The biology of nerve injury in leprosy.
The steps in the pathogenesis of nerve injury in leprosy are depicted in Figure 1. Localisation of M. leprae to nerve, Schwann cell infection & responses, as yet unknown mechanisms of injury, axonal atrophy, and finally demyelination. These steps, and the mechanisms responsible for them, occur quickly in the course of this disease (as noted, even the earliest diagnostic lesions have sensory abnormalities), but they are also chronic processes that may contribute to progressive nerve injury over a period of many years unless interrupted by treatment, and even after cure of the infection in some patients. A common feature throughout this pathogenesis is inflammation--within and around the nerve. Inflammation is not only defined by its chemical mediators such as cytokines and chemokines, but by one of the most basic phenomena of inflammation--edema. The extent to which edema might contribute to nerve injury in leprosy has not been reviewed because it has not been studied in nerves affected by leprosy, although clinically, surgeons who perform neurolysis are convinced that they are decompressing nerves sustaining injury due to increased (edematous?) pressure. Inflammation in and around nerves is undoubtedly driven, in part, by the immunological responses in each of the portions of the immunologic spectrum of leprosy, but some inflammatory phenomena may be non-specific inflammation related to infection and foreign material (i.e., mycobacterial components). Few if any fixed associations can be made between the steps outlined in this conceptual framework of events; even the depicted sequence of these events is uncertain. Considerable additional data is needed to determine the connections between these processes and their underlying mechanisms. Additionally, although much emphasis is given to myelinated fibres (and demyelination) in studies of the biology of leprosy neuropathy, the small, sensory fibres in the skin are not myelinated. Additional studies of mechanisms of injury to these nerves is required. The results of all of these studies can be reasonably expected to identify new points for clinical intervention in--and possibly the prevention of--nerve injury in leprosy.
Scollard
David M
DM
National Hansen's Disease Programs, LSU-SVM, Skip Bertman Dr. Baton Rouge, LA 70803, USA. dscoll1@lsu.edu
D000818:Animals; D001135:Armadillos; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000503:physiopathology; D007918:Leprosy / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D051379:Mice; D009166:Mycobacterium leprae / Q000472:pathogenicity*; D009474:Neurons / Q000382:microbiology / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D051381:Rats; D012583:Schwann Cells / Q000382:microbiology / Q000473:pathology