Leprosy is a chronic infection caused by the acid-fast bacillus Mycobacterium leprae, which has a unique tropism for peripheral nerves, skin, and mucous membranes. 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.
Because without treatment, people with leprosy are visibly disfigured and often have significant disability, they have long been feared and shunned by others. Although leprosy is not highly contagious, rarely causes death, and can be effectively treated with antibiotics, it still causes anxiety. As a result, people with leprosy and their family members often have psychologic and social problems.
During 2007, > 250,000 new cases were reported. About 90% of these cases occurred in the following 8 countries (from the most cases to the least): India, Brazil, Indonesia, Congo, Bangladesh, Nigeria, Nepal, and Ethiopia. In 2006, 137 new cases were reported in the US. Cases occurred in 30 states, but more than half occurred in 6 states: California, Florida, 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.
How leprosy is spread is unclear. It is thought to be passed 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:
Leprosy can also be classified by cellular response and clinical findings:
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.
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:
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.
Diagnosis is suggested by the clinical picture 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.
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). Standard regimens recommended by the WHO differ somewhat from those used in the US.
The standard WHO regimen includes dapsone, rifampin, and clofazimine. Patients take rifampin 600 mg and clofazimine 300 mg po once/mo under a health care practitioner's supervision and dapsone 100 mg plus clofazimine 50 mg once/day without supervision. This regimen is continued for 12 to 24 mo, depending on disease severity.
In the US, the regimen is rifampin 600 mg po once/day and dapsone 100 mg po once/day for 3 yr. 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 once/day without supervision for 6 mo. People who have only a single skin lesion are given a single 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 6 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 generally 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 temporary skin pigmentation.
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. 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.
Last full review/revision September 2009 by Edward A. Nardell, MD