Morbus Hansen (Lepra)

Introduction

Background

Leprosy is a chronic infection caused by the acid-fast, rod-shaped bacillus Mycobacterium leprae. Leprosy can be considered 2 connected diseases that primarily affect superficial tissues, especially the skin and peripheral nerves. Initially, a mycobacterial infection causes a wide array of cellular immune responses. These immunologic events then elicit the second part of the disease, a peripheral neuropathy with potentially long-term consequences.

The social and psychological effects of leprosy, as well as its highly visible debilities and sequelae, have resulted in a historical stigma associated with leprosy (see Image 1). To minimize the prejudice against those with leprosy, the condition is also known as Hansen disease, named after G.A. Hansen, who is credited with the 1873 discovery of M leprae. This mycobacterium grows extremely slowly and has not been successfully cultured in vitro.

In the 1990s, the World Health Organization (WHO) launched a campaign to eliminate leprosy as a public health problem by 2000. Elimination, as defined by the WHO, was defined as a reduction of patients with leprosy requiring multidrug therapy to fewer than 1 per 10,000 population. This goal was achieved in terms of global prevalence by 2002, but 15 of the 122 countries where leprosy was endemic in 1985 still have prevalence rates of greater than 1 per 10,000 population.¹

Although multidrug regimens have been used globally to cure nearly 14 million patients with leprosy since 1985, the number of new leprosy cases remained relatively unchanged from 1980 to 2000, ranging from 500,000-700,000 worldwide per year.² Access and delivery of antibiotics continues to be a problem in the most endemic nations. With the precise transmission mechanism of leprosy still unknown and a lack of an effective vaccine, leprosy will probably continue to pose an ongoing public health problem in the coming decades.

Pathophysiology

Leprosy can manifest in different forms, depending on the host response to the organism.

Individuals who have a vigorous cellular immune response to M leprae have the tuberculoid form of the disease that usually involves the skin and peripheral nerves. The number of skin lesions is limited, and they tend to be dry and hypoesthetic. Nerve involvement is usually asymmetric. This form of the disease is also referred to as paucibacillary leprosy because of the low number of bacteria in the skin lesions (ie, <5>

Individuals with minimal cellular immune response have the lepromatous form of the disease, which is characterized by extensive skin involvement. Skin lesions are often described as infiltrated nodules and plaques, and nerve involvement tends to be symmetric in distribution. The organism grows best at 27-30°C; therefore, skin lesions tend to develop in the cooler areas of the body, with sparing of the groin, axilla, and scalp. This form of the disease is also referred to as multibacillary leprosy because of the large number of bacteria found in the lesions (ie, >6 lesions, with possible visualization of bacilli on smear). Results of skin tests with antigen from killed organisms are nonreactive.

Patients may also present with features of both categories; however, over time, they usually evolve to one or the other (indeterminate or borderline leprosy). Interestingly, most individuals who are exposed to leprosy never develop the disease.

Classification of leprosy: Leprosy has 2 classification schemas: the 5-category Ridley-Jopling system and the simpler and more commonly used WHO standard.

• Ridley-Jopling: Depending on the host response to the organism, leprosy can manifest clinically along a spectrum bounded by the tuberculoid and lepromatous forms of the disease. Most patients fall into the intermediate classifications, which include borderline tuberculoid leprosy, midborderline leprosy, and borderline lepromatous leprosy. The classification of the disease typically changes as it evolves during its progression or management. The Ridley-Jopling system is used globally and forms the basis of clinical studies of leprosy. It may also be more useful in guiding treatment regimens and assessing risk of acute complications. Physical findings in each subtype are presented in the Clinical section.
• WHO system: The WHO recommends classifying leprosy according to the number of lesions and the presence of bacilli on a skin smear. This method is useful in countries where biopsy analysis in unavailable.
  • Paucibacillary leprosy is characterized by 5 or fewer lesions with absence of organisms on smear. Paucibacillary leprosy generally includes the tuberculoid and borderline lepromatous categories from the Ridley-Jopling system.
  • Multibacillary leprosy is marked by 6 or more lesions with possible visualization of bacilli on smear. Lepromatous leprosy, borderline lepromatous leprosy, and midborderline leprosy on the Ridley-Jopling scale are included in the multibacillary leprosy category.

