Leprosy is a chronic infection caused by the acid-fast, rod-shaped

bacillus Mycobacterium leprae. Leprosy can be considered 2 connected diseases that

primarily affect superficial tissues, especially the skin and peripheral nerves. Initially, a
mycobacterial infection causes a wide array of cellular immune responses. These
immunologic events then elicit the second part of the disease, a peripheral neuropathy
with potentially long-term consequences.
The social and psychological effects of leprosy, as well as its highly visible debilities and
sequelae (as seen in the image below), have resulted in a historical stigma associated
with leprosy. To minimize the prejudice against those with leprosy, the condition is also
known as Hansen disease, named after G.A. Hansen, who is credited with the 1873
discovery of M leprae. This mycobacterium grows extremely slowly and has not been
successfully cultured in vitro.

Hands with Z-thumbs,

clawing, contractures, and shortening of fingers due to repetitive injury and
healing. Ho Chi Minh City, Vietnam. Courtesy of D. Scott Smith, MD.
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In the 1990s, the World Health Organization (WHO) launched a campaign to eliminate
leprosy as a public health problem by 2000. Elimination, as defined by the WHO, was
defined as a reduction of patients with leprosy requiring multidrug therapy to fewer than
1 per 10,000 population. This goal was achieved in terms of global prevalence by 2002.
As of 2014, none of the 122 countries where leprosy was endemic in 1985 still have
prevalence rates of greater than 1 per 10,000 population. [1]
Although multidrug regimens had been used globally to cure nearly 14 million patients
with leprosy since 1985, the number of new leprosy cases remained relatively
unchanged from 1980 to 2000, ranging from 500,000-700,000 worldwide per
year. [2] Between 2001 and 2006, the global incidence of leprosy declined suddenly,
largely owing to new case reductions in India. There is debate as to whether this decline
in India reflects genuine progress against the disease or an interruption of active case
detection. [3]
The goal of the WHO by the end of 2015 is to reduce the rate of new cases with grade-2
disabilities worldwide by at least 35%. This will be carried out by enforcing activities to
decrease the delay in diagnosing the disease and actuate treatment with multidrug
therapy. This will also have the impact of reducing transmission of the disease in the
community. [2] The results of this effort have yet to be published.
Access and delivery of antibiotics continues to be a problem in the most endemic
nations. With the precise transmission mechanism of leprosy still unknown and lack of
an effective vaccine, leprosy will probably continue to pose an ongoing public health
problem in the coming decades.

Pathophysiology
Leprosy can manifest in different forms, depending on the host response to
the organism.
Individuals who have a vigorous cellular immune response to M leprae have
the tuberculoid form of the disease that usually involves the skin and
peripheral nerves. The number of skin lesions is limited, and they tend to be
dry and hypoesthetic. Nerve involvement is usually asymmetric. This form of
the disease is also referred to as paucibacillary leprosy because of the low
number of bacteria in the skin lesions (ie, < 5 skin lesions, with absence of
organisms on smear). Results of skin tests with antigen from killed organisms
are positive in these individuals.
Individuals with minimal cellular immune response have the lepromatous form
of the disease, which is characterized by extensive skin involvement. Skin
lesions are often described as infiltrated nodules and plaques, and nerve
involvement tends to be symmetric in distribution. The organism grows best at
27-30C; therefore, skin lesions tend to develop in the cooler areas of the
body, with sparing of the groin, axilla, and scalp. This form of the disease is
also referred to as multibacillary leprosy because of the large number of
bacteria found in the lesions (ie, >6 lesions, with possible visualization of
bacilli on smear). Results of skin tests with antigen from killed organisms are
nonreactive.
Patients may also present with features of both categories; however, over
time, they usually evolve to one or the other (indeterminate or borderline
leprosy). Interestingly, most individuals who are exposed to leprosy never
develop the disease.
Classification of leprosy
Leprosy has 2 classification schemas: the 5-category Ridley-Jopling system
and the simpler and more commonly used WHO standard. [4]
Ridley-Jopling: Depending on the host response to the organism, leprosy can
manifest clinically along a spectrum bounded by the tuberculoid and
lepromatous forms of the disease. Most patients fall into the intermediate
classifications, which include borderline tuberculoid leprosy, midborderline
leprosy, and borderline lepromatous leprosy. The classification of the disease
typically changes as it evolves during its progression or management. The
Ridley-Jopling system is used globally and forms the basis of clinical studies
of leprosy. It may also be more useful in guiding treatment regimens and
assessing risk of acute complications. Physical findings in each subtype are
presented in the Clinical section.
According to the WHO, in an endemic area, an individual is considered to
have leprosy if he or she shows either of the two following signs: [4]
A skin lesion consistent with leprosy and definite sensory loss, with or
without thickened nerves
Positive skin smears

