Early diagnosis and treatment of leprosy in the United States

Early diagnosis and treatment of leprosy in the United States

Alec Style

Leprosy, or Hansen’s disease, is a chronic disease of the skin and peripheral nerves, caused by Mycobacterium leprae. On a worldwide basis, 5.5 million active cases were known in 1991,(1) and in the United States, more than 7,000 were known in 1992 (personal communication, March 1993, National Ambulatory Hansen’s Disease Program, Carville, La.). Most new cases in this country occur in immigrants from areas where the disease is endemic, who often develop clinical disease after arriving in the United States.

In the United States, the diagnosis of leprosy is frequently delayed because physicians fail to recognize the early symptoms and signs of the disease. Sometimes this delay results in permanent, crippling deformities that are potentially preventable. The purpose of this article is to raise physician awareness of the existence of leprosy in the United States, thus improving the ability to diagnose the disease at an early stage.

Epidemiology

The major endemic areas for leprosy are subSaharan Africa, the Indian subcontinent, Southeast Asia and Brazil. The disease is less common but still prevalent in China, the Caribbean islands, Central America, South America, the Pacific Islands and southern Europe.(2)

In the United States, leprosy is indigenous to California, Texas, Louisiana, Florida and Hawaii, as well as Puerto Rico.(2) In 1991, 154 new cases were reported, with most new cases occurring in California, Texas, New York and Hawaii.(3) Major cities with large immigrant populations, such as New York, have significant case loads. Although about one-third of patients registered with the National Ambulatory Hansen’s Disease Program since 1950 were born in the United States (Table 1), most new cases are found among immigrants. The disease affects people of all ages but tends to present in young adults (Table 2).

TABLE 1 Birth Countries of U.S. Patients with Leprosy

Country of origin Number of patients(*)

China 117

Laos 130

Dominican Republic 160

India 228

Cuba 247

American Samoa 291

Cambodia 304

Puerto Rico 376

Vietnam 616

Philippines 1,289

Mexico 1,289

United States 1,464

(*)–Statistics provided for countries of origin with more than 100 patients, for the years 1950-1991.

Data provided by the National Ambulatory Hansen’s Disease Program, Carville, La.

TABLE 2 Patients’ Age at Diagnosis of Leprosy

Patient age (years) Number of patients(*)

15 1,041

25 1,716

35 1,201

45 910

55 739

65 577

75 260

85 51

(*)–Statistics given for the years 1951-1990.

Data provided by the National Ambulatory Hansen’s Disease Program, Carville, La.

Bacteriology

M. leprae is a slow-growing, acid-fast bacillus. The incubation period for the disease is two to five years, although it can be 15 to 20 years or more.(4)

Leprosy is probably spread primarily by airborne droplets from the nasal mucosa and upper airways. The disease may also be transmitted by insects, skin contact, breast milk and the placenta of infected mothers.(4) It is believed that armadillos may transmit the infection, but this theory is unproved. The communicability of leprosy is very low; perhaps 90 percent or more of humans are not susceptible to it. Established cases become noncommunicable within one week of starting treatment.

Classification

Leprosy has two classifications. The World Health Organization (WHO) classification is used primarily to determine treatment strategies and has two categories: multibacillary, when acid-fast bacilli are present in skin biopsies or smears, and paucibacillary, when no bacteria are seen in biopsies or smears. The second classification of leprosy is based on the clinical features of the disease and includes three major types: tuberculoid, lepromatous and borderline.

Clinical Presentation

TUBERCULOID LEPROSY

Leprosy of the tuberculoid type develops in patients with a high level of cellular immunity. Tuberculoid leprosy usually presents as a solitary (occasionally more) small plaque or macule, with a well-defined border and a healing center, which may occur on any part of the body except the warm areas (Figure 1). The lesion is hypopigmented in dark-skinned people and may be hypopigmented or copper-colored in fair-skinned people. An important clinical finding is that the lesion’s center is anesthetic or hypoesthetic. Skin smears and biopsies are negative for acid-fast bacilli.

[ILLUSTRATION OMITTED]

Another important clinical finding is an enlarged nerve near the skin lesion. Enlargement may affect a sensory nerve supplying the lesion or a large peripheral nerve; for example, the ulnar nerve at the elbow, the medial nerve at the wrist, the posterior tibial nerve at the ankle and the common peroneal nerve. Nerve enlargement may result in permanent neuropathy. Although the skin lesion frequently heals spontaneously, prompt treatment may still limit neurologic damage.

