LEPROSY (go to bottom for : Lepromatous)

 (Skin Pathology, D. Weedon, 2nd Ed. Churchill-Livingstone)

Leprosy (lepra) is a chronic infection caused by Mycobacterium leprae. It affects mainly the skin, nasal mucosa and peripheral nerves. Leprosy is most prevalent in tropical countries, particularly India , Southeast Asia , Central Africa and Central and South America . In India , which has two-thirds of the global leprosy burden, the case detection rate has remained stubbornly around 5 per 10 000 population.

M . leprae is an obligate, intracellular, Gram-positive organism which is also acid fast, though less so than M. tuberculosis. The organism cannot be grown in vitro, although claims of successful cultivation are made from time to time. M. leprae can be grown in the footpads of mice and in the nine banded armadillo, an animal in which natural infection also occurs. M. leprae shares many antigens with other mycobacteria; it also possesses a unique antigen, phenolic glycolipid-I (PGL-1). Experimental studies are currently attempting to determine the exact role of the various components of the immune system in the defense against this organism. M. leprae is found predominantly in three main cell types in the skin, Schwann cells, endothelial/perithelial cells and cells of the monocyte-macrophage system.

The incubation period of leprosy is not known with certainty, but is thought to average 5 years. This uncertainty and the long period make any study of the mode of transmission difficult. The organism is of low infectivity, and prolonged and/or close contact with patients who have the disease is considered necessary for transmission to occur. The incidence of conjugal leprosy is low, further testimony to its low infectivity. Contact with the armadillo may be an important source of infection in some countries. There may also be a genetic predisposition to the disease. The portal of entry of the organism is not known, but the skin and upper respiratory tract, particularly the nasal mucosa, are probable sites. Droplet infection is the most likely mode of transmission, although rare cases of inoculation infection have been recorded.

Concurrent infection with M. tuberculosis is rare, even in endemic countries.

Clinical classification of leprosy

Leprosy exhibits a spectrum of clinical characteristics that correlate with the histopathological changes and the immunological status of the individual. At one end of the spectrum is tuberculoid leprosy (TT), which is a highly resistant form with few lesions and a paucity of organisms (paucibacillary leprosy). At the other end is lepromatous leprosy (LL), in which there are numerous lesions with myriad bacilli (multibacillary leprosy), and an associated defective cellular immune response

Lepromatous leprosy (LL) usually develops from borderline or borderline­ lepromatous forms by a downgrading reaction. Polar and subpolar forms have been recognized. It is a systemic disease, although the primary clinical manifestations are in the skin. Mucosal involvement may lead to ulceration of the nasal septum, whereas nerve lesions may result in acral anesthesia, claw hand and foot drop. The cutaneous lesions, which are usually symmetrical, include multiple small macules, infiltrated plaques and nodules with poorly defined borders. Multiple facial nodules give a bovine appearance, and this is usually accompanied by sparse eyebrows. Various autoantibodies have been demonstrated in this form of leprosy. This may explain the increased incidence of vitiligo.

Histopathology

Skin biopsies should include the full thickness of the dermis and should be taken from the most active edge of a lesion. The bacilli may be detected in tissue sections using the Fite-Faraco staining method or an immunofluorescent technique.

Two distinct types of histological changes are found in leprosy: the lepromatous reaction, in which large numbers of macrophages in the dermis are parasitized with acid-fast bacilli, and the tuberculoid reaction, in which there are tubercle-like aggregates of epithelioid cells, multinucleate giant cells and lymphocytes, bacilli being difficult to find. These histological patterns are seen at either end of the clinical spectrum of leprosy; features overlapping with those of borderline forms may be present. Sometimes there is a disparity between the clinical and the histological subclassification of leprosy. Early lesions are mostly of indeterminate or tuberculoid type.

Lepromatous leprosy (polar and subpolar) is characterized by collections and sheets of heavily parasitized macrophages with a sparse sprinkling of lymphocytes, the majority of which are of suppressor type. In older lesions the macrophages have a foamy appearance (lepra cells, Virchow cells). Numerous acid-fast bacilli are present in macrophages, sweat glands, nerves, Schwann cells and vascular endothelium a finding which has been confirmed by electron microscopy. The macrophages express S100 protein. The organisms in the macrophages may be arranged in parallel array, forming clusters, or in large masses known as globi. In the subpolar form, there are fewer globi and a few more T lymphocytes than in the polar form.