Rapid downregulation of innate immune cells, interleukin-12 and interleukin-23 in generalized pustular psoriasis with infliximab in combination with acitretin

Dermatology. 2012;225(4):338-43. doi: 10.1159/000346243. Epub 2013 Jan 18.

Abstract

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.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Acitretin / therapeutic use*
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Down-Regulation
  • Drug Therapy, Combination
  • Humans
  • Infliximab
  • Interleukin-12 / blood*
  • Interleukin-23 / blood*
  • Male
  • Psoriasis / blood
  • Psoriasis / drug therapy*
  • Psoriasis / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Interleukin-23
  • Interleukin-12
  • Infliximab
  • Acitretin