Hansen’s Disease (Leprosy) : Leprous Neuropathy

Introduction

Leprosy is a chronic infectious disease caused by Mycobacterium leprae ( M. leprae ), an acid-fast, Gram-positive, rod-shaped, obligate intracellular parasite which has the unique propriety of systematic invasion and multiplication inside peripheral nerves. Although mostly known due to the resulting skin manifestations, most of the feared consequences of leprosy result from nerve damage. Although known from time immemorial, it is still a poorly understood disease, affecting thousands of people in poor countries and constituting a diagnostic problem in most wealthy countries.

The introduction of multidrug therapy in 1981 dramatically changed leprosy epidemiology around the world. The 2013 Global Leprosy Update reported that the number of new cases detected in 2012 was 232,857, 95% of these originating from only 16 countries, led by India (134,752), Brazil (33,303) and Indonesia (18,994). Grade 2 disability was already present at diagnosis in 14,049 cases, attesting to late diagnosis. The proportion of children among new cases ranged from 0.6% in Argentina to 41.3% in Micronesia, indicating that transmission is still very active in several world regions.

Leprosy affects people of any age, from infancy to elderly, and of both sexes, although in many areas men are mostly affected (in a proportion of 2:1). The main portal of exit of M. leprae is the nasal mucosa, which can eliminate up to 1 million viable organisms in a single day. Similarly the main portal of entry seems to be the nasal mucosa, although it seems that skin may also be an alternative, via abrasions and cuts followed by hematological dissemination. M. leprae bacilli preferentially invade and multiply inside nonmyelinating Schwann cells in the coldest regions of the body, as the ideal temperature for M. leprae is around 30°C. The incubation period varies from 6 months to 20 years. M. leprae has a very long generation time (~13 days). Approximately 95% of the population is naturally resistant and does not develop infection after exposure. Among those who are susceptible, those in the “tuberculoid” pole have a strong cell-mediated immunity and delayed hypersensitivity response, effectively controlling the infection and not transmitting the disease. These patients develop localized manifestations, with only one or a few well-demarcated skin and nerve lesions. There is a severe granulomatous response that may completely destroy the nerve and the bacilli. At the other extreme, the “lepromatous” patients have no cellular immune response to M. leprae , developing slowly progressive and disseminated skin and nerve injury, and being highly infectious. Most patients [borderline (BB), borderline-tuberculoid (BT), and borderline lepromatous (BL)] have reactions to infection between these extremes. These subjects may develop a more severe disease, especially those in the BT group, in whom the immune response cannot prevent bacterial dissemination, but which is then sufficient to destroy M. leprae bacilli and infected tissue.

Skin Manifestations

The typical skin manifestations are hypopigmented macules, papules, or nodules, which sometimes have a reddish or copper-colored appearance. These are most frequently localized in the trunk and abdomen, although the limbs may also be affected. Thermoalgesic and tactile sensation are usually compromised in these areas, which may also show anhidrosis and alopecia. Plantar ulcers and other trophic disturbances usually develop late in the course of the disease in those with significant sensory loss.