7/30/2017 Leprosy: Background, Pathophysiology, Epidemiology

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Leprosy
Updated: Jun 16, 2017
Author: Darvin Scott Smith, MD, MSc, DTM&H; Chief Editor: Michael Stuart Bronze, MD more...

OVERVIEW

Background
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.
View Media Gallery

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]
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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.
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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.

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Leprosy prevalence rates, 2014. Courtesy of WHO, Leprosy: Global situation, http://www.who.int/lep/situation/en/,
accessed April 28, 2016.
View Media Gallery

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.
View Media Gallery

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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.

Clinical Presentation

References

1. Reibel F, Cambau E, Aubry A. Update on the epidemiology, diagnosis, and treatment of leprosy.
Mdecine et Maladies Infectieuses. 2015 Sept 02. Volume 45, Issue 9:383393.

2. Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The continuing
challenges of leprosy. Clin Microbiol Rev. 2006 Apr. 19(2):338-81. [Medline]. [Full Text].

3. Schreuder PAM, Noto S, Richardus JH. Epidemiologic trends of leprosy for the 21st century.
Clinics in Dermatology. 2015 Nov 04. Volume 34, Issue 1:24-31.

4. The World Health Organization. Diagnosis of Leprosy. Leprosy Elimination. Available at

http://www.who.int/lep/diagnosis/en/. Accessed: April 15, 2016.

5. U.S. Department of Health and Human Services. National Hansen's Disease (Leprosy)
Program. Health Resources and Services Administration. Available at
http://www.hrsa.gov/hansensdisease/. Accessed: March 23, 2016.

6. Fred F. Ferri. Leprosy. Ferri's Clinical Advisor 2015: 5 books in 1. Philadelphia, PA:
Elsevier/Mosby; 2015. 687.e4-687.e5.

7. Truman RW, Singh P, Sharma R, et al. Probable zoonotic leprosy in the southern United States.
N Engl J Med. 2011 Apr 28. 364(17):1626-33. [Medline].

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8. Joyce MP, Scollard DM. Leprosy (Hansen's Disease). Conn's Current Therapy. 2004. 100-105.

9. Ustianowski AP, Lockwood DN. Leprosy: current diagnostic and treatment approaches. Curr
Opin Infect Dis. 2003 Oct. 16(5):421-7. [Medline].

10. Anderson GA. The surgical management of deformities of the hand in leprosy. J Bone Joint Surg
Br. 2006 Mar. 88(3):290-4. [Medline].

11. The World Health Organization. Transmission of Leprosy. Leprosy Elimination. Available at
http://www.who.int/lep/transmission/en/. Accessed: April 15, 2016.

12. Walker SL, Lockwood DN. Leprosy. Clin Dermatol. 2007 Mar-Apr. 25(2):165-72. [Medline].

13. Anderson H, Stryjewska B, Boyanton BL, et al. Hansen disease in the United States in the 21st
century: a review of the literature. Arch Pathol Lab Med. 2007 Jun. 131(6):982-6. [Medline].

14. Martinez AN, Talhari C, Moraes MO, Talhari S. PCR-based techniques for leprosy diagnosis:
from the laboratory to the clinic. PLoS Negl Trop Dis. 2014 Apr. 8 (4):e2655. [Medline].

15. Health and Human Resources Administration. Hansens Disease. National Hansen's Disease
(Leprosy) Clinical Center. Available at http://www.hrsa.gov/hansensdisease/clinicalcenter.html.
Accessed: April 15, 2016.

16. Van Veen NH, Nicholls PG, Smith WC, Richardus JH. Corticosteroids for treating nerve damage
in leprosy. Cochrane Database Syst Rev. 2007 Apr 18. CD005491. [Medline].

17. Kai M, Nguyen Phuc NH, et al. Analysis of Drug-Resistant Strains of Mycobacterium leprae in an
Endemic Area of Vietnam. Clin Infect Dis. Mar 2011;52(5):e127-32.

