Tips when Interviewing PALs:

1. Before calling, send a message that you will be calling them.

2. Introduce yourself.
3. State the reason why you are interviewing the person.
4. Assure the person the confidentiality of the interview. If you want to
record the interview, ask for permission.
5. Ask the person how is she/he? Make her/him feel at ease by asking general
questions.
6. You may ask questions like: where do they live, if they have families, etc.
7. Allow the person to relax and be at ease; ask them how they want to be
addressed. Do they have a nickname?
8. Proceed with the guide questions.
9. Allow the person to explain or clarify by asking questions.
10.Be objective and try not judge the person’s actions or explanations.
11.You may give suggestions but do not impose your opinion.
12.Be polite.
13.End your interview with a friendly note.
Hansen’s disease (also known as leprosy) is an infection caused by slow-
growing bacteria called Mycobacterium leprae. It can affect the nerves, skin,
eyes, and lining of the nose (nasal mucosa). With early diagnosis and
treatment, the disease can be cured. People with Hansen’s disease can
continue to work and lead an active life during and after treatment.

Leprosy was once feared as a highly contagious and devastating disease, but
now we know it doesn’t spread easily and treatment is very effective.
However, if left untreated, the nerve damage can result in crippling of hands
and feet, paralysis, and blindness.

Hansen’s disease (also known as leprosy) is an infection caused by bacteria

called Mycobacterium leprae. These bacteria grow very slowly and it may take
up to 20 years to develop signs of the infection.

The disease can affect the nerves, skin, eyes, and lining of the nose (nasal
mucosa). The bacteria attack the nerves, which can become swollen under
the skin. This can cause the affected areas to lose the ability to sense touch
and pain, which can lead to injuries, like cuts and burns. Usually, the affected
skin changes color and either becomes:

 lighter or darker, often dry or flaky, with loss of feeling, or

 reddish due to inflammation of the skin.

If left untreated, the nerve damage can result in paralysis of hands and feet.
In very advanced cases, the person may have multiple injuries due to lack of
sensation, and eventually the body may reabsorb the affected digits over
time, resulting in the apparent loss of toes and fingers. Corneal ulcers and
blindness can also occur if facial nerves are affected. Other signs of advanced
Hansen’s disease may include loss of eyebrows and saddle-nose
deformity resulting from damage to the nasal septum.

Early diagnosis and treatment usually prevent disability that can result from

the disease, and people with Hansen’s disease can continue to work and lead
an active life. Once treatment is started, the person is no longer contagious.
However, it is very important to finish the entire course of treatment as
directed by the doctor.
Each year, about 150 people in the United States and 250,000 around the
worldExternal get the illness. In the past, Hansen’s disease was feared as a
highly contagious, devastating disease, but now we know that it’s hard to
spread and it’s easily treatable once recognized. Still, a lot of stigma and
prejudice remains about the disease, and those suffering from it are isolated
and discriminated against in many places where the disease is seen.
Continued commitment to fighting the stigma through education and
improving access to treatment will lead to a world free of this completely
treatable disease.

How do people get Hansen’s disease?

It is not known exactly how Hansen’s disease spreads between people.
Scientists currently think it may happen when a person with Hansen’s
disease coughs or sneezes, and a healthy person breathes in the droplets
containing the bacteria. Prolonged, close contact with someone with
untreated leprosy over many months is needed to catch the disease.

You cannot get leprosy from a casual contact with a person who has

Hansen’s disease like:

 Shaking hands or hugging

 Sitting next to each other on the bus
 Sitting together at a meal

Hansen’s disease is also not passed on from a mother to her unborn baby
during pregnancy and it is also not spread through sexual contact.

Due to the slow-growing nature of the bacteria and the long time it takes to
develop signs of the disease, it is often very difficult to find the source of
infection.

In the southern United States, some armadillos are naturally infected with
the bacteria that cause Hansen’s disease in people and it may be possible
that they can spread it to people. However, the risk is very low and most
people who come into contact with armadillos are unlikely to get Hansen’s
disease.
For general health reasons, avoid contact with armadillos whenever possible.
If you had a contact with an armadillo and are worried about getting
Hansen’s disease, talk to your healthcare provider. Your doctor will follow up
with you over time and perform periodic skin examinations to see if you
develop the disease. In the unlikely event that you have Hansen’s disease,
your doctor can help you get treatment.

Who Is at Risk?
In the U.S., Hansen’s disease is rare. Around the world, as many as 2 million
people are permanently disabled as a result of Hansen’s disease.

Overall, the risk of getting Hansen’s disease for any adult around the world is
very low. That’s because more than 95% of all people have natural immunity
to the disease.
In the southern United States, some armadillos are naturally infected with
the bacteria that cause Hansen's disease.
You may be at risk for the disease if you live in a country where the disease is
widespread. Countries that reported more than 1,000 new cases of Hansen’s
disease to WHO between 2011 and 2015 are:

 Africa: Democratic Republic of Congo, Ethiopia, Madagascar,

Mozambique, Nigeria, United Republic of Tanzania
 Asia: Bangladesh, India, Indonesia, Myanmar, Nepal, Philippines, Sri
Lanka
 Americas: Brazil

You may also be at risk if you are in prolonged close contact with people who
have untreated Hansen’s disease. If they have not been treated, you could
get the bacteria that cause Hansen’s disease. However, as soon as patients
start treatment, they are no longer able to spread the disease.

Geographical Distribution of New Cases of Hansen’s Disease Reported to

WHO in 2015

The distribution of new leprosy cases by country among 136 countries that
reported to WHO in 2015. India reported 127,326 new cases, accounting for
60% of the global new leprosy cases; Brazil, reported 26,395 new cases,
representing 13% of the global new cases; and Indonesia reported 17,202
new cases, 8% of the global case load. No other countries reported >10,000
new cases. Eleven countries reported between 1000 and 10,000 cases: from
Africa, the Democratic Republic of Congo, Ethiopia, Madagascar,
Mozambique, Nigeria and United Republic of Tanzania; from Southeast Asia,
Bangladesh, Myanmar, Nepal and Sri Lanka; and from Western Pacific, the
Philippines. Collectively, these countries reported 19,069 new cases, 14% of
all new cases globally. The remaining 10,286 new cases (5%) were reported
by 92 countries. Thirty countries reported zero new cases. Ninety-two
countries did not report, several of which are known to have cases of leprosy.

Symptoms mainly affect the skin, nerves, and mucous membranes (the soft,
moist areas just inside the body’s openings).

The disease can cause skin symptoms such as:

A large, discolored lesion on the chest of a person with Hansen’s disease.

 Discolored patches of skin, usually flat, that may be numb and look
faded (lighter than the skin around)
 Growths (nodules) on the skin
 Thick, stiff or dry skin
 Painless ulcers on the soles of feet
 Painless swelling or lumps on the face or earlobes
 Loss of eyebrows or eyelashes

Symptoms caused by damage to the nerves are:

 Numbness of affected areas of the skin

  Muscle weakness or paralysis (especially in the hands and feet)
 Enlarged nerves (especially those around the elbow and knee and in
the sides of the neck)
 Eye problems that may lead to blindness (when facial nerves are
affected)

Enlarged nerves below the skin and dark reddish skin patch overlying the
nerves affected by the bacteria on the chest of a patient with Hansen’s
disease. This skin patch was numb when touched.
Symptoms caused by the disease in the mucous membranes are:

 A stuffy nose
 Nosebleeds

Since Hansen’s disease affects the nerves, loss of feeling or sensation can
occur. When loss of sensation occurs, injuries such as burns may go
unnoticed. Because you may not feel the pain that can warn you of harm to
your body, take extra caution to ensure the affected parts of your body are
not injured.

If left untreated, the signs of advanced leprosy can include:

 Paralysis and crippling of hands and feet

 Shortening of toes and fingers due to reabsorption
 Chronic non-healing ulcers on the bottoms of the feet
 Blindness
  Loss of eyebrows
 Nose disfigurement

Other complications that may sometimes occur are:

 Painful or tender nerves

 Redness and pain around the affected area
 Burning sensation in the skin

How is the disease diagnosed?

Hansen’s disease can be recognized by appearance of patches of skin that
may look lighter or darker than the normal skin. Sometimes the affected skin
areas may be reddish. Loss of feeling in these skin patches is common. You
may not feel a light touch or a prick with a needle.

To confirm the diagnosis, your doctor will take a sample of your skin or nerve
(through a skin or nerve biopsy) to look for the bacteria under the
microscope and may also do tests to rule out other skin diseases.

How is the disease treated?

Hansen’s disease is treated with a combination of antibiotics. Typically, 2 or 3
antibiotics are used at the same time. These are dapsone with rifampicin,
and clofazimine is added for some types of the disease. This is called
multidrug therapy. This strategy helps prevent the development of antibiotic
resistance by the bacteria, which may otherwise occur due to length of the
treatment.

Treatment usually lasts between one to two years. The illness can be cured if
treatment is completed as prescribed.

If you are treated for Hansen’s disease, it’s important to:

 Tell your doctor if you experience numbness or a loss of feeling in

certain parts of the body or in patches on the skin. This may be caused
by nerve damage from the infection. If you have numbness and loss of
 feeling, take extra care to prevent injuries that may occur, like burns
and cuts.
 Take the antibiotics until your doctor says your treatment is complete.
If you stop earlier, the bacteria may start growing again and you may
get sick again.
 Tell your doctor if the affected skin patches become red and painful,
nerves become painful or swollen, or you develop a fever as these may
be complications of Hansen’s disease that may require more intensive
treatment with medicines that can reduce inflammation.

If left untreated, the nerve damage can result in paralysis and crippling of
hands and feet. In very advanced cases, the person may have multiple
injuries due to lack of sensation, and eventually the body may reabsorb the
affected digits over time, resulting in the apparent loss of toes and fingers.
Corneal ulcers or blindness can also occur if facial nerves are affected, due to
loss of sensation of the cornea (outside) of the eye. Other signs of advanced
leprosy may include loss of eyebrows and saddle-nose deformity resulting
from damage to the nasal septum.

Antibiotics used during the treatment will kill the bacteria that cause leprosy.
But while the treatment can cure the disease and prevent it from getting
worse, it does not reverse nerve damage or physical disfiguration that may
have occurred before the diagnosis. Thus, it is very important that the
disease be diagnosed as early as possible, before any permanent nerve
damage occurs.

In the U.S., people with Hansen’s disease may be treated at special clinics run
by the National Hansen’s Disease ProgramExternal. There are several
federally supported outpatient clinicsExternal throughout the U.S. and
Puerto Rico.

Hansen’s disease is a chronic infectious disease caused by Mycobacterium

leprae and usually affects the skin and peripheral nerves, but can have a
wide range of possible clinical manifestations.

Patients can be classified into three groups, each with slightly different signs
and symptoms:
 1. Paucibacillary (PB), or tuberculoid, Hansen’s disease is characterized
by one or a few hypopigmented or hyperpigmented skin macules that
exhibit loss of sensation (anesthesia) due to infection of the peripheral
nerves supplying the region. The body’s immune response may also
result in swelling of the peripheral nerves; these enlarged nerves may be
palpated under the skin, and may or may not be tender to the touch. The
nerves most often found to have swelling are:
o Great auricular nerve
o Ulnar nerve above the elbow and dorsal cutaneous branches at the
wrist
o Median nerve at the wrist (in the carpal tunnel)
o Radial nerve (superficial at wrist)
o Common peroneal nerve (also femoral cutaneous and lateral
popliteal nerves where they wind around the neck of the fibula)
o Posterior tibial nerve, posterior to the medial malleolus
o Sural nerve

This patient presented to a clinical setting with an inflammatory cutaneous

lesion on the thorax, which was determined to be the paucibacillary form of
Hansen’s disease. Note the enlarged costal nerves below the skin that were
affected by the disease and which were supplying the leprous lesion.
This patient presented to a clinical setting with an active cutaneous lesion on
the left hand, which was determined to be due to paucibacillary Hansen’s
disease.

