• Clinical science

Leprosy (Hansen disease)

Summary

Leprosy (Hansen disease) is a chronic infectious disease caused by prolonged exposure to Mycobacterium leprae, an acid-fast, slow-growing, fastidious bacillus. Leprosy primarily occurs in tropical and/or developing countries and is rarely observed in the US. There are various forms whose descriptions differ among two different classification systems, but the three cardinal clinical manifestations of leprosy are hypopigmented skin lesions, nerve thickening, and peripheral nerve palsies. Long-standing cases of leprosy classically develop deformities as a result of contractures following motor nerve palsies and/or repeated injury due to sensory loss. Other chronic complications include uveitis, orchitis, and nasal septal perforation. Patients with leprosy may also present with acute lepra reactions that are characterized by painful skin lesions and neuritis. The diagnosis is usually confirmed with the help of a biopsy. Lepromin tests aid in the classification of various forms of leprosy. Treatment consists of prolonged MDT (multi-drug therapy) with dapsone and rifampin. Clofazimine is added to the therapeutic regimen in patients with multibacillary leprosy.

Epidemiology

  • Incidence: ∼ 150 new cases annually [1]
  • Prevalence: ∼ 0.2/10,000 worldwide [2]
  • Peak incidence: 10–15 and 30–65 years [3]
  • Sex: > [4]
  • Endemic to tropical regions: India, Brazil, Indonesia, Nepal, Myanmar, Nigeria

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Pathogen: Mycobacterium leprae is an obligate, intracellular, acid-fast bacillus that cannot be cultured and thrives in cold temperatures. [5]
  • Route of transmission
    • Close contact with fomites, contaminated soil , infected individuals, and nine-banded armadillos (in rare cases)
    • Respiratory droplet transmission
      • Risk factors are close contact with infected individuals or contaminated soil.
      • Although transmission is rare, infected animals (e.g., armadillos, mangabey monkeys, sphagnum moss) pose a potential risk in the US.
    • Transmission usually requires prolonged exposure, and some individuals seem more predisposed than others.
  • Infectious type: lepromatous leprosy (see “Pathophysiology” below)
  • Reservoirs: infected humans; , nine-banded armadillos in the US

Pathophysiology

Pathophysiology of lepromatous and tuberculoid leprosy [6]
Lepromatous leprosy (LL) Tuberculoid leprosy (TT)
Characteristics

Leprosy is a slowly progressive, chronic infection with a spectrum of clinical manifestations depending on the degree of cell-mediated immunity.

Clinical features

  • Incubation period: 3–5 years
  • The clinical manifestations vary depending on the type of leprosy (LL, TT, or several intermediate forms collectively known as borderline leprosy.
Clinical features of lepromatous and tuberculoid leprosy [8]
Lepromatous leprosy (LL) Tuberculoid leprosy (TT)
Cutaneous manifestations
  • Multiple symmetrical macules, plaques, and/or nodules
    • Generalized involvement of the skin
    • Nodules on the face may coalesce → leonine facies
    • Nodules may ulcerate
  • Hypesthesia of the skin lesion is less common and occurs only in the late stages of the disease.
  • Supraciliary and ciliary madarosis
  • Few (usually 1–3 lesions), localized, hypopigmented macules, plaques, and/or papules with well-defined, erythematous, and/or raised margins
  • Lesions are dry, scaly, anhidrotic .
  • Hair loss
  • Hypesthesia of the skin lesion is common and occurs early (hypoaesthesia of the skin develops in later stages). [9]
Nerve involvement
  • Occurs late but is more extensive
  • Acral, distal, symmetrical anesthesia
  • Usually begins as glove-and-stocking neuropathy that spreads proximally
  • Occurs early but is localized
  • Asymmetric enlargement of one or many peripheral nerves
  • Acute neuritis does not occur.
Systemic manifestations
  • Not involved

The three cardinal clinical manifestations of leprosy are hypopigmented skin lesions, nerve thickening, and peripheral nerve palsies.

All peripheral nerves can become affected in leprosy, but the most commonly affected are the ulnar and the peroneal nerves.

Lepromatous leprosy manifests with Leonine facies. The Low cell-mediated immunity in this condition makes it more Lethal (more communicable).

Diagnostics

Diagnostic characteristics of lepromatous and tuberculoid leprosy
Diagnostic test Test characteristics Lepromatous leprosy (LL) Tuberculoid leprosy (TT)
Skin scraping or slit-skin smear
  • Smears are positive for AFB at any location.
  • Smears are negative for AFB at all locations.
Punch biopsy
  • Punch biopsy followed by histopathological examination with modified Ziehl-Neelsen staining and PCR of the biopsy sample are used to confirm the diagnosis. [11]
Lepromin test [12]
  • Negative
  • Positive

Diffuse hypergammaglobulinemia associated with lepromatous leprosy can cause false-positive VDRL, RF, and/or ANA tests and thus result in diagnostic confusion.