18. Singh P, Busso P, Paniz-Mondolfi A, et al. Molecular Drug Susceptibility Testing and Genotyping
of Mycobacterium leprae Strains from South America. Antimicrob Agents Chemother. 2011 Jun.
55(6):2971-3. [Medline]. [Full Text].

19. Bakker MI, Hatta M, Kwenang A, et al. Risk factors for developing leprosy--a population-based
cohort study in Indonesia. Lepr Rev. 2006 Mar. 77(1):48-61. [Medline].

20. Britton WJ, Lockwood DN. Leprosy. Lancet. 2004 Apr 10. 363(9416):1209-19. [Medline].

21. Deps PD, Guedes BV, Bucker Filho J, Andreatta MK, Marcari RS, Rodrigues LC. Characteristics
of known leprosy contact in a high endemic area in Brazil. Lepr Rev. 2006 Mar. 77(1):34-40.
[Medline].

22. Jacobson RR, Krahenbuhl JL, Yoder L. Overview of Leprosy. UpToDate. 2006.

23. Leprosy. World Health Organization. Available at www.who.org.

24. Moschella SL. An update on the diagnosis and treatment of leprosy. J Am Acad Dermatol. 2004
Sep. 51(3):417-26. [Medline].

25. National Hansen's Disease (Leprosy) Program. U.S. Department of Health and Human
Services. Available at http://www.hrsa.gov/hansensdisease/index.html. Accessed: July 21, 2014.

26. Rao PS, Sugamaran DS, Richard J, et al. Multi-centre, double blind, randomized trial of three
steroid regimens in the treatment of type-1 reactions in leprosy. Lepr Rev. 2006 Mar. 77(1):25-
33. [Medline].

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27. Sridharan R, Lorenzo N, Narasimhan L. Leprosy. Medscape Reference. 2005.

28. van Beers SM, Hatta M, Klatser PR. Patient contact is the major determinant in incident leprosy:
implications for future control. Int J Lepr Other Mycobact Dis. 1999 Jun. 67(2):119-28. [Medline].

Media Gallery

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.
Patient with facial nerve palsy and contractures of the hand. Daloa, Ivory Coast. Courtesy of D.
Scott Smith, MD.
Chronic insensate patch due to leprosy infection. Ho Chi Minh City, Vietnam. Courtesy of D.
Scott Smith, MD.
Characteristic clawed hand deformity caused by ulnar involvement in leprosy. Daloa, Ivory
Coast. Courtesy of D. Scott Smith, MD.
Chronic nonhealing ulcer at the metatarsal head resulting from loss of sensation in the feet.
Karigiri, Tamil Nadu, India. Courtesy of Tara Ramachandra.
Multiple flat hypopigmented lesions on shoulder and neck, suggestive of multibacillary leprosy.
Note ulceration of hypothenar area of hand, indicative of ulnar neuropathy. Redwood City,
California, United States. Courtesy of D. Scott Smith, MD.
Man with advanced deformities caused by unmanaged leprosy. Keratitis, loss of eyebrow,
thickened skin, and typical hand impairments. Ho Chi Minh City, Vietnam. Courtesy of D. Scott
Smith, MD.
Histopathology of leprosy: Large numbers of acid-fast bacilli (in clusters) in histiocytes and within
nerves. Fite-Faraco stain 500 X. Courtesy of Tara Ramachandra and D. Scott Smith, MD.
Patient with multibacillary leprosy showing subsequent erythema nodosum leprosum reaction.
Santa Clara, California. Courtesy of D. Scott Smith, MD.
Patient with erythema nodosum leprosum type 2 reaction several weeks after initiation of drug
therapy. This photograph was taken after tendon release. Redwood City, California. Courtesy of
D. Scott Smith, MD.
Increased pigmentation on the face due to clofazimine therapy. Courtesy of D. Scott Smith, MD.
WHO Multidrug Therapy Regimens. Courtesy of WHO, Leprosy Elimination,
http://www.who.int/lep/mdt/en/, accessed April 15, 2016.
Leprosy prevalence rates, 2014. Courtesy of WHO, Leprosy: Global situation,
http://www.who.int/lep/situation/en/, accessed April 28, 2016.

