Leprosy

Generality

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which mainly affects the skin, peripheral nerves, mucous membranes of the upper respiratory tract and eyes .

Once, leprosy was a common disease on all continents. Currently, there are sporadic cases in developed countries, while some endemic areas remain, most of which are located in Africa and Asia.

Leprosy is also known as Hansen's disease and is one of the oldest diseases known to mankind. The ancient civilizations of China, Egypt and India feared leprosy, as it represented an incurable disease, mutilating, contagious and often surrounded by negative stigmas. In fact, leprosy is an easily diagnosable and treatable disease with antibiotic therapy, and only if neglected can progressively cause serious and permanent damage to skin, nerves, limbs and eyes.

Contagion

M. leprae multiplies very slowly (twelve or more days) and the symptoms can take several years before appearing. Leprosy has a rather modest capacity for infection .

Transmission occurs through the close and prolonged contact with infected individuals, even if the mechanism is not yet completely clear. It is believed that the infection can be favored by exposure to body fluids emitted by the sick person by airborne diffusion, such as nasal secretions or through droplets of saliva expelled from the mouth with coughing or sneezing (droplet transmission). These particles should constitute an aerosol, which can come into contact with the eyes or mucous membranes of the upper airways and be inhaled to the lungs.

Mycobacterium leprae can also be released into the environment from skin lesions of infected patients. In ideal conditions, the infectious agent can survive even weeks outside the human body.

Most people exposed and infected with M. leprae do not develop the disease, as their immune response is adequate to combat the infecting agent. People whose immune systems are weakened by chronic concomitant diseases (diabetes, HIV / AIDS or heart disease) are more exposed to the risk of contracting leprosy, since their defenses are not strong enough to effectively attack and eliminate mycobacteria.

The commitment of the WHO

Early diagnosis and multi-drug therapy (MDT) remain the key elements to solve the disease. The multi-pharmacological therapeutic strategy (MDT, multi-drug therapy) has been made available free of charge by the WHO (World Health Organization) to all patients in the world, since 1995, and provides a simple but effective cure for all clinical forms of leprosy.

The widespread use of multi-pharmacological treatment has drastically reduced the incidence of the disease globally. Currently the efforts of the WHO are focused on the elimination of leprosy at national level in the remaining endemic countries and, from others, at sub-national level, so that it no longer represents a public health problem.

Symptoms and clinical forms

To learn more: Symptoms Leprosy

The course of leprosy is very slow: the average incubation period of the mycobacterium is approximately 5-7 years, but it can vary from a few months to 10 years. The appearance of symptoms depends on the form in which the disease occurs. Mycobacterium leprae has a characteristic affinity for peripheral nerves; in 90% of patients the '‹first sign of leprosy, in fact, is a feeling of numbness, due to the involvement of nerve endings.

The first skin lesion is usually of the "indeterminate" type and causes one or a few hypopigmented skin spots (lighter than normal skin color) or erythematous (slightly red), before evolving into the tubercoloid, lepromatous or borderline form (ie with characteristics intermediate).

Depending on the type of leprosy, onset symptoms may include:

• Hypopigmented or erythematous skin lesions, which do not heal after several weeks or months;
• Numbness or lack of sensitivity to touch, heat or pain in the extremities (hands, arms, feet and legs);
• Muscle weakness.

Leprosy can progressively damage nerves, bones, joints and muscles. Furthermore, the evolution of the disease can be associated with the onset of macules, papules, blisters, nodules (called lepromas) and isolated or confluent plaques on the skin, which often follow ulcerations and tissue destruction.

There are different forms of leprosy: the nature and severity of the developing disease are related to the type of immune response activated in the host organism following infection. In fact, leprosy has many methods of clinical presentation (with related further subdivisions): the most common forms are tubercoloid leprosy and lepromatous leprosy. Both forms produce skin lesions, however the lepromatous type is more severe.

Leprosy type	Features
Tubercoloid Leprosy	At the skin level it is manifested by a few macules or plaques (often a single lesion) hypopigmented or erythematous, sometimes with grouped papular lesions; The lesions are always well demarcated, with unilateral asymmetric distribution, with dry, rough to the touch and alopecic (without hair) surface. Some of these can become hypo-anesthetic (lose sensitivity). The lesions have a characteristic infiltrate, which indicates the cell-mediated immune reaction against M. Leprae ; The affected nerve termination appears edematous and thickened, with possible consequent loss of function (neurological damage) and appearance of trophic ulcers in the relative innervated region; Spontaneous resolution of tubercoloid leprosy may occur in a few years or may develop into borderline or lepromatous forms (rarely).
Lepromatous leper	The lepromatous leprosy is a real systemic disease, able to affect many organs like kidneys, testicles, eyes and nose. This type of leprosy is the most serious and most contagious form. The first symptoms are a stuffy nose, with frequent secretions and epistaxis. Early nervous involvement can go unnoticed. At the onset of the disease, hypochromic macules appear on the skin with blurred margins, followed by the rapid dissemination of numerous lesions of all types (papules, nodules, isolated or confluent plaques, etc.), both for contiguity and blood flow to other skin areas, to nerves, mucous membranes and all organs. If neglected, the following signs may occur: The facial lesions thicken the skin on the forehead ("facies leonina"), with alopecia of eyelashes and eyebrows, thickening of the auricles, deformation or destruction of cartilage, septum and nasal bones. The skeleton is attached directly; mainly the fingers and toes are affected, in addition to the alveolar process of the maxillary bone. Eye involvement causes photophobia (light sensitivity), glaucoma and blindness. The voice becomes hoarse due to the involvement of the larynx. The skin on the legs thickens and is affected by ulcers, when the nodules break. In men, testicular damage can cause sterility and gynecomastia. Infections of internal organs cause hepatic and lymph node enlargement. Kidney damage can also be important. The slow scarring of peripheral nerves with consequent edema and thickening, induces a sensory impairment, which in turn causes the appearance of ulcerations that become complicated with infections, necrosis and deformations making necessary amputations of the extremities.

