Analysis of spatial structure of epidermal nerve entry point patterns based on replicated data

Epidermal nerve fiber (ENF) density and morphology are used to diagnose small fiber involvement in diabetic, HIV, chemotherapy induced, and other neuropathies. ENF density and summed length of ENFs per epidermal surface area are reduced, and ENFs may appear clustered within the epidermis in subjects with small fiber neuropathy compared to healthy subjects. Therefore, it is important to understand the spatial behaviour of ENFs in healthy and diseased subjects. This work investigates the spatial structure of ENF entry points, which are locations where the nerves enter the epidermis (the outmost living layer of the skin). The study is based on suction skin blister specimens from two body locations of 25 healthy subjects. The ENF entry points are regarded as a realization of a spatial point process and a second-order characteristic, namely Ripley's K function, is used to investigate the effect of covariates (e.g. gender) on the degree of clustering of ENF entry points. First, the effects of covariates are evaluated by means of pooled K functions for groups and, secondly, the statistical significance of the effects and individual variation are characterized by a mixed model approach. Based on our results the spatial pattern of ENFs in samples taken from calf is affected by the covariates but not in samples taken from foot.