of 13

Tables

Table 1. Multidrug Therapy Plan Recommended by the WHO

Table 2. US Recommendations for Multidrug Therapy [15]

Table 1. Multidrug Therapy Plan Recommended by the WHO

Daily, Self- Monthly Months of

Type of Leprosy
Administered Supervised Treatment

Paucibacillary Dapsone 100 mg Rifampicin 600 mg 6

Single-lesion Rifampicin 600 mg, N/A Single dose

paucibacillary

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Ofloxacin 400 mg,

Minocycline 100 mg

Rifampicin 600 mg,

Dapsone 100 mg,

Multibacillary Clofazimine 300 12

Clofazimine 50 mg
mg

Rifampicin 10
Dapsone 2 mg/kg, mg/kg,

Pediatric Same as in adults

Clofazimine 1 mg/kg Clofazimine 6
mg/kg

Table 2. US Recommendations for Multidrug Therapy [15]

Daily, Self- Monthly Months of

Type of Leprosy
Administered Supervised Treatment

Dapsone 100 mg,

Paucibacillary N/A 12
Rifampicin 600 mg

Single-lesion Dapsone 100 mg, N/A 12

paucibacillary

Rifampicin 600 mg

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Dapsone 100 mg,

Rifampicin 600 mg,

Multibacillary N/A 24

Clofazimine 50 mg

Back to List

Contributor Information and Disclosures

Author

Darvin Scott Smith, MD, MSc, DTM&H Adjunct Associate Clinical Professor, Department of
Microbiology and Immunology, Stanford University School of Medicine; Chief of Infectious Diseases
and Geographic Medicine, Department of Internal Medicine, Kaiser Permanente Medical Group

Darvin Scott Smith, MD, MSc, DTM&H is a member of the following medical societies: American
Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society
of America, International Society of Travel Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Emily Anderson Kelly Stanford University

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical
Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine,
Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of
Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical
Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

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Charles V Sanders, MD is a member of the following medical societies: American College of

Physicians, Alliance for the Prudent Use of Antibiotics, The Foundation for AIDS Research, Southern
Society for Clinical Investigation, Southwestern Association of Clinical Microbiology, Association of
Professors of Medicine, Association for Professionals in Infection Control and Epidemiology, American
Clinical and Climatological Association, Infectious Disease Society for Obstetrics and Gynecology,
Orleans Parish Medical Society, Southeastern Clinical Club, American Association for the
Advancement of Science, Alpha Omega Alpha, American Association of University Professors,
American Association for Physician Leadership, American Federation for Medical Research, American
Geriatrics Society, American Lung Association, American Medical Association, American Society for
Microbiology, American Thoracic Society, American Venereal Disease Association, Association of
American Medical Colleges, Association of American Physicians, Infectious Diseases Society of
America, Louisiana State Medical Society, Royal Society of Medicine, Sigma Xi, Society of General
Internal Medicine, Southern Medical Association

Disclosure: Received royalty from Baxter International for other.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine,
Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma
Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases
Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha,
American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical
Investigation, Association of Professors of Medicine, American College of Physicians, Infectious
Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Fred A Lopez, MD Associate Professor and Vice Chair, Department of Medicine, Assistant Dean for
Student Affairs, Louisiana State University School of Medicine

Fred A Lopez, MD is a member of the following medical societies: Alpha Omega Alpha, American
College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America,
Louisiana State Medical Society

Disclosure: Nothing to disclose.

Shwetha Ravindranath Katta, MD JJM Medical College, Davangere, India

Disclosure: Nothing to disclose.

Acknowledgements

Tara Ramachandra, MD Stanford University School of Medicine

Disclosure: Nothing to disclose.

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