Role of S-100 staining in differentiating leprosy from other granulomatous diseases of the skin.

Since Mycobacterium leprae are rarely demonstrable in the tuberculoid spectrum of leprosy, a confirmatory diagnosis of leprosy can be made on the basis of finding active destruction of cutaneous nerves by granulomatous inflammation in a skin biopsy. Immunoperoxidase staining for S-100 protein, which is a marker for Schwann cells, was used to delineate nerves in lesional skin biopsies of 25 patients with tuberculoid and borderline tuberculoid leprosy as well as 15 controls with nonleprous granulomatous inflammation. Four different patterns of nerve damage were observed: infiltrated, fragmented, absent, and intact. All of the nonleprous granulomatous dermatoses showed only intact nerves, either inside or outside the granuloma, and so S-100 staining can be used to rule out leprosy.

Histological studies in primary neuritic leprosy: changes in the apparently normal skin.

The visually normal skin of 196 patients diagnosed clinically to have primary neuritic leprosy was studied histologically to determine whether there were any specific changes due to the disease in this site. Histological changes due to leprosy were seen in 32.1% of the patients, and included, indeterminate leprosy in 19.4%, borderline tuberculoid leprosy in 6.6% and borderline lepromatous leprosy in 6.1%. The remaining biopsies showed mild non-specific dermal inflammation, mild nerve changes or no significant lesion. The nerve inflammation and/or granulomas were mostly in the deep dermal nerves or neurovascular complexes. This study shows that there is a cutaneous component to primary neuritic leprosy and the disease is not totally confined to nerves. The absence of visible hypopigmented patches in these patients is probably related to the deep location of the dermal inflammation.

Pemphigus herpetiformis.

A 70-year old Indian lady with a two year history of a blistering eruption is described. This eruption clinically resembled dermatitis herepetiformis and responded to dapsone, however, histological and immunological investigations showed features of pemphigus herepetiformis.

An ultrastructural study of dermal nerves in early human leprosy.

Skin biopsies from the cutaneous lesions of seven patients with indeterminate, BT, BL, and LL leprosy of less than 1 year's duration were examined by light and electron microscopy. Inflammatory cells, which marked the location of Mycobacterium leprae in bacilliferous cases (BL and LL) were most frequently and consistently found in relation to dermal blood vessels, neurovascular bundles, nerves, arrector pili muscles, and skin adnexa. The number of bacilli and inflammatory cells in the epineurium was in great excess of those in the perineurium and endoneurium. Perineurial infiltration by lymphocytes and bacillated macrophages was seen to occur through gaps between the constituent cells of a loosened and sometimes proliferated perineurium. Bacillation of Schwann cells and associated inflammation in the endoneurium was minimal. M. leprae were identified in endothelial cells, arrector pili muscles, macrophages and Schwann cells. At this stage, inflammatory destruction of nerve fibers was not encountered. It is concluded that M. leprae which are extruded from the circulation into the epineurium (or perineurium) may be carried in inflammatory cells across the perineurium which is loosened and rendered permeable to inflammatory cells as a consequence of chronic inflammation in the adjacent epineurium. This is suggested as a very probable route for M. leprae to enter nerves.

An ultrastructural study of the response of traumatized rabbit tibial nerve to epineurial infection with Mycobacterium leprae.

Crushed rabbit tibial nerves were inoculated with a suspension of living Mycobacterium leprae at and just distal to the site of nerve trauma. The resulting changes occurring over a period of time from 40 min to 72 hr post-inoculation were studied electron microscopically. Bacilli were seen in perineurial cells and in macrophages that had infiltrated the perineurium adjacent to epineurial deposits of M. leprae. It is suggested that trauma may weaken the perineurial barrier and facilitate the transperineurial passage of phagocytes, some of which may be laden with M. leprae, and may thus be a means whereby M. leprae enter the endoneurium of peripheral nerves.

Segmental necrotizing granulomatous neuritis of leprosy.

In leprosy, the occurrence of necrotizing nodular lesions in peripheral nerves is a relatively uncommon complication. Despite clinical and gross similarities, there are microscopical differences among groups of such cases, indicating that in all probability different pathogenetic mechanisms are operative. Furthermore, the vast majority of such cases are not true abscesses but are characterized by caseous necrosis and granulomatous inflammation. The traditional collective name "nerve abscess" is therefore inappropriate. Presented herein is an analytic study of 30 cases of the commonest variant, which we suggest should be called segmental necrotizing granulomatous neuritis of leprosy (SNGN). This lesion commonly affects the right ulnar nerve just above the elbow and occurs most often in those with the borderline tuberculoid form of leprosy. It appears to represent the result of a hypersensitivity phenomenon marked by a preponderance of epithelioid cells rather than a reaction of immunity in which lymphocytes predominate. Acid fast bacilli were demonstrable in the lesion in 77% of cases.

The early cellular response to M. leprae. An ultrastructural study.

The ultrastructural changes that develop in mouse peritoneal macrophages from 10 minutes up to 14 weeks after exposure to Mycobacterium leprae are presented. Phagocytosis occurred by a process of engulfment by cytoplasmic processes and incorporation into a phagosome, into which lysosomal enzymes were subsequently introduced. Electron transparent zones (E.T.Z.) were not observed around phagocytosed bacilli in this study, however discrete droplets of lipid-like material appeared in the cytoplasm of macrophages, between 2 and 4 weeks after ingestion of the micro-organisms. Phagosomes with double limiting membranes were observed in macrophages harvested as early as 40 minutes after exposure to M. leprae, contrary to the observations of Evans and Levy (1972).

The early cellular response to M. leprae

The ultrastructural changes that develop in mouse peritoneal macrophages from 10 minutes up to 14 weeks after exposure to Mycobacterium leprae are presented. Phagocytosis occurred by a process of engulfment by cytoplasmic processes and incorporation into a phagosome, into which lysosomal enzymes were subsequently introduced. Electron transparent zones (E.T.Z.) were not observed around phagocytosed bacilli in this study, however discrete droplets of lipid-like material appeared in the cytoplasm of macrophages, between 2 and 4 weeks after ingestion of the micro-organisms. Phagosomes with double limiting membranes were observed in macrophages harvested as early as 40 minutes after exposure to M. leprae, contrary to the observations of Evans and Levy (1972).