02599nas a2200361   4500000000100000008004100001260001300042653002900055653001100084653002000095653001100115653002500126653001200151653001700163653001900180653001400199653002300213653000900236653001700245653002600262653002800288100001200316700001300328700001500341700001500356700001600371700001200387245011400399300001200513490001700525520168100542022001402223       1998                            d  c1998 Dec10aAutonomic Nervous System10aBiopsy10aHot Temperature10aHumans10aImmunohistochemistry10aleprosy10aNerve Fibers10aNervous System10aSensation10aSensory Thresholds10aSkin10aSweat Glands10aThiolester Hydrolases10aUbiquitin Thiolesterase1 aFacer P1 aMathur R1 aPandya S S1 aLadiwala U1 aSinghal B S1 aAnand P00aCorrelation of quantitative tests of nerve and target organ dysfunction with skin immunohistology in leprosy.  a2239-470 v121 ( Pt 12)3 a<p>Loss of nociception and hypohidrosis in skin are hallmarks of leprosy, attributed to early invasion by Mycobacterium leprae of Schwann cells related to 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 biopsy of both sites. Unaffected sites showed normal skin innervation, when antibodies to the pan-neuronal marker PGP (protein gene product) 9.5 were used, 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 nerve fibres in the subepidermis, e.g. axon-reflex flux units (means+/-SEM) for no detectable innervation; decreased innervation; and clinically unaffected skin, were 23+/-3.1; 41.2+/-7.3; and 84.5+/-4.0, respectively. Reduced nicotine-induced axon-reflex sweating was correlated with decreased innervation of sweat glands. Where methacholine-induced direct activation of sweat glands was affected, there was inflammatory infiltrate and loss of sweat gland structure. This study demonstrates a correlation between selective nerve dysfunction on clinical tests and morphological changes in skin, irrespective of the type of leprosy, and is the first to show that loss of sweating in leprosy may result either from decreased innervation and/or involvement of the sweat glands. The findings have implications for the selection and monitoring of patients with leprosy in clinical trials which aim to restore cutaneous function.</p>  a0006-8950