A large lesion on the man’s left chest is shown here, attributed to

paucibacillary (PB) Hansen’s disease.
Visible enlargement of the great auricular nerve due to infection with M.
leprae.

2. Multibacillary (MB), or lepromatous, Hansen’s disease is

characterized by generalized or diffuse involvement of the skin, a
thickening of the peripheral nerves under microscopic examination, and
has the potential to involve other organs, the eyes, nose, testes, and
bone. The nodular form of this condition is the most advanced form of
the disease. Ulcerated nodules contain large numbers of M. leprae acid-
fast bacilli packed in macrophages that appear as large foamy cells. MB
form of Hansen’s disease is associated with:
o multiple, symmetrically-distributed skin lesions that might not
exhibit loss of sensation
o nodules
o plaques
o thickened dermis
o frequent involvement of the nasal mucosa resulting in nasal
congestion and epistaxis

The face of this male patient exhibited some of the pathologic characteristic
associated with a case of nodular lepromatous, or multibacillary (MB),
Hansen’s disease. Of note is the presence of cutaneous nodules upon the
forehead, nose, cheeks, lips, and chin. The eyebrows are diminished as well.

3. Borderline, or dimorphous, Hansen’s disease is the most common

form. When compared to tuberculoid or lepromatous forms, it is of
intermediate severity. The skin lesions seem to be of the tuberculoid
type, but are more numerous, and may be found anywhere on the body.
Peripheral nerves are affected as well, with ensuing weakness and
anesthesia.

This young woman presented with a case of borderline Hansen’s disease

with bilateral involvement of the patient’s buccinator, or cheek muscles, as
well as dermatomyositis evidenced by the cutaneous rash-like discoloration
overlying the muscles beneath.

The agent that causes Hansen’s disease is an acid fast rod-shaped

bacillus Mycobacterium leprae. The organism multiplies very slowly (dividing
approximately once every 13 days) and is an obligate intracellular pathogen
that lacks several genes needed for independent survival, thus it has never
been grown in bacteriologic media. However, it has been grown in mouse
foot pads by injecting ground tissue from lepromatous nodules or nasal
scrapings from leprosy patients into the foot pad of the animal. Typically, the
granuloma appears at the inoculation site within 6 months. Armadillos can
also be experimentally infected and will develop systemic disease, and are
now the most common animal used to study Hansen’s disease and its
treatment.

Hansen’s disease is diagnosed based on clinical presentation and the

diagnosis is confirmed by skin or nerve biopsy and acid fast staining. In the
United States, the National Hansen’s Disease ProgramExternal provides
diagnostic services.
Some serological tests have been developed and promoted by some
investigators, but they lack sufficient sensitivity and specificity to be used as
diagnostic tests. For this reason they are not used to diagnose Hansen’s
disease.

Specimens and Tests

Depending on the form of leprosy suspected by the treating physician, the
following specimens may be collected:

 Skin smears from the earlobes, elbows, and knees

 Skin biopsy from edges of active patches
 Nerve biopsy from thickened nerves

Skin and nerve biopsy

Biopsies are needed to definitively confirm a diagnosis of Hansen’s disease
and to classify the disease, and slit skin smear may also be helpful in
diagnosing those with mutlibacillary disease.

In the multibacillary form of Hansen’s disease, tissue biopsy of various

affected sites may reveal typical histopathologic changes that show large
numbers of foam cells. Foam cells are macrophages that have ingested, or
phagocytized, M. leprae bacteria, but are unable to digest the organisms, who
in turn multiply and use the macrophage as a method of transport
throughout the body. This is how the bacteria cause the multiple lesions that
may appear in all parts of the body in MB leprosy patients.
This photomicrograph reveals some of the classic histopathologic changes
found in a skin section from an individual with a case of the leprosy, which
may have been the paucibacillary form of the disease, though this has not
been confirmed. Shown here is a nerve surrounded by a dense infiltrate
consisting of undifferentiated histiocytes and large numbers of lymphocytes.
The nerve sheath and endoneural region of the nerve were also infiltrated.
This neural involvement was found to be independent of any pathology of
the upper corium.

This photomicrograph reveals some of the histopathologic changes in a

specimen of human testicular tissue, which included a large number of “foam
cells”. These changes were attributed to a case of multibacillary (MB) leprosy.
Acid fast staining
The Ziehl-Neelson method using 5% sulphuric acid as decolorizing agent is
used. The presence of acid-fast bacilli confirms the diagnosis of Hansen’s
disease.
This acid-fast-stained photomicrograph of a tissue sample extracted from a
patient with leprosy shows a chronic inflammatory lesion known as a
granuloma, within which numerous red-colored M. leprae bacteria are visible.

This photomicrograph of a skin tissue sample from a patient with leprosy

shows a cutaneous nerve, which had been invaded by numerous M.
leprae bacteria (shown in red).

Hansen’s disease is treated with multidrug therapy (MDT) using a

combination of antibiotics depending on the form of the disease:

 Paucibacillary form – 2 antibiotics are used at the same time, daily

dapsone and rifampicin once per month
 Multibacillary form – daily clofazimine is added to rifampicin and
dapsone.
Treatment usually lasts between one to two years. The illness can be cured if
treatment is completed as prescribed.

In the U.S., people with the disease may be treated at special clinics run by
the National Hansen’s Disease ProgramExternal. There are several federally
supported outpatient clinicsExternal throughout the U.S. and Puerto Rico.

World Health Organization (WHO) published a detailed guide to classification

and treatment of leprosyExternal.

Leprosy
Synonyms of Leprosy
 Hansen's Disease

Subdivisions of Leprosy
 Borderline Lepromatous Leprosy
 Borderline Tuberculoid Leprosy
 Indeterminate Leprosy
 Lepromatous Leprosy
 Midborderline Leprosy
 Tuberculoid Leprosy

General Discussion
Leprosy is a chronic infectious disease of humans caused by the bacteria Mycobacterium
leprae. For many years, it was considered a mysterious disorder associated with some
type of curse, and persons with the disease were isolated and ostracized. Today, there is
effective treatment and the disease can be cured. There is no longer any justification for
isolating persons with leprosy.
The disease can affect the skin, mucous membranes, and eyes and some of the nerves
that are located outside the central nervous system (peripheral nerves). These are
primarily the nerves of the hands, feet, and eyes, and some of the nerves in the skin. In
severe, untreated cases, loss of sensation, muscle paralysis of hands and feet,
disfigurement, and blindness may occur.
Leprosy has traditionally been classified into two major types, tuberculoid and
lepromatous. Patients with tuberculoid leprosy have limited disease and relatively few
bacteria in the skin and nerves, while lepromatous patients have widespread disease and
large numbers of bacteria. Tuberculoid leprosy is characterized by a few flat or slightly
raised skin lesions of various sizes that are typically pale or slightly red, dry, hairless, and
numb to touch (anesthetic). Lepromatous leprosy is at the other end of the spectrum,
with a much more generalized disease, diffuse involvement of the skin, thickening of
many peripheral nerves, and at times involvement of other organs, such as eyes, nose,
testicles, and bone. There are also intermediate subtypes between these two extremes
that are commonly known as borderline leprosy. The intermediate subtypes are
borderline tuberculoid, midborderline, and borderline lepromatous leprosy. Borderline
leprosy and the subtypes are characterized by more extensive disease than polar
tuberculoid, with more numerous skin lesions and more nerve involvement, but not as
widespread disease as in lepromatous leprosy. Indeterminate leprosy refers to a very
early form of leprosy that consists of a single skin lesion with slightly diminished
sensation to touch. It will usually progress to one of the major types of leprosy.
In 1982, the World Health Organization proposed a simplified classification that has only
two classifications, Paucibacillary (PB) and Multibacillary (MB), leprosy. This classification
is now used worldwide for treatment purposes. The older and somewhat more complex
classification is still used in some programs, especially for clinical research studies. The
Paucibacillary classification encompasses indeterminate, tuberculoid and borderline
tuberculoid leprosy. The Multibacillary classification includes midborderline, borderline
lepromatous and lepromatous leprosy.
Signs & Symptoms
The earliest symptoms are usually skin lesions that are typically flat, pale
(hypopigmented) or reddish (erythematous) spots in the skin with slightly decreased
sensitivity to touch or pain. These lesions typically do not present with other symptoms,
such as burning or pain. There may be some hair loss in the affected area. As the skin
lesions progress, they may become raised and, in some cases, nodules may form. The
symptoms of nerve involvement include diminished sensation or feeling in the affected
areas (anesthesia) and, sometimes, burning and tingling sensations (paresthesias). In
more advanced cases, there may be weakness, paralysis, and atrophy of muscle in the
hands or feet.
Persons with tuberculoid and borderline tuberculoid leprosy have limited disease with
relatively few skin lesions and only a few affected nerves. However, early in the course
of the disease, they may have significant sensory loss and muscle weakness, even though
only one hand or foot is involved. Persons with lepromatous leprosy may have minimal
loss of sensation at the onset; however, if untreated, they will develop extensive
involvement of the skin and nerves. The complications that may occur include eye
involvement and deformities of the face, hands, and feet. Deformities of the face can
result from destruction of the partition in the nose that divides the nostrils (nasal
septum) and other facial tissues. In advanced disease, persons with lepromatous leprosy
may lose their eyebrows and eyelashes, and the eyelids may become paralyzed so that
individuals cannot blink or close their eyes properly. The earlobes may enlarge or
become wrinkled. Deformities of the hands and feet may result from muscle paralysis
and repeated trauma that is not felt due to sensory loss.
The most serious complication of leprosy is the nerve damage that may occur sometimes
even after treatment is begun. Much of the nerve damage occurs during a type of
immunologic problem that occurs in 25 to 50% of patients during treatment and is
commonly known as a reaction. Reactions are not drug reactions or allergies, but are the
patient’s own immune system reacting against the dead bacteria that are still in the skin
and nerves. Patients with the intermediate or borderline type of disease may get a type
of reaction known as reversal reaction, in which there is redness and swelling of the skin
lesions and swelling, tenderness, and pain in the nerves of the hands and feet. During
this process, nerve damage can occur.
The second type of reaction occurs only in borderline lepromatous and lepromatous
disease, and is known as erythema nodosum leprosum (ENL). This syndrome is
characterized by fever and raised, red, painful skin nodules. There may also be pain and
tenderness of the nerves with subsequent nerve damage in the hands and feet. ENL may
also be associated with joint disease (polyarthralgia), eye inflammation, and inflammation
of the testicles.
During reactions and at times without any signs of reaction, there may be damage to the
nerves of the face resulting in weakness of closure of the eyelids and loss of feeling in
the cornea (corneal anesthesia). This can result in corneal dryness and scarring and lead
to blindness. Persons with lepromatous leprosy may also have inflammation of the iris
and the sclera of the eye, which can lead to visual impairment and, in some cases,
blindness.
Causes
Leprosy is a chronic infectious disease of humans caused by the bacteria Mycobacterium
leprae. The disease has been known and described for several thousand years in India
and China. Over 100 years ago, Armauer Hansen in Norway identified the bacteria as the
cause of leprosy.
The way in which the disease is transmitted is not fully understood. The bacteria grow
only in living hosts and have not been grown in laboratory media, except in certain kinds
of mice, rats, and armadillos. Some wild armadillos also carry the bacteria. The most likely
way of spread appears to be through the respiratory tract, since large numbers of
bacteria are sometimes found in the noses and mouths of untreated patients. When
these are released into the environment, they can be inhaled by other susceptible
persons.
Most people have a natural immunity to the disease and will not contract it even if they
are exposed to it. Only about 5 percent of all people are susceptible to the disease. More
than one-half of new cases give no history of any known contact with a leprosy patient.
Affected Populations
Leprosy is relatively rare in the United States but is prevalent in some countries of Asia,
Africa, and South America. There are about 7,000 persons in the United States that have
been treated for the disease, and from 150-200 new cases are reported annually in the
United States. About 85% of the U.S. cases are persons who have immigrated from other
countries. North American Indians in the U.S.A. appear to be immune to this disease.
Worldwide, there are about 700,000 new cases reported each year, with about 800,000
cases under treatment in 1998. There are an additional estimated two to three million
persons who have residual deformities and disabilities from the disease, even though
they have been cured of the infection. Some of the countries with the largest number of
cases are India, Brazil, Indonesia, Bangladesh, Myanmar, Nigeria, and Mozambique.
Related Disorders
There are no closely related diseases.
Diagnosis
The diagnosis can usually be made by the history and characteristic findings on
examination. The important findings are decreased ability to feel light touch in a skin
spot, enlarged or tender nerves in the arms or legs, numbness in a hand or foot, and
finding the bacteria in the skin. There may also be loss of hair in the affected skin areas.
A special type of skin smear is commonly done and will demonstrate the bacteria in the
skin in lepromatous and borderline lepromatous cases. The bacteria are too few in
tuberculoid cases to be found in a skin smear. A skin biopsy of a lesion can also be
helpful to confirm the diagnosis. There are no blood tests or skin tests at the present
time that are helpful in the diagnosis.
Standard Therapies
Treatment
Leprosy is a treatable and curable disease. The vast majority of patients can take their
medication at home and continue their regular work and other activities. Patients with
leprosy do not need to be isolated. It is important to note that the drugs used to treat
leprosy are very effective in killing the bacteria, and patients on treatment are not
infectious and do not spread the disease.
The currently available drugs are very effective, and treatment is much shorter than was
common 20 years ago. The major drugs are dapsone, rifampin, and clofazimine. Dapsone
and rifampin can be given for six months for patients with PB disease (indeterminate,
tuberculoid or borderline tuberculoid disease), and dapsone, rifampin, and clofazimine
are given for two years for patients with MB disease (midborderline, borderline
lepromatous and lepromatous disease). Even shorter regimens using the above drugs are
being developed, and used in some parts of the world, and in some areas patients with
only one skin lesion are treated with only a single dose of medication. Several other
drugs, minocycline, oflaxacin, and clarithromycin, have also been found effective for
treatment and are used in cases in which there are allergies or intolerance to the three
commonly used drugs.
Patients with mild reactions, as described above, can be treated symptomatically with
analgesics, but most cases will also require prednisone or similar drugs for control of the
reactions. These may need to be given for many months at times. The drug thalidomide
(Thalomid) has been approved by the FDA as a treatment for erythema nodosum
leprosum (ENL), an inflammatory complication sometimes associated with leprosy that
results in painful skin lesions. It is not effective in reversal reaction and does not kill
bacteria. Thalidomide can have severe effects on a developing fetus and must be
administered with extreme caution. It cannot generally be given to women of
childbearing potential.
Ocular complications of erythema nodosum leprosum (ENL) must be treated promptly to
prevent permanent damage to the eyes. Local atropine and hydrocortisone eye drops
may be used to keep the pupils dilated and reduce the inflammation until the reaction
subsides. Patients with corneal dryness are treated with eye drops and substitutes for
the eye's natural lubricants.
Leprosy can be cured, and most disabilities and deformities can be prevented. Contrary
to common perceptions, leprosy does not cause fingers and toes to drop off. The loss of
fingers and toes that is sometimes seen is not due to the leprosy infection but to injuries
that occur because of nerve damage and loss of feeling in the extremities. These injuries
may become secondarily infected with other kinds of bacteria and cause the toes or
fingers to lose infected bone and ultimately shorten. If the injuries can be prevented,
much of the disability will not occur. The most important thing that can be done to
prevent permanent disability is to diagnose and treat patients at the very earliest stages
of the disease. They need to be started on appropriate drugs to kill the bacteria, and
reactions must be treated promptly if they occur. For those who already have had some
nerve damage, health education in the care of hands, feet, and eyes is very important to
prevent further injury and deformity.
Some people with leprosy may benefit from special shoes that compensate for loss of
sensation in the feet. Gloves or special tools can be used to prevent injury to hands that
have lost sensation. Surgery may be necessary to treat eye problems or correct certain
deformities of the hands and feet. The goal of surgery is to improve function and the
quality of life.

