PRACTICE POINTS

• Leprosy is an infectious disease that can be transmitted from human to human. Household contacts of an affected person are at approximately 5 times increased risk of infection.
• Definitive diagnosis of leprosy requires identification of acidfast bacilli in the skin.
• Consider leprosy in patients presenting with anesthetic skin lesions on several areas of the body, particularly in immigrants from endemic areas or in those who have traveled to such regions within the past 3 to 5 years.
• Multidrug therapy is the mainstay of treatment. After the initial dose, patients are no longer contagious.

Leprosy, also called Hansen's disease, has affected humankind since ancient times.¹ Its causative agent is Mycobacterium leprae, a grampositive, obligate intracellular acid-fast bacillus, which was first identified by the Norwegian physician Gerhard Hansen in 1873.² Although its primary host is the human, the bacteria has also been found in armadillos in southwestern North America³ and in some monkeys in Africa.⁴

Prevalence

Worldwide coordination of antileprosy treatment did not begin until the early 1980s, when the World Health Organization (WHO) recommended multidrug therapy to combat the growing resistance of M leprae to monotherapy.⁵ Since then, the global prevalence of leprosy has steadily declined—from about 12 million in 1985 to less than 1 million in 2000 and less than 500,000 new cases in 2004.⁶ The number of patients with leprosy who have been cured during the past 2 decades exceeds 12 million, and the disease prevalence rate has fallen by 90%.⁵ Of the 407,791 new cases reported in 2004, the majority were in Southeast Asia (298,603), followed by the Americas (52,662) and Africa (46,918).⁷ Areas of high incidence may reflect socioeconomic conditions, the scarcity of health care, or environmental exposure.²

In the United States, the incidence of newly diagnosed leprosy has steadily declined since 1991, when 297 cases were reported. In that year, the WHO established the goal of eliminating leprosy as a public health problem by the year 2000.⁸ In 2002, a total of 96 cases were reported to the Centers for Disease Control and Prevention.⁹ Roughly 85% of leprosy diagnoses in the United States are made in immigrants.⁸

Illustrative Case

A 28-year-old Hispanic man came to our internal medicine clinic complaining of a reddish rash. It had started on his forehead 2 years ago and gradually spread over his face, ears, chest, and back. The rash had become more prominent and pruritic, and his hair had thinned. In the past year, his feet and lower legs had become increasingly numb. He had been taking hydroxyzine (Atarax, Vistaril) and ibuprofen, which had been prescribed at various community clinics, but his rash had not improved.

Examination showed the patient was in no distress. His face had diffuse, flesh-colored nodules, which were particulary prominent on his brow, nose, lips, and ears (Figure 1). His auricles were elongated, and the bridge of his nose was depressed. The patient said he was born and raised in southern Mexico. He had moved to the United States 12 years ago and had lived primarily in Arizona and southern California. Generally healthy and without any notable medical or surgical history, he lived with family and friends and denied any ill contacts. His family was healthy, and he did not have any pets and had not been exposed to chemicals.

Cardiovascular, pulmonary, and abdominal examinations were normal. Light-touch sensation was equally diminished in both legs. HIV and syphilis tests were negative.

A skin biopsy showed histiocytic granulomatous dermatitis with M leprae bacteria consistent with leprosy (Figure 2).

After further questioning the patient revealed he had eaten armadillo meat about 14 years ago. Old photographs suggested that the clinical disease had begun more than 2 years before his current presentation (Figure 3). He was started on the current antileprosy multidrug therapy. A follow-up visit 1 month later showed little change in his appearance.

