leprosy

—leprotic /le prot"ik/, adj.

/lep"reuh see/, n. Pathol.

a chronic, mildly infectious disease caused by Mycobacterium leprae, affecting the peripheral nervous system, skin, and nasal mucosa and variously characterized by ulcerations, tubercular nodules, and loss of sensation that sometimes leads to traumatic amputation of the anesthetized part. Also called Hansen's disease.

[1525-35; perh. < ML leprosia (recorded only as synonym for LEPROSARIUM) < Gk lépros(is) leprosy + -ia -Y³]

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or Hansen disease

Chronic disease of the skin and superficial nerves, caused by the bacterium Mycobacterium leprae.

In the lepromatous (cutaneous) type, grainy masses infiltrate inflamed tissue under the skin, in the lining of the upper respiratory tract, and in the testes; if this form of the disease is left untreated, the outlook is poor. The tuberculoid type, marked by spots having raised, reddish borders and patches that spread and lose feeling, may not progress or may improve. Long-term sulfa drug therapy usually helps; rehabilitation is usually also needed. Leprosy has a long history, but the disease seen today may not be the same one known in antiquity. A variety of infectious diseases that reached Europe from the East, especially with the returning Crusaders, led to the creation of leper colonies, where the ill were segregated and cared for. How leprosy spreads is still unclear; prolonged close contact with an infected person usually precedes infection. Prevention depends on recognizing cases for isolation and treatment.

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Introduction

also called  Hansen disease 

      chronic infectious disease that affects the skin, the peripheral nerves (nerves outside the brain and spinal cord), and the mucous membranes of the nose, throat, and eyes. It is caused by the leprosy bacillus, Mycobacterium leprae. Destruction of the peripheral nerves by the bacillus leads to a loss of sensation, which, together with progressive tissue degeneration, may result in the extremities' becoming deformed and eroded.

      In almost all cultures throughout history, leprosy has aroused dread and loathing about the prospect of incurable disease and a lifetime of progressive disfigurement. At one time “lepers,” as those with the disease were long called, were ostracized as unclean and were gathered into isolated “leper colonies” in order to keep them out of sight, to control their contagiousness, and to offer them what little treatment was available. In reality, the leprosy bacillus is not highly infectious, in most cases passing from one person to another only after prolonged and close contact (as, for instance, among family members). In addition, thanks to modern therapy with a number of effective drugs, the disease is now entirely curable, and the term leper, connoting somebody who has had and always will have the disease, thus no longer has meaning and in fact is considered to be offensive because of the social stigma long associated with the disease. Health care officials today do not consider a cured former leprosy patient to be any more “leprous” than a cured former cancer patient is “cancerous.”

      Despite modern therapy, leprosy is still a persistent disease in many parts of the world, and in many cases the disfigurement and disability caused by the infection cannot be reversed. Millions of people alive today either have or have had leprosy, and more than 500,000 currently require drug treatment. Some 600,000 new cases arise every year. The disease has almost disappeared from most temperate countries, but it is still common in Asia, Africa, Central and South America, and the Pacific Islands. India has the largest number of cases, with more than 60 percent of the world's infected persons.

Mysteries of the disease

      Mycobacterium leprae, the organism responsible for leprosy, is a relative of M. tuberculosis, the bacillus that causes tuberculosis. (A bacillus is a rod-shaped bacterium.) Scientists theorize that the leprosy bacillus enters the body through a break in the skin or through the mucous membranes of the nose. The disease can be transmitted from person to person by prolonged close contact, but even today scientists are uncertain of the exact mechanism. In fact, much about leprosy remains mysterious. At least in part this is because the bacillus has never been grown in a test tube, and the only tools for studying its transmission have been a limited number of animal models, chiefly armadillos and mice.

      The geographic distribution of the leprosy bacillus is another mystery. Some scientists suspect that the organism exists in the soil in many parts of the world, but again, because it cannot be grown in a laboratory culture, the only evidence of its presence in a given region is the appearance of the disease itself in humans or other animals that are susceptible to it. Besides humans, the only animals known to develop leprosy in nature are New World armadillos (armadillo) and African primates. For experimental purposes scientists have been able to grow the bacillus in the footpads of laboratory mice.

      Given that the organism that causes leprosy is widely distributed and the disease is contagious, it seems logical to ask why leprosy is not a great deal more prevalent than it is. The answer is that the infection apparently is quite difficult to contract. The vast majority of people (95 percent or so) simply are not susceptible to the bacillus and, even under repeated exposure, will never develop the disease. Among the few individuals who do contract the disease, in most cases it will be self-limiting and disappear before any symptoms become evident. Even in cases where early symptoms of leprosy develop, most patients will self-heal. This rather unusual pattern of infection, along with a three- to five-year incubation period (the time that elapses between contact with the bacillus and the onset of symptoms), makes the epidemiology of leprosy particularly difficult to study.

Transmission

      In the many centuries since leprosy was first described, a number of theories have been proposed to explain how the bacillus is transmitted. In the 19th century leprosy was believed to be a hereditary ailment. This made sense, as it frequently occurred in households among individuals who were members of a single family. In 1873, however, G.H. Armauer Hansen, a physician working in a leprosy hospital in Bergen, Norway, discovered the leprosy bacillus in a sample of tissue from one of his patients. Hansen was able to identify the organism under the microscope because its propensity to collect iron caused it to appear brownish in colour compared with the tissue itself. His discovery demonstrated that leprosy is an infectious disease propