Introduction

Leprosy, also called Hansen’s disease, is a bacterial infection affecting the skin, nerves, respiratory tract and the eyes, that can result in long-term disability and disfigurement. Two bacteria, Mycobacterium leprae and Mycobacterium lepromatosis, are the main causative agents of the disease. Approximately 200,000 new cases of leprosy are detected each year, and more than 70% of these occur in India, Indonesia, and Brazil.¹ An individual contracts leprosy by inhaling droplets with the bacteria released when someone with leprosy coughs or sneezes, or through prolonged close contact with broken skin.² Shaking hands, sharing a meal or sitting next to a person having leprosy will not cause it to spread. An individual infected with leprosy can show a wide spectrum of clinical symptoms depending on the immune response they elicit against the bacteria. Accordingly, two different classification systems have been put forward by the World Health Organisation (WHO) and by two scientists, D. S. Ridley and William Jopling.³ Treatment depends on the type of leprosy and with proper treatment, leprosy is completely curable.⁴ 

Pathophysiology

Once the organisms enter a healthy individual, they mainly infect macrophages and Schwann cells.⁵ Macrophages are a type of white blood cell involved in the destruction of foreign organisms, and Schwann cells form a covering around nerve cells to provide protection. Once the bacteria enter these cells, they start dividing slowly until the immune system gets activated. Depending on genetic and other factors, different people elicit immune responses of different degrees, which lead to the appearance of varying clinical symptoms.⁶ If the cellular immune response is organised, specific and intense, only a few, well-demarcated lesions will appear with fewer organisms in the lesion. In the absence of a strong, specific immune response, multiple lesions involving multiple regions of skin and nerve involvement would be seen with a large number of organisms within. According to the immune response and varying clinical manifestations, the Ridley-Jopling and the WHO classifications have been created.

The Ridley-Jopling classification spectrum

This classification was introduced by two scientists, D. S. Ridley and William Jopling, in 1966. According to this, two poles and an intermediate state are described:⁶ tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), and lepromatous (LL) leprosy. 

The clinical features of each of these types are,

Tuberculoid leprosy (TT)

Tuberculoid leprosy usually presents as a single or a few small, well-demarcated lesions in the skin. The borders of the patch will appear reddened and raised with a hypopigmented centre. There will be a loss of sensation over the patch, and the skin will appear dry without sweating. Bacteria will be absent on microscopy of a skin smear taken from the lesion. The lepromin skin test (described in detail below) will be positive as these patients have a good cellular immune response. They generally have a good prognosis due to strong immunity. 

Borderline tuberculoid (BT)

Lesions in borderline tuberculoid leprosy are similar to those of tuberculoid leprosy, but there will be a higher number of lesions, larger and with less demarcated borders. Loss of sensation over the patches is more pronounced than in tuberculoid leprosy, and nerve involvement is more common. Skin smears are usually negative with a positive lepromin skin test. 

Mid-borderline (BB)

Mid-borderline leprosy is a relatively rare stage that can progress into either the tuberculoid or lepromatous form. Lesions of BB are usually reddened or skin coloured, multiple and large, with varying sizes and distribution. Centrally punched-out lesions with sloping edges are characteristic of mid-borderline leprosy. 

Borderline lepromatous (BL)

Patches, nodules and raised lesions appear widespread throughout the body in a symmetric fashion. These can have a variety of shapes and colours. Sensation on the lesion itself will be intact, but numbness over the hands and feet (classically known as glove and stocking distribution) may be present. Lesions will demonstrate a high load of bacteria, but the lepromin test will be negative as the immune response is poor.

Lepromatous leprosy (LL)

Individuals with lepromatous leprosy have diffuse skin involvement. Poorly demarcated red or hypopigmented patches with a shiny surface appear widespread throughout the body, which progress to form large nodules and plaques. Infiltration of the skin of the face results in a thickened skin with loss of eyebrows, deepened creases and a broad nose, resembling that of a lion. This appearance is characteristically called “leonine facies”. Nerve damage is generalised and symmetric. Involvement of other organs is also commonly seen. Nasal involvement results in nasal stuffiness, bleeding from the nose and reduced sense of smell. Damage to the eyes by the bacteria can cause ulcers and abrasions of the cornea, and even permanent blindness. 

As those with lepromatous leprosy have a very poor immune reaction, the skin smears from lesions will show multiple organisms, and therefore, the lepromatous form is considered more infectious. 

