Correlation of quantitative tests of nerve and target organ dysfunction with skin immunohistology in leprosy

Loss of nociception and hypohidrosis in skin are hallmarks of leprosy, attr ibuted to early invasion by Mycobacterium leprae of Schwann cells related t o unmyelinated nerve fibres, We have studied skin lesions and contralateral clinically unaffected skin in 28 patients across the leprosy spectrum with a range of selective quantitative sensory and autonomic tests, prior to bi opsy of both sites. Unaffected sites showed normal skin innervation, when a ntibodies to the pan-neuronal marker PGP (protein gene product) 9.5 were us ed, with the exception of intraepidermal fibres which were not detected in the majority of cases. Elevation of thermal thresholds and reduced sensory axon-reflex flare responses in affected skin correlated with decreased nerv e fibres in the subepidermis, e.g. axon-reflex flux units (means +/- SEM) f or no detectable innervation; decreased innervation; and clinically unaffec ted skin, were 23 +/- 3.1; 41.2 +/- 7.3; and 84.5 +/- 4.0, respectively. Re duced nicotine-induced axon-reflex sweating was correlated with decreased i nnervation of sweat glands. Where methacholine-induced direct activation of sweat glands was affected, there was inflammatory infiltrate and loss of s weat gland structure. This study demonstrates a correlation between selecti ve nerve dysfunction on clinical tests and morphological changes in skin, i rrespective of the type of leprosy, and is the first to show that loss of s weating in leprosy may result either from decreased innervation and/or invo lvement of the sweat glands. The findings have implications for the selecti on and monitoring of patients with leprosy in clinical trials which aim to restore cutaneous function.