Diagnosis

Although our patient's disease was diagnosed relatively late in the disease course, his was a classic clinical presentation. Often, disturbing skin lesions are the chief complaint.⁸ In fact, leprosy is one of the most common causes of peripheral neuropathy in developing countries.¹⁰ The neuropathy can be the result of factors such as perineural granuloma formation or nonspecific inflammatory infiltrate and/or fibrosis.¹¹ Nerve thickening may help the clinician differentiate leprosy from other conditions with similar lesions, such as secondary syphilis, cutaneous leishmaniasis, yaws, cutaneous fungal infections, or sarcoidosis.¹²

Some experts argue that leprosy may be diagnosed clinically, but definitive diagnosis requires identification of acid-fast bacilli in the skin.^1,2 Fullthickness skin biopsy is the definitive modality, but the use of the slit-smear technique is more practical, as it is readily available worldwide.^1,2

Other laboratory methods, including various skin tests (eg, Lepromin, Mitsuda), serologic assays for anti-M leprae antibodies, and the newer polymerase chain reaction (PCR) test for M leprae, are not widely available or accepted for leprosy diagnosis.¹³ In addition, in regions with a low incidence of leprosy, such as the United States, PCR analysis is only useful when the diagnosis is in doubt because of atypical clinical or histologic findings.⁸

Clinical Manifestations, Classification

Leprosy has a great variety of clinical manifestations, which are determined by the host's cell-mediated immune response, for which there may be a genetic basis (Table 1).² At one pole of the spectrum lies the tuberculoid type, characterized by one or a few asymmetric plaques or macules with sharp, raised borders. In dark-skinned people, these lesions are often centrally hypopigmented with erythematous borders. The central areas are scaly, hairless, and anesthetic (ie, without sensation). Patients may have palpable, enlarged nerves innervating cooler areas of their bodies. By the time the skin lesions are apparent, nerve damage and sensory loss have often already occurred.¹ The tuberculoid type involves a vigorous and specific cell-mediated immune response, as evidenced by a positive Mitsuda skin test.¹⁴

On the other pole lies the lepromatous type, of which our patient is a good example. In this type, there is a very high antigen burden with little or no cell-mediated immunity, leading to diffuse, innumerable pleomorphic but often less erythematous lesions; almost any area of even normal-appearing skin contains bacilli. Disfigurement results from expanding dermis, yielding findings such as leonine facies, madarosis, saddle-nose deformity, blindness, or loss of teeth. Compared with the tuberculoid type, nerve damage is more slowly progressive and insidious but eventually is severe and diffuse. Testicular damage can lead to azoospermia and gynecomastia.¹⁵

Between the polar tuberculoid and lepromatous types lie the unstable borderline types, which often evolve into one of the polar forms of the disease. Borderline tuberculoid, borderline, and borderline lepromatous types of leprosy represent the range of this disease, with respectively increasing antigen burden and decreasing leprosy-specific immunity.¹

The earliest detectable form of leprosy is the indeterminate type, which is a diagnosis of exclusion that is rarely made, except in close contacts of known patients. It is usually manifested as a single hypopigmented macule, 2 to 4 cm in diameter, with a poorly defined border that lacks erythema, induration, and dysesthesia.

As many as 50% to 75% of patients with the indeterminate type of leprosy heal spontaneously, and 25% to 50% progress to one of the classic forms.¹³ Leprosy is also divided into paucibacillary and multibacillary types for purposes of selecting treatment (Table 2).

Risk of Transmission

There is little information about the exact route of transmission of leprosy, but evidence suggests the most common is human-to-human transmission in respiratory droplets,⁹ since there are high levels of bacillary shedding in nasal secretions.^1,13 Other possible modes of transmission are gastrointestinal, transplacental, or direct inoculation with trauma to the skin or insect bites.^1,13 Contact with armadillos is generally considered to carry a negligible risk, despite occasional case reports.¹

The risk of transmission increases with increasing contact with an affected person; household contacts are at an approximately 5 times higher risk.¹⁶ The rate of transmission in hospital and clinic settings is so low that there is no need for any special infection control precautions.¹⁷ Still, about 85% of leprosy cases in endemic areas have no history of household exposure.¹⁶ The majority of those infected never manifest the disease, and many cases, especially the tuberculoid or intermediate types, resolve spontaneously without specific treatment.

