Leprosy overview

# Overview
Leprosy is a chronic infectious disease caused by the bacterium Mycobacterium leprae. Leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the primary external symptom. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs, and eyes.

# Historical Perspective
Mycobacterium leprae, the causative agent of leprosy, was discovered by G. H. Armauer Hansen in Norway in 1873, making it the first bacterium to be identified as causing disease in man. Historically, individuals with leprosy have been known as lepers, however, this term is falling into disuse due the pejorative connotation of the term.

# Classification
The Ridley Jopling classification and the WHO classification are the two most widely used systems to classify Leprosy. These classification systems are based on clinical, microbiologic and histopathological features, and are used to determine the patient's prognosis and the treatment regimen.

# Pathophysiology
The clinical manifestations of leprosy largely reflect the immune response of the host towards the infection. Once the bacterial cells penetrate and multiply within the hosts skin and peripheral nerve cells, the immune system mounts a response toward the infected cells, which results in clinical symptoms.  Several single-nucleotide polymorphisms such as TNF-, IL-10, IFN-, TLR 1  have been associated with a greater susceptibility to leprosy as have other genetic markers.

# Causes
Mycobacterium leprae is a gram-positive obligate intracellular, acid-fast bacillus, responsible for the development of leprosy, or Hansen's disease. This organism has a very slow growth and has a predilection to affect colder parts of the body, such as the skin, superficial nerves and upper respiratory mucous membranes. Although a route of transmission has not been absolutely defined yet, studies are pointing to a colonization of the dermis and respiratory mucosa of the infected patients. It is an uncommon bacteria, since it has only been noticed to infect and grow in some species of primates and in the nine-banded armadillo.

# Differential Diagnosis
Leprosy must be differentiated from other diseases that cause skin lesions, nodules, plaques  paresthesias and nerve pain, such as autoimmune diseases, SLE, parasitic infections, vitiligo or cutaneous tuberculosis.

# Epidemiology and Demographics
Current prevalence rate of leprosy per 100,000 is 3.7. The disease is more prevalent in endemic areas, which represent a potential source of spread of the disease to the rest of the world.

# Risk Factors
Risk factors for contracting leprosy include close contact with an untreated, active multibacillary disease patient with the subtype of lepromatous leprosy, living in an endemic region (Angola, Brazil, Central African Republic, Democratic Republic of Congo, Federated States of Micronesia, India, Kiribati, Madagascar, Mozambique, Nepal, Republic of Marshall Islands, United Republic of Tanzania), age between 5 and 15 as well as over 30, Armadillo contact, tattoos, and genetic variants of the NOD2-mediated signaling pathway.

# Natural History, Complications and Prognosis
Leprosy may lead to severe complications if not diagnosed and treated early, which will affect the prognosis.

# Diagnosis

## Diagnostic Criteria
The diagnosis of leprosy requires at least 1 of 3 criteria to be present: 1) loss of sensation of a hipopigmented skin patch, 2) a thickened peripheral nerve concomitantly with weakness or loss of sensation of the area, and/or 3) confirmation of mycobacterium leprae in a skin smear.

## History and Symptoms
Common symptoms of leprosy include hypopigmented, anesthetic, red skin lesions, that are hard to heal, nodular growths on the skin, muscle weakness and paresthesia of the extremities and eye problems. If left untreated blindness and paralysis may occur.

## Physical Examination
Although the findings on physical examination may vary depending upon the subytpe of leprosy, common findings include hypopigmented skin lesions, thickened dermis, and loss of sensation.

## Laboratory Findings
There are no laboratory tests that diagnose leprosy.

## X Ray
Osteoporosis is a common finding in leprosy patients which along with the loss of sensation may lead to fractures.

## Other Imaging Findings
There are no other imaging studies that diagnose leprosy.

## Other Diagnostic Studies
Biopsy of skin lesions and skin smear tests are important for the diagnosis of leprosy in patients whose clinical examination is suspicious of the disease.

# Treatment

## Medical Therapy
The medical treatment of leprosy is made with a multiple drug regimen, for 6 to 12 months. This drug regimen may include 2 or 3 drugs: rifampicin, dapsone and clofazimine, or rifampicin and dapsone, depending on the class of the disease.

## Surgery
Surgery is not indicated in the treatment of leprosy, yet it may treat or decrease the impact of some of the complications that may arise from the disease.

## Primary prevention
Primary prevention of leprosy includes immunoprophylaxis, chemoprophylaxis and education of the populations to prevent infection by the Mycobacterium leprae.

## Secondary Prevention
There is no secondary prevention of leprosy available because it is not possible to know if contact with leprosy will lead to the development of the disease, until first symptoms appear.

## Tertiary prevention
After treatment has been initiated, other measures to minimize further damage to the patient include: education of the individual and family members to monitor and treat skin ulcers and other lesions, primary care facilities to provide help to the populations and to direct patients to a specialist, whenever necessary.

## Cost-effectiveness of Therapy
After the results of the campaign of the WHO to eradicate leprosy, the treatment of this disease may be considered cost-effective.

## Future or Investigational Therapies
Ongoing research focuses on the the mechanism of leprosy transmission as well as the identification of patients at high risk of infection in order to improve disease prevention and to treat infected individuals earlier.   Identification of alternatives to existing drugs, such as rifampicin is also critical in so far as these agents may be contraindicated either because of toxicity or resistance.