Leprosy: Epidemiology, microbiology, clinical

manifestations, and diagnosis
Authors:
David Scollard, MD, PhD
Barbara Stryjewska, MD
Mara Dacso, MD, MS
Section Editor:
C Fordham von Reyn, MD
Deputy Editor:
 Elinor L Baron, MD, DTMH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2021. | This topic last updated: Jun 02, 2021.

INTRODUCTION Leprosy (also known Hansen's disease) is an infectious disease

caused by Mycobacterium leprae and Mycobacterium lepromatosis that involves the skin and

peripheral nerves.
M. leprae and M. lepromatosis comprise "Mycobacterium leprae complex" [1]. The DNA
sequences of M. leprae and M. lepromatosis differ enough to distinguish them as separate
species, but they share many similarities (both are obligate intracellular parasites with a tropism
for nerves) and cause the same clinical disease [2].
Leprosy is an important global health concern. Contrary to popular folklore, leprosy is not highly
contagious, and very effective treatment is available [3,4]. Early diagnosis and treatment are
necessary to minimize the likelihood of disability involving the eyes, hands, and feet due to
neuropathy as these are often not reversible and may require lifelong care [5].
The epidemiology, microbiology, clinical manifestations, and diagnosis of leprosy are reviewed
here. Issues related to treatment are discussed separately. (See "Leprosy: Treatment and
prevention".)

EPIDEMIOLOGY In the 1990s, the World Health Organization (WHO) established

a goal of eliminating leprosy as a public health problem by the year 2000; "elimination" was
defined as a reduction in prevalence to <1 case per 10,000 population in all endemic countries.
Between 1985 and 2011, the number of registered cases fell from 5.4 million to 219,075; the
prevalence rate per 10,000 fell from 21.1 to 0.37; these figures exclude Europe [6]. The WHO
reports that 202,256 new leprosy cases were registered globally in 2019, of which 14,893 were
children below 14 years. Among all new cases, 10,816 had grade 2 disabilities at diagnosis [7].
The prevalence of leprosy is variable; the overwhelming majority of cases are found in resource-
limited settings. The top five countries reporting new cases are India, Brazil, Indonesia, Nepal,
and Bangladesh [8]. With increasing international travel, however, patients with leprosy may
present anywhere.
Epidemiologic data for leprosy are highly sensitive to operational factors; nearly all data are
based on passive case finding. A study using active case finding by house-to-house surveys in
Bangladesh recorded nearly fivefold more cases than were believed to exist in the area by
passive case finding alone [9].
According to the Registry of the National Hansen's Disease Programs, 159 new cases were
detected in the United States in 2020 [10]. Approximately 75 percent of new cases detected
annually in the United States are among immigrants. Among native-born United States citizens
developing the disease, exposure to leprosy overseas accounts for some cases. Contact with a
known case in the United States can sometimes be established; some cases are attributable to
exposure to infected armadillos [11-13]. However, in many patients, no history of exposure can
be established.
Infection with M. lepromatosis has been reported in Canada, Asia, several Mexican provinces,
South America, and Central America [14-16]. M. lepromatosis has also been identified in red
squirrels in Scotland [17]; however, leprosy is exceedingly rare in humans in the United
Kingdom and Europe [18]. Other animal reservoirs for leprosy may exist, and persistent zoonotic
transmission of organisms in the M. leprae complex may occur [18,19].
In general, leprosy is more common among males with a ratio of approximately 1.5 to 1. In
2009, lepromatous (multibacillary) cases accounted of 61 percent of new patients in the United
States; the figure ranged from 33 to 94 percent globally [20].
Transmission — The means of transmission is not fully understood. The disease is probably
spread by the respiratory route; nasal discharge from untreated patients with lepromatous
(multibacillary) disease frequently contains large numbers of bacilli [21,22]. Once the upper
respiratory tract of the new host is infected, widespread dissemination within the host may occur.
Occasionally, the organisms may enter through broken skin [21]. Contact with armadillos
(handling, killing, or eating) has been reported in some cases [11].
The mechanism of M. leprae transmission and potential environmental reservoirs remain active
areas of investigation [23]. The nine-banded armadillo (Dasypus novemcinctus) remains the only
well-documented zoonotic reservoir [11,13]; however molecular evidence of M. leprae and M.
lepromatosis have been found in red squirrels (Sciurus vulgaris) in the United Kingdom [17,24].
Under experimental conditions, M. leprae has been shown to be ingested by amebae and survive
within them [25,26] and to remain viable within amoebic cysts for as long as eight months [27].
Preliminary evidence also suggests that ticks may be able to ingest M. leprae and transfer the
organism to their eggs [28]. It is unknown whether either of these phenomena occur in the
natural environment, but the feasibility of these and other investigations of potential
environmental reservoirs and vectors is greatly enhanced by the availability of molecular tools to
identify M. leprae and assess its viability.
In general, most individuals do NOT develop the disease following exposure. Development of
disease depends on a variety of factors, including immune status and genetic influences, as
discussed below. (See 'Risk factors' below.)
Risk factors — Risk factors that have been proposed for acquisition of leprosy include:
●Close contact – Contacts of patients with leprosy have a higher risk of developing leprosy
than the general population [29]. Close physical distance to the index case was associated
with an increased risk of leprosy in one study [30].
●Type of leprosy in index patient – Some studies have suggested that contacts of patients
with lepromatous (multibacillary) leprosy have a higher risk than contacts of patients with
tuberculoid (paucibacillary) leprosy or single-lesion leprosy [29,31]. (See 'Classification
and terminology' below.)
●Armadillo exposure – In the southern United States, M. leprae infection is enzootic in the
nine-banded armadillo (Dasypus novemcinctus); the mechanism of transmission from
armadillos to humans is not understood. Using molecular strain-typing techniques, one
study identified the same strain of M. leprae in wild armadillos and in patients from the
region who did not have foreign exposure [11].
●Age – Older individuals appear to be at increased risk for leprosy. In one study, the effect
of age was bimodal, with an increased risk between age 5 and 15 years; the risk increased
again after age 30 [30].
●Genetic influences – The immunologic response to M. leprae consists of two components:
innate and acquired immunity. Innate immunity is determined by genetic factors, including
 alleles of the PARK2/PACRG gene [32] as well as other genes [33]. In a genome-wide
association study of patients in China, variants of genes in the NOD2-mediated signaling
pathway (which regulates the innate immune response) were found to be associated with
susceptibility to leprosy [34]. Such immunity is understood to be mediated through cells of
monocyte/dendritic cell origin; the mechanisms of this immunity are under investigation
[35].
Individuals with sufficient exposure and susceptibility to M. leprae complex may develop a
broad range of clinical manifestations, which vary depending upon the host's ability to
mount an acquired immune response to infection. This cellular immune response appears to
be controlled by a number of non-human leukocyte antigen (HLA) genes [30,36,37].
It is difficult to discern the relative contribution of genetic factors following exposure. A
prospective cohort study including 1037 patients newly diagnosed with leprosy, along with
their 21,870 contacts, demonstrated that genetic relationship was a relevant risk factor,
independent of physical distance for exposure [30].
●Immunosuppression – Immunosuppression increases susceptibility to this infection, as
evidenced by the development of leprosy following solid organ transplantation [38],
chemotherapy, HIV infection [39], or use of biologic agents for management of
rheumatologic conditions [40].
Drug resistance — Drug resistance in leprosy is relatively uncommon [41]. In a WHO
surveillance study that evaluated the rate of M. leprae antimicrobial resistance (AMR) among
more than 1900 patients in 19 countries between 2009 and 2015, the overall rates of resistance
were: rifampin (3.8 percent), dapsone (5.3 percent), and ofloxacin (1.3 percent) [42]. The rate of
rifampin resistance in new cases was 2 percent and in relapsed cases was 5 percent. The rate of
rifampin resistance was highest among new cases in Brazil and India (15 and 8 percent,
respectively) and among relapsed cases in Colombia and Mozambique (24 and 20 percent,
respectively).
These findings suggest that resistant strains continue to emerge, especially in the countries with
high disease prevalence. To improve the quality of data on global AMR in M. leprae, testing for
AMR resistance mutations is warranted for at least 10 percent of new leprosy cases. In the
United States, the Molecular Biology Laboratory of the National Hansen's Disease Programs
provides testing for drug resistance when indicated [43]. There is no role for routine baseline
resistance testing. (See "Leprosy: Treatment and prevention", section on 'Relapse'.)