Susceptibility to Leprosy

In endemic areas, 5% of the population are nasal carriers of M leprae DNA, and acid-fast bacilli have been found on the skin and nasal mucosa of healthy individuals.¹⁸ The typical incubation period is believed to be 3 to 5 years, but it is generally shorter for the tuberculoid and lepromatous forms.¹³ These long incubation periods are supported by the reality that leprosy most commonly affects young adults who presumably had long exposure to a parent index case.¹

Therefore, physicians in developed countries should consider leprosy in the differential diagnosis of patients presenting with characteristic lesions who have either immigrated from or visited endemic areas in the past 3 to 5 years.⁵

Multidrug Therapy

Effective management of leprosy has 3 main goals: early diagnosis, medical treatment, and the prevention of disability and, if needed, rehabilitation.² The backbone of treatment is medication, but counseling for the psychosocial effects of the disease, physical and occupational therapy, and surgical procedures for nerve or other tissue destruction are an important part of the approach to this disease.¹⁹ There should be no social (eg, employment, education, travel) restrictions for patients compliant with their multidrug treatment, because after the first multidrug dose, patients are no longer infectious.⁵

Oral medications provide definitive, specific treatment for leprosy (Table 3). The 3 main agents used for the treatment of leprosy are dapsone, rifampin (Rifadin), and clofazimine (Lamprene). Because of resistance to dapsone when used as monotherapy, multidrug treatment is recommended for all patients.⁵ Antileprosy medications are very effective when used together, killing a very high proportion of bacilli within days.¹ Pregnant women, HIV-infected patients, and those being treated for tuberculosis can safely receive these 3 mainstay medications.^1,2 Other drugs that can be used for leprosy treatment are ofloxacin (Floxin), minocycline (Dynacin, Minocin, Myrac), and clarithromycin (Biaxin).²

At the end of the multidrug treatment course, patients must be educated about the signs and symptoms of relapse. Close posttreatment follow-up and reporting of all relapses are vital.² Relapses are treated with the same multidrug treatment courses used for initial therapy, which have been shown to be effective.²⁰ If the M leprae responds to the initial therapeutic regimen, drug resistance is unlikely when it is used again for a relapse.¹⁹

Of utmost importance worldwide is the role of health education and the alleviation of poverty to decrease leprosy transmission if the disease is truly to be eliminated.^5,19

Conclusion

Leprosy is an infectious disease that is curable if recognized promptly and treated early before disability develops. Although the WHO did not achieve its 1991 goal of eliminating leprosy as a public health problem by the year 2000 (defined as a prevalence <1 case per 10,000 population), the use of multidrug therapy has substantially reduced the burden of the disease.

Nevertheless, physicians in the United States must still consider leprosy in the differential diagnosis of patients presenting with anesthetic skin lesions, nodules, plaques, thickened dermis, nasal congestion, and epistaxis, particularly in individuals who are immigrants from endemic areas or in persons who have traveled to such regions within the past few years.

SELF-ASSESSMENT TEST

1. Which of these tests should be used to confirm the diagnosis of leprosy?

1. Full-thickness skin biopsy
2. PCR
3. Anti-M leprae antibody assay
4. Acid-fast bacillus staining of slit-skin smear

2. All these are features of leprosy, except:

1. Anesthetic skin lesions
2. Pruritic skin lesions
3. Hyperpigmented lesions
4. Thickened nerves

3. Which of these descriptions is most characteristic of lepromatous leprosy?

1. Multiple, disfiguring lesions of the face, gums, and testes
2. Multiple symmetric plaques with sharp, raised borders and central scaling
3. Single hypopigmented macule with poorly defined border
4. 3 to 4 asymmetric plaques with raised borders

4. What does the WHO recommend for treatment of multibacillary leprosy?

1. Rifampin plus ofloxacin
2. Dapsone plus rifampin
3. Dapsone plus clofazimine plus rifampin
4. Dapsone plus clofazimine plus rifampin plus monocycline

5. Which of these is the most appropriate treatment for a leprosy relapse?

1. Same multidrug therapy initially used, but at half the dosages
2. Same multidrug therapy initially used, but at double the dosages
3. Same multidrug therapy initially used, at the same initial dosages
4. Multidrug therapy, with at least 1 of the agents being different from the ones used for initial therapy