Treatment

Definitive therapy [13]

Multidrug treatment of leprosy
Lepromatous leprosy (LL) Tuberculoid leprosy (TT)
Dapsone Yes Yes
Rifampin Yes Yes
Clofazimine Yes No

Supportive therapy [6]

Complications

Leprosy reactions
Type of lepra reaction Type 1 (reversal reaction) [14] Type 2 (erythema nodosum leprosum, ENL) [15][16] Lucio phenomenon [17][18]
Mechanism
  • Possibly immune-complex deposition
  • Cutaneous vasculitis probably due to immune-complex reaction
Cutaneous lesions
  • Pre-existing lepromatous lesions become red, warm, swollen, and painful.
  • Multiple, red, painful, subcutaneous nodules (1–2 cm) appear symmetrically on the face, arms, and/or legs in crops.
  • Large, sharply marginated, ulcerative lesions that appear in crops over the lower limbs and may recur episodically
Neuritis
  • Common and severe
  • Common and severe
  • Not common
Systemic manifestations
  • Not common
  • Not common
Treatment

Treatment of leprosy should not be stopped when leprosy reactions occur.

The presence of tender nerves in a patient with leprosy indicates a leprosy reaction.

We list the most important complications. The selection is not exhaustive.

  • 1. Centers for Disease Control and Prevention. What is Hansen’s Disease?. https://www.cdc.gov/leprosy/about/about.html. Updated February 10, 2017. Accessed November 3, 2020.
  • 2. World Health Organization. Leprosy. https://www.who.int/en/news-room/fact-sheets/detail/leprosy. Updated September 10, 2019. Accessed November 3, 2020.
  • 3. Joyce MP. Leprosy. Elsevier; 2005: pp. 455–465.
  • 4. Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White NJ. Manson's Tropical Diseases. Saunders Limited.; 2013.
  • 5. Agnew D, Nofs S, Delaney MA, Rothenburger JL. Xenartha, Erinacoemorpha, Some Afrotheria, and Phloidota. Elsevier; 2018: pp. 517–532.
  • 6. Pardillo FEF, Fajardo TT, Abalos RM, Scollard D, Gelber RH. Methods for the Classification of Leprosy for Treatment Purposes. Clinical Infectious Diseases. 2007; 44(8): pp. 1096–1099. doi: 10.1086/512809.
  • 7. M. Patricia Joyce. Leprosy (Hansen's Disease). Elsevier; 2008: pp. 543–554.
  • 8. Nunzi E, Massone C. Leprosy. Springer Milan; 2012.
  • 9. Fischer M. Leprosy - an overview of clinical features, diagnosis, and treatment. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2017; 15(8): pp. 801–827. doi: 10.1111/ddg.13301.
  • 10. Centers for Disease Control and Prevention. Hansen's Disease (Leprosy). Laboratory Diagnostics. https://www.cdc.gov/leprosy/health-care-workers/laboratory-diagnostics.html. Updated February 10, 2017. Accessed November 3, 2020.
  • 11. 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; 8(4): p. e2655. doi: 10.1371/journal.pntd.0002655.
  • 12. U.S. National Library of Medicine. Lepromin skin test. https://medlineplus.gov/ency/article/003383.htm. Updated October 8, 2020. Accessed November 3, 2020.
  • 13. Scollard D, Stryjewska B. Treatment and prevention of leprosy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/treatment-and-prevention-of-leprosy. Last updated December 1, 2016. Accessed November 29, 2017.
  • 14. Nery JA da C, Bernardes Filho F, Quintanilha J, Machado AM, Oliveira S de SC, Sales AM. Understanding the type 1 reactional state for early diagnosis and treatment: a way to avoid disability in leprosy. An Bras Dermatol. 2013; 88(5): pp. 787–792. doi: 10.1590/abd1806-4841.20132004.
  • 15. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Elsevier Saunders; 2015.
  • 16. World Health Organization. WHO Guidelines for the management of severe erythema nodosum leprosum (ENL) reactions. https://www.who.int/lep/research/WHOenlguide.pdf. Accessed November 4, 2020.
  • 17. Chandrashekar L, Kumari R, Thappa D, Badhe B, Ranugha P. Is it lucio phenomenon or necrotic erythema nodosum leprosum?. Indian J Dermatol. 2013; 58(2): p. 160. doi: 10.4103/0019-5154.108087.
  • 18. Sharma P, Kumar A, Tuknayat A, Thami GP, Kundu R. Lucio Phenomenon: A Rare Presentation of Hansen's Disease. The Journal of clinical and aesthetic dermatology. 2019; 12(12): pp. 35–38. pmid: 32038763.
  • 19. Rêgo JL, de Lima Santana N, Machado PRL, et al. Whole blood profiling of leprosy type 1(reversal) reactions highlights prominence of innate immune response genes. BMC Infect Dis. 2018; 18(1). doi: 10.1186/s12879-018-3348-6.
last updated 11/10/2020
{{uncollapseSections(['zRcrpX0', 'YicnJX0', 'ZicZJX0', '7ic4GX0', 'aicQJX0', 'bicHJX0', 'cicaqX0', '1ic2qX0'])}}