MICROBIOLOGY Leprosy is caused by acid-fast bacilli of the M. leprae complex,

which includes M. leprae and M. lepromatosis. M. leprae multiplies very slowly (generation

time approximately 12.5 days) and is an obligate intracellular organism; it cannot be cultured in
artificial media. M. leprae has less than half of the functional genes of Mycobacterium
tuberculosis.
Studies in animal models indicate that M. leprae grows best at 27 to 33ºC, correlating with its
predilection to affect cooler areas of the body (the skin, nerve segments close to the skin, and the
mucous membranes of the upper respiratory tract) [4]. M. leprae grows extensively in the nine-
banded armadillo (Dasypus novemcinctus), which has a core body temperature of 34ºC. Leprosy
is found in wild armadillos in the south central United States [44] and has been found in a
chimpanzee, sooty mangabey monkeys, and a cynomolgus macaque [45].
The genomes of M. leprae and M. lepromatosis have been fully sequenced [2,46]. Both genomes
contain a large number of pseudogenes, and genes for key enzymes of many essential metabolic
pathways are missing [18,31,46]. This accumulation of pseudogenes has allowed these
mycobacteria to develop a highly adaptive niche as obligate intracellular organisms [18].
M. lepromatosis was identified as the causative agent of leprosy in several patients with diffuse
lepromatous leprosy [18,47]. Select M. lepromatosis gene and pseudogene sequences
demonstrated 9 percent difference in nucleotides compared with the highly conserved genome
of M. leprae [2]. Subsequent de novo sequencing of the M. lepromatosis genome demonstrated
significant differences in single-nucleotide polymorphisms, leading to the hypothesis that these
two organisms evolutionarily diverged from a common ancestor approximately 13.9 million
years ago [1,2]. Thus far, M. lepromatosis has not been cultured in animals and other basic
biologic aspects remain unknown [48].
Clinically, M. leprae and M. lepromatosis  are indistinguishable [14,15,18,19,49]. They present
with the same clinical manifestations, respond to treatment with the same antimycobacterial
agents, and have comparable prognosis.
Molecular techniques are available for the identification of several mutations associated with
resistance to individual agents [50]. The rpoB gene of M. leprae and other mycobacteria is
associated with rifampin resistance [42,50]. Mutations in the dihydropteroate synthase gene
(folP1) predicted dapsone resistance in a survey of 38 M. leprae strains isolated from skin
biopsies of patients with multibacillary leprosy [42]. (See 'Drug resistance' above.)
Genotyping of M. leprae may be performed using a combination of single nucleotide
polymorphisms (SNP) and variable number tandem repeats [51]. The genotype of M. leprae is
remarkably well conserved and the SNP frequency is significantly less than that seen in other
human pathogens [52]. Four  M. leprae SNP types and 17 subtypes have been identified, and an
increasing number of genotypes are being identified [53]. Such genotyping has been used to
demonstrate that in the United States, some armadillos carry M. leprae genotypes not seen
elsewhere in the world and that humans and armadillos share the same genotypes [11,13]. As the
technology advances, it is likely that genotyping will facilitate identification of transmission
clusters, assisting control efforts and advancing epidemiologic understanding.

CLASSIFICATION AND TERMINOLOGY Leprosy has a wide array of

clinical and histopathologic manifestations, reflecting the broad range of cellular immune
response to the M. leprae complex.
Ridley-Jopling classification — The Ridley-Jopling classification provides the optimal
classification of leprosy as it reflects the entire spectrum of these clinical and pathologic features
[54]. The leprosy disease spectrum ranges from a form with a robust immune response and very
few organisms (tuberculoid or paucibacillary) to a form with a weaker immune response and a
higher burden of organisms (lepromatous or multibacillary). The classification is based on the
cutaneous, neurologic, and biopsy findings, all of which correlate with immunological capability
of the individual (figure 1). The categories also correlate with the number of acid-fast bacilli
present in the dermis [55]:
●Tuberculoid (TT)
●Borderline tuberculoid (BT)
●Mid-borderline (BB)
●Borderline lepromatous (BL)
 ●Lepromatous (LL)
●Indeterminate (I)
Patients with a high degree of cell-mediated immunity and delayed hypersensitivity to M.
leprae complex antigens present with one to three well-demarcated lesions with central
hypopigmentation and hypoesthesia [56]. Histologically, these demonstrate well-developed
granulomatous inflammation and rare acid-fast bacilli in the tissues; this is termed polar
tuberculoid (figure 1).
At the other extreme, patients with no apparent resistance to M. leprae complex bacilli present
with numerous, poorly demarcated, raised or nodular lesions on all parts of the body.
Histologically, these reveal sheets of foamy macrophages in the dermis containing very large
numbers of bacilli. This form of infection with a high burden of disease is termed polar
lepromatous. Notably, these patients are not immunosuppressed but have a selective inability to
mount cellular immunity to M. leprae.

The majority of patients fall into a broad borderline category between TT and LL. This is
subdivided into borderline lepromatous, mid-borderline, and borderline tuberculoid.

Very early lesions may present as relatively nonspecific perineural infiltrates in which rare acid-
fast bacilli can be demonstrated. In the absence of sufficient criteria for classification, these are
called indeterminate. Indeterminate lesions are usually observed in the setting of contact
investigation, often in children, and may heal spontaneously [57]. The indeterminate
classification should be used only when the biopsy sample shows definite diagnostic evidence of
leprosy (both nerve involvement and acid-fast bacilli) but is not advanced enough to identify the
patient's position in the leprosy spectrum. "Indeterminate" should not be used if the diagnosis of
leprosy is not clearly established, since a diagnosis of leprosy may often have significant impact
on a patient's family, employment, and psychological and social status.
WHO classification — The World Health Organization (WHO) classification system was
designed for use in situations in which there is little or no clinical expertise or laboratory support;
it is based upon the number of skin lesions present [58]. Paucibacillary (PB) leprosy is defined as
five or fewer skin lesions without detectable bacilli on skin smears. Patients with only a single
skin lesion are classified separately as single-lesion PB. Multibacillary (MB) leprosy is defined
as six or more lesions and may be skin smear positive. Counting skin lesions alone may lead to
misclassification of many patients with PB leprosy rather than MB leprosy, leading to
undertreatment in some cases [55].

CLINICAL MANIFESTATIONS AND DIAGNOSIS Leprosy should be

considered in the setting of skin lesions that are chronic and not responding to standard treatment
for more common conditions or when sensory loss is observed within lesions or in extremities
[59]. Additional clues include presentation of cuts or burns in the absence of pain and travel
history including residence in endemic countries (foreign birth, military experience, etc).

Frequently, the diagnosis is established largely on the basis of clinical manifestations, although
laboratory tools can be useful for diagnostic confirmation. The diagnosis is definitively
established when at least one of the physical findings below is present and a skin biopsy obtained
from the leading edge of the skin lesion confirms the presence of acid-fast bacilli in a cutaneous
nerve. In areas where leprosy is endemic and frequently recognized clinically, a diagnosis based
on clinical manifestations alone may be sufficient. In areas where leprosy is relatively
uncommon, however, skin biopsy can be helpful for diagnostic confirmation and/or to rule out
other causes of disease.

Physical examination — The diagnosis of leprosy should be considered in patients with skin

lesions and/or enlarged nerve(s) accompanied by sensory loss. Leprosy should be suspected in
the setting of the following symptoms:
●Hypopigmented or reddish patch(es) on the skin
●Diminished sensation or loss of sensation within skin patch(es)
●Paresthesias (tingling or numbness in the hands or feet)
●Painless wounds or burns on the hands or feet
●Lumps or swelling on the earlobes or face
●Tender, enlarged peripheral nerves
Late findings include weakness of the hands with claw fingers, foot drop, facial paralysis or
lagophthalmos, lack of eyebrows and eyelashes (picture 1), collapsed nose, or perforated nasal
septum. Clinical findings correlate with the extent of nerve involvement, classification of
disease, and presence of the immunologic complications known as reactions. (See 'Immunologic
reactions' below.)
The examination should include evaluation of skin lesions and palpation of peripheral nerves for
enlargement and/or tenderness, including the ulnar nerve at the elbow, median and superficial
radial cutaneous nerve at the wrist, great auricular nerve in the neck (picture 2), and common
peroneal nerve at the popliteal fossa. A sensory examination of skin lesions, distal extremities,
and motor evaluation should also be performed. Eyes should be examined by simple inspection
of the conjunctiva and cornea, as well as assessment of corneal sensation.
Skin lesions
●Tuberculoid leprosy (TT) (picture 3) generally has one or two larger macular
hypopigmented or erythematous anesthetic lesions, which have a well-defined, often raised
margin; occasionally, they are scaly plaques.
●Borderline tuberculoid (BT) (picture 4) lesions are sharply defined macules, sometimes
appearing as "target" lesions with central clearing. In BT disease, lesions are more
numerous than in TT disease and are usually on one side of the body. TT and BT lesions are
considered "paucibacillary" (PB) in the World Health Organization (WHO) classification.
●Lesions in the mid-borderline (BB) and lepromatous portion of the spectrum are
considered "multibacillary" (MB) in the WHO classification. Mid-borderline (picture 5)
clinically may resemble borderline tuberculoid leprosy or borderline lepromatous leprosy
with few to several "punched out" lesions; central areas are often anesthetic.
●Borderline lepromatous leprosy (BL) (picture 6) lesions may consist of erythematous
macules, papules, and/or nodules and are distributed symmetrically on the body. There are
areas of normal skin found between lesions, but the margins of the lesions are often diffuse
rather than sharply defined. Larger lesions, either macules or plaques, are in asymmetrical
distribution.
●Lepromatous leprosy (LL) (picture 7 and picture 8) is usually generalized at diagnosis and
may consist of erythematous macules, papules, and/or nodules. Characteristic features of
advanced disease include body hair loss, especially of eyebrows and lashes [60], and
nodular thickening of earlobes (picture 7). In some instances, lepromatous leprosy presents
with diffuse infiltration and palpable thickening of the skin rather than with discrete lesions.
 Invasion of the mucosa of the nose may imitate nasal stuffiness, as with a common cold.
Septal perforation and/or collapse (saddle nose) may follow unless the condition is treated.
Asymptomatic, intermittent bacteremia occurs during lepromatous disease, during which M.
leprae may develop focal lesions in various organs [61]. Therefore, occasionally the
organism may be observed in liver or bone marrow biopsies performed in the evaluation for
fever of unknown origin [62]. The disease can also involve other areas, such as the testicles
(reduced testosterone) and larynx (hoarseness) [63].
●Indeterminate disease (picture 9) usually presents as a small hypopigmented or
erythematous macule with diminished sensation. In some cases, these infections do not
progress. Bacilli are rarely found in the biopsy. If the lesion does not fully resolve, it will
develop into one of the established types in the leprosy spectrum.
Neuropathy — Nerve involvement occurs very early in the course of leprosy, as evidenced by
the decrease or absence of sensation in the earliest diagnostic lesions [4]. Preventing or
minimizing injury to peripheral nerves is a major goal of treatment, and assessment of peripheral
nerves is an essential component of every clinical examination for every patient. Most
commonly, neuropathy manifests with loss of sensory perception, though, in some cases, patients
can present with painful neuropathy, often later in the course of the disease [64,65].