A subtype of tuberculoid leprosy is called pure neural leprosy. Patients with this subtype have peripheral neuropathy without skin lesions. This type is more common in patients from the Indian subcontinent.

LEPROMATOUS LEPROSY

Lepromatous leprosy develops in patients who have little or no cellular immunity. Consequently, their skin lesions (macules, papules or nodules) are numerous and symmetrically located over the body. These small lesions may ulcerate and have poorly defined edges. Their centers do not show healing and are not anesthetic.

Nerve damage occurs late in the clinical course of lepromatous leprosy and is symmetrically distributed. Sensory nerve loss resembles “glove and stocking” anesthesia of the hands and feet. It can spread to other parts of the body but spares warmer areas, such as the groin and axillae. Peripheral nerves often are not enlarged. Autonomic nerve damage causes anhidrosis, so the skin of the hands and feet becomes dry and cracked. This dry skin problem leads to secondary infections and ulcerations (Figure 2). Finally, muscles become weak as a result of nerve damage or direct invasion by bacteria.

[ILLUSTRATION OMITTED]

Major deformities of the hands and feet are common in patients with lepromatous leprosy (Figure 3). Repeated trauma, abnormal pressure points, ulcerations and secondary infections lead to osteomyelitis, bone resorption, edema, fractures and shortening of digits. Bacteria can invade body organs such as the testes, causing testicular atrophy and secondary gynecomastia. When left untreated, the disease progresses slowly, and death is usually the result of renal failure, acute infections, tuberculosis or the complications of old age.(5)(pp37-9) With appropriate treatment, patients will not die of leprosy.

[ILLUSTRATION OMITTED]

Some patients show the distinctive “Leonine facies” (Figure 4). Characteristically, nodules occur on the face, ear, cheeks, nose and eyebrows (Figure 5), and the skin may become thickened. Bacteria may infiltrate the mucous membranes of the nose, resulting in ulceration, infection and collapse of the nasal bones. Teeth can be lost because of bacterial invasion of the mouth.

[ILLUSTRATION OMITTED]

Leprosy affects the eyes in a variety of ways.(6) Patients with lepromatous disease may lose their eyebrows (madarosis). Damage to the seventh cranial nerve may prevent proper eye closure (lagophthalmos), leading to drying of the cornea with subsequent susceptibility to trauma and secondary infection. Direct bacterial invasion of the eyes may cause keratitis and iritis. These complications, if untreated, can lead to permanent blindness.

BORDERLINE LEPROSY

Most cases of leprosy fall between the two polar types and are referred to as borderline leprosy. The clinical features depend on whether the disease is closer to the tuberculoid or lepromatous ends of the spectrum. It is important to note that borderline leprosy is immunologically unstable and can cause widespread nerve damage.

When to Suspect Leprosy

Although leprosy can present in many ways (Table 3), the two most common presentations are an unusual skin rash and/or peripheral neuropathy. The skin lesions mimic lesions associated with many other diseases. Peripheral neuropathy presents with either the signs and symptoms of acute neuritis or the secondary complications of sensory or motor nerve damage.(7) These secondary complications include cracked and dry skin, burns, muscle wasting and ulcerations. The disease can also present as a persistent and sometimes painful red eye. Leprosy should be suspected in any patient who has these problems and comes from an endemic area.

TABLE 3

Presentations Suggestive of Leprosy

Persistent red eye

Unusual skin rash

Peripheral neuropathy

Thickened nerves

Ulceration of hands or feet

Deformities of hands or feet

Leonine facies

Patient is from endemic area

Diagnosis

The physician should look for the four cardinal features of leprosy: sensory loss, thickened peripheral nerves, skin lesions and acid-fast bacilli in biopsies or skin smears.(5)(p57) The presence of two of the first three signs or a positive skin biopsy or smear are necessary to make the diagnosis.

Clinical assessment requires patients to be completely undressed and the skin of the entire body examined for rashes, burns and ulcerations. Any skin lesions should be tested for loss of light touch; testing with a nylon monofilament is preferable, but a finger or cotton swab will suffice. Peripheral nerves should be palpated for enlargement, and the hands and the feet examined for signs of peripheral neuropathy. The face should also be examined, including a gentle test of the cornea for sensory loss, and patients should be asked to close their eyes tightly to determine the presence of lagophthalmos. A slit-lamp examination by an ophthalmologist may be necessary if eye disease is suspected.

