Leprosy can induce a wide spectrum of disease activity characterized by its variations in clinical, histopathological, and immunological findings. Five forms of leprosy have been classified on the basis of these properties (Ridley and Jopling, 1966) as follows:
1. Tuberculoid leprosy (TT)
2. Borderline tuberculoid leprosy (BT) 3. Mid-borderline leprosy (BB)
4. Borderline lepromatous leprosy (BL) 5. Lepromatous leprosy (LL)
In this spectrum, only polar forms of TT and LL are stable. The other types are unstable, especially BT, which can swing to BB or BL in the absence of treatment. It has been shown that exposure to some environmental mycobacteria may influence the type of leprosy developed by susceptible individuals (Lyons and Naafs, 1987). Most leprosy cases can be exactly classified using the Ridley-Jopling or other methods, but from the point of view of therapy it is simpler to discuss them in terms of paucibacillary (PB) and multibaciUary (MB) disease. Using the World Health Organization’s definition (WHO Expert Committee, 1988), paucibacillary refers to patients with a bacterial index (BI) of 0 on the Ridley scale at all skin smear sites, and multibaciUary to patients with a BI of 1+ or more at any site. Thus paucibacillary would usually include indeterminate, tuberculoid, and some borderline-tuberculoid cases. MultibaciUary can be applied to the others.
Mycobacterium leprae is an obligate intracellular parasite that multiplies within the mononuclear phagocytes, especiaUy the histiocytes of the skin and Schwann cells of the nerves. This bacillus has an especiaUy strong propensity for nerves (Willett, 1992).
T uberculoid leprosy (TT). In this form, the bacilli invade the nerves and selectively colonize the Schwann ceUs, multiply within them and slowly destroy them. The dermal nerve twigs are destroyed, and
the larger nerves are swollen and destroyed by granulomas and surrounded by a zone of lymphocytes: occasionally, there may be caseation within a dermal nerve (Ridley, 1974). The nerve damage is nonspecific and arises as a consequence of the cell-mediated immune response.
In tuberculoid leprosy, skin biopsy specimens show mature granuloma formation in the dermis that consists of epithelioid cells, giant cells, and rather extensive infiltration of lymphocytes. The tuberculoid granuloma leads to the nerve’s destruction, and this in turn results in anaesthesia and/or muscle weakness, depending on the type of nerve involved. Acid-fast bacilli (AFB) are rarely seen (Willett, 1992; Jopling and McDougall, 1988).
B orderline types of leprosy (BT, BB, and BL). In these types, nerves are attacked in the same way as described for TT but higher concentrations of bacilli are required to elicit a cellular response, depending on the position of the patient in the borderline spectrum. The cellular response is less focal and less destructive, and microscopic examination reveals zones of epithelioid cells adjacent to areas of bacillated Schwann cells. Bacilli will be found within affected nerves, in small numbers at the tuberculoid end of the spectrum and in large numbers at the lepromatous end.
characteristic features. In borderline-tuberculoid leprosy (BT) there is an epithelioid cell granuloma more diffuse than in TT with a free, but narrow, papillary zone. Giant cells tend to be of foreign body type rather than of Langhans type, and dermal nerves are moderately swollen by cellular infiltrate or may show only Schwann cell proliferation. AFB are usually absent from the dermis, but a few are likely to be found within dermal nerves. In mid-borderline leprosy (BB) there is a diffuse epithelioid cell granuloma with scanty lymphocytes and no giant cells. The papiUary zone is clear and dermal nerves show slight swelling and cellular infiltrate. AFB are present within the dermis and within dermal nerves in moderate numbers. In borderline-lepromatous leprosy (BL) there is a macrophage granuloma in which some of the cells may show slight foamy change, and lymphocytes are present in dense clumps or are widely distributed in parts of the granuloma; a few epithelioid cells occasionally may be seen. Dermal nerves contain some cellular infiltrate. The papillary zone is clear, AFB are plentiful, distributed singly or in clumps, and sometimes in small globi (Jopling and McDougall, 1988).
L eprom atous leprosy (LL). The histopathology of lepromatous leprosy is notably different. Epithelioid and giant cells are absent, and lymphocytes are rare and diffusely distributed. The inflammatory infiltrate consists largely of histiocytes with a unique foamy appearance
resulting from the accumulation of bacterial lipids. Large numbers of AFB are found within the macrophages. It has been calculated that the number of bacilli within 1 cm^ of infiltrated skin, in a lepromatous subject, varies between 1XI0^ and 7X10^; the mean for 6 patients was 2.5X10^ (Hanks, 1945). Knowing the long generation time of M. leprae (possibly 10-12 days) it seems incredible that there can be such a build-up of bacilli in the space of a few years. M. leprae tends to invade vascular channels, which results in a continuous bacteraemia in leprom atous patients and consistent involvem ent of the reticuloendothelial system. The nerves are also infected, and numerous bacilli can be seen within the Schwann cells. Damage to the nerve structure, however, is less than in tuberculoid leprosy. Tissues bearing the brunt of the disease are: nerves; skin; eyes; reticuloendothelial system (this system includes lymph nodes and specialised cells of the liver, spleen, and bone marrow); mucosa of the mouth, nose, pharynx, larynx, and trachea; endothelium of small blood vessels; involuntary (plain) muscle, such as errector pili and dartos; skeletal (voluntary) muscle; and, in the male, testes. LL is considered to be the most infectious type of leprosy (Jopling and McDougall, 1988; Willett, 1992).
Indeterm inate leprosy (I). This type is an early and transitory stage of leprosy. It is found in persons (usually children) whose
immunological status has yet to be determined. A scattered non-specific histiocytic and lymphocytic infiltration is seen that is diagnosable as leprosy in those cases in which there is a cellular reaction within a dermal nerve, or one or more leprosy bacilli are found in a situation, such as a dermal nerve, the subepidermal zone, or arrectores pilorum muscles (Jopling and McDougall, 1988). Subsequently, if not treated, indeterminate leprosy (I) can self heal, or progress towards PB or MB disease.
The im portance of classification in leprosy. The reasons are as follows:
I. A correct classification will give essential information on whether a patient is infectious or not, on the prognosis, on the choice of chemotherapy and the length of treatment, and on the likelihood of complications, such as lepra reaction.
II. A classification which is widely known and applied enables clinicians to communicate intelligently with others.
III. When patients are selected for research projects, it is essential that their leprosy is accurately classified if faulty conclusions are to be avoided (Jopling and McDougall, 1988).