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Rapid Downregulation of Innate Immune Cells, Interleukin-12 and Interleukin-23 in Generalized Pustular Psoriasis with Infliximab in Combination with Acitretin

Background: Generalized pustular psoriasis (GPP) is a severe inflammatory disease characterized by recurrent eruptions of sterile pustules on erythematous skin. Although tumor necrosis factor (TNF) antagonists may lead to a rapid resolution of GPP, the mechanism of action of these agents remains to be investigated. Here, we sought to evaluate markers of immune response in the skin of a patient who experienced a rapid amelioration of GPP after treatment with infliximab and acitretin. Methods: A skin biopsy was obtained before and 72 h after initiation of treatment. Immunohistochemical stainings were performed to characterize alterations of the infiltrates, the apoptosis marker caspase 3 and key cytokines like TNFα, interleukin (IL)-12, IL-23 and the chemokine CXCL8/IL-8. Results: Parallel with clinical improvement, a striking decline of neutrophils, myeloid and plasmacytoid dendritic cells, M1 macrophages and partly of CD4+ T cells was observed. There was no evidence of increased apoptosis mediated through the caspase-3 pathway. A marked reduction particularly of IL-12 and IL-23 and, to a lesser degree, of TNFα and CXCL8/IL-8 was observed. Conclusion: A swift clinical improvement of GPP by infliximab and acitretin is associated with a marked reduction particularly of innate and partially of the acquired immune cells as well as IL-12 and IL-23.