Desired response to phototherapy vs photoaggravation in psoriasis: what makes the difference?

Abstract

Psoriasis commonly responds beneficially to UV radiation from natural sunlight or artificial sources. Therapeutic mechanisms include the proapoptotic and immunomodulating effects of UV, affecting many cells and involving a variety of pro-and anti-inflammatory cytokines, downregulating the Th17/IL-23 response with simultaneous induction of regulatory immune cells. However, exposure to UV radiation in a subset of psoriasis patients leads to exacerbation of the disease. We herein shed light on the predisposing factors of photosensitive psoriasis, including genetics (such as HLACw*0602 or CARD14), gender and coexisting photodermatoses such as polymorphic light eruption (PLE) in the context of potential molecular mechanisms behind therapeutic photoresponsiveness or photoaggravation. UV-induced damage/pathogenassociated molecular patterns, damage to self-coding RNA (signalling through Toll-like receptors), certain antimicrobial peptides and/or inflammasome activation may induce innate immunity, leading to psoriasis at the site of UV exposure when there is concomitant, predisposing resistance against UV-induced suppression of the adaptive immune response (like in PLE) that otherwise would act to reduce psoriasis. K E Y W O R D S

Frequency of occurrence of polymorphic light eruption in patients treated with photohardening and patients treated with phototherapy for other diseases

“…Notably, our results showed a very low prevalence of PLE in psoriasis patients undergoing phototherapy (0.7%, [3/421]), even though PLE in psoriasis might not be so rare in the general population . PLE seems to be highly linked to photosensitive variants of psoriatic disease.…”

For better or for worse, UV in psoriasis

“…A better understanding of the pathogenesis of psoriasis and the UV therapeutic mechanism(s) should contribute to the desired optimization of a sustainable and effective UV treatment of psoriasis as a chronic disease. The Viewpoint of Wolf et al . on the desired versus adverse responses to phototherapy provides several leads for the optimization.…”

Cutaneous infiltration of plasmacytoid dendritic cells and T regulatory cells in skin lesions of polymorphic light eruption

“…Recent works have also suggested that innate antimicrobial peptides (AMP) may be involved in pathogenesis of PLE . Normally, UVR‐induced AMP contributes to immunosuppression inducing Tregs, otherwise in early stages of PLE a dysregulated AMP expression following UVR could play some part in the failure of photoimmunosuppression .…”