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(Hansen Disease; Hansen's Disease)

by Dylan Tierney, MD, Edward A. Nardell, MD

Leprosy is a chronic infection usually caused by the acid-fast bacilli Mycobacterium leprae, which has a unique tropism for peripheral nerves, skin, and mucous membranes of the upper respiratory tract. Symptoms are myriad and include anesthetic polymorphic skin lesions and peripheral neuropathy. Diagnosis is clinical and confirmed by biopsy. Treatment is typically with dapsone plus other antimycobacterial drugs. Patients rapidly become noncontagious after starting therapy.

M. leprae was the only known cause of leprosy until 2008, when a second species, M. lepromatosis was identified in Mexico.

Although leprosy is not highly contagious, rarely causes death, and can be effectively treated with antibiotics, it continues to be associated with considerable social stigma. Misunderstanding about the disease probably exists because leprosy was incurable before the advent of effective antibiotic therapy in the 1940s. People with the disease would become disfigured and often have significant disability, causing them to be feared and shunned by others. Because of this social stigma, the psychologic impact of leprosy is often significant.


Globally, the number of leprosy cases is declining. During 2011, about 219,000 new cases were reported. About 80% of these cases occurred in India, Brazil, and Indonesia. In 2009, 213 new cases were reported in the US; 65% occurred in 7 states: California, Florida, Hawaii, Louisiana, Massachusetts, New York, and Texas. Most cases of leprosy in the US involve people who emigrated from developing countries.

Leprosy can develop at any age but appears most often in people aged 5 to 15 yr or > 30.


Humans are the main natural reservoir for M. leprae. Armadillos are the only confirmed source other than humans, although other animal and environmental sources may exist.

Leprosy is thought to be spread by passage from person to person through nasal droplets and secretions. Casual contact (eg, simply touching someone with the disease) and short-term contact does not seem to spread the disease. About half of people with leprosy probably contracted it through close, long-term contact with an infected person. Even after contact with the bacteria, most people do not contract leprosy; health care workers often work for many years with people who have leprosy without contracting the disease. Most (95%) immunocompetent people who are infected with M. leprae do not develop leprosy because of effective immunity. People who do develop leprosy probably have a poorly defined genetic predisposition.

M. leprae grow slowly (doubling in 2 wk). The usual incubation period ranges from 6 mo to 10 yr. Once infection develops, hematogenous dissemination can occur.


Leprosy can be categorized by type and number of skin areas affected:

  • Paucibacillary: 5 skin lesions with no bacteria detected on samples from those areas

  • Multibacillary: 6 skin lesions, bacteria detected on samples from skin lesions, or both

Leprosy can also be classified by cellular response and clinical findings:

  • Tuberculoid

  • Lepromatous

  • Borderline

People with tuberculoid leprosy typically have a strong cell-mediated response, which limits disease to a few skin lesions (paucibacillary), and the disease is milder, less common, and less contagious. People with lepromatous or borderline leprosy typically have poor cell-mediated immunity to M. leprae and have more severe, systemic infection with widespread bacterial infiltration of skin, nerves, and other organs (eg, nose, testes, kidneys). They have more skin lesions (multibacillary), and the disease is more contagious.

In both classifications, the type of leprosy dictates long-term prognosis, likely complications, and duration of antibiotic treatment.

Symptoms and Signs

Symptoms usually do not begin until > 1 yr after infection (average 5 to 7 yr). Once symptoms begin, they progress slowly.

Leprosy affects mainly the skin and peripheral nerves. Nerve involvement causes numbness and weakness in areas controlled by the affected nerves.

  • Tuberculoid leprosy: Skin lesions consist of one or a few hypoesthetic, centrally hypopigmented macules with sharp, raised borders. The rash, as in all forms of leprosy, is nonpruritic. Areas affected by this rash are numb because of damage to the underlying peripheral nerves, which may be palpably enlarged.

