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.

Cigarette Smoke Underlies the Pathogenesis of Palmoplantar Pustulosis via an IL-17A–Induced Production of IL-36γ in Tonsillar Epithelial Cells

“…Second, although smoking induces an overexpression of IL-36g in the tonsillar epithelial cells of patients with PPP, it remains unclear whether this condition is involved in the localized palmoplantar skin lesions. A tonsilepalmoplantar skin axis might be involved in the pathogenesis of PPP (Harabuchi and Takahara, 2019;Mrowietz and van de Kerkhof, 2011). Cigarette smoke ingredients dissolved in the blood circulation might enhance an IL-17Aeinduced production of proinflammatory cytokines in palmoplantar acrosyringium lesions.…”

Tonsillitis as a possible predisposition to synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome

“…The tonsil is a common site for occult chronic infection, and tonsillitis has been demonstrated to be associated with a variety of rheumatic diseases, namely TIAS 2 . In the present study, we first investigated tonsillitis in SAPHO patients.…”

“…Pustulotic arthro‐osteitis (PAO) and palmoplantar pustulosis (PPP), sharing overlapping features with SAPHO syndrome, were demonstrated to be related to focal infections and were exacerbated following tonsillitis and other infections. In addition, after tonsillectomy, marked clinical improvements in skin lesions were observed in several previous PPP studies, 2 and patients experienced improved PAO‐induced arthralgia after the operation 3,4 . These diseases are denoted as tonsil‐induced autoimmune/inflammatory syndrome (TIAS), since they might be triggered by chronic indigenous infection in the tonsil.…”

Tonsillectomy as an effective treatment for arthralgia of SAPHO syndrome

“…Although the pathogenesis of SAPHO remains unclear, it has been hypothesized that SAPHO syndrome represents an autoimmune and inflammatory process triggered by the breakdown of immune tolerance to resident bacteria in the tonsils [ 10 ]. It has been speculated that activated tonsillar T cells are increased by a hyperimmune response against α-streptococci (i.e.…”

“…In the tonsils of patients with PPP, such a novel immune response leads to the activation of T cells through the abnormal expression of secondary stimulation molecules, such as cytotoxic T-lymphocyte-associated protein-4, inducible co-stimulator and Smad7. These tonsillar T cells, with enhanced expression of lymphocyte antigen, CCR6 and β1-integrin–vascular cell adhesion protein-1 binding, may migrate to PPP skin lesions or affected joints and then produce sterile pustules and joint pain [ 6 , 10 ]. Therefore, tonsillectomy is considered to be effective for PPP and PAO, which are related to SAPHO syndrome.…”