Chapter 29 Hansen’s disease (leprosy)
1. What causes leprosy?
2. Why is leprosy called Hansen’s disease?
Leprosy is referred to as Hansen’s disease to honor Gerhard Armauer Hansen, a Norwegian physician, who discovered the leprosy bacterium in 1873. Mycobacterium leprae was the first bacillus to be associated with a human disease. In addition, as with acquired immune deficiency syndrome, there are considerable social stigmata associated with having leprosy. Therefore, rather than referring to patients as lepers and the disease as leprosy, it is often preferable to use the term Hansen’s disease.
3. How is leprosy transmitted?
Although the mode of transmission is still uncertain, current evidence favors respiratory transmission. Average incubation times are 2 to 5 years for tuberculoid leprosy and 8 to 12 years for lepromatous cases. Evidence for congenital and percutaneous transmission has been presented, but these are probably rare.
4. Are children and adults equally susceptible to acquiring leprosy?
Children and young adults seem to be most susceptible to acquiring leprosy. Only about 5% of adults at risk, such as marriage partners, develop leprosy. As many as 60% of children who have a parent with leprosy develop the disease. M. leprae may be present in breast milk; there is some evidence to suggest that the infection can be transmitted via the placenta.
5. Are humans the only host for M. leprae?
It was once believed that humans were the only natural reservoir for M. leprae. More recently, four other animals have been shown to carry the infection: the nine-banded armadillo, chimpanzee, sooty mangabey monkey, and cynomolgus macaque. Up to 10% of wild armadillos in Louisiana and eastern Texas have naturally acquired leprosy.
7. How common is leprosy?
There were about 2.7 million persons with leprosy worldwide in 1994, with 600,000 new cases yearly. Leprosy is endemic in 53 countries, including India, Bangladesh, and Brazil. There are approximately 6,500 cases of leprosy in the United States. Around 200 to 250 new cases are reported each year in the United States, with about 175 of these being new cases diagnosed for the first time; 166 new cases were reported in the U.S. in 2005.
9. How is leprosy recognized clinically?
The three most useful features are skin lesions, areas of cutaneous anesthesia, and thickened nerves. Other features are nasal stuffiness, inflammatory eye changes, and loss of eyebrows. A reactional state in lepromatous leprosy causes multiple tender red nodules resembling erythema nodosum (erythema nodosum leprosum).
10. Is there more than one kind of leprosy?
Four major variants of leprosy represent a spectrum of disease: indeterminate leprosy, tuberculoid leprosy, lepromatous leprosy, and dimorphous (or borderline) leprosy (Fig. 29-1). The lepromatous form is seen twice as frequently in men as in women. Although it varies from country to country, about 90% of the leprosy cases in the United States are of the lepromatous type.
11. Does indeterminate leprosy mean that you do not know what type it is?
No. Indeterminate leprosy is believed to be the very first sign of infection with the leprosy bacillus. It usually manifests as a solitary macular skin lesion that is vaguely defined and either erythematous or hypopigmented. Patients with indeterminate leprosy may clear spontaneously or progress to one of the other three types of leprosy.
12. What are the two “polar” forms of leprosy? How do they differ?
Tuberculoid leprosy and lepromatous leprosy are considered the two polar forms, and they tend to remain stable clinically. Patients with tuberculoid leprosy have a high degree of immunity against M. leprae and have few skin lesions and few organisms in their skin. Patients with lepromatous leprosy have low immunity against M. leprae and have many skin lesions and millions of organisms in their skin (Table 29-1).
13. Describe dimorphous leprosy.
Dimorphous leprosy, also known as borderline leprosy, shows features intermediate between tuberculoid and lepromatous leprosy. It is a less stable form of leprosy, and its clinical features and immune status may change over time. If dimorphous leprosy develops more features of lepromatous leprosy, it is referred to as dimorphous-lepromatous. If it develops features of tuberculoid leprosy, it is called dimorphous-tuberculoid.