In patients with tuberculoid disease, sensory and/or motor loss generally occurs in the
distribution of nerves in the vicinity of the skin lesion; in patients with lepromatous disease,
nerve damage may become more generalized. Commonly, nerve trunks involved include the
ulnar and median nerves (claw hand), the common peroneal nerve (foot drop), the posterior tibial
nerve (claw toes and plantar insensitivity), the facial nerve (lagophthalmos), the radial cutaneous
nerve, and the great auricular nerve.

Subclinical neuropathy appears to be more prevalent in leprosy than was previously believed
[66]. Testing using monofilaments and other sensitive methods has demonstrated that functional
nerve impairment occurs earlier in the course of lepromatous disease than in tuberculoid disease,
even though patients with tuberculoid disease may be aware of numbness or weakness earlier in
the course of their illness than patients with lepromatous disease [67-69]. In a prospective study
of early neuropathy diagnosis in leprosy, sensory nerve conduction, cold and warmth perception
were the most frequently and earliest affected tests; in a large proportion of patients, these
became abnormal ≥3 months or more before abnormalities were identified using monofilaments
[70].
Segmental demyelination appears to be the final common pathway of nerve injury in leprosy; the
mechanisms leading to this are poorly understood [4,66,71]. Traditional approaches to study
pathogenesis, such as biopsy of the affected tissue, are not feasible with the major peripheral
nerve trunks involved in leprosy.
The experimentally infected armadillo serves a model for some aspects of nerve injury
pathogenesis in leprosy [72]. M. leprae antigens may provoke a humoral response inducing
nerve damage. The lipoarabinomannan (LAM) molecule of M. leprae has been observed to
colocalize with the membrane attack complex (MAC) in nerves of biopsies from leprosy patients
[73]. Another M. leprae antigen, PGL-1, has been shown to induce macrophages to produce
nitric oxide (NO) that damages the mitochondria of axons in a zebrafish model [74].
Ophthalmic injury — Impairment of nerves innervating of the musculature of the eyelids and
providing sensory innervation to the cornea may lead to lagophthalmos, drying of the cornea,
corneal abrasion, and corneal ulceration [75]. Careful inspection of the cornea and conjunctiva is
an essential part of the examination of every leprosy patient. The ability to close the eyelids fully
should also be assessed.
Immunologic reactions — Immunologic reactions are systemic inflammatory complications
that may occur before treatment (some patients initially present for medical attention in the
setting of a reaction), during treatment, or months to years after treatment has been completed.
These reactions may affect 30 to 50 percent of all leprosy patients [76].
There are two types of leprosy reactions: type 1 (may be referred to as T1R, reversal reaction, or
RR) and type 2 (may be referred to as T2R, erythema nodosum leprosum, or ENL). T1R
typically occurs in patients with borderline disease (BT-BL), while T2R occurs in patients with
lepromatous disease (BL-LL) (figure 1); distinguishing between the types can be difficult. The
two types of reactions appear to have different underlying immunologic mechanisms, but both
are poorly understood and the factors that initiate them are unknown [4,77].
A general feeling of fatigue, malaise, and fever may be present with both reaction types. Other
manifestations include neuritis, arthritis, iritis, and nasopharyngeal symptoms. The inflammation
associated with reactions can lead to severe nerve injury with subsequent paralysis and
deformity. The reaction may simulate drug allergy, worsening of disease, new-onset neuropathy,
or, in severe cases, septic shock. It is important for the clinician and patient to understand that
immunologic reactions are NOT drug reactions and that drug treatment should be continued,
although modification in rifampin usage may be needed when prednisone is used for
management of the reaction. (See "Leprosy: Treatment and prevention", section on 'Treatment of
immunologic reactions'.)
Type 1 reaction (T1R, reversal reaction) — Type 1 reaction typically occurs in patients with
BT, BB, or BL disease. Clinical manifestations include:
●A red, swollen patch in preexisting skin lesion on the face or overlying a major nerve trunk
●Erythema and induration of preexisting skin lesions (picture 10)
●The inflammation associated with reactions can lead to severe nerve injury with
subsequent paralysis and deformity
●Significant edema of the hands or feet, sometimes associated with small joint pain
●Ulcerated skin lesions
●Pain or tenderness in one or more nerves (eg, painful elbow, due to ulnar nerve
involvement)
●Loss of nerve function with muscle weakness or loss of sensation (eg, new wound on the
hand from coffee-mug burn) (picture 11)
In the absence of treatment, the natural course of T1R is several months. T1R appears to result
from spontaneous enhancement of cellular immunity and delayed-type hypersensitivity to M.
leprae antigens [4]. Skin biopsies may reveal edema, increased granulomatous organization, or
increased numbers of multinucleated giant cells, although these findings are seen in only about
half of the cases [78]. As a result, often the diagnosis must be made on clinical grounds alone.
No routine laboratory tests are available to assist in the diagnosis. Elevated serum levels of
chemokine CXCL10 have been strongly associated with the occurrence of T1R, although
CXCL10 is not elevated in advance of the reaction and therefore does not appear to be predictive
[79,80].
Risk factors and triggering events are not well understood [81,82]. Therefore, it is not possible to
predict which patients may experience this reaction; no changes should be made to the basic
treatment regimen in an attempt to avoid a reaction.
Treatment of type 1 reactions is discussed separately. (See "Leprosy: Treatment and prevention",
section on 'Type 1 reaction (T1R, reversal reaction)'.)
Type 2 reaction (T2R, erythema nodosum leprosum, ENL) — Type 2 reaction occurs in
patients with BL and LL disease. A clinical severity scale for ENL has been developed that can
assist clinicians in characterizing ENL and following response to treatment [83,84].
Clinically, T2R characterized by sudden eruption of numerous painful nodules (picture 12),
which may be superficial or deep in the dermis. These can form pustules and may ulcerate,
discharging yellow pus that contains polymorphs and degenerating acid-fast bacilli but is sterile
on culture. Lesions are commonly found on the extensor surfaces of the limbs and on the face.
They may last for a few days and may be succeeded by crops of new ones. As lesions fade, they
may appear as brawny induration on the forearms and thighs. Biopsy of a new lesion within 24
hours demonstrates an infiltrate of polymorphs superimposed upon the chronic inflammation and
heavy bacterial load of M. leprae. This is a very useful diagnostic test, since polymorphs are
extremely rare in all other types of leprosy lesions.
Other clinical manifestations include high fever, headache, insomnia, and/or depression due to
generalized pain, tender lymphadenopathy, orchitis, iridocyclitis, muscle tenderness, and painful
and/or swollen joints. In the absence of treatment, the natural course of T2R is one to two weeks,
but, frequently, the reaction is recurrent, sometimes over many months. Laboratory tests
frequently demonstrate an elevated leukocyte count, low hemoglobin, and hematocrit. Elevation
of liver function tests and serum C-reactive protein may be observed [85].
The Lucio phenomenon is a very rare complication presenting as sudden necrotizing
vasculopathy in patients with longstanding, untreated lepromatous leprosy [86]. It occurs
primarily in patients whose ancestry is from Mexico, particularly the Sinaloa area. It presents
with necrotizing, punched-out ulcerations that may be extensive in distribution and may be life
threatening.
Risk factors for T2R include puberty, pregnancy, and lactation [87].
The mechanism of T2R is poorly understood. It is widely regarded as an immune complex
disorder, although the evidence for this is not compelling [4]. Elevated circulating levels of
tumor necrosis factor-alpha and other proinflammatory cytokines have been observed, but their
roles in pathogenesis remain unclear. Subsets of T cells [88] and B cells [89] are altered during
ENL, and neutrophils have been observed in the tissue lesions [90].
Management of T2R is discussed separately. (See "Leprosy: Treatment and prevention", section
on 'Type 2 reaction (T2R, erythema nodosum leprosum, ENL)'.)
Laboratory tools — Laboratory tools include histopathologic examination of skin biopsies and
polymerase chain reaction (PCR). No reliable blood or skin tests are available for diagnosis of
leprosy.
The National Hansen's Disease Programs (NHDP) Clinical Center in Baton Rouge, Louisiana,
and its clinics around the United States offer consultations and evaluations for leprosy (1-800-
642-2477) [43]. The NHDP Laboratory also offers histopathology services and molecular assays
for detection of M. leprae and M. lepromatosis in tissues [91].
Skin biopsy — To assess the extent and type of infiltrate and involvement of dermal nerves, a
full-thickness skin biopsy should be taken from the most active margin of the most active lesion,
entirely within a lesion (picture 13). Routine hematoxylin and eosin sections demonstrate the
range of findings across the spectrum discussed above. Examination of hematoxylin and eosin
sections and Fite stains can aid in the early diagnosis and management of leprosy across the
spectrum of disease.
Polymorphonuclear leukocytes are a hallmark of T2R, and fibrin thrombi are characteristic of
Lucio lesions . No reliable histologic criteria have been identified for T1R so this remains a
clinical diagnosis. Mycobacterial culture should be performed on biopsies from skin lesions to
exclude cutaneous infections due to M. tuberculosis and nontuberculous mycobacteria. To
demonstrate M. leprae and/or M. lepromatosis, the Fite stain is superior to the standard Ziehl
Neelsen stain.

Skin smears, in which a small incision is made (on the ears, elbows, and/or knees) to collect a
dermal fluid sample, are no longer widely used.

Polymerase chain reaction — PCR is available for detection of M. leprae and M.

lepromatosis  DNA in tissue [2,91]. PCR is more useful as an identification tool (eg, when
clinical or histologic features are inconclusive) than as a detection tool. In one study, PCR on
biopsies from patients with lepromatous disease had sensitivity and specificity of >90 percent
and 100 percent; PCR on biopsies from patients with tuberculoid disease had sensitivity and
specificity of 34 and 80 percent, respectively [92]. The NHDP laboratory performs PCR on
biopsies submitted for pathologic review.
The lepromin test is not a useful diagnostic tool; it consists of injecting a calibrated number of
autoclaved M. leprae injected into the skin; the results are assessed after three to four weeks. The
test does not measure exposure or infection [93]. A positive test reflects the ability to develop a
granuloma following exposure to M. leprae antigens; a positive test does NOT indicate exposure
to leprosy [94]. Tuberculin skin tests (TSTs) do not significantly cross-react with M.
leprae infection; in one study of a population in which tuberculosis was highly endemic, 70
percent of controls had positive TST, but only 15 to 50 percent of leprosy patients had positive
TST [95].
Serologic tests — Serologic tests for M. leprae phenolic glycolipid-1 (PGL-1) are described but
are not available in the United States because they are not sufficiently sensitive to provide a
reliable measure of infection without other clinical or histologic evidence [96-98]. Patients with
lepromatous disease develop a strong polyclonal antibody response to M. leprae that is not
beneficial for fighting infection (but produces many false-positive serologic tests); these
individuals have positive serologic responses to PGL-1. Patients with tuberculoid disease seldom
produce antibody to PGL-1, and therefore the test is not helpful for diagnosis in these patients
(for whom the diagnosis is usually most difficult). Many contacts have been found to have
antibodies to PGL-1 also, but only a small percentage of them go on to develop the infection [99-
101]. Thus, PGL-1 alone is not a reliable diagnostic test nor is it satisfactorily predictive of the
development of infection.