Complications

If left untreated, leprosy can cause the general health conditions to deteriorate. Involvement of the peripheral nervous system can induce permanent damage and affect the ability to perceive pain and temperature in structures innervated by damaged branches. Neurological outcomes can be disabling (extensive deformities).

Other complications of leprosy may include:

• Disfiguring skin wounds (sores, ulcers, etc.);
• Blindness or glaucoma;
• Disfigurement of the face;
• Muscle weakness, with limb hypofunction;
• Permanent damage inside the nose can lead to frequent epistaxis;
• Erectile dysfunction and infertility in men (especially in lepromatous leprosy);
• In severe cases, leprosy can also damage the kidneys, leading to chronic renal failure.

Diagnosis

Leprosy shows well-defined clinical features, but the diagnosis must be confirmed with certainty due to the need to establish a specific antibiotic therapy. The diagnosis of leprosy is clinical and histological.

There are three fundamental signs that allow defining the diagnosis of leprosy:

• Hypopigmented or erythematous skin lesions with lack of sensitivity;
• Enlarged peripheral nerves;
• Positive bacteriological examination for the Hansen bacillus: Mycobacterium leprae is a Gram-positive bacterium, alcohol-resistant acid (colored with the Ziehl-Neelsen method), not cultivable in vitro (it is not able to grow in artificial culture media ), but morphologically recognizable by bacteriological examination (rod-shaped bacillus).

Additional exams are available and include:

• Mitsuda-Hayashi intradermal reaction: consists of a skin test with lepromine ( M. leprae killed by heat), which can be used to distinguish the lepromatous form from the tubercoloid, but it is not used to directly diagnose the disease;
• Skin biopsy of the lesion : in case of suspicion, the doctor can take a small sample of abnormal skin (biopsy) and send it to a laboratory for histopathological characterization of the lesion. The test subjects the tissue sample to a special staining to identify acid-resistant bacteria and, in the tubercoloid form, to highlight the presence of granulomas, formed by lymphocytes, epithelioid cells and Langhans cells.

Treatment

Leprosy is a disease that can be treated. This important result was achieved thanks to the introduction of multi-pharmacological therapy (MDT, multi-drug therapy):

• The first step for the pharmacological treatment of leprosy was carried out starting from 1940 with the development of dapsone, a drug that allowed to stop the course of the disease. However, the therapeutic protocol lasted many years (even a lifetime), making it difficult to manage patients. In 1960, M. leprae began to develop resistance to dapsone, the only drug applied until then that was considered valid in the management of leprosy.
• In the early 1960s, rifampicin and clofazimine, the other two components of polychemotherapy, were discovered.
• In 1981, an WHO study group recommended the MDT, consisting of 3 drugs in combination: dapsone, rifampicin and clofazimine . This combination allows the elimination of the pathogen and the effective care of the infected subjects.
• Since 1995, the WHO has been providing free MDT for all patients worldwide. Over the past two decades, more than 14 million people have been treated with leprosy. Modern multi-pharmacological therapy applied on a global scale has an indicative duration of 6-24 months.

The therapeutic management of leprosy is aimed at blocking the infection and minimizing potential complications, allowing the person to lead a normal lifestyle. Today, different therapeutic regimes are used which involve the combination of at least two drugs (MDT), depending on the type of leprosy and the severity of the infection. The duration of treatment, depending on these considerations, is variable. The first line antibiotics used to eliminate infectious agents are dapsone, rifampicin and clofazimine. Other antibiotics include minocycline, ofloxacin and clarithromycin. Some oral corticosteroids (example: prednisone) and thalidomide are useful in controlling inflammation and preventing damage to the nervous system, as they can reduce the edema affecting the injured region.

Patient education is essential. Leprosy can be cured, but to be effective it is essential to take the drug for the entire duration of the therapeutic protocol. Antibiotics can exert their action on Mycobacterium leprae from the host organism, but they cannot reverse the neurological damage (anesthesia and paralysis) or deformities caused by leprosy. Sometimes, surgery can be used to drain any abscesses and to improve the aesthetic or functional appearance of the affected areas.

To learn more: Drugs for the Treatment of Leprosy »

Prevention

Even if the risk of contracting leprosy is low, it is still possible to reduce the possibility of contracting the disease. The best way to prevent infection is to avoid close physical contact with untreated people .

Leprosy today

The incidence of leprosy has significantly decreased thanks to the implementation of global programs by the WHO.

Currently, high-endemic regions still remain in some areas of Brazil, Indonesia, the Philippines, the Democratic Republic of the Congo, India, Madagascar, Mozambique, Nepal and the United Republic of Tanzania.

All endemic countries are strongly committed to eliminating the disease and continue to intensify leprosy control activities.