Neuropathy associated with leprosy

Ravindra Kumar Garg MD (Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.)
Louis H Weimer MD, editor. (Dr. Weimer of Columbia University has received consulting fees from Roche.)
Originally released July 14, 2004; last updated May 11, 2017; expires May 11, 2020

This article includes discussion of neuropathy associated with leprosy, Hansen disease, Hanseniasis, leprous neuropathy, leprous neuritis, and leprosy neuropathy. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Leprosy is still 1 of the most prevalent and treatable causes of neuropathy in the world. Data suggest that 96% of new leprosy cases were reported from 14 countries and only 4% of new cases from the rest of the world. Neuropathy in leprosy is important because it is often associated with severe disability and handicap. Advances in immunology and molecular biology have led to a greater understanding of the disease as well as to hopes for improved diagnostic tests and vaccination strategies. Human genetic factors strongly influence susceptibility to leprosy as well as the severity of the disease. Toll-like receptor 2, a pattern recognition receptor of innate immune system present on human Schwann cells and other inflammatory cells, is critical in the immune response against mycobacterial infection. A group of researchers showed that the leprosy bacteria reprogram Schwann cells into programmed stem cell-like cells or programmed mesenchymal stem cells. Conversion of Schwann cells into programmed stem cell-like cells promotes bacterial spread to distant sites. Leprosy is rare in developed countries, and unawareness of this disease often leads to misdiagnosis. For treatment, the World Health Organization recommends multidrug therapy regimens consisting of a combination of rifampicin, dapsone, and clofazimine. The exact role of corticosteroids is not established and needs more data. An observation revealed that red squirrels (Sciurus vulgaris) from around the UK and Ireland carry several strains of leprosy and possibly function as a reservoir for human leprosy. The author describes the epidemiology, pathogenesis and pathophysiology, clinical features, differential diagnosis, and management of neuropathy associated with leprosy.

Key points

 

• Leprosy is 1 of the oldest diseases known to mankind. Three cardinal features of leprosy are hypoesthetic skin lesions, thickened peripheral nerves, and positive skin smear for bacilli.

 

• The Ridley-Jopling classification divides leprosy into 3 major categories: tuberculoid leprosy, lepromatous leprosy, and borderline leprosy.

 

• Leprosy reactions are important acute events in the course of leprosy and are often associated with significant nerve damage.

 

• Among physiological functions of a peripheral nerve, sensory functions are most severely affected in leprosy.

 

• For confirmation of diagnosis, slit-skin smears, skin biopsy, and nerve biopsy are employed.

 

• The World Health Organization recommends multidrug therapy regimens consisting of a combination of rifampicin, dapsone, and clofazimine for the treatment of leprosy.

Historical note and terminology

Leprosy is 1 of the oldest diseases known to mankind. It is a disease that has long been stigmatized, and persons afflicted with it have frequently been segregated from the rest of society. The term leprosy came from the Latin word Lepros, which means defilement. Leprosy has extensively been described in ancient Chinese, Egyptian, and Indian literature as early as 600 BC. Returning soldiers of Alexander the Great brought leprosy from India to the Mediterranean region in 237 to 326 BC (Mark 2002). Using comparative genomics it has been demonstrated that the disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years (Monot et al 2005).

A Norwegian physician, GHA Hansen, discovered the causative organism of leprosy in 1873. The breakthrough in treatment of leprosy occurred in the 1940s with the development of the drug dapsone. The World Health Organization (WHO) in1982 introduced multidrug therapy, which has proved to be the most important advance in the management and control of leprosy (World Health Organization 1982). Multidrug therapy has helped in reducing the number of registered leprosy cases worldwide. During the past 3 years, the global number of new cases detected continued to decrease dramatically. In 1991 WHO and its member countries pledged to eliminate leprosy by the year 2000. Elimination was defined as a prevalence of less than 1 case per 10,000 population. By the end of 2003, more than 13 million patients had been cured by multidrug therapy (World Health Organization 2004).

In 1 major development, an observation revealed that red squirrels (Sciurus vulgaris) from around the UK and Ireland carry several strains of leprosy and possibly function as a reservoir for human leprosy. The authors found Mycobacterium lepromatosis in squirrels from England, Ireland, and Scotland, and Mycobacterium leprae in squirrels from Brownsea Island, England. Phylogenetic comparisons of British and Irish Mycobacterium lepromatosis with 2 Mexican strains from humans showed that they had a common ancestor around 27,000 years ago. The Mycobacterium leprae strain detected was phylogenetically similar to 1 that circulated in medieval England (Avanzi et al 2016).

Classification. The Ridley-Jopling classification is currently the most widely accepted system of leprosy classification. According to host's immune response against mycobacterial antigen, leprosy is divided into 3 major categories: tuberculoid leprosy, lepromatous leprosy, and borderline leprosy (Ridley and Jopling 1966).

 

(1) Tuberculoid leprosy is characterized by active immune reaction against Mycobacterium leprae; active cell-mediated immunity restricts the disease to a few peripheral nerves or skin lesions.

 

(2) Lepromatous leprosy is characterized by lack of immune response against Mycobacterium leprae, which results in extensive proliferation of bacilli in skin and nerves along with disseminated tissue infiltration.

 

(3) Borderline leprosy has features of 2 polar forms. Borderline-tuberculoid leprosy is close to tuberculoid leprosy, whereas borderline-lepromatous leprosy is close to lepromatous leprosy.

 

(4) Indeterminate leprosy is an early transitional form of disease and is characterized by smaller and fewer skin lesions. This form of leprosy often resolves spontaneously or, less frequently, may evolve into 1 of the definite forms of leprosy. Indeterminate leprosy is not a part of the Ridley-Jopling classification.

WHO classifies leprosy, on the basis of findings from skin smears, as paucibacillary and multibacillary leprosy. In WHO classification, patients showing negative skin smears for acid-fast bacillus at all sites examined are grouped as paucibacillary leprosy, whereas patients having positive skin smear for acid-fast bacillus from any site are grouped as multibacillary leprosy. For field surveys, patients having 5 or fewer skin lesions are grouped in paucibacillary leprosy, whereas patients having more than 5 skin lesions are grouped in multibacillary leprosy (World Health Organization 1998). According to data from the WHO, among newly detected cases in 2002, approximately 39% of patients were clinically classified as having multibacillary leprosy (World Health Organization 2004).

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