14. What is the unusual feature of the cell-mediated immunity in lepromatous leprosy?
Patients with lepromatous leprosy have a specific anergy to M. leprae. This is in contrast to diseases such as sarcoidosis and Hodgkin’s lymphoma, in which there is loss of immunity to a wide variety of antigens. The clinical spectrum of leprosy appears to depend mainly on an individual’s ability to develop effective cell-mediated immunity against M. leprae. In endemic areas, most individuals appear to be completely resistant to infection with the leprosy bacillus.
15. Define the cytokine response to M. leprae in tuberculoid versus lepromatous patients.
Studies of circulating cytokines in leprosy patients and cytokine production in skin show those tuberculoid patients have a helper T cell type I (Th1) response to M. leprae with predominant interleukin-2 (IL-2) and interferon (IFN)-? production, while lepromatous cases have a response of Th2-type cytokines.
16. How is the diagnosis of leprosy usually made?
The diagnosis of leprosy is usually made by demonstrating cutaneous anesthesia, by finding enlarged superficial nerves, and by demonstrating leprosy bacilli in the skin.
• Cutaneous anesthesia is best diagnosed by using a wisp of cotton to demonstrate loss of light touch. In tuberculoid and dimorphous leprosy, sensation is lost within the center of skin lesions, which are often annular. In lepromatous leprosy, the loss of light touch sensation typically occurs first in fingers and toes, while anesthesia in individual skin lesions may be variable.
• Nerve enlargement in tuberculoid and dimorphous leprosy occurs within or adjacent to specific skin lesions. In lepromatous leprosy, large peripheral nerves can be palpated. The easiest nerves to palpate are the posterior auricular nerve behind the ear and the ulnar nerve at the elbow (Fig. 29-2).
18. Can the same acid-fast stain used for Mycobacterium tuberculosis be used for the leprosy bacillus?
19. What are Virchow cells?
Lepromatous leprosy exhibits an extensive cellular infiltrate separated from the epidermis by a narrow grenz zone of collagen. In florid early lesions, macrophages contain abundant live bacilli. In time, and with therapy, degenerate bacilli accumulate in macrophages, and these cells are called lepra cells or Virchow cells; they have foamy cytoplasms and are Fite stain–positive.
20. Is the lepromin skin test helpful in making a diagnosis of leprosy?
No, but it is useful in classifying leprosy into the various subtypes. Lepromin is a crude preparation of killed bacteria from a lepromatous nodule or from infected armadillo liver. An intradermal injection of 0.1 mL of lepromin is read at 48 hours for erythema (Fernandez reaction) or at 3 to 4 weeks for a papule or nodule (Mitsuda reaction). Patients with tuberculoid leprosy have strongly positive reactions, while dimorphous and lepromatous patients are usually negative. The reaction in indeterminate leprosy is variable.
21. Is the neuropathy in lepromatous leprosy the same as that in diabetic neuropathy?
No. Although the neuropathy is similar in the two diseases, it is a true “stocking-glove” anesthesia in diabetes mellitus. In leprosy, the cooler parts of the skin and nerves are affected, which gives the peripheral neuropathy a spotty and variable expression. For example, the dorsal aspects of the hands may be anesthetic, while the palms are partially spared. This has led some neurologists to misdiagnose leprosy patients as malingerers or neurotics.
22. Describe a patient with advanced lepromatous leprosy.
The skin shows widespread, hyperpigmented papules and nodules with a predilection for cool parts of the body, such as the earlobes, nose, fingers, and toes. There may be loss of the lateral eyebrows (madarosis) (Fig. 29-4), redness of the conjunctiva, a stuffy nose, flattening of the nasal bridge (Fig. 29-5A), and a palpable postauricular nerve. There is marked anesthesia of the extremities with some atrophy of the thenar and hypothenar muscles (Fig. 29-5B). Contraction of the fourth and fifth fingers may be seen, resulting in difficulty in extending the fingers fully. Ulcers or sores of the hands and feet may be present secondary to minor trauma or burns (Fig. 29-5C). A plantar ulcer surrounded by hyperkeratotic skin (mal perforans ulcer) may be present over a pressure area (Fig. 29-5D). The physician should inquire whether the patient is from an endemic area for leprosy.
