The puzzle of polymorphous light eruption : Patients and pathogenesis

Abstract

Polymorphous light eruption (PLE) is a photosensitivity disorder of which the pathogenesis is not fully understood. Patient history in PLE is important since lesions are transient and often not present at time of consultation. Phototesting is done to reproduce the PLE skin lesions and to obtain information about the responsible action spectrum and the UV dose necessary to elicit skin lesions. However, phototesting is a time consuming procedure. Therefore, we wondered whether it would be possible to assess severity of disease based on the patient history alone. In chapter 2, we showed that the severity assessment in PLE based on patient history did not correlate with the severity as assessed by phototesting. Furthermore, many different phototesting protocols exist, resulting in very different success rates. In chapter 3, it was demonstrated that a maximum of 4 daily irradiations using UVA and UVB light sources is suitable and optimal for diagnostic phototesting in the majority of the PLE patients. More extensive test protocols have no clinical implications, however less extensive protocols may lead to substantial loss of positive test results. PLE lesions can be visible even within a few hours after UV exposure. Therefore, we hypothesized that an early induced mechanism is responsible for the initiation of PLE. In chapter 4, we showed that in PLE patients significantly less neutrophils infiltrate the skin at 18 h after 3 MED UVB irradiation compared with healthy controls, most probably due to local and not systemic pathomechanisms. The intrinsic chemotactic capacity of neutrophils, as well as the expression pattern of cell surface receptors, was similar in PLE patients and healthy controls, indicating that the reduced neutrophil infiltration in PLE skin is most probably not caused by an impaired function of circulating neutrophils. In chapter 5, sequential changes in mRNA regulating a broad spectrum of proteins involved in UV-induced inflammation of the skin in the first 18 hours after UVB exposure were found. After a single dose of 3 MED UVB, a gene specific expression time-dependency was observed in skin of PLE patients and healthy controls. At 3 and 6 h after UVB irradiation, no distinctive early mRNA expression pattern between PLE patients and healthy controls was shown. However, 18 h after UVB exposure, PLE patients showed a significantly increased mRNA expression of ICAM-1, CD25 and FOXP3 compared with healthy controls. Furthermore, we found that the expression of IL-1β was decreased in unirradiated skin of PLE patients. The increased mRNA expression of CD25 and FOXP3 suggests that T-cells expressing a regulatory phenotype play a role during the early phase of the UVB-induced response in PLE patients. Cis-urocanic acid (UCA) is present in the UV-exposed skin and has immunosuppressive properties. In chapter 6, we observed that PLE patients have significantly increased amounts of total- and trans-UCA in unirradiated buttock skin. After UVB irradiation significantly increased concentrations of trans- and cis-UCA were found in the skin of PLE patients. We hypothesized that the increase in cis-UCA might be responsible for a decreased neutrophil skin infiltration after UVB.