  • Lepromatous leprosy: Much of the skin and many areas of the body, including the kidneys, nose, and testes, may be affected. Patients have skin macules, papules, nodules, or plaques, which are often symmetric. Peripheral neuropathy is more severe than in tuberculoid leprosy, with more areas of numbness; certain muscle groups may be weak. Patients may develop gynecomastia or lose eyelashes and eyebrows.

  • Borderline leprosy: Features of both tuberculoid and lepromatous leprosy are present. Without treatment, borderline leprosy may become less severe and more like the tuberculoid form, or it may worsen and become more like the lepromatous form.


The most severe complications result from the peripheral neuropathy, which causes deterioration of the sense of touch and a corresponding inability to feel pain and temperature. Patients may unknowingly burn, cut, or otherwise harm themselves. Repeated damage may lead to loss of digits. Muscle weakness can result in deformities (eg, clawing of the 4th and 5th fingers caused by ulnar nerve involvement, foot drop caused by peroneal nerve involvement).

Papules and nodules can be particularly disfiguring on the face.

Other areas of the body may be affected:

  • Feet: Plantar ulcers with secondary infection are a major cause of morbidity, making walking painful.

  • Nose: Damage to the nasal mucosa can result in chronic nasal congestion and nosebleeds and, if untreated, erosion and collapse of the nasal septum.

  • Eyes: Iritis may lead to glaucoma, and corneal insensitivity may lead to scarring and blindness.

  • Sexual function: Men with lepromatous leprosy may have erectile dysfunction and infertility. The infection can reduce testosterone and sperm production by the testes.

  • Kidneys: Amyloidosis and consequent renal failure occasionally occur in lepromatous leprosy.

Leprosy reactions

During the course of untreated or even treated leprosy, the immune system may produce inflammatory reactions. There are 2 types.

Type 1 reactions result from a spontaneous increase in cell-mediated immunity. These reactions can cause fever and inflammation of the preexisting skin and peripheral nerve lesions, resulting in skin edema, erythema, and tenderness and worsening nerve function. These reactions, particularly if not treated early, contribute significantly to nerve damage. Because the immune response is increased, these reactions are termed reversal reactions, despite the apparent clinical worsening.

Type 2 reactions (erythema nodosum leprosum, or ENL) are systemic inflammatory reactions that appear to be a vasculitis or panniculitis and probably involve circulating immune complex deposition or increased T-helper cell function. They have become less common since clofazimine was added to the drug regimen. Patients may develop erythematous and painful papules or nodules that may pustulate and ulcerate and cause fever, neuritis, lymphadenitis, orchitis, arthritis (particularly in large joints, usually knees), and glomerulonephritis. Hemolysis or bone marrow suppression may cause anemia, and hepatic inflammation may cause mild abnormalities in liver function tests.


  • Microscopic examination of skin biopsy specimen

Diagnosis is often delayed in the US because clinicians are unfamiliar with the clinical manifestations. The disease is suggested by the presence of skin lesions and peripheral neuropathy and confirmed by microscopic examination of biopsy specimens. The organism does not grow on artificial culture media. Biopsy specimens should be taken from the advancing edge of tuberculoid lesions or, in lepromatous leprosy, from nodules or plaques.

Serum IgM antibodies to M. leprae are specific but insensitive (present in only two thirds of patients with tuberculoid leprosy). Diagnostic usefulness is further limited in endemic areas because such antibodies may be present in asymptomatic infection.


  • Long-term, multidrug regimens with dapsone, rifampin, and sometimes clofazimine

  • Sometimes lifelong maintenance antibiotics

Antibiotics can stop the progression of leprosy but do not reverse any nerve damage or deformity. Thus, early detection and treatment are vitally important. Because of antibiotic resistance, multidrug regimens are used. The drugs chosen depend on the type of leprosy; multibacillary leprosy requires more intensive regimens and a longer duration than paucibacillary does. Advice about diagnosis and treatment is available from the National Hansen’s Disease Program in Baton Rouge, LA (1-800-642-2477) or the US Health Resources and Services Administration at HRSA . Standard regimens recommended by the WHO differ somewhat from those used in the US.