A skin sample should be taken from the edge of an active lesion for biopsy to confirm the diagnosis. In addition, skin smears should be made from the center of a lesion and from six peripheral sites (ears, elbows, knees). The smears are negative for acidfast bacilli in paucibacillary leprosy and positive in multibacillary leprosy. (Detailed instructions on performing skins smears are available from the National Ambulatory Hansen’s Disease Program, Gilles W. Long Hansen’s Disease Center, 5445 Point Clear Rd., Carrville, LA 70721-9607; telephone: 800-642-2477.)

The lepromin test is a guide to cell-mediated immunity against leprosy.(8) It is not useful as a diagnostic test, because many patients with leprosy have no cellular immunity to the disease. In practice, it is rarely used.

Leprosy Reactions

Patients may develop acute hypersensitivity reactions to leprosy antigens. These “lepra reactions” are medical emergencies that must be given prompt treatment or they can cause permanent nerve damage.(9) Two types of hypersensitivity reaction may occur: type 1, reversal reaction, and type 2, erythema nodosum leprosum.

Type 1 reactions occur most commonly within six months of commencing treatment in patients who are near the tuberculoid end of the spectrum. Skin lesions in these patients become inflamed and tender, and may ulcerate. Nerves lying next to the lesions may become tender and thickened.

Erythema nodosum leprosum occurs in borderline lepromatous and lepromatous patients, usually in the second year of treatment. Immune complexes are deposited in various tissues of the body. Red, tender nodules or plaques appear in crops and may ulcerate (Figure 6). Limbs can become quite edematous. A systemic illness with fever and malaise sometimes develops, and the immune complexes may damage the eyes, testes, bones and lymph nodes.

[ILLUSTRATION OMITTED]

Patients may also have silent neuritis, in which peripheral nerves lose their function without clinical signs, such as pain or tenderness.(10) For this reason, an examination of the peripheral nerves, especially of the hands and feet, should be conducted annually in all patients to detect any deterioration of function. These examinations should continue for several years after treatment has ended.

Drug Treatment

WHO recommends multiple-drug therapy to prevent drug resistance.(11) The three main drugs used in leprosy treatment are dapsone, rifampin (Rifadin, Rimactane) and clofazimine (Lamprene). The WHO regimens have considerably reduced the length of therapy. Many American leprologists do not accept the WHO treatment guidelines, however, because they consider them untested. They prefer to follow the traditional treatment regimens.(12) For detailed information on drug therapy for patients with leprosy, physicians should consult a standard textbook about infectious diseases or leprosy,(12)(13) or contact the National Ambulatory Hansen’s Disease Program.

WHO recommends treating paucibacillary leprosy for six months with dapsone, 100 mg daily, and rifampin, 600 mg monthly. The latter drug is given under supervision. Multibacillary disease is treated for 24 months with dapsone, 100 mg daily, and clofazimine, 50 mg daily. In addition, rifampin, 600 mg monthly, and clofazimine, 300 mg monthly, are given under supervision.

Multiple-drug therapy is highly effective.(14) In patients with multibacillary disease, the relapse rate is less than 1 percent on follow-up at seven years. Treatment can be stopped after 24 months even when skin smears are still positive, as the bacterial index will continue to fall. This treatment approach is not universally accepted, however, and some leprologists recommend treating multibacillary patients until their skin smears are negative.(15) Patients should be monitored for several years after treatment for relapse, reactions and progressive neuropathy.

Treatment of Leprosy Reactions

It is possible only to outline the treatment of leprosy reactions in this article. Mild reactions without neuritis may be treated with simple analgesics. Major reactions, with neuritis or severe inflammation of the skin, must be treated as an emergency to prevent permanent deformities. These patients should be treated with prednisone in dosages sufficient to control the pain and tenderness (40 to 80 mg for one week). The drug should be tapered by 5 mg each one to two weeks, according to clinical response. When the dosage level reaches 30 mg, the drug should be tapered more slowly over several months.(10)

Thalidomide is quite effective in controlling moderate to severe erythema nodosum leprosum.(5)(p128)(10) Thalidomide should not be given to any woman of childbearing potential, however, because of its severe teratogenic effects. If thalidomide is unavailable or contraindicated, prednisone should be given. Questions about thalidomide should be referred to the National Ambulatory Hansen’s Disease Program, because the drug is investigational and closely controlled.