Frequency

United States

In the United States, an average of 150 cases are diagnosed each year. In 2004, 69 new cases of leprosy were detected and 131 total persons were reported to have the disease, according to the WHO. Most cases of leprosy in the United States are found in immigrants, although endemic foci exist in parts of Louisiana, Florida, and Texas along the Gulf of Mexico; in Mexican and Asian California populations; and in Spanish Americans in New York City. Around 85% of these detected leprosy cases involve patients who have lived in foreign countries, primarily Asia, Africa, and Latin America.³

International

According to WHO figures, the global registered prevalence of leprosy at the start of 2005 was 286,063 cases. Global annual detection rates have declined from 2001 to 2004, when 763,262 and 407,791 new cases were reported, respectively. Leprosy is still deemed a public health problem in 9 countries: Angola, Brazil, Central African Republic, Democratic Republic of the Congo, India, Madagascar, Mozambique, Nepal, and the United Republic of Tanzania. These countries account for 84% of reported cases. Furthermore, more than 94% of new cases of leprosy in Latin America are reported in Brazil.¹

Mortality/Morbidity

Leprosy is rarely fatal, and the primary consequence of infection is nerve impairment and debilitating sequelae. According to one study, 33-56% of newly diagnosed patients already displayed signs of impaired nerve function.⁴ According to estimates, 3 million people who have completed multidrug therapy for leprosy have sustained disability due to nerve damage. Although both lepromatous leprosy and tuberculoid leprosy involve the skin and peripheral nerves, tuberculoid leprosy has more severe manifestations. Nerve involvement results in loss of sensory and motor function, which may lead to frequent trauma and amputation. The ulnar nerve is most commonly involved.

• Damage in the following nerves is associated with characteristic impairments in leprosy:
  • Ulnar and median - Clawed hand
  • Posterior tibial - Plantar insensitivity and clawed toes
  • Common peroneal -Foot drop
  • Radial cutaneous, facial, and greater auricular nerves (may also be involved; see Image 2)
• Infiltration by bacteria may lead to destruction of nasal cartilage (lepromatous leprosy), ocular involvement, and diffuse thickening of the skin. Advanced cases of leprosy involve the loss of eyebrows and lashes, but these deformities are less common today.
• Worldwide, leprosy is considered the most common cause of crippling of the hand, which is caused by ulnar nerve involvement.⁵ Peroneal nerve involvement can lead to foot drop, posterior tibial nerve involvement, and clawed toes.

Race

Leprosy was once endemic worldwide, and no racial predilection is known. In the late 1800s, the incidence of leprosy in northern Europe and North America dropped dramatically, and the disease is now reported primarily in tropical areas.

Sex

Leprosy is generally more common in males than in females, with a male-to-female ratio of 1.5:1. In some areas in Africa, the prevalence of leprosy among females is equal to or greater than that in males.²

Age

Leprosy can occur at any age, but, in developing countries, the age-specific incidence of leprosy peaks in children younger than 10 years, who account for 20% of leprosy cases. Leprosy is very rare in infants; however, they are at a relatively high risk of acquiring leprosy from the mother, especially in cases of lepromatous leprosy or midborderline leprosy.

Clinical

History

• Symptoms
  • Painless skin patch accompanied by loss of sensation but not itchiness (Loss of sensation is a feature of tuberculoid leprosy, unlike lepromatous leprosy, in which sensation is preserved; see Image 3.)
  • Loss of sensation or paresthesias where the affected peripheral nerves are distributed
  • Wasting and muscle weakness
  • Foot drop or clawed hands (may result from neuritic pain and rapid peripheral nerve damage; see Image 4)
  • Ulcerations on hands or feet (see Image 5)
  • Lagophthalmos, iridocyclitis, corneal ulceration, and/or secondary cataract due to nerve damage and direct bacillary skin or eye invasion⁶
• Symptoms in reactions
  • Type 1 (reversal) - Sudden onset of skin redness and new lesions
  • Type 2 (erythema nodosum leprosum [ENL]; see Image 10) - Many skin nodules, fever, redness of eyes, muscle pain, and joint pain
• Travel: Leprosy should be considered in anyone who has lived in the tropics or who has traveled for prolonged periods to endemic areas.
• Exposure: The incubation period of leprosy is long, ranging from a few months to 20-50 years. The mean incubation time is estimated to be 10 years for lepromatous leprosy and 4 years for tuberculoid leprosy. The organism's slow dividing time (once every 2 wk) contributes to the challenge of epidemiologically linking exposures to the development of disease.
• Because of immunologic reasons, only around 5-10% of the population is estimated to be susceptible to infection.

