Leprosy (also known as Hansen’s disease) is an infectious disease affecting skin and peripheral nerves.
- Prevalence: < 1 in 10,000 since 2002
- Highest incidence in India, Brazil, Indonesia, Bangladesh, and Nigeria
- In 2015, there were 178 new cases of leprosy in the United States.
- Immigrants account for 75% of new cases in the United States.
Leprosy is caused by Mycobacterium leprae complex bacteria:
- Includes M. leprae and M. lepromatosis
- Acid-fast bacilli
- Aerobic, obligate intracellular rod-shaped bacteria
Risk factors for acquisition:
- Close contact with leprosy patients
- Exposure to armadillos (natural reservoir of M. leprae)
- Older age
- Genetic factors
- Bacteria are inhaled or transmitted through direct skin contact and are taken up by alveolar macrophages and disseminated in the blood.
- M. leprae spreads to nerves and skin, where it proliferates (especially in Schwann cells).
- Leprosy can manifest in different forms that reflect a spectrum of the host immune response.
- Ridley–Jopling classification of leprosy:
- Tuberculoid (TT)
- Borderline tuberculoid (BT)
- Mid-borderline (BB)
- Borderline lepromatous (BL)
- Lepromatous (LL)
- Indeterminate (I)
- Tuberculoid and lepromatous forms are at the 2 ends of the spectrum:
- Tuberculoid leprosy:
- Good cellular immune response (type 1 T helper (TH1) cell response)
- Delayed-type hypersensitivity with interferon-γ and macrophage activation
- Involves the skin (localized) and peripheral nerves
- Lepromatous leprosy:
- Minimal cellular immune response
- Humoral (antibody) response (activated by type 2 T helper (TH2) cells)
- Extensive skin involvement
- Nerve involvement tends to be symmetric.
- Tuberculoid leprosy:
- Well demarcated in tuberculoid leprosy:
- Usually 1 or 2 lesions
- Central hypopigmentation or erythematous
- Poorly demarcated in lepromatous leprosy:
- Can be macular, raised, or nodular
- Numerous; appear all over body
- Neuropathy, paresthesias
- Enlarged and tender peripheral nerves (tuberculoid leprosy)
- Painless extremity wounds
- Facial or ear lumps
- Ophthalmic injury:
- Lagophthalmos (inability to close eyelids completely)
- Corneal abrasions/ulcerations
|Presentation||Immunocompetent individuals||Immunocompromised individuals|
|Location||Skin and nerves||Skin and nerves|
Late findings may include:
- Facial paralysis
- Collapsed nose
- Clawed fingers
- Foot drop
- Lack of eyelashes/eyebrows
Possible immunologic reactions:
- Systemic inflammatory complications
- May occur before, during, or after treatment
- Two types:
- Type 1: reversal reaction
- Type 2: erythema nodosum leprosum
- Can be difficult to distinguish clinically
- Symptoms include:
- Fatigue, fever, malaise
- Neuritis, arthritis, iritis, nasopharyngeal symptoms
- Very rare complication of lepromatous leprosy
- Necrotizing vasculopathy
World Health Organization (WHO) diagnostic criteria
The WHO defines leprosy as appearing in an individual who has not completed a course of treatment and has one or more of the following:
- Painless hypopigmented or reddish skin lesions
- Peripheral nerve thickening and associated loss of sensation
- Skin smear positive for acid-fast bacilli
The WHO bases diagnosis on the above clinical presentation combined with a confirmatory laboratory test.
- Skin biopsy:
- Full-thickness sample taken from most active margin of most active lesion
- The Ziehl–Neelsen or Fite stain can show the presence of acid-fast bacilli, confirming the diagnosis of leprosy.
- Slit-skin smear can help in diagnosing those with lepromatous disease.
- M. leprae cannot be cultured in artificial media.
- Mycobacterial culture may need to be performed to rule out other pathogens (M. tuberculosis).
