Microbiology and Epidemiology

Leprosy is a nonfatal chronic infectious disease caused by M. leprae, an obligate intracellular bacterial species indistinguishable microscopically from other mycobacteria. The organism is confined to humans, armadillos (in some locales), and sphagnum moss.

• M. leprae cannot yet be cultured in vitro. The organism has a doubling time in mice of 2 weeks (compared with 20 min for Escherichia coli and 1 day for M. tuberculosis).
• Leprosy, which is associated with poverty and rural residence, is a disease of the developing world; its global prevalence is difficult to assess and is variously estimated at 0.6-8 million.
  • More than 80% of the world's cases occur in a few countries: India, China, Myanmar, Indonesia, Nepal, Brazil, Nigeria, and Madagascar.
  • In the United States, ∼4000 people have leprosy and 100-200 new cases are reported annually.
• The route of transmission is uncertain but may be via nasal droplets, contact with infected soil, or amoeba insect vectors.

Clinical Manifestations

The spectrum from polar tuberculoid to polar lepromatous disease is associated with an evolution from asymmetric localized macules and plaques to nodular and indurated symmetric generalized skin manifestations, an increasing bacterial load, and loss of M. leprae-specific cellular immunity. Prognosis, complications, and intensity of antimicrobial therapy depend on where a pt presents on the clinical spectrum. The incubation period ranges from 2 to 40 years but is usually 5-7 years.

Tuberculoid (TT) Leprosy At the less severe end of the disease spectrum, TT leprosy results in symptoms confined to the skin and peripheral nerves.

• One or several hypopigmented macules or plaques with sharp margins that are hypesthetic and have lost sweat glands and hair follicles are present. AFB are few or absent.
• There is asymmetric enlargement of one or several peripheral nerves-most often the ulnar, posterior auricular, peroneal, and posterior tibial nerves-associated with hypesthesia and myopathy.

Lepromatous (LL) Leprosy Pts develop symmetrically distributed skin nodules, raised plaques, and diffuse dermal infiltration that can cause leonine facies, loss of eyebrows and lashes, pendulous earlobes, and dry scaling.

• Numerous bacilli are present in skin (up to 10⁹ /g), nerves, and all organs except the lungs and CNS.
• Nerve enlargement and damage are usually symmetric and are due to bacillary invasion.

Complications

• Reactional states: These common, immunologically mediated inflammatory states cause considerable morbidity. Erythema nodosum leprosum-characterized by painful erythematous papules that resolve spontaneously in ∼1 week-occurs in ∼50% of pts near the LL end of the disease spectrum within 2 years of initiation of therapy.
• Extremities:Neuropathy results in insensitivity and affects fine touch, pain, and heat receptors. The loss of distal digits in leprosy is a consequence of insensitivity, trauma, secondary infection, and-in lepromatous pts-a poorly understood and sometimes profound osteolytic process.
• Eyes: Owing to cranial nerve palsies, lagophthalmos and corneal insensitivity may complicate leprosy, resulting in trauma, secondary infection, and (without treatment) corneal ulcerations and opacities. Leprosy is a major cause of blindness in low-income countries.
• Nerve abscesses: Pts with leprosy can develop abscesses of nerves (most commonly the ulnar) and require urgent surgical decompression to prevent irreversible sequelae.

Diagnosis

In TT leprosy, the advancing edge of a skin lesion should be biopsied. In LL leprosy, biopsy of even normal-appearing skin often yields positive results. Serology, skin testing, and PCR of the skin offer little diagnostic assistance.