Hansen Disease (Leprosy)

A 28-year-old man presented with a 1-year history of nodular, plaque-like, nontender, pruritic lesions on his face, ears, elbows, and feet. He was born in Mexico but had been residing in the United States for the past 6 years. He worked in construction, was an active smoker, and denied use of alcohol or illicit drugs. The patient had not been taking any oral medications and had no recent history of trauma.

Six months before this presentation, the patient presented to a different clinic and received a prescription for a topical corticosteroid. After 6 months of use, the lesions were more numerous and extensive, prompting him to seek further medical attention.

Findings from the physical examination were remarkable for nodular, plaque-like lesions localized to the forehead, elbows (Figure 1), knees, feet, and ears. Leonine facies, a facial characteristic associated with leprosy, and ulcerative lesions at the nares with no associated bleeding were evident (Figure 2). The skin on his forehead was diffuse, thickened, smooth, and shiny, and alopecia of the eyebrows and eyelashes was noted. All lesions were nontender or hypoesthetic. There were no hypertrophied nerves, and the neurological examination findings were remarkable for right-sided weakness on handgrip.

Figure 1

Figure 2

Achest radiograph and laboratory findings, including an HIV test, were unremarkable. Biopsy material from the ears and nose and scrapings from nasal lesions demonstrated acid-fast bacilli (Mycobacterium leprae) with WadeFite staining (Figure 3, magnification X400).

Figure 3

After a brief hospitalization, the patient was discharged home on a standard regimen of 12-month therapy for multibacillary leprosy. This consisted of oral dapsone, 100 mg daily; clofazimine, 50 mg daily; rifampin, 600 mg monthly; and clofazimine, 300 mg monthly. Follow- up consultation with an infectious disease specialist was scheduled.

First described in 1873, leprosy is caused by an M leprae infection.¹ This chronic granulomatous disease primarily affects the skin, mucous membranes, and peripheral nervous system. Areas in which leprosy is endemic include various locations throughout Asia, Africa, and Central and South America.² In the United States, 166 cases of leprosy were reported in 2005.³ In early 2006, 219,826 cases of leprosy were reported globally.²

M leprae is an obligate, intracellular, slow-growing mycobacterium that survives optimally at 27C (80.6F) to 33C (91.4F). Humans are the primary reservoir of M leprae, but animal reservoirs, such as armadillos and certain primates, have been identified.⁴ The definite route of transmission for leprosy is unknown, although many experts believe that transmission occurs via aerosol spread from infected nasal secretions to nasal and oral mucosa. It is usually not spread by direct contact, but close contacts may be more vulnerable to the disease. Risk factors include older age and impaired cellular immunity.⁵

The World Health Organization classifies leprosy as either paucibacillary or multibacillary. Paucibacillary disease is characterized by 5 or fewer skin lesions (patches, papules, nodules), whereas multibacillary disease involves 6 or more lesions. Alternatively, the Ridley-Jopling system uses skin, motor, sensory, and biopsy findings to classify the disease as indeterminate, tuberculoid, borderline tuberculoid, midborderline, borderline lepromatous, or lepromatous.⁶

Indeterminate, tuberculoid, and borderline-tuberculoid types are classified as paucibacillary disease; midborderline, borderline lepromatous, and lepromatous types are classified as multibacillary disease.⁵ The lesions can vary from erythematous macules to nodules to plaques and tend to affect cool areas of the body, such as the earlobes, knees, superficial peripheral nerves, testes, and chin. Hypopigmentation and hypoesthesia also can occur.

Peripheral neuropathies most commonly affect the posterior peroneal nerve and manifest as loss of sensation to temperature, light touch, pain, and pressure. Damage to the median and ulnar, common peroneal, and posterior tibial nerves can result in clawhand, footdrop, or clawtoes, respectively.⁵ Loss of eyebrows and eyelashes is not uncommon.

Acid-fast and modified Wade-Fite staining of skin scrapings or biopsy specimens are the preferred methods to confirm a diagnosis of leprosy. Up to 70% of patients with leprosy can have a negative skin test result.⁵ Polymerase chain reaction and antiphenolic antibody assays can also be used to help confirm the diagnosis.⁷

Treatment depends on the type of disease, patient allergies, comorbidities, and patient's place of residence. A multidrug regimen is the standard of care for leprosy worldwide. For paucibacillary disease, a 6-month course of oral dapsone, 100 mg daily, and oral rifampin, 600 mg monthly, is recommended.⁸ However, patients with leprosy diagnosed in the United States tend to have more active disease than those presenting in other areas of the world and often receive daily rifampin in addition to daily oral dapsone and an extended treatment course of 1 year.⁸ For multibacillary disease, the recommended treatment is oral dapsone, 100 mg daily; clofazimine, 50 mg daily; and monthly doses of rifampin, 600 mg, and clofazimine, 300 mg.⁸ The treatment duration for multibacillary disease is 12 months.

Roughly 25% of patients with borderline and lepromatous types of leprosy experience an adverse reaction to treatment. There are 2 types of adverse reactions that can occur. A reversal reaction (type 1 reaction) is characterized by erythema and edema of skin lesions with neuritis and occasional ulceration.⁸ If neuritis occurs, prednisone should be initiated immediately to prevent permanent nerve damage.⁶ Another adverse reaction is erythema nodosum leprosum (type 2 reaction), which is an immune complex disorder characterized by fever and multiple erythematous tender nodules.⁸ Neuritis, edema, arthralgia, leukocytosis, iridocyclitis, pretibial periostitis, orchitis, and nephritis may also be present. Thalidomide, 300 to 400 mg daily, typically lessens the type 2 reaction within 48 hours.

Although infrequent in the United States, leprosy is an important disease worldwide. Given the diverse US population, recognizing typical features of leprosy is crucial for accurate diagnosis and early treatment.

References:

• Lewis FS. Leprosy. http://www.emedicine.com/derm/topic223.htm. Accessed April 11, 2008.

• World Health Organization. Global leprosy situation, 2006. Wkly Epidemiol Rec. 2006;81:309-316.

• Health Resources and Services Administration, US Department of Health and Human Services. National Hansen’s disease (leprosy) program. http://www.hrsa.gov/hansens/. Accessed April 11, 2008.

• Valverde CR, Canfield D, Tarara R, et al. Spontaneous leprosy in a wildcaught cynomolgus macaque. Int J Lepr Other Mycobact Dis. 1998;66:140-148.

• Britton WJ. Leprosy. In: Cohen J, Powderly WG, eds. Infectious Diseases. New York: Mosby; 2004:1507-1513.

• Smith WC, Anderson AM, Withington SG, et al. Steroid prophylaxis for prevention of nerve function impairment in leprosy: randomised placebo controlled trial (TRIPOD 1). BMJ. 2004;328:1459.

• Butlin CR, Soares D, Neupane KD, et al. IgM anti-phenolic glycolipid-I antibody measurements from skin-smear sites: correlation with venous antibody levels and the bacterial index. Int J Lepr Other Mycobact Dis. 1997;65:465-468.

• Jacobson RR, Krahenbuhl JL, Yoder L. Overview of leprosy. http://uptodate.com. Updated October 15, 2007. Accessed May 27, 2008.