- Serologic assays:
- Detect phenolic-glycolipid-1 and lipoarabinomannan
- 95% sensitivity for lepromatous leprosy
- 30% sensitivity for tuberculoid leprosy
- Molecular probes:
- Detect 40%–50% of cases missed on histologic evaluation
- Can fail to identify tuberculoid leprosy
- Gene probes with M. leprae–specific sequences
- Can be used to identify mycobacterium in biopsy samples, skin, nasal smears, blood, and tissue sections
- Lymphocyte migration inhibition test:
- Tests for cell-mediated immunity to M. leprae
- Absent in patients with lepromatous leprosy
- Present in those with tuberculoid leprosy
- Lepromin test:
- Not available in the United States
- Test is done by injecting antigen intradermally.
- Check the injection site for induration, similar to what is done for the tuberculin skin test.
- Not reliable: detects ability to develop granulomas when exposed to antigen but not the actual exposure
- Multidrug therapy (MDT) regimen:
- Necessary to prevent drug resistance
- Dapsone + rifampin for 12 months for tuberculoid leprosy
- Dapsone + rifampin + clofazimine for 24 months for lepromatous leprosy
- Alternative medications:
- Immunologic reactions:
- Can be managed supportively if mild and no neuritis is present
- Neuritis must be managed aggressively to prevent permanent nerve damage.
- Steroids and immunosuppressants
- No drug prophylaxis in nonendemic areas
- BCG vaccine is partly protective.
- Close contacts of affected individuals should be monitored annually for at least 5 years.
- In endemic areas, single-dose rifampin can be given for prophylaxis.
- Paralysis and crippling of hands and feet
- Autoamputation of toes and fingers
- Chronic nonhealing ulcers on bottoms of feet
- Loss of eyebrows
- Nose disfigurement
- Testicular atrophy
- Neurofibromatosis type 1: a genetic neural disorder of benign tumors that arise from the neural crest cells in the peripheral nerve sheath: Neurofibromatosis type 1 presents in the teen years as soft, painless skin nodules. Genetic testing can confirm the diagnosis after the physical exam and biopsy. Management includes surgical resection and antitumor drugs.
- Dermatofibroma (DF): a common, benign, fibrohistiocytic proliferation reaction, usually in reaction to trauma, a viral infection, or an insect bite: Dermatofibroma presents on the anterior surfaces of the lower legs as a firm, indurated, mobile nodule that retracts beneath the skin during an attempt to compress and elevate it. Diagnosis is by biopsy. Management includes surgical resection.
- Systemic lupus erythematosus: a systemic autoimmune disorder most commonly affecting women: Patients can present with involvement of multiple organs. Cutaneous manifestations of lupus include facial “butterfly rash” or generalized erythematous macular–papular eruption involving sun-exposed areas. Diagnosis is based on clinical suspicion and the presence of certain antibodies. Management involves steroids, immunosuppressants, and biologic agents.
- Scleroderma: an autoimmune condition characterized by diffuse collagen deposition and fibrosis: The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Diagnosis is established by a combination of physical findings and serology. There is no curative treatment. Management options are limited but include immunosuppressive medications and symptomatic treatment.
- Scollard D, Stryjewski B, Dasco M. (2020). Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis. UpToDate. Retrieved March 3, 2021, from https://www.uptodate.com/contents/leprosy-epidemiology-microbiology-clinical-manifestations-and-diagnosis
- Smith D. (2020). Leprosy. Emedicine. Retrieved March 2, 2021, from https://emedicine.medscape.com/article/220455-overview
- Moschella SL. (2004). An update on the diagnosis and treatment of leprosy. J Am Acad Dermatol 51:417.
- World Health Organization. (2010). Surveillance of drug resistance in leprosy. Wkly Epidemiol Rec 86:237–240.
- World Health Organization. (2019). Guidelines for the diagnosis, treatment, and prevention of leprosy. ARO/Department of Control of Neglected Tropical Diseases. March 2, 2021, from https://www.who.int/en/news-room/fact-sheets/detail/leprosy
- Centers for Disease Control and Prevention. CDC Immigration Requirements: Technical Instructions for Hansen’s Disease (Leprosy) for Panel Physicians. Retrieved March 2, 2021, from Xxxxx
- World Health Organization. (2016). Global leprosy update, 2015: time for action, accountability and inclusion. Source: Wkly Epidemiol Rec 91:405–420.