Br J Dermatol. 2009 Nov;161(5):1081-8. Epub 2009 Jun 5.
Cytokine imbalance with increased production of interferon-alpha in psoriasiform eruptions associated with antitumour necrosis factor-alpha treatments.
Seneschal J, Milpied B, Vergier B, Lepreux S, Schaeverbeke T, Taïeb A.
SourceDepartment of Dermatology and Pediatric Dermatology, Saint André and Pellegrin Hospitals, Bordeaux University Hospitals, 33075 Bordeaux Cedex, France.

Abstract
BACKGROUND: Psoriasiform eruptions occur in association with antitumour necrosis factor (TNF)-alpha treatments in autoinflammatory diseases. The major reported clinical presentation is palmoplantar pustulosis, sometimes accompanied with plaque-like psoriasis. In some reports, histological findings suggest psoriasis whereas others favour a lichenoid drug reaction. We present a case series with a comprehensive clinical, histopathological and immunohistochemical study.

OBJECTIVES: To investigate the mechanism involved in psoriasiform eruptions in patients receiving anti-TNF-alpha inhibitors.

METHODS: Between July 2004 and May 2008, 13 patients with psoriasiform eruptions arising under anti-TNF-alpha treatment were enrolled in the study. Punch biopsy specimens of lesions were processed for standard and immunohistochemical analyses using antibodies against CD3, CD4, CD8, CD20, CD1a, KP1, CXCR3, CXCL9, Tia1 and MxA, which is specifically induced by type I interferons (IFNs). Additionally, we analysed biopsies from lesional skin of patients with cutaneous discoid lupus erythematosus, lichen planus and psoriasis. Control biopsies were taken from unaffected skin.

RESULTS: All patients developed psoriasiform plaques on the body accompanied with palmoplantar keratoderma or pustulosis in three patients. Histological and immunohistochemical findings showed a psoriasiform pattern with focal lichenoid and spongiotic features. We detected strong production of the MxA protein in inflammatory cells, indicating involvement of type I IFNs, and the expression was higher than in control psoriasis samples. Expression of MxA was closely associated with the recruitment of CXCR3+ lymphocytes in the skin bearing markers of cytotoxic capacity.

CONCLUSIONS: Results support the hypothesis that psoriasiform eruptions are a new model of drug reaction characterized by an increased expression of type I IFNs induced by anti-TNF-alpha

 

 

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