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.


CONCLUSIONS
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.
Department of Dermatology, Bern University Hospital and University of Bern, Bern, Switzerland. minmoon2005@yahoo.com
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Tang
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Spanou
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Tang
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Schibler
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Pelivani
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Yawalkar
D017255:Acitretin / Q000627:therapeutic use*; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D006801:Humans; D000069285:Infliximab; D018664:Interleukin-12 / Q000097:blood*; D053759:Interleukin-23 / Q000097:blood*; D008297:Male; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D053759:Interleukin-23; D018664:Interleukin-12; D000069285:Infliximab; D017255:Acitretin