WHO classification

The World Health Organisation has classified leprosy into two categories for the purpose of quick diagnosis and treatment.³  

• Paucibacillary leprosy - When fewer than 5 lesions are present. Includes tuberculoid (TT) and borderline tuberculoid (BT) leprosy of the Ridley-Jopling classification
• Multibacillary leprosy - When more than 5 lesions are present. Includes lepromatous (LL), borderline lepromatous (BL) and mid-borderline(BB) categories of the Ridley-Jopling classification

Diagnostic methods

Leprosy can be suspected by the presence of characteristic or suggestive skin lesions and neural involvement. For confirmation following tests can be performed.

Slit skin smears

A small cut is made over the skin of the forehead, ear lobe or a lesion, and the dermal tissue is scraped onto a glass slide. The material is stained by chemicals and examined under the microscope to check for the presence of bacteria.⁶ This test can accurately identify the organism if present, and a positive test can confirm multibacillary leprosy. However, if the test is negative, this cannot rule out leprosy as paucibacillary forms can give negative results.³ 

Skin biopsy

A small piece of skin tissue, together with the deeper layers and fat tissue, is taken for examination. The best site to take a biopsy is from the margins of an active lesion. After staining with specific methods, the presence of the bacteria and other different cell types can help in localising the specific type of leprosy an individual is affected by.⁷ 

Lepromin skin test

In the lepromin skin test, a small amount of dead leprosy bacteria is injected under the skin of the forearm, and the reaction to it is read in 2 days (Fernandez reaction) and 21 days (Mitsuda reaction). If a person already has immunity developed against leprosy, a reaction will occur. A positive test is indicated by the development of a reddish elevation of the injection site of more than 5mm in diameter.  Individuals with multibacillary leprosy (tuberculoid and borderline tuberculoid) will demonstrate a strongly positive reaction, while those with paucibacillary forms (mid-borderline, borderline lepromatous and lepromatous) will have a negative reaction.³ 

Polymerase Chain Reaction (PCR)

PCR detects the genetic material (DNA) of leprosy bacteria from samples taken from a slit skin smear or a skin biopsy. It can detect multibacillary leprosy better than paucibacillary forms, and can be used for early diagnosis, confirmation of diagnosis in doubtful and difficult cases. However, the cost and need of specialised equipment and trained technologists mean that this technique is not highly available, especially in the developing world, and is not frequently used in everyday diagnosis.³  

Blood tests

The presence of antibodies against certain antigens of the leprosy bacteria can be detected using blood tests. 

Treatment overview

Leprosy is treated with multiple drugs at the same time - a method called multidrug therapy (MDT) to minimise the development of resistance by the organisms. With treatment, individuals become non-infectious, fast. The WHO recommends three drugs: dapsone, rifampicin and clofazimine as MDT. Treatment should be taken for 12 months in multibacillary leprosy and for 6 months in paucibacillary leprosy. The WHO provides MDT free of cost in blister packs. In cases of resistance, other drugs like clarithromycin and minocycline are used.⁸  

For individuals who have had significant close contact with a patient diagnosed with leprosy, a single dose of rifampicin is recommended.⁹ 

Summary

• Leprosy is a bacterial infection caused by Mycobacterium leprae and Mycobacterium lepromatosis affecting the skin, nerves, and the respiratory tract
• It is spread via inhalation of respiratory droplets and prolonged close contact with broken skin
• The clinical features of leprosy depend on the immune response elicited by the host, which can range from localised single lesions to widespread involvement
• Symptoms include reddish or hypopigmented patches, nodules, plaques, thickened nerves, areas of numbness and in severe cases, permanent disfigurement and blindness
• The Ridley-Jopling classification categorises leprosy into 5 groups according to the symptoms and immunity: tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), and lepromatous (LL) leprosy
• The tuberculoid pole has less number of localised lesions with a strong cell-mediated immunity, and the lepromatous pole has widespread infiltration of the skin, nerve damage, and involvement of other organs
• For easier treatment, the WHO has classified leprosy into multibacillary (many bacterial cells present in lesions) and paucibacillary (fewer bacterial cells in the lesions) leprosy
• Leprosy is diagnosed by detecting bacteria in a slit skin smear or a skin biopsy. Other tests include lepromin skin test, polymerase chain reaction and blood tests for antibodies
• The WHO recommends multidrug therapy with dapsone, rifampicin and clofazimine for 6 months for paucibacillary leprosy and 12 months for multibacillary leprosy.
• When diagnosed early and treated properly, leprosy is completely curable. However, delayed treatment can result in permanent disability and disfigurement with stigma