Degree of skin denervation and its correlation to objective thermal sensory test in leprosy patients

Abstract

Background: Leprosy is an infectious disease affecting skin and peripheral nerves resulting in increased morbidity and physical deformities. Early diagnosis provides opportune treatment and reduces its complications, relying fundamentally on the demonstration of impaired sensation in suggestive cutaneous lesions. The loss of tactile sensitivity in the lesions is preceded by the loss of thermal sensitivity, stressing the importance of the thermal test in the suspicious lesions approach. The gold-standard method for the assessment of thermal sensitivity is the quantitative sensory test (QST). Morphological study may be an alternative approach to access the thin nerve fibers responsible for thermal sensitivity transduction. The few studies reported in leprosy patients pointed out a rarefaction of thin dermo-epidermal fibers in lesions, but used semi-quantitative evaluation methods.

Methodology/principal findings: This work aimed to study the correlation between the degree of thermal sensitivity impairment measured by QST and the degree of denervation in leprosy skin lesions, evaluated by immunohistochemistry anti-PGP 9.5 and morphometry. Twenty-two patients were included. There were significant differences in skin thermal thresholds among lesions and contralateral skin (cold, warm, cold induced pain and heat induced pain). The mean reduction in the density of intraepidermal and subepidermal fibers in lesions was 79.5% (SD = 19.6) and 80.8% (SD = 24.9), respectively.

Conclusions/significance: We observed a good correlation between intraepidermal and subepidermal fibers deficit, but no correlation between these variables and those accounting for the degree of impairment in thermal thresholds, since the thin fibers rarefaction was homogeneously intense in all patients, regardless of the degree of sensory deficit. We believe that the homogeneously intense denervation in leprosy lesions should be objective of further investigations focused on its diagnostic applicability, particularly in selected cases with only discrete sensory impairment, patients unable to perform the sensory test and especially those with nonspecific histopathological finds.

Figure 1. Sensitivity in leprosy lesions.

(A) Patients with preserved or just slightly impaired tactile sensitivity in their lesions tended to present a longer evolution time until diagnosis. p = 0.759 (Kruskal-Wallis test). (B) Distribution of warm and (C) cold perception thresholds in lesions stratified according to the results of the tactile sensitivity test. There was a trend towards an association between worsening WPT (A) and CPT (B) and the degree of tactile sensitivity loss.

Figure 2. Immunohistochemical staining for PGP 9.5 in leprosy patients.

(A) Subepidermal fibers in the contralateral skin (arrows). (B) Inflammatory infiltrate (arrowheads) in the lesion skin. Notice the scarcity of stained nerve fibers. (C) Intraepidermal fibers (arrows) in the contralateral skin are demarked with a dotted line in (D) showing visible nerve endings varicosities (arrows). (E) Notice the scarcity of intraepidermal fibers in the magnified field of the lesion skin. Bar = 30 µM.