Clofazimine helps to control erythema nodosum leprosum reactions. The initial dosage is 300 mg daily for six weeks only, as these high doses can cause abdominal pain. It is then reduced to 200 mg daily for two to six months, depending on the response. Finally, it is reduced to a maintenance dose of 100 mg daily.(10) Many patients refuse to take clofazimine, because it causes dark pigmentation of the skin and colors urine and body fluids organge.

If lepra reactions involve the eyes, the patient should be referred promptly to an ophthalmologist.

Final Comment

Family physicians in the United States should be alert to the possible existence of leprosy in their communities. Certainly, physicians who treat patients coming from endemic areas should be vigilant for the signs of leprosy, because early treatment may prevent chronic disability.

Unfortunately, many patients with leprosy are left with severe deformities and require extensive rehabilitation.(16) In addition, patients who are refugees may have multiple medical, psychologic and social problems.(17) The family physician should coordinate the wide range of rehabilitative services required by these patients. Rehabilitation services and consultation on any aspect of leprosy may be obtained from the National Ambulatory Hansen’s Disease Program.

It is important to remember that in most cultures, leprosy is a highly stigmatizing condition. Cambodian patients, for example, may be rejected by their families and community.(18) Because of the derogatory connotation of the word in English, it is customary to use the term Hansen’s disease in place of the word leprosy with patients, families and the community.

REFERENCES.

(1.)Noordeen SK, Lopez Bravo L, Sundaresan TK. Estimated number of leprosy cases in the world. Bull World Health Organ 1992; 70:7-10.

(2.)Trautman JR. Epidemiological aspects of Hansen’s disease. Bull N Y Acad Med 1984; 60:722-31.

(3.)Summary of notifiable diseases, United States 1991. MMWR Morb Mortal Wkly Rep 1992; 40:5.

(4.)Meyers WM. Leprosy. Dermatol Clin 1992; 10(1):73-96.

(5.)Bryceson A, Pfaltzgraff RE, eds. Leprosy. 3d ed. New York: Churchill Livingstone, 1990.

(6.)Hogeweg M. Eye complications in leprosy. Trop Doct 1992; 22(Suppl 1):15-21,57-9.

(7.)Myers B, Bryceson AD. Leprosy–an important cause of peripheral neuropathy in Asian immigrants. Practitioner 1987; 231(1429):637-8.

(8.)Thangaraj RH, Yawalkar SJ, eds. Leprosy for medical practitioners and paramedical workers. Basle, Switzerland: Ciba-Geigy, 1992:68.

(9.)Malin AS, Waters MF, Shehade SA, Roberts MM. Leprosy in reaction: a medical emergency. BMJ 1991; 302:1324-6.

(10.)Yoder LJ. Management of reaction in Hansen’s disease. Carville, La.: The Star. January/February 1987; 1-7.

(11.)WHO Expert Committee on Leprosy: Sixth Report. Geneva, Switzerland: World Health Organization, 1988:31.

(12.)Jacobson RR. Treatment. In: Hastings RC, ed. Leprosy. New York: Churchill Livingstone, 1985: 195-209.

(13.)Lockwood DN, McAdam KP. Leprosy. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious diseases. Philadelphia: Saunders, 1992:1264-5.

(14.)Consensus development statement on the chemotherapy of leprosy. Int J Lepr Other Mycobact Dis 1992; 60:644-52.

(15.)Bechelli LM. Prospects of global elimination of leprosy as a public health problem by the year 2000. Int J Lepr Other Mycobact Dis 1994; 62:284-92.

(16.)Brand PW, Fritschi EP. Rehabilitation in leprosy. In: Hastings RC, ed. Leprosy. New York: Churchill Livingstone, 1985:287-319.

(17.)Style A. The comprehensive care of Cambodians with Hansen’s disease in a large American city [Abstract]. 14th International Leprosy Congress. Orlando, Fla., 1993. Int J Lepr Other Mycobact Dis 1993; 61(4 Suppl):1A-175A.

(18.)Style A. Caring for Southeast Asian patients with leprosy. Proceedings of the Chemotherapy of Leprosy Conference. April 6-8, 1992. Greenville, S.C.

COPYRIGHT 1995 American Academy of Family Physicians

COPYRIGHT 2004 Gale Group