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Leprosy

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.

  • 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.

  • 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-bandedarmadillos in the US
Pathophysiology of lepromatous and tuberculoid leprosy [6]
Lepromatous leprosy (LL) Tuberculoid leprosy (TT)
Characteristics
  • ↑ Th2 response
    • Reciprocal inhibition of Th1 response → inadequate cell-mediated immune response → many lepra bacilli
    • ↑ Antibody production (hypergammaglobulinemia)
  • Nerve lesions are the result of M. leprae invasion.
  • M. leprae thrives at cool areas on the body (skin, mucous membranes, peripheral nerves, anterior chamber of the eye, upper respiratory tract, testes). [7]
  • ↑ Th1 response → strong cell-mediated immune response → granuloma with epithelioid cells and lymphocytes but few or no lepra bacilli
  • Nerve demyelination is the result of a T-cell mediated response.

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

  • 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, hypopigmentedmacules, plaques, and/or papules with well-defined, erythematous, and/or raised margins
  • Lesions are dry, scaly, anhidrotic.
  • Hair loss
  • Hyperesthesia of the skin lesion is common and occurs early (hypoesthesia of the skin develops in later stages). [9]
Nerve involvement
  • Occurs late but is more extensive
  • Acral, distal, symmetrical anesthesia
  • Usually begins with stocking glove pattern that spreads proximally
  • Occurs early but is localized
  • Asymmetric enlargement of one or many peripheral nerves
  • Acute neuritis does not occur.
  • Nerve involvement leads to nerve enlargement and peripheral nerve palsies which present with sensory, motor, and/or autonomic deficits.
    • Ulnar nerve palsy : clawing of the fourth and fifth fingers, wasting of dorsal interosseous nerves, loss of sensation
    • Peroneal nerve palsy: foot drop
    • Posterior auricular nerve
    • Posterior tibial nerve
Systemic manifestations
  • Early prodromal symptoms: nasal stuffiness, epistaxis
  • Hepatomegaly
  • Nontender lymphadenopathy
  • 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).

Diagnostic characteristics of lepromatous and tuberculoid leprosy
Diagnostic test Test characteristics Lepromatous leprosy (LL) Tuberculoid leprosy (TT)
Skin scraping or slit-skin smear
  • Modified Ziehl-Neelsen staining of scrapings from skin lesions, nasal swabs, and/or slit skin smears from ear lobes are used to screen for leprosy. [10]
  • Acid-fast bacilli smear microscopy (AFB smear microscopy): rapid microscopic test for the detection of acid-fast bacilli (AFB)
  • 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]
  • Foamy histiocytes full of bacilli
  • Few lymphocytes
  • Numerous lepra bacilli
  • Granulomas formed by epithelioid cells and Langhans giant cells
  • Many lymphocytes with a CD4:CD8 ratio of 1.2:1
  • No lepra bacilli
Lepromin test [12]
  • Antigen is injected intradermally on the ventral forearm.
  • The test is positive if induration is > 5 mm.
  • Measures the ability of a patient to mount a T cell response (does not diagnose leprosy)
    • Can be positive in patients with no exposure or infection to leprosy
    • Can distinguish between lepromatous leprosy (negative result due to inadequate cell-mediated immune response) and tuberculoid leprosy (positive result due to strong cell-mediated immune response)
  • Negative
  • Positive

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

Definitive therapy [13]

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

Supportive therapy [6]

  • Treatment of leprosy reactions (see “Complications” below)
  • Rehabilitation
    • Physiotherapy to prevent contractures
    • Surgery to correct deformities (e.g., tendon transfer surgery for ulnar nerve palsy)
  • Wound care
  • Secondary deformities
    • Bone destruction → shortened digits, autoamputation
    • Neuropathic ulcers on the dorsum of the foot
    • Charcot joints
  • Nasal complications
    • Saddle nose deformity
    • Anosmia
    • Nasal septum perforation
  • Ocular complications
    • Lagophthalmos and corneal insensitivity → corneal ulcers
    • Invasion of the anterior chamber → chronic uveitis → blindness
  • Other complications
    • Orchitis → testicular atrophy → hypergonadotropic hypogonadism
    • Reactive amyloidosis
    • Leprosy reactions
Leprosy reactions
Type of lepra reaction Type 1 (reversal reaction) [14] Type 2 (erythema nodosum leprosum, ENL) [15][16] Lucio phenomenon [17][18]
Mechanism
  • Delayed hypersensitivity reaction [19]
  • 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
  • Fever, malaise, joint pain
  • Tender lymphadenopathy
  • Acute uveitis
  • Orchitis
  • Glomerulonephritis
  • Not common
Treatment
  • Prednisolone
  • Supportive therapy to control fever and pain (e.g., NSAIDs)
  • Prednisolone
  • Clofazimine
  • Supportive therapy (e.g., wound care)
  • Prednisolone

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.