Comparative Analysis of Phototherapy Outcomes in Adjacent Skin Lesions Cohorts

Thesis Abstract

Phototherapy is a cornerstone treatment for various dermatologic conditions, yet variability in outcomes between adjacent skin lesions within the same patient remains poorly understood and clinically consequential. This study addresses the problem by evaluating whether phototherapy outcomes differ between anatomically proximate lesions of similar morphology, and to what extent lesion microenvironmental factors mediate treatment response. The aim is to determine if adjacent lesion cohorts exhibit statistically and clinically meaningful differences in therapeutic response, and to identify predictors of differential outcomes. Specific objectives include (1) quantifying changes in lesion size, clearance rate, and relapse frequency following standardized phototherapy regimens; (2) comparing response patterns between paired adjacent lesions (e.g., plaque versus plaque or plaque margins) using within-patient analyses; (3) examining the associations of epidermal thickness, vascularization, melanin index, and lesion microenvironment measures with phototherapy response; (4) evaluating potential moderating effects of phototherapy modality (UVA, UVB, narrowband UVB) and treatment duration on adjacency-related outcomes; and (5) synthesizing findings to inform clinical decision-making on personalized phototherapy strategies. A parallel, prospective cohort design will be employed, enrolling 120 patients with at least two adjacent, morphologically similar lesions across trunk and extremities, diagnosed with conditions commonly treated by phototherapy (pachydermic variants of psoriasis or vitiligo). Each patient will have matched lesion pairs randomized to receive identical phototherapy regimens, with lesion-level outcomes captured at baseline, mid-treatment (6 weeks), end of treatment (12 weeks), and follow-up at 6 months. Data collection instruments will include standardized lesion measurement tools (digital planimetry for area, high-resolution dermoscopy for structural changes), spectrophotometric skin color analysis for melanin and erythema indices, and noninvasive imaging (ultrasound or optical coherence tomography) to quantify epidermal thickness and microvascular density. Patient-reported outcomes will be obtained via validated dermatology life quality indices. Data on phototherapy parameters (dose, frequency, cumulative dose), concurrent topical therapies, and adverse events will be recorded. Analytical approaches will combine within-patient paired comparisons and multilevel modeling to account for inter-individual confounding and intra-patient lesion pairs. Descriptive statistics will summarize baseline characteristics. Paired t-tests or Wilcoxon signed-rank tests will compare pre- and post-treatment lesion metrics within adjacent pairs. Multivariate linear mixed-effects models will assess the influence of lesion-specific factors (epidermal thickness, melanin index, vascularity) and treatment variables on outcomes, with patient-level random intercepts to capture between-patient heterogeneity. Interaction terms will test whether adjacency modifies the effect of phototherapy modality or total dose. Logistic regression will model achievement of clinical clearance (yes/no) at 12 weeks. Time-to-event analyses (Kaplan-Meier and Cox proportional hazards) will explore relapse-free survival post-therapy, stratified by lesion adjacency characteristics. The study will draw on theories of tissue microenvironmental influence on photobiology and the biopsychosocial model of dermatologic treatment response, integrating the concept of field cancerization-like effects in chronic inflammatory dermatoses. A conceptual model will illustrate pathways linking lesion proximity, microenvironmental variables, phototherapy exposure, and clinical outcomes. Expected findings include greater heterogeneity in response between adjacent lesions compared with non-adjacent lesions, with microenvironmental factors such as increased epidermal thickness and higher local melanin content attenuating phototherapeutic efficacy in certain modalities. The study anticipates that narrowband UVB may yield more consistent responses across adjacent lesions due to its deeper penetration profile, whereas broad-spectrum therapies might exhibit greater adjacency-related variability. These results are anticipated to advance knowledge on intra-patient lesion heterogeneity and the role of microenvironment in phototherapy, contributing to personalized treatment planning and optimization of phototherapy regimens. The study will contribute to dermatology by elucidating the determinants of differential adjacency responses, informing clinicians about the need for lesion-tailored dosing and monitoring strategies, and providing a framework for future investigations into spatially resolved phototherapeutic outcomes. Recommendations include adopting lesion-specific documentation of microenvironmental factors, considering adaptive phototherapy dosing within patients, and conducting larger multicenter trials to validate adjacency-based treatment tailoring and improve overall therapeutic equity.