Physical

The cardinal signs of leprosy include hypoesthesia, skin lesions, and peripheral neuropathy. The first physical signs of leprosy are usually cutaneous. The subtype of leprosy often determines the degree of skin involvement.

• Physical examination should include the following:
  • Evaluation of skin lesions
  • Careful sensory and motor examination
  • Palpation of peripheral nerves for pain or enlargement, with particular attention paid to the following locations:
    • Elbows - Ulnar nerve
    • Wrist - Superficial radial cutaneous and median nerves
    • Popliteal fossa - Common peroneal nerve
    • Neck - Great auricular nerve
• Physical findings in specific leprosy subtypes include the following:
  • Tuberculoid leprosy
    • The initial lesion is often a sharply demarcated hypopigmented macule that is ovoid, circular, or serpiginous. The lesions may be somewhat elevated with a dry scaly center and erythematous borders.
    • Common lesion sites include the buttocks, face, and extensor surfaces of limbs. The perineum, scalp, and axilla are not normally involved because of the temperature differential in these zones, as predilection is toward cooler zones.
    • As the disease progresses, lesions tend to destroy the normal skin organs such as sweat glands and hair follicles.
    • Superficial nerves that lead from the lesions tend to enlarge and are sometimes palpable. The patient may experience severe neuropathic pain. Nerve involvement can also lead to trauma and muscle atrophy.
  • Lepromatous leprosy
    • This form is characterized by extensive bilaterally symmetric cutaneous involvement, which can include macules, nodules, plaques, or papules (see Image 6).
    • Unlike lesions in tuberculoid leprosy, those in lepromatous leprosy have poorly defined borders and raised and indurated centers. As in all forms of leprosy, lepromatous lesions are worst on cooler parts of the body. Common areas of involvement include the face, ears, wrists, elbows, buttocks, and knees.
    • Hoarseness, loss of eyebrows and eyelashes, and nasal collapse secondary to septa perforation may occur in advanced cases of disease. Involvement of the eye may include keratitis, glaucoma, or iridocyclitis (see Image 7).
    • The leonine facies associated with leprosy develop as the disease progresses, and the facial skin becomes thickened and corrugated.
    • Axillary and inguinal adenopathy may develop, in addition to scarring of the testes and subsequent gynecomastia and sterility.
    • Nerve involvement in lepromatous leprosy is not as severe as in tuberculoid leprosy, since nerves, although visibly thickened and highly infected, still function reasonably well in early stages of the disease.
  • Borderline tuberculoid leprosy: The lesions are few or moderate and asymmetric with almost complete anesthesia. Peripheral nerves are often involved and thickened asymmetrically, and cutaneous nerves are sometimes enlarged.
  • Midborderline leprosy: The number of skin lesions is moderate, and they are asymmetrical and somewhat anesthetic. Peripheral nerves may be somewhat symmetrically enlarged, but cutaneous nerves are not.
  • Borderline lepromatous leprosy: Moderate to numerous slightly asymmetrical skin lesions appear with minor or no anesthesia. Peripheral nerves are often enlarged symmetrically, but cutaneous nerves are not.
  • Indeterminate leprosy: Skin lesions are typically either hypopigmented or hyperpigmented macules or plaques. Patients may note that these lesions are anesthetic or paresthetic.

Causes

• M leprae is the causative agent associated with leprosy, which has been recognized as an infectious disease for the last 2 millennia. M leprae was discovered as the causative agent in 1873. The acid fast, gram-positive bacillus is an obligate intracellular organism with a predilection for Schwann cells and macrophages. M leprae has not been successfully grown using artificial media.
• The route of transmission has not been definitively established, although human-to-human aerosol spread of nasal secretions is thought to be the most likely mode of transmission in most cases. Leprosy is not spread by touch, since the mycobacteria are incapable of crossing intact skin. Living near people with leprosy is associated with increased transmission. Among household contacts, the relative risk for leprosy is increased 8- to 10-fold in multibacillary and 2- to 4-fold in paucibacillary forms. Animal reservoirs do exist (armadillos, certain nonhuman primates), and cases of suspected zoonotic transmission have been reported.