Leprosy

 

                                                Leprosy 

                                            P.K.Ghatak, MD

The history of Leprosy began with the Bible, how the “lepers” were healed by the Divine grace. Much earlier than any other religious texts, the Vedas from India, have written about leprosy. In Atharva Veda, leprosy was called Kustha, meaning a disease that eats away the flesh.

It is natural to think leprosy originated in India and it must have been endemic in the ancient time and may still be at present. According to the WHO 182, 000 new cases were detected in 2023 and ½ of them came from India. In Surshururt Samhita, written in 600 BCE, a complete description of leprosy appeared and advised Chaulmoogra oil as the remedy. It is said that Alexander the Great brought leprosy to Europe from India with his troupes. European colonists and slave traders brought leprosy to the Americas from Europe. Chinese was the first noticed perforated nasal septum in leprosy and one time Roman included psoriasis, eczema, other chronic skin conditions and even sebaceous cysts under leprosy. The earliest documentary evidence also comes from Rajasthan, India. Evidence of syphilis was found in a skeleton, from the the time of Indus Valley Civilization 4000 years ago.

These old concepts of the origin and spread of leprosy has undergone modification because of DNA analysis of Mycobacterium leprae. This proved that all cases of leprosy were attributed to a single clone of a single Nucleotide polymorphisms. It is now established that Leprosy originated in Eastern Africa or Near East and then spread with human migration to different lands.

These are the 4 different strains of Mycobacterium leprae, one of which dominates in one location.

Strain 1. - East Africa, Asia, Pacific islands.

Strain 2. - Ethiopia, Malawi, Nepal, India and New Caledonia.

Strain 3.- Europe, North Africa, Americas.

Strain 4. - West Africa, and Caribbean.

Mycobacterium leprae.

The organism Mycobacterium leprae was identified in a tissue sample in 1873 by a Norwegian physician, Dr.G.H Armauer Hansen. These organisms are rod shaped, bunched together side by side like a packet of cigarette. When stained with acid fast stain they resemble Mycobacterium tuberculosis (M.TB) with the following differences – organisms are numerous and intracellular, rods are slightly curved and some are branched.

Mycobacterium leprae are 1-8 micro meter long and 0.3 -0.6 micro meter in diameter, slightly curved, nonmotile, have a thick waxy coat, stain poorly with Gram stain. The organism prefer a low temperature and takes 14 days to multiply. Cultures are done for research purpose by inoculating fluid from skin lesion in the foot pads of mice. Recently, Mycobacterium leprae was successfully cultured in Sabouraud media fortified with thyroxine hormone. In the wild, the banded armadillo and certain rodents act as reservoir and are an additional source of human infection.

Human to human infection is the usual mode of the spread but requires prolonged exposure, probably by spread by aerosolized droplet and contact with nasal secretion from ulcerated lesion. Nasal mucosa and tattoos are the route of infection. Leprosy is not sexually transmitted, and mother to child intrauterine transmission does not occur. Malnourished people living in unhygienic conditions are susceptible to leprosy. Those who have deficiency in the cellular immunity are predisposes to leprosy but mode of transmission and mutated genes are not preciously known. Incubation period is between 5 and 30 years.

Inflammatory response to M.leprae infection.

Interleukin 2 (IL-2) and Interferon gamma initiate activation of T-helper cells, which in turn activates T-2 cells and cyclooxygenase II locally. Two distinct types of reactions follows the infection – one is Tuberculoid leprosy and the second is Lepromatous leprosy. In tuberculoid leprosy the granulomatous inflammation like that is produced by Mycobacteria tuberculosis, appears as skin tubercules. Only upto 5 tubercules are included in this type. The facial tubercules produce striking disfigurement.

 In lepromatous leprosy, the dermis is rich with parasitized macrophages, inflamed blood vessels and dermal appendages. The peripheral nerve fibers in the dermis are typically hypertrophied. The skin lesions appear shiny, devoid of hairs and sweat, hypopigmented or reddish patches, generally several but always more than 5 skin lesions. The lesions and the surrounding skin is insensitive to light touch and temperature.

 Mycobacterium leprae preferentially attach themselves to Schwann cells of the peripheral nerve fibers and as they grow they damage the nerves. Loss of sensation is an important clinical feature. Loss of sensations results in injuries, infection and gradual loss of digits of fingers and toes and disfigurement of the face, often nose is replaced by a simple opening. The pinna (cartilaginous part of the ear) often fractured and falls off. Hairs from the eyebrows and eyelids are lost giving an ire look of the patients.

Incidence of Leprosy.

Before Dapsone was used for the treatment of leprosy, there were tens of millions of infected people scattered in 160 countries. In 1960 the number of new cases fell to 250, 000/year and since then the number is still going down. At present India, Brazil, Indonesia account for most new cases of leprosy followed by Tanzania, Madagascar, and Mozambique in Africa. In the USA, about 200 cases are seen on a yearly basis, chiefly among the new immigrants.

Clinical features of leprosy.

Classically, clinical features of leprosy are discussed under Tubercular and Lepromatous leprosy. WHO use different nomenclature – Paucibacillary and Multibacillary leprosy.

 Initial symptoms of Paucibacillary are muscle weakness. Skeletal muscle atrophy, loss of digits and toes and presence of only few patches of discolored skin.

In Multibacillary leprosy common symptoms are Erythema nodosum, fever, loss of hairs from eyebrows and eyelashes and many patches of reddish pink patches.

Other symptoms equally shared by both are anesthesia, paresthesia, dry skin. Itching, blisters, secondary infection, claw hand, foot pain and disfigurement of face.

Diagnosis.

In countries where leprosy is common, any superficial skin lesion with hypothesia of the surrounding skin is considered as leprosy and a skin scrapings are obtained and stained for fungus and acid fast mycobacteria. This is followed by biopsy of skin taken from the edge of the skin lesion and stained by acid fast stain.

Treatment.

From the days of treatment of leprosy with Chaulmoogra oil to Promin (sodium glucosulfone) in 1940s, Dapsone in 1950s. Clofazine in 1960s and Refampin in 1970s more and more favorable outcome was achieved in each stage. In late 1970 Dr. Schantaram Yawalkar in India, used a combination drug therapy with greater success and in 1981 WHO advocated triple therapy- a combination of Dapsone, Refampin and Clofazine.

Because of drug resistance the WHO modified the treatment regimen are added Moxifloxacin and Clarithromycin or Monocycline. The dose and duration of treatment are published by the WHO and should be obtained from the WHO publication. In general, for Tubercular leprosy the duration of treatment is 12 months and Lepromatous leprosy for 24 months.

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