Letter: pathogenesis of tumour necrosis factor‐alpha antagonists‐induced psoriasiform lesions

Abstract

We read with interest the article by Buisson et al.1 As described by the authors, the pathogenesis of the tumour necrosis factor-alpha antagonists (anti-TNF-α)-induced psoriasiform lesions has not yet been fully clarified.2 The most widely accepted hypothesis is based on an interaction between the reduction in TNF-α and the increase in interferon-alpha (IFN-α),2, 3 instead of the increase of interferon-γ described in the study.1 It is believed that plasmocytoid dendritic cells (natural IFN-α producers) are capable of inducing psoriasis through IFN-α production.4, 5 Since such plasmocytoid cells are usually down-regulated by TNF-α, its inhibition by the biological may determine increased and uncontrolled IFN-α production and consequently induce or exacerbate psoriasis.6 In the literature, in addition to the in vitro studies described by the authors,1 there are other reports3, 7 that support such a relationship between IFN-α and anti-TNF-α-induced psoriasiform lesions. A study3 detected strong production of protein MxA (a specific marker for IFN signalling) in the inflammatory cells of skin samples of anti-TNF-α-induced psoriasis as compared with controls. Another study7 found increased IFN-α expression in the psoriatic lesions of patients receiving anti-TNF-α therapy, as compared with spontaneous psoriasis. Furthermore, since the time between anti-TNF-α administration and the development of psoriatic lesions may be extremely variable,2 an environmental trigger could be involved in this pathophysiological mechanism.8 In addition, since TNF-α antagonists have been administered to more than two million patients worldwide9 and cases of this adverse cutaneous event remains in the hundreds,2 this paradoxical phenomenon may be related to a genetic predisposition.2, 10 Consequently, future genetic studies may be able to help with the identification of predisposed patients as well as with the elucidation of the specific immunopathogenic mechanism. Declaration of personal and funding interests: None.