 1 binding, and assemble in the skin through CCL20–CCR6 binding. Hyperimmune responses to autoantigens such as keratin and heat shock proteins could also be involved in PPP pathogenesis, through the stimulation of the T‐helper 17 reaction.