Staging nerve involvement in M. leprae infection
To the Editor:
It is assumed that leprosy is primarily an infectious disease of the peripheral nerve even though skin manifestations remain an important clinical sign of the disease. The nerve may be affected alone (pure neural) or may be the first site to be involved (primarily neural), the other possibility being concomitant skin and nerve involvement.
Briefly, Mycobacterium leprae infection cannot be conceived without nerve involvement. Leprosy neuropathy is essentially a neuritis. The inflammatory reaction within the nerve contributes to the pathogenesis of leprous neuropathy through a variety of effector mechanisms (8). It is assumed that in leprosy an immunopathological mechanism plays an important role in the pathogenesis of nerve damage (5). Staging this nerve involvement is important in order to find a new therapeutic approach for the prevention of clinical neuropathy. We propose the following four steps:
1. Subclinical stage I, which may be called stage of involvement, can be considered as characterized by an inflammatory reaction within the nerve trunk ("neuritis") but as yet without either subjective or objective manifestations. However, it may be assumed that during this stage the immunopathological mechanism has been triggered.
2. Subclinical stage II, which may be called the stage of nerve damage. We consider that this stage may be accompanied or not by subjective clinical manifestations such as pain or tenderness, but loss of function is absent. Manifestation of pain seems to be related to the rate and kind of nerve fiber degeneration (2). This stage may not be associated with pain and tenderness in the so called "silent neuropathy" (we have previously proposed the expression of "silently arising clinical neuropathy") (3).
3. Clinical stage I, which may be called stage of destruction. This clinical stage may be described as characterized by loss of function, but with possible recovery.
4. Clinical stage II, this is the stage of scarring; recovery is not possible.
Pearson and Ross (4) assume that as much as 30% of the nerve fibers have to be destroyed before sensory impairment becomes detectable. In the same line of thought, Weller and Cervos-Navaro (7) underline that a large proportion of nerve has been damaged before the appearance of clinically detectable neurological deficit.
We think that prevention of clinical neuropathy (meaning destruction of more than 30% of nerve fibers) has to be addressed at the subclinical stage. How can this early subclinical stage be recognized? Is there any indicator clinical sign contemporary to the subclinical neuropathy? In animal models, Crawford, et al. (1) have demonstrated that the hypopigmented skin macule is an indicator of a hypersensitivity reaction to sensory nerve myelin. McDougall (6) has put forward an attractive theory on the mechanism of hypopigmentation in leprosy. He relates the hypopigmentation as a consequence of free radical formation during the cell-mediated immune response. We may assume that a hypopigmented skin lesion is, therefore, an early indicator of the im- munopathological mechanism affecting the nerve trunk.
The above-mentioned hypothesis allows us to raise questions on the possible modalities of preventive therapy to be established for patients without clinically detectable loss of nerve function but classified on the basis of skin lesion.
How important is the close association between the subclinical neuropathy and the skin lesion? Can we consider that in leprosy the earliest skin lesion may be considered a forerunner of clinical neuropathy?
- Yohannes Negesse, M.D.
ALERT/AHRI
P.O. Box 1005
Addis Ababa, Ethiopia
REFERENCES
1. Crawford, C. L., Evans, D. H. and Evans, E. M. Experimental allergic neuritis induced by sensory nerve myelin may provide a model for nonlepromatous leprosy. Nature 251(1974)223-225.
2. Dyck, P. J., Lambert, E. H. and O'Brien, P. C. Pain in peripheral neuropathy related to rate and kind of liber degeneration. Neurology 26(1976)466-471.
3. Negesse, Y. "Silently arising clinical neuropathy" and extended indication of steroid therapy in leprosy neuropathy. (Letter) Lepr. Rev. 67(1996) 230-231.
4. Pearson, J. M. H. and Ross, W. F. Nerve involvement in leprosy: pathology, differential diagnosis and principles of management. Lepr. Rev. 46(1975) 199-212.
5. Rook, G. A. W. and Stanford, J. L. Slow bacterial infections or autoimmunity? Immunol. Today 13(1992)160-164.
6. Ryan, T. J. and McDougall, A. C. (eds.). Essays on Leprosy . Oxford, Alden Press, 1988, p. 119.
7. Weller, R. O. and Cervos-Navaro, J. Pathology of Peripheral Nerves . London: Butterworth & Co., Ltd.. 1977, pp. 133, 134.
8. Younger, D. S., Rosoklija, G., Hays, A. P., Trojaborg, W. and Latov, N. Diabetic peripheral neuropathy: a clinico-pathologic and immunohisto-chemical analysis of sural nerve biopsies. Muscle Nerve 19(1996)722-727.