Biophysical and Raman Spectroscopy Assessment of Drug-Induced Photosensitivity: Insights from a Randomised Controlled Pilot Study

Drug-induced photosensitivity is a recognised adverse reaction, yet systematic quantification remains limited. This study investigates the quantitative impact of commonly prescribed drugs on human skin physiology following oral intake and subsequent UV exposure. Ten drugs with known photosensitising potential were selected: acetylsalicylic acid, amiodarone, diclofenac, doxycycline, enalapril, furosemide, hydrochlorothiazide, pantoprazole, verapamil, and voriconazole. Twelve healthy volunteers received five allocated substances, separated by washout periods. Defined skin areas were exposed to gradual UVA and UVB doses according to individual skin type. Skin parameters including confocal Raman spectroscopy (CRS), transepidermal water loss (TEWL), stratum corneum (SC) hydration, skin surface pH, melanin and erythema indices were measured 24 hours after exposure. Highest increase in erythema was caused by enalapril, amiodarone, furosemide and verapamil in response to both UVA and UVB irradiation. UVA predominantly increased melanin levels, while UVB caused pronounced erythema. No deterioration of natural moisturising factor or urea was observed throughout the entire analysed skin depth; TEWL remained unaffected. Trends towards increased SC hydration after irradiation were noted, but CRS analysis of minimal erythema dose skin sites did not reveal significantly increased water mass within the upper 30 µm of the skin. Average skin pH increase remained below 10%. The study underlines the need for standardisation of assessment tools for evaluating drug-induced photosensitivity, which complement visual evaluation. The marked interindividual variability across all skin parameters demonstrates the complexity of skin reactions.