The standard WHO regimen includes dapsone, rifampin, and clofazimine. WHO provides these drugs free for all leprosy patients throughout the world. Patients take rifampin 600 mg po and clofazimine 300 mg po once/mo under a health care practitioner’s supervision and dapsone 100 mg po plus clofazimine 50 mg po once/day without supervision. This regimen is continued for 12 mo.

In the US, the regimen is rifampin 600 mg po once/day, dapsone 100 mg po once/day, and clofazimine 100 mg po once/day for 24 mo. Dapsone is continued indefinitely for lepromatous leprosy and for 10 yr for borderline leprosy.


In the standard WHO regimen, patients take rifampin 600 mg po once/mo with supervision and dapsone 100 mg po once/day without supervision for 6 mo. People who have only a single skin lesion are given a one-time oral dose of rifampin 600 mg, ofloxacin 400 mg, and minocycline 100 mg.

In the US, the regimen is rifampin 600 mg po once/day and dapsone 100 mg po once/day for 12 mo. Dapsone is continued for 3 yr for indeterminate and tuberculoid leprosy and for 5 yr for borderline tuberculoid.

Drugs for leprosy

Dapsone is relatively inexpensive and generally safe to use. Adverse effects include hemolysis and anemia (which are usually mild) and allergic dermatoses (which can be severe); rarely, dapsone syndrome (exfoliative dermatitis, high fever, mononucleosis-like WBC differential) occurs.

Rifampin, is primarily bactericidal for M. leprae and is even more effective than dapsone. However, if given at the recommended US dosage of 600 mg po once/day, it is too expensive for many developing countries. Adverse effects include hepatotoxicity, flu-like syndromes, and, rarely, thrombocytopenia and renal failure.

Clofazimine is extremely safe. The main side effect is reversible skin pigmentation, but discoloration may take months to resolve. Clofazimine can be obtained in the US only from the Department of Health and Human Services as an investigational new drug (contact number for the case officer is 225-756-3709).

Leprosy reactions

Patients with type 1 reactions (except minor skin inflammation) are given prednisone 40 to 60 mg po once/day initially, followed by low maintenance doses (often as low as 10 to 15 mg once/day) for a few months. Minor skin inflammation should not be treated.

First and 2nd episodes of ENL may be treated, if mild, with aspirin or, if significant, with 1 wk of prednisone 40 to 60 mg po once/day plus antimicrobials. For recurrent cases, thalidomide 100 to 300 mg po once/day is the drug of choice (in the US, available through the National Hansen’s Disease Program). However, because of its teratogenicity, thalidomide should not be given to women who may become pregnant. Adverse effects are mild constipation, mild leukopenia, and sedation.


Because leprosy is not very contagious, risk of spread is low. Only the untreated lepromatous form is contagious, but even then, the infection is not easily spread. However, household contacts (particularly children) of patients with leprosy should be monitored for development of symptoms and signs of leprosy. Once treatment has begun, leprosy cannot be spread. Avoiding contact with bodily fluids from and the rash on infected people is the best prevention.

The BCG vaccine, used to prevent TB, provides some protection against leprosy but is not often used for that purpose. There is no role for chemoprophylaxis.

Key Points

  • Leprosy is a chronic infection usually caused by the acid-fast bacilli Mycobacterium leprae.

  • Leprosy is not very contagious in untreated patients and not at all contagious once treatment starts.

  • Leprosy affects mainly the skin and peripheral nerves.

  • The most severe complications result from loss of the sense of touch, pain, and temperature; muscle weakness that can result in deformities; and disfiguring lesions of the skin and nasal mucosa.

  • Inflammatory reactions called leprosy reactions can occur and require treatment with corticosteroids.

  • Diagnose based on biopsy; M. leprae cannot be grown in culture.

  • Treatment depends on the form of leprosy but involves multidrug regimens typically using dapsone, rifampin, and sometimes clofazimine.

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