Immunopathogenesis of polymorphic light eruption, role of cytokines, effector and regulatory T-cells and its therapeutic implications.

Polymorphic light eruption (PMLE) is mediated by a type IVc delayed-type hypersensitivity (DTH) reaction to ultraviolet radiation (UVR) induced neoantigens. While UVR normally exerts an immunosuppressive effect with increased regulatory T-cells (Tregs) and an accentuated T helper 2 (Th2) response, PMLE shows a heightened Th1 response. Existent data in PMLE suggests a Th1-skewed immune response with reduced Treg numbers and function, lack of Langerhans cells activity, and increased CD8+ resident memory T-cells. Keratinocytes (KCs) contribute to inflammation by releasing interleukin (IL)-1β, Vascular Endothelial Growth Factor-alpha (VEGF-α), and adhesion molecules, which facilitate various immune cell infiltration. The disturbed cytokine milieu with elevated IL-1, IL-12, IL-31, IL-36, IL-15, interferon-gamma (IFN-γ), and decreased IL-4 and IL-10, contributes to disease pathogenesis. IL-15 accounts for the recurrence of lesions. Various drugs, including immunosuppressive agents and antioxidants, have been tried in PMLE with limited evidence. Emerging therapies include cytokine-targeting agents and Janus kinase inhibitors such as tofacitinib, which modulate cytokine milieu via Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. Eradication of microbiota is a novel concept that mitigates the cytokine imbalance. Photohardening with narrow band ultraviolet B (NBUVB) or ultraviolet A (UVA) is believed to be effective as it enhances Treg activity. We emphasise the need for further cytokine profiling in PMLE to tailor targeted therapies, as there is an increasing evidence of a Th1 cytokine overexpression which is not curtailed by Treg cells, and thus, drugs targeting the implicated cytokines would achieve long-term results.