Epidemiology
Frequency
United States
In 2014, according to the U.S. Department of Health and Human Services,
175 new cases of leprosy were detected in the United States. [5]
Eighty-five percent of leprosy cases in the United States are found in
immigrants, [6]although endemic foci exist in parts of Louisiana, Florida, and
Texas along the Gulf of Mexico; in Mexican and Asian California populations;
and in Spanish Americans in New York City.
Some cases among native US citizens can be accounted for by exposure to
leprosy overseas. Some cases can be attributed to a contact with a known
case of leprosy or exposure to infected armadillos.
Based on genetic analysis studies, wild armadillos and many patients with
leprosy in the southern United States are infected with the same strain of M
leprae. [7]Leprosy may be a zoonosis in the southern United States because
armadillos are a large reservoir for this disease.
Nonetheless, history of exposure cannot be verified in many patients. [8]
International
According to WHO figures and as reported by 130 countries, the global annual
detection rates have declined from 2004-2010, when 407,791 and 228,474
new cases were reported, respectively (see the images below). The
prevalence registered worldwide at the beginning of 2010 was 192,246 cases.
Of the new cases, 95% were detected worldwide during 2010 in the following
countries: Angola, Bangladesh, Brazil, China, Democratic Republic of the
Congo, India, Ethiopia, Indonesia, Madagascar, Mozambique, Myanmar,
Nepal, Nigeria, Philippines, Sri Lanka, Sudan, and United Republic of
Tanzania. [2] These countries still exhibit pockets of high endemicity.

Leprosy prevalence rates,

2014. Courtesy of WHO, Leprosy: Global situation,
http://www.who.int/lep/situation/en/, accessed April 28, 2016.
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Mortality/Morbidity
Leprosy is rarely fatal, and the primary consequence of infection is nerve
impairment and debilitating sequelae. According to one study, 33-56% of
newly diagnosed patients already displayed signs of impaired nerve
function. [9]According to estimates, 3 million people who have completed
multidrug therapy for leprosy have sustained disability due to nerve damage.
Although both lepromatous leprosy and tuberculoid leprosy involve the skin
and peripheral nerves, tuberculoid leprosy has more severe manifestations.
Nerve involvement results in loss of sensory and motor function, which may
lead to frequent trauma and amputation. The ulnar nerve is most commonly
involved.
Damage in the following nerves is associated with characteristic impairments
in leprosy:
Ulnar and median - Clawed hand
Posterior tibial - Plantar insensitivity and clawed toes
Common peroneal - Foot drop
Radial cutaneous, facial, and greater auricular nerves (may also be
involved; as seen in the image below)
 Patient with facial nerve
palsy and contractures of the hand. Daloa, Ivory Coast. Courtesy of D.
Scott Smith, MD.
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Infiltration by bacteria may lead to destruction of nasal cartilage (lepromatous
leprosy), ocular involvement, and diffuse thickening of the skin. Advanced
cases of leprosy involve the loss of eyebrows and lashes, but these
deformities are less common today.
Worldwide, leprosy is considered the most common cause of crippling of the
hand, which is caused by ulnar nerve involvement. [10] Peroneal nerve
involvement can lead to foot drop, posterior tibial nerve involvement, and
clawed toes.
Race
Leprosy was once endemic worldwide, and no racial predilection is known. In
the late 1800s, the incidence of leprosy in northern Europe and North America
dropped dramatically, and the disease is now reported primarily in tropical
areas.
Sex
Leprosy is generally more common in males than in females, with a male-to-
female ratio of 2:1. In some areas in Africa, the prevalence of leprosy among
females is equal to or greater than that in males. [11]
Age
Leprosy can occur at any age, but, in developing countries, the age-specific
incidence of leprosy peaks in children younger than 10 years, who account for
20% of leprosy cases. Leprosy is very rare in infants; however, they are at a
relatively high risk of acquiring leprosy from the mother, especially in cases of
lepromatous leprosy or midborderline leprosy.