DIFFERENTIAL DIAGNOSIS Lack of sensory perception to light touch or

pinprick distinguishes leprosy lesions from other conditions, although it is not invariably present.
The diagnosis of leprosy can generally be established via skin biopsy. The differential diagnosis
includes:
●Granuloma annulare – Localized granuloma annulare classically presents as an
asymptomatic, non-scaly, erythematous annular plaque with peripheral papules, a firm,
rope-like border, and central clearing (picture 14A-D). The most frequent sites are the
 wrists, ankles, dorsal hands, and dorsal feet. The diagnosis is based on clinical
manifestations and biopsy if needed. (See "Granuloma annulare".)
●Fungal infection – Tinea typically begins as a pruritic, ring-shaped, erythematous, scaling
patch or plaque that spreads centrifugally, followed by central clearing; the advancing
border is erythematous and slightly raised (picture 15A-C). The diagnosis is established by
potassium hydroxide preparation. (See "Dermatophyte (tinea) infections".)
●Annular psoriasis – Annular lesions are not a classic feature of psoriasis but occasionally
occur. The diagnosis is facilitated by concomitant detection of features that are more typical
of psoriasis such as classic plaques or signs of nail disease. The diagnosis is based on
clinical manifestations and biopsy if needed. (See "Approach to the patient with annular
skin lesions".)
●Keloid – Keloids are raised dermal lesions that form at a wound site and extend beyond the
boundaries of the original wound to invade the surrounding skin. Keloids may also develop
in the absence of a clear inciting stimulus. The diagnosis is based on clinical manifestations
and biopsy if needed. (See "Keloids and hypertrophic scars".)
●Systemic lupus erythematosus – Cutaneous manifestations of lupus may be localized
("butterfly rash") or generalized, with an erythematous macular-papular eruption involving
sun-exposed skin. The diagnosis is based on clinical diagnostic criteria. (See "Overview of
cutaneous lupus erythematosus".)
●Cutaneous leishmaniasis – Lesions of cutaneous leishmaniasis tend to occur on exposed
areas of the skin; localized disease begins as a pink papule that enlarges and develops into a
nodule, leading to painless ulceration with an indurated border (picture 16). The diagnosis is
established by skin biopsy. (See "Cutaneous leishmaniasis: Clinical manifestations and
diagnosis".)
●Mycosis fungoides – Mycosis fungoides is characterized by heterogenous cutaneous
manifestations including patches, plaques, tumors, generalized erythroderma, alopecia, or,
rarely, papules. The diagnosis is established by skin biopsy. (See "Clinical manifestations,
pathologic features, and diagnosis of mycosis fungoides".)
●Neurofibromatosis – Cutaneous manifestations of neurofibromatosis include café-au-lait
macules, axillary and/or inguinal freckling, and neurofibromas. The diagnosis is based on
characteristic clinical features. (See "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical
features, and diagnosis".)

SOCIETY GUIDELINE LINKS Links to society and government-sponsored

guidelines from selected countries and regions around the world are provided separately.
(See "Society guideline links: Leprosy".)

SUMMARY

●Leprosy (also known Hansen's disease) is an infectious disease caused by mycobacteria of

the Mycobacterium leprae complex that involve the skin and peripheral nerves. Leprosy is
an important global health concern; early diagnosis and a full course of treatment are critical
for preventing lifelong neuropathy and disability. (See 'Introduction' above.)
 ●The majority of leprosy cases occur in resource-limited settings; countries with high
numbers of cases include India, Brazil, Indonesia, Bangladesh, and Nigeria. With increasing
international travel, however, patients with leprosy may present anywhere. In the United
States, a few hundred new cases are detected per year; approximately 75 percent of cases
are among immigrants. (See 'Epidemiology' above.)
●Leprosy is probably spread by the respiratory route, though the means of transmission is
not fully understood. In the United States, it is also a zoonosis; contact with armadillos has
been documented in some cases. Other risk factors include close contact with known cases,
older age, genetic predisposition, and immunosuppression. (See 'Transmission' above
and 'Risk factors' above.)
●Early physical exam findings include hypopigmented or reddish skin patches, diminished
sensation or loss of sensation in involved areas, paresthesias, painless wounds or burns, and
tender, enlarged peripheral nerves. Neuropathy and ophthalmic injury can also occur. The
diagnosis is established when at least one of these physical findings is present and a skin
biopsy obtained from the leading edge of the skin lesion confirms the presence of acid-fast
bacilli in a cutaneous nerve, or M. leprae and/or M. lepromatosis DNA by polymerase chain
reaction. (See 'Physical examination' above and 'Laboratory tools' above.)
●Leprosy is classified using the following categories: tuberculoid (TT), borderline
tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), lepromatous (LL),
and indeterminate (I) (figure 1). Patients with a high degree of cell-mediated immunity and
delayed hypersensitivity present on the tuberculoid end of the spectrum with relatively few
well-demarcated lesions. Patients with no apparent resistance to M. leprae present on the
lepromatous end of the spectrum with numerous, poorly demarcated lesions.
(See 'Classification and terminology' above.)
●Immunologic reactions are systemic inflammatory complications that occur either before
treatment (some patients initially present for medical attention in the setting of a reaction),
during treatment, or months to years after treatment has been completed. There are two
types of leprosy reactions: type 1 (typically occurs in patients with borderline disease) and
type 2 (occurs in patients with lepromatous disease), but distinguishing between the types
can be difficult. (See 'Immunologic reactions' above.)

Leprosy: Treatment and prevention

Authors:
David Scollard, MD, PhD
Barbara Stryjewska, MD
Mara Dacso, MD, MS
Section Editor:
C Fordham von Reyn, MD
Deputy Editor:
Elinor L Baron, MD, DTMH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2021. | This topic last updated: Jul 27, 2020.
 INTRODUCTION Leprosy (also known Hansen's disease) is an infectious disease

caused by Mycobacterium leprae and Mycobacterium lepromatosis that involves the skin and

peripheral nerves.
M. leprae and M. lepromatosis comprise "Mycobacterium leprae complex" [1]. The DNA
sequences of M. leprae and M. lepromatosis differ enough to distinguish them as separate
species, but they share many similarities (both are obligate intracellular parasites with a tropism
for nerves) and cause the same clinical disease [2].
Leprosy is an important global health concern. Contrary to popular folklore, leprosy is not highly
contagious, and very effective treatment is available [3-6]. Early diagnosis and treatment are
necessary to minimize the likelihood of disability involving the eyes, hands, and feet due to
neuropathy as these are often not reversible and may require lifelong care [7].
Not all patients have access to appropriate therapy and not all countries have the infrastructure to
support leprosy control efforts [8]. Worldwide, the number of dedicated leprosy programs is
declining, and international migration is bringing patients to nearly every region [9].
The treatment and prevention of leprosy are reviewed here. The epidemiology, microbiology,
clinical manifestations, and diagnosis of leprosy are discussed separately. (See "Leprosy:
Epidemiology, microbiology, clinical manifestations, and diagnosis".)

CLASSIFICATION Leprosy has been classified into the following categories based

on the Ridley-Jopling classification (figure 1):

●Tuberculoid (TT)
●Borderline tuberculoid (BT)
●Mid-borderline (BB)
●Borderline lepromatous (BL)
●Lepromatous (LL)
●Indeterminate (I)
The classification of leprosy is discussed in further detail separately. (See "Leprosy:
Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Classification
and terminology'.)

TREATMENT Treatment of leprosy consists of multiple-drug therapy (MDT) to

prevent development of resistance [6]. MDT is active against M. leprae and rapidly renders the
patient noninfectious; in addition, use of MDT reduces the likelihood of emergence of drug
resistance [10,11]. First-line medications include dapsone, rifampin, and, for lepromatous
disease, clofazimine. Used in combination, these have proven to be effective [12]. Conventional
anti-leprosy therapy is effective in treating both M. leprae and M. lepromatosis [13-15].
Promine, a sulfone, was the first antimicrobial agent successfully used to treat leprosy;
subsequently, efficacy was also demonstrated with dapsone, its parent compound [16-18]. After
many years of monotherapy with these agents, drug resistance was observed [19,20].
In the 1980s, a World Health Organization (WHO) study group met to consider multidrug
therapy for leprosy, mindful of the experience with the development of drug resistance after
monotherapy for tuberculosis. In light of the "imperative need for therapeutic regimens," the
WHO published guidelines in 1982 with an empiric recommendation for use
of dapsone and rifampin for treatment of tuberculoid leprosy and addition of clofazimine for
treatment of lepromatous disease [3].
Subsequent WHO guidelines were published in 1998 and 2018 [4,6].
The efficacy of the individual agents had been demonstrated clinically and in mouse studies and
was subsequently confirmed in vitro [21-23]. No controlled trials comparing drug combination
regimens have been done; designing trials for treatment of a noncultivable pathogen is
complicated by the lack of an accurate quantitative endpoint. In addition, a very long observation
period is required for identification of relapse (approximately 15 to 20 years) [18].
(See 'Relapse' below.)
Selecting a regimen — Our approach to treatment of leprosy is as follows:
●For patients with tuberculoid disease, we favor treatment with dapsone (100 mg daily) and
rifampicin (600 mg daily) for duration 12 months.
●For patients with lepromatous disease, we favor treatment with dapsone, rifampicin,
and clofazimine (50 mg daily) for duration 24 months.

This approach is consistent with the United States National Hansen's Disease Program (NHDP)
but differs from guidelines issued by the WHO.

