Adam D. Quick, MD
DESCRIPTION
Leprosy is an infectious disease that mainly affects the skin, the peripheral nerves, the mucosa of the upper respiratory tract, and the eyes. Leprous neuropathy is the most common type of peripheral neuropathy worldwide. It is caused by direct bacterial infiltration of small-diameter peripheral nerves.
EPIDEMIOLOGY
Leprosy is indigenous to Hawaii and portions of Florida, Louisiana, and Texas in the US. It is also seen in immigrants from India, Southeast Asia, and central Africa.
- Incidence/Prevalence
- Prevalence of 0.9 million cases worldwide in 1996. It has been gradually but steadily declining over several decades.
- Prevalence exceeds 10 per 1,000 in endemic areas such as Asia and Africa.
- 144 new cases in the US in 1995. The majority of leprosy cases diagnosed in the US are in immigrants from leprosy-endemic countries.
- Race
- No racial predilection known
- Age
- Leprosy can present at any age but is rare in infancy.
- Sex
- Equal in children but 2:1 male preponderance in adults
RISK FACTORS
Exposure to nasal discharge of individuals infected with leprosy.
Genetics
There is evidence that HLA-associated genes influence the type of leprosy an individual develops.
ETIOLOGY
The etiologic agent is Mycobacterium leprae, an acid-fast bacillus that grows best at 30°C (86°F), which explains its predilection for skin and peripheral nerves. Leprosy is transmitted via transfer of bacteria in nasal discharge of infected individuals to the respiratory tract of susceptible individuals, followed by hematogenous dissemination. The intensity of the cell-mediated immune response to the bacteria correlates with the type of disease expression. Patients with an intense cellular immune response develop disease types toward the tuberculoid end of the spectrum. Little or no cellular immune response is associated with development of lepromatous leprosy.
- Indeterminate leprosy (initial infection)
- Solitary hypopigmented macule, which may resolve (about 75%) or persist to progress to one of the other types of leprosy.
- Classification of leprosy types is that of a continuous spectrum based on clinicopathologic features: Lepromatous, borderline lepromatous, borderline, borderline tuberculoid, and tuberculoid.
- Lepromatous leprosy
- Multiple symmetric skin lesions affecting face (especially cheeks and nose), limbs, and buttocks, initially macular and evolving into plaques and nodules, typically fairly symmetric. Lesions centers are convex and indurated, and margins are ill defined.
- Nasal congestions and epistaxis
- Ocular: Pain, photophobia, loss of vision, glaucoma
- Testicular: Sterility, impotence, gynecomastia
- Sensory loss (especially pain, temperature) in distal limbs (palms and soles spared), pinnae of the ears, breasts, buttocks
- Nerve root enlargement, especially superficial nerves such as the greater auricular in the neck, ulnar, peroneal as it passes around the fibula, superficial radial, median
- Motor involvement is late: Amyotrophy, claw hand, foot drop
- Reflexes preserved
- Cranial nerve involvement: Preferentially V and VII (eye closure and perioral musculature)
- Lucio reaction or phenomenon, a type of necrotizing vasculitis that can occur in lepromatous disease with high mortality
- Tuberculoid leprosy
- Sharply marginated erythematous or hypopigmented macules or plaques that are solitary and asymmetric, occurring in the trunk, buttocks, and face. Tuberculoid leprosy lesions exhibit earlier sensory loss compared with lepromatous lesions.
- Nerve enlargement occurs early and involves nerves contiguous to skin lesions.
- Neuritic pain
- Muscle atrophy, especially in the intrinsic hand muscles
- Resorption of phalanges (late)
- Borderline leprosy
- Skins lesions vary in number and character depending on whether the case is more toward the tuberculoid or lepromatous end of the spectrum.
- Nerve involvement may precede skin lesions in this type, with segmental enlargement and tenderness of nerve trunks.
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
- ELISA to serum antibody to phenolic glycolipid I, a capsular antigen of M. leprae, is positive in most patients with multibacillary disease (lepromatous or borderline lepromatous) and often negative in patients with paucibacillary forms of the disease (tuberculous or borderline tuberculous).
- Diagnosis is generally made from demonstration of acid-fast bacteria from smears from affected skin or nasal mucosa.
Diagnostic Procedures/Other
- Dermal scraping or slit-skin biopsy is sent for acid-fast stain or, alternatively, the Ziehl–Neelsen stain to identify M. leprae. In tuberculoid leprosy, noncaseating granulomas are present and bacilli often are scant or absent. In lepromatous leprosy, a diffuse granulomatous reaction is present, often with many demonstrable bacilli.