24. What are the reactional states of leprosy?
There are two types of reactions that may occur spontaneously but often follow the initiation of antibacterial therapy by months to years. Approximately half of all leprosy patients experience one of these acute inflammatory episodes at some point in their disease course.
Type I reactions (reversal reactions) complicate unstable dimorphous leprosy and represent alterations in the patient’s cell-mediated immunity. The immunity may be either upgraded or downgraded. Typically, in type I reactions, existing lesions become acutely inflamed.
Type II reactions (most commonly erythema nodosum leprosum [ENL]) occur in lepromatous leprosy (Fig. 29-6). ENL reactions are believed to represent immune complex precipitation in blood vessels due to released antigens from M. leprae organisms that have been damaged by antibiotic therapy. The patients develop red, tender nodules mainly on their extremities, associated with constitutional symptoms including fever, arthralgias, lymphadenitis, and neuritis.
25. What drugs are used in multidrug therapy for leprosy?
Because of the resistance to dapsone, multidrug therapy is currently used for leprosy and has resulted in a dramatic improvement in prognosis and a decrease in reported new cases worldwide. Only four drugs are readily available in the United States to treat leprosy: dapsone, rifampin, clofazimine, and ethionamide. Of these agents, only rifampin is bactericidal.
26. Do the recommendations of the World Health Organization (WHO) differ from those of the U.S.?
Due to economic and other factors, the WHO treatment recommendations are different from those of the U.S. The WHO multidrug therapy (MDT) recommends for multibacillary leprosy rifampin, 600 mg, and clofazimine, 300 mg once a month, and daily dapsone 100 mg and clofazimine 50 mg for 12 months. Paucibacillary leprosy is treated with dapsone, 100 mg/day, and rifampin, 600 mg/month for 6 months. Since 1995, WHO has provided free MDT for all leprosy patients worldwide.
Key Points: Hansen’s Disease (Leprosy)
1. Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae, affecting primarily skin and peripheral nerves.
2. The mode of transmission of leprosy is still not proven, but current evidence favors respiratory transmission.
3. The diagnosis of leprosy is usually made based on skin lesions, cutaneous anesthesia, and enlarged superficial nerves and by demonstrating leprosy bacilli in the skin.
27. What are the side effects of the drugs for leprosy treatment?
Overall, dapsone is a safe drug, and it is safe to use during pregnancy. All patients on dapsone experience hemolysis of older red blood cells with a mild drop in hematocrit. Patients who are glucose-6-phosphatase dehydrogenase deficient may develop severe hemolysis. Methemoglobinemia is also regularly observed but is usually not a significant problem, because the level usually does not exceed 12% of the total hemoglobin. Idiosyncratic reactions such as pancytopenia, peripheral neuropathies, acute psychosis, and a potentially fatal infectious mononucleosis-like condition may also develop. Rifampin, as a P450 inducer, may decrease the effect of other drugs. Hepatotoxicity and red urine are banal.
28. What is the most bothersome cutaneous side effect of clofazimine?
The most bothersome side effect of clofazimine is a red to brown to purple discoloration of the skin (see Fig. 29-4A). Some patients may also demonstrate acquired ichthyosis.
29. How are the reactional states of leprosy treated?
For type I reactions, because of the risk of permanent nerve damage, prednisone, 40 to 80 mg/day, is recommended. Mild type II reactions may be controlled with aspirin, nonsteroidal antiinflammatory agents, and rest. More severe type II reactions may be controlled with thalidomide, 400 mg at night. Thalidomide should not be given to women of childbearing age because of its severe teratogenic effects. If thalidomide is not available, type II reactions can usually be controlled with prednisone, 40 to 80 mg/day.
31. Can leprosy be eliminated as a worldwide disease, as smallpox has been?