We are in agreement with the treatment approach advocated by the NHDP. This approach
follows the WHO 1982 guidelines [3] and advocates the treatment regimen summarized in the
tables (table 1 and table 2). Specifically, the NHDP favors a longer duration of therapy (as in the
1982 WHO recommendation, compared with subsequent WHO guidelines) and advocates daily
rather than monthly administration of rifampin [5]. The duration of treatment recommended by
the WHO in 1982 was 6 to 12 months for tuberculoid disease (TT and BT) and 24 months for
lepromatous disease (BB, BL, and LL) [3].
The 1998 WHO guidelines reduced the recommended duration to 6 months and 12 months,
respectively [4]. The shortened durations reflect cost considerations for resource-limited settings;
however, shorter treatment regimens have been associated with a greater incidence of relapse
[24]. Based on these guidelines, treatment for patients with TT consists of dapsone (100 mg
daily) and rifampin (600 mg rifampin once monthly) for 6 months; treatment for patients with
LL consists of dapsone (100 mg daily), clofazimine (50 mg daily plus 300 mg once monthly),
and rifampin (600 mg once monthly) for 12 months.
The 2018 WHO guidelines recommend uniform MDT; the recommendations for treatment
duration from 1998 are retained [6]. The approach consists of administration of three drugs
(rifampin, dapsone, and clofazimine) to all patients, regardless of disease classification. The
change consists of addition of daily clofazimine to regimen for patients with paucibacillary
disease; the approach for patients with multibacillary disease is unchanged. It has been proposed
that use of uniform MDT reduces the likelihood of undertreating patients with multibacillary
disease who may be misclassified as having paucibacillary disease; however, this approach is
controversial since it entails routine use of clofazimine which may be unnecessary in some
patients.
Alternative agents for treatment of leprosy
include minocycline, ofloxacin, levofloxacin, clarithromycin, and moxifloxacin. Evidence for the
efficacy of newer drug combinations or shorter regimens is weak [25]. Earlier attempts to treat
patients with "single-lesion paucibacillary disease" with a single-dose combination
of rifampin (600 mg), ofloxacin (400 mg), and minocycline (100 mg) were based on a
multicenter trial in which this regimen demonstrated slightly less clinical improvement compared
with the standard WHO paucibacillary (PB) regimen during 18 months of follow-up [10,26].
Another report indicated that one month of rifampin plus ofloxacin was insufficient for the
treatment of lepromatous (multibacillary [MB]) disease [27].
Drugs for treatment of leprosy
Overview — In the United States, medication for the treatment of leprosy are provided free of
charge by the NHDP (1-800-642-2477) [9]. Outside the United States, the WHO distributes
medications through the Ministry of Health in each country [28].
●Dapsone – Dapsone is inexpensive and generally well tolerated in the doses used for the
treatment of leprosy. Adverse effects include dapsone hypersensitivity syndrome,
methemoglobinemia, and agranulocytosis. Shortened red cell survival is common with
dapsone, though severe hemolytic anemia is uncommon except in those with a severe
glucose-6-phosphate dehydrogenase (G6PD) deficiency; all patients should be screened for
G6PD deficiency before receiving dapsone. Because the antibacterial activity of dapsone is
inhibited by p-aminobenzoic acid (PABA), it is thought that dapsone has a mechanism of
action similar to that of the sulfonamides, which involves inhibition of folic acid synthesis.
(See "Methemoglobinemia" and "Drug-induced neutropenia and
agranulocytosis" and "Drug-induced hemolytic anemia".)
A dose of 100 mg daily is weakly bactericidal against M. leprae, but such a dose exceeds
the minimum inhibitory concentration (MIC) of the organism by a factor of about 500. Such
doses even inhibit the multiplication of M. leprae mutants with low to moderate degrees
of dapsone resistance. The maximum dose should be used from the start and should not be
reduced during immunologic reactions. Dapsone resistance is generally reported in areas
where monotherapy has been used; it is extremely rare in the United States [29].
●Rifampin – Rifampin is the most bactericidal drug available for the treatment of leprosy.
An estimated 99.999 percent of bacilli are killed with three monthly doses. The standard
dose in the United States dose is 600 mg daily, but even a single dose of 600 mg monthly,
as used in the WHO regimens, is highly bactericidal. Rifampin binds the DNA-dependent
RNA polymerase complex, uncoupling transcription. The target for rifampin is the beta
subunit of the RNA polymerase encoded by rpoB61.
Toxicity of the drug is relatively low but is related to the size of the dose and the interval
between doses. The standard doses for leprosy have proven relatively nontoxic, although
occasional cases of renal failure, bone marrow suppression, "flu-like" syndrome, and
hepatitis have been reported. Daily administration of rifampin has major effects on drug
metabolism by the liver cytochrome 3A4 (CYP3A4), which greatly affects other
medications such as oral contraceptives, corticosteroids, and HIV protease inhibitors,
among many others. (See "Rifamycins (rifampin, rifabutin, rifapentine)".)
●Clofazimine – Clofazimine is well tolerated in the standard dose of 50 mg daily used for
leprosy. The major effect seen is pigmentation of the skin (especially within skin lesions),
since the drug is lipophilic and accumulates in the lipid-rich cell wall of M. leprae. At
higher doses (200 mg daily), hyperpigmentation may be noticeable within four weeks; at
lower doses, it may take four to six months. Clofazimine causes phototoxicity, which can
accelerate darkening of the skin with sun exposure. This pigmentation usually clears within
 one to two years after treatment is discontinued. Some patients are reluctant to take
clofazimine because of the pigmentation but will usually accept it if the temporary nature of
the pigmentation and the benefit of reducing the likelihood of a debilitating treatment
reaction are carefully explained. The higher doses of clofazimine (up to 300 mg daily)
sometimes used for the control of reactions may occasionally produce severe
gastrointestinal side effects.
The mechanisms of action of clofazimine are not known. The drug is weakly bactericidal
against M. leprae, but the combination of clofazimine and dapsone is much more active
than either drug alone, killing 99.999 percent of bacilli in mouse studies within three
months [30].
Clofazimine is not available in pharmacies in the United States. It is classified by the US
Food and Drug Administration (FDA) as an investigational drug. Requests for clofazimine
to treat leprosy should be directed to the NHDP (an agency within the Department of Health
and Human Services), which holds the investigational new drug protocol for this indication,
at 1-800-642-2477 (phone).
●Minocycline – Minocycline is the only tetracycline with significant activity against M.
leprae. This may be due to its lipophilic properties, which allow the drug to penetrate cell
walls. It is bactericidal for M. leprae to a somewhat greater degree than clarithromycin but
much less so than rifampin. Minocycline was very effective when given as monotherapy for
two months in a small series of eight lepromatous or borderline lepromatous patients,
although monotherapy is not recommended [31]. Minocycline inhibits protein synthesis via
reversible binding at the 30S ribosomal subunit, thereby blocking the binding of aminoacyl-
transfer RNA to the mRNA ribosomal complex. Side effects include discoloration of teeth
in children, occasional pigmentation of the skin and mucous membranes, gastrointestinal
complaints, and central nervous system (CNS) toxicity, including dizziness and
unsteadiness.
●Macrolides – Several macrolides have been evaluated for activity against M.
leprae; clarithromycin is the only effective agent. The drug has potent bactericidal activity
but is less bactericidal than rifampin. At a dose of 500 mg daily in leprosy patients, 99
percent of M. leprae are killed in 28 days and 99.9 percent by 56 days [32]. The drug acts
by inhibition of bacterial protein synthesis by linking to the 50S ribosomal subunit, thereby
preventing elongation of the protein chain. Gastrointestinal irritation, nausea, vomiting, and
diarrhea are the most common adverse effects, but they do not usually necessitate
discontinuation of the drug.
●Fluoroquinolones – Ofloxacin has good antibacterial activity and is the most widely
accepted fluoroquinolone for treatment of leprosy [30]. It acts by interfering with bacterial
DNA replication by inhibiting the A subunit of the DNA gyrase. A single 400 mg dose has
bactericidal activity against M. leprae, although less than that demonstrated by a single dose
of rifampin, and two doses are capable of killing 99.99 percent of the viable M.
leprae. Levofloxacin, the active L-racemer of ofloxacin, has replaced ofloxacin in many
United States formularies. Moxifloxacin is also highly bactericidal against M. leprae;
further study of rifampin and moxifloxacin as combination short-term therapy is needed
[33,34]. Ciprofloxacin is not active against M. leprae (see "Fluoroquinolones").
Drug resistance — The epidemiology of drug resistance is discussed separately. (See "Leprosy:
Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Drug
resistance'.)
We are in agreement with the WHO 2018 guidelines for treatment of drug-resistant leprosy, as
follows [6]:
●Patients whose isolate demonstrates rifampicin resistance may be treated using at least two
of the following second-line drugs: clarithromycin, minocycline, or a fluoroquinolone
(ofloxacin, levofloxacin, or moxifloxacin), plus clofazimine daily for 6 months, followed by
clofazimine plus one of the second-line drugs daily for an additional 18 months.
●Patients whose isolate demonstrates resistance to both rifampicin and fluoroquinolones
may be treated with the following drugs: clarithromycin, minocycline, and clofazimine for 6
months followed by clarithromycin or minocycline plus clofazimine for an additional 18
months.
Clinical response and follow-up — The erythema and induration of skin lesions may diminish
within a few months of initiating therapy. It may take a few years for cutaneous lesions to
resolve fully, depending on the initial number of lesions and severity of infection. Most lesions
heal without scarring.
Once killed, dead bacilli are removed from the tissues very slowly; some may persist in the
tissues for several years (picture 1) [35]. Since M. leprae and M. lepromatosis cannot be grown
in culture and its viability cannot be assessed in biopsies, a definitive bacteriologic endpoint for
treatment is not available. The presence of bacilli in smears or biopsies during and after
treatment does not, in itself, indicate treatment failure or drug resistance. There is no evidence
that prolonged antimicrobial treatment enhances the removal of dead M. leprae from tissues.
Given the lack of a definitive therapeutic endpoint, assessing compliance is especially important
in assessing completeness of treatment. Laboratory evidence indicates that M. leprae are killed
rapidly after exposure to rifampin and the other drugs used [36]. Experience with multidrug
therapy has provided good evidence of cure with very few relapses using NHDP or WHO
protocols with one to two years of treatment [7]. Therefore, if adherence to the well-established
MDT protocols is good, killing of the bacilli and resolution of the lesions can be expected.

While on treatment, the first follow-up visit should be done in two to four weeks to evaluate for
side effects of medications. After that, routine follow-up visits should be scheduled every three
months. Visits should consist of a clinical examination, including assessment of the skin, nerves,
limbs, and eyes, as well as laboratory studies to assess drug toxicity. Patients should report any
new skin lesions, sensory or motor loss, eye symptoms, reactions, or other complaints.

Disease progression that occurs during therapy is almost always due to poor adherence to
treatment. Therefore, patient education is an important part of each visit; compliance with a
prolonged drug regimen is unlikely unless the patient fully understands the necessity for it.
Cooperation of the family is also important.

For areas of the hands and feet where sensation has been lost, patients need to be taught to
evaluate these areas regularly for evidence of injury and to obtain treatment promptly. Special
protective shoes may be needed to avoid injury or ulceration. Motor loss resulting in deformities
may require corrective surgery.

Examination of the eyes should include assessment of lid closure, cornea, and conjunctiva [37].
Complex problems such as iridocyclitis should be managed by a specialist. Corneal anesthesia
and lagophthalmos require protective measures and corrective surgery.
In lepromatous (MB) cases, skin biopsies from the same lesion can be performed at one to two
year intervals to assess the response to treatment by evaluating the reduction of inflammation and
the decline of bacilli in the tissues. Processing and interpretation of biopsies for this purpose are
available from the NHDP at no cost.
Routine laboratory studies to assess drug toxicity while on treatment include a complete blood
count, urinalyses, creatinine, and liver function tests (table 3). Drug toxicity is relatively
uncommon after the first year of treatment, and serious toxicity may manifest clinically before it
is detected in the laboratory. Asymptomatic liver enzyme elevation of up to three times normal is
acceptable.

After completion of treatment, annual follow-up for three more years is warranted for patients
with tuberculoid disease and for five more years is warranted for patients with lepromatous
disease. Patients should be advised to return for evaluation if new lesions or other problems
develop.

TREATMENT OF IMMUNOLOGIC REACTIONS Immunologic

reactions are systemic inflammatory complications that occur either before treatment (some
patients initially present for medical attention in the setting of a reaction), during treatment, or
months to years after treatment has been completed [38]. A general feeling of fatigue, malaise,
and fever may be present. Other manifestations include neuritis, arthritis, iritis, and
nasopharyngeal symptoms. The inflammation associated with reactions can lead to severe nerve
injury with subsequent paralysis and deformity. Immunologic reactions are discussed further
separately. (See "Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis",
section on 'Immunologic reactions'.)
In general, antimicrobial therapy should be continued in the setting of immunologic reactions,
and patients should be reassured that the symptoms are not a reaction to the medications. Options
for treatment of immunologic reactions include prednisone with or without other anti-
inflammatory agents. Use of prednisone should prompt reduction in rifampin administration
from 600 mg daily to 600 mg once monthly. Patients should be monitored carefully for
neuropathy or neuritis and treated aggressively if these develop or worsen. Tapering of
prednisone and other anti-inflammatory agents is empiric, based on clinical response.
Progression of the infection may occur in cases of noncompliance or drug resistance. Clinically,
skin lesions may remain unchanged or may appear to worsen (with erythema and swelling)
during the first year of treatment. In the setting of true disease progression, skin biopsies may
demonstrate an increase in bacterial load, but this is difficult to document unless the biopsies are
taken from adjacent sites of the same lesion. Drug resistance in leprosy is rare; in general,
inadequate response to treatment is almost always due to inadequate adherence. Moreover, new
lesions are almost always due to immunologic reactions, for which there are no well-established
laboratory markers. (See 'Drug resistance' above.)
Type 1 reaction (T1R, reversal reaction) — Clinical manifestations of T1Rs are described
separately. (See "Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis",
section on 'Type 1 reaction (T1R, reversal reaction)'.)
Mild reactions without neuritis, ulceration, or other severe symptoms can be managed with
supportive care. Severe T1Rs with neuritis require prompt treatment with corticosteroids to avoid
permanent nerve damage [39]. Prednisone (40 to 60 mg/day) should be started and slowly
tapered when the reaction has been controlled (in general, from three months in borderline
tuberculoid to nine months in borderline lepromatous) [40]. Occasional patients with severe,
protracted reactions require extended corticosteroid treatment for several additional months due
to severe nerve pain, and some data suggest that higher doses and longer duration are more
beneficial in ameliorating pain and other inflammatory symptoms than lower doses and shorter
duration of corticosteroid treatment [41]. However, a review of clinical trials has demonstrated
that prolonged corticosteroid regimens of many months do not provide long-term functional
neurologic benefits for most patients [42]. No long-term benefit has been associated with
prophylactic corticosteroid treatment for prevention of T1Rs [43]. In patients with concomitant
diabetes, methotrexate may be used as a steroid sparing regimen [44].
Cyclosporine may be a useful second-line treatment for severe T1Rs in patients not responding
to or unable to take corticosteroids [45]. It has been demonstrated to improve sensory nerve
impairment and skin lesions in small numbers of patients in Brazil, Ethiopia, and Nepal; some
significant toxicity was also noted [46,47]. Further study is needed to determine optimal dosing
and to compare the efficacy and toxicity with corticosteroids.
Type 2 reaction (T2R, erythema nodosum leprosum, ENL) — Clinical manifestations of
T2Rs are described separately. (See "Leprosy: Epidemiology, microbiology, clinical
manifestations, and diagnosis", section on 'Type 2 reaction (T2R, erythema nodosum leprosum,
ENL)'.)