- Nerve biopsy is not usually necessary to make a diagnosis of leprous neuropathy, except in rare cases of isolated nerve involvement.
- Nerve conduction studies/electromyography are helpful to document neuropathy and delineate pattern of involvement.
DIFFERENTIAL DIAGNOSIS
- Leprosy should be considered in presentations with the combination of a skin rash and peripheral neuropathy. The differential also includes the broad differential of peripheral neuropathy.
MEDICATION
- Dapsone (diaphenylsulfone), a folate antagonist, is the primary therapy.
- The regimen recommended by the US Public Health Service Hospital Long Hansen's Disease Center in Louisiana is given below. These recommendations differ from the World Health Organization (WHO) recommendations, which include a broader regimen because of concerns of dapsone resistance.
- US Public Health Service Hospital Long Hansen's Disease Center in Louisiana Regimen
- Paucibacillary disease (tuberculoid end of spectrum)
- Dapsone 100 mg po daily
- Rifampin 600 mg daily
- Duration 1 year
- Multibacillary disease (lepromatous end of spectrum)
- Dapsone 100 mg po daily
- Rifampin 600 mg po daily
- Clofazimine 50 mg po daily
- Duration 2 years
- WHO-Recommended MDT Regimens
- Multibacillary leprosy
- Rifampicin 600 mg once per month
- Dapsone 100 mg daily
- Clofazimine 300 mg once per month and 50 mg daily
- Duration 12 months
- Paucibacillary leprosy
- Rifampicin 600 mg once per month
- Dapsone 100 mg daily
- Duration 6 months
- Single skin lesion paucibacillary leprosy
- Contraindications
- All medications are contraindicated in patients with a known history of hypersensitivity reactions.
- Clofazimine and thalidomide are not safe for use during pregnancy.
- Precautions
- Adverse effects of dapsone are relatively uncommon but include hemolysis, agranulocytosis, hepatitis, and severe exfoliative dermatitis.
- Clofazimine may cause reddish discoloration of the skin, diarrhea, and abdominal pain.
- Patients may actually have a worsening of their neuropathy or rash when treatment is initiated due to several types of reactions (see Patient Monitoring).
ADDITIONAL TREATMENT
General Measures
Treatment is given to eradicate the bacteria and to prevent secondary immune reactions that might cause further injury to the nerves. Patients should be evaluated by an ophthalmologist for ophthalmologic manifestations that might threaten vision. Family members should be evaluated for leprosy.
COMPLEMENTARY AND ALTERNATIVE THERAPIES
- Symptomatic treatment
- Patients should be counseled about the risks of inadvertent injury, such as severe burns to areas rendered insensate by peripheral neuropathy. Insensate limbs should be protected by good footwear, and patients should be warned about the risk of burns.
- Adjunctive treatment
SURGERY/OTHER PROCEDURES
Occasionally release of contractures and nerve and tendon transplants can improve function. Plastic surgery may be useful to correct or improve facial or other deformities.
IN-PATIENT CONSIDERATIONS
Admission Criteria
Not generally required except in severe reactions to treatment (see Patient Monitoring).
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Patients with leprosy must be followed closely for several types of adverse reactions to treatment.
- Leprae type 1 reaction (reversal reaction) is an acute immunologically mediated inflammatory reaction seen in about 50% of patients with borderline leprosy in the first year of therapy. It is manifested as swelling and worsening of skin lesions and of peripheral nerves. Nerve pathology shows inflammation with granulomata and vasculitic changes. Prednisone at an initial dose of 60 mg/day is recommended, with treatment required for several months or more and taper guided by clinical response.
- Leprae type 2 reaction (erythema nodosum leprosum) is a reaction that occurs in approximately 50% of patients with lepromatous leprosy during the first year of treatment and is attributed to immunologic reaction to massive death of M. leprae bacilli (Arthus reaction with deposition of immunoglobulin/complement in skin vessels). This leads to the development of multiple tender skin nodules, as well as fever, arthritis, iridocyclitis, edema, and new peripheral nerve injury in an acute mononeuritis multiplex pattern. Prednisone is also used to treat this reaction. Thalidomide 100–300 mg qhs is useful if prednisone does not quell the reaction.
PATIENT EDUCATION
PROGNOSIS
In most patients with lepromatous leprosy, skin lesions typically resolve over months to several years. The peripheral neuropathy may improve, but this depends on the degree of damage present at the time of initiation of treatment. In tuberculoid leprosy, the skin lesions may improve or remain unchanged, and sensory loss often is permanent.