Mild reactions without neuritis, ulceration, or other symptoms can be managed with supportive
care.

Severe T2Rs with neuritis and systemic symptoms require prompt treatment with corticosteroids
to avoid permanent nerve damage. Prednisone (40 to 60 mg/day) should be started and quickly
tapered (over a two-week period) when the reaction has been controlled; in the absence of
clinical response, higher doses of prednisone may be administered. A relatively short course may
be sufficient, but the reaction can recur and intermittent symptoms may continue for a year or
more. If prolonged therapy will be needed in such cases, transitioning prednisone dosing to an
every-other-day schedule may diminish steroid side effects [48].

Prolonged use of high doses of corticosteroids for both T1R and T2R entails the risk of many
serious side effects.

Methotrexate (7.5 to 20 mg weekly), together with low doses of corticosteroids, may be effective

as a steroid-sparing agent for treatment of leprosy reactions [49]. Further study of methotrexate
for management of leprosy reactions is ongoing.
Clofazimine is not useful for the management of acute T2R, but may be of value in chronic
cases. It is generally increased to a dose of 300 mg daily for four weeks and tapered slowly after
response to 100 mg/day within 12 months. Gastrointestinal complaints may limit the use of
higher doses. The clofazimine component of the multibacillary (MB) regimen may have some
protective effect in preventing reactions since T2R appears to have become less common after
the introduction of multiple-drug therapy. Clofazimine is not available in pharmacies and in the
United States can only be obtained through the National Hansen's Disease Programs (NHDP;
phone 1-800-642-2477).
Thalidomide is very effective in treating type 2 leprosy reactions [50], but teratogenicity limits
its use in women of childbearing age. Of note, the efficacy of thalidomide in treating T2Rs is the
only reason it has not been completely banned. Thalidomide is approved for marketing only
under a special restricted distribution program approved by the US Food and Drug
Administration (FDA) called "Risk Evaluation and Management Strategy" (REMS). Under this
restricted distribution program, only prescribers and pharmacists registered with the program are
allowed to prescribe and dispense the product. In addition, patients must be advised of, agree to,
and comply with the requirements of the REMS program in order to receive the drug.
Thalidomide is administered initially in a dose of 300 to 400 mg daily; frequently, this regimen
controls the reaction within 48 hours. Subsequently, the dose should be tapered to a maintenance
level, generally around 100 mg daily; every few months, attempts are made to taper off the drug.
To control erythema nodosum leprosum, thalidomide may be continued for several years.
Development of neuropathy should prompt immediate discontinuation. In the authors'
experience, a few patients with severe, prolonged T2Rs have continued to use thalidomide for up
to 10 years.
Management of the Lucio phenomenon (necrotizing vasculopathy in patients with longstanding
untreated lepromatous leprosy) requires antimicrobial therapy and corticosteroids as well as skin
and wound care comparable with that given for extensive burns [51].
Alternative agents — Cytokines and their inhibitors are not routinely used for the treatment of
leprosy or associated immunologic reactions; prospective data are lacking. Successful use of
tumor necrosis factor-alpha (TNF-a) for management of rare cases of severe T2R has been
described; however, these agents should be used cautiously and with close monitoring. In one
review, use of TNF-a inhibitors was successful for treatment of four patients with intractable
T2R; however, among 10 patients with arthritis or other conditions treated with TNF-a
inhibitors, use of these agents was a risk factor for development of leprosy [52]. In addition, we
are aware of unpublished cases in which use of these agents was not successful for management
of T2R [53].
Experimental treatment of lepromatous leprosy by intralesional injection of recombinant
interferon-gamma [54,55] or interleukin 2 [56] has demonstrated some evidence of improvement
[57] but has also been associated with the development of T2R in an unusually high percentage
of patients [58].
Other immunosuppressive drugs have been tested in the treatment of T2Rs,
including cyclosporine, azathioprine, methotrexate, pentoxifylline, and mycophenolate mofetil,
but no consistently beneficial results have been observed [45].

OTHER TREATMENT ISSUES

Relapse — Relapse of leprosy is relatively rare and must be distinguished from immunologic

reaction (which is more common). The World Health Organization has reported a slowly
increasing trend in the number of relapses, with 3120 cases worldwide in 2009 (1.3 percent of
the number of new cases reported) [7].
Most relapses occur 5 to 10 years after completion of treatment. Relapse is more likely to occur
in the setting of incomplete treatment or a very high bacterial load at the onset of treatment [59].
During true relapse, the tissue bacterial load generally rises steadily. The bacterial load may be
expressed as bacteriologic index (BI), which is the number of bacilli per 100x field, expressed as
a logarithmic scale (over 1000 bacilli per average field = 6+; 100 to 1000 bacilli = 5+, etc) [60].
An increase in the biopsy or skin smear BI of 2 or more indicates probable relapse [61].
Relapse can be distinguished from immunologic reaction in that the latter should improve after a
short course of prednisone. (See 'Treatment of immunologic reactions' above.)
There is little evidence to guide the approach to retreatment after relapse. In general, treatment
consists of reinitiating the same regimen used for initial therapy [61]. Patients who presented
initially with tuberculoid (paucibacillary [PB]) disease but relapse with lepromatous
(multibacillary [MB]) leprosy should be retreated with an MB regimen. Drug resistance is
extremely unlikely to have developed as long as the original M. leprae strain was fully sensitive
to the drugs used, although there is no role for baseline testing of drug resistance. When
indicated, testing for mutations can be done from paraffin-embedded tissues taken at the time of
diagnosis (ie, before treatment) and at the time of suspected relapse or resistance. (See 'Drug
resistance' above.)
Leprosy and HIV — There has been no increase in leprosy in regions where HIV is prevalent.
In patients coinfected with M. leprae and HIV, initiation of antiretroviral therapy may trigger a
type 1 reaction (T1R); this is a manifestation of the immune reconstitution inflammatory
syndrome [62-64]. (See "Immune reconstitution inflammatory syndrome".)
The response to leprosy treatment in HIV-infected individuals appears to be comparable with the
response in HIV-uninfected individuals [64].
Leprosy in pregnancy — Immunologic reactions appear to occur more frequently in pregnant
and postpartum women [65-67]. In two small series, such reactions were observed in up to 38
percent of patients [68,69]. Type 2 reactions were observed more frequently during pregnancy;
T1Rs were observed more frequently in the postpartum period.
Management of leprosy and immunologic reactions in pregnancy is the same as described above
for other patients. Dapsone, rifampin, clofazimine, clarithromycin, and ofloxacin are listed by the
US Food and Drug Administration as category C for use in pregnancy; minocycline is category
D. Regimens of all medications must be modified appropriately if the mother is breastfeeding.
(See 'Treatment' above.)

PREVENTION

General principles — Control measures for leprosy include clinical management of active cases
as well as contact management. Household contacts should be evaluated annually for evidence of
disease for at least five years and should be educated to seek immediate attention if suspicious
skin or neurologic changes develop. In the United States, free diagnostic clinics are available
[70]. Issues related to prophylaxis are discussed below. (See 'Prophylaxis' below.)
Vaccination with Bacillus Calmette-Guérin (BCG) is partially protective for leprosy; a single
dose appears to be 50 percent protective, and two doses further increase protection [71,72]. BCG
is administered at birth in most countries with high rates of leprosy; vaccination for prevention of
leprosy in other regions is not economically feasible except in areas with an extremely high
incidence of the disease [73]. Development of an improved BCG vaccine, BCG booster, or
alternate vaccine strain is an important research goal that could benefit control of both
tuberculosis and leprosy. Skin test antigen studies and the identification of the appropriate
protective M. leprae genomic DNA sequence could also lead to an improved vaccine for leprosy
[74].
Prophylaxis — Outside endemic areas, no prophylactic treatment is recommended.
Within endemic areas, the World Health Organization (WHO) 2018 guidelines recommend
prophylaxis (with single-dose rifampin [SDR]) for adults and children ≥2 years [6]. Several
studies are underway to evaluate the benefit of this practice [75]. In a cluster-randomized
controlled trial in Bangladesh including 28,092 contacts of 1037 patients with newly diagnosed
leprosy, use of SDR in adults (600 mg) and children (300 mg) was associated with a reduction in
number of new cases for a period of two years by 57 percent (confidence interval 33 to 72
percent) [76]. After this time, however, the number of new cases in treated and control
populations was the same.
Neuritis (pain, burning or tingling, sudden numbness, or loss of function) must be treated
aggressively to prevent or minimize nerve injury and subsequent deformity and disability.
Neuritis is treated primarily with corticosteroids. Nerve function appears to improve after
corticosteroid treatment in 60 to 70 percent of patients, but it may remain impaired in patients
with pre-existing or recurrent neuritis [77]. About one-third of impaired nerves do not improve
with corticosteroid treatment [78]. In a controlled trial of treatment for type 1 reactions with
three different treatment regimens, the greatest improvement in nerve function occurred in the
group receiving higher dose of prednisone (60 mg) and longer duration (20 weeks or longer)
[41]. Treatment is best individualized; in some cases, even higher doses and longer duration of
prednisone may be required. No long-term benefit has been associated with prophylactic
corticosteroid treatment for prevention of neuritis [43]. (See 'Treatment of immunologic
reactions' above.)
Elimination and control — In the early 1990s, the WHO and others promoted elimination of
leprosy as a public health problem by the year 2000 [79]. Others have argued that leprosy is a
poor choice for an elimination target given its long incubation time and other factors [80].
Moreover, 'elimination as a public health problem' has been confused with 'eradication,' leading
to unrealistic expectations [81].
In 2000, the World Health Assembly declared that the goal of elimination of leprosy as a public
health problem had been reached globally [82]. After this, many countries greatly reduced or
eliminated their leprosy control programs. However, the annual number of newly diagnosed
cases has remained steady since 2000, indicating that transmission has not been interrupted in
many endemic areas [83]; in addition, it is likely that millions of cases have not been counted
[83].
In 2018, a new Global Partnership for Zero Leprosy was inaugurated, incorporating
nongovernmental organizations and other stakeholders [84]. The Partnership's approach is
somewhat more nuanced, recognizing different specific goals for zero transmission, zero
disability, and zero discrimination. However, the biological challenges of leprosy remain,
including poor understanding of transmission. Even once disease elimination has been achieved,
the implications for people with social, physical, or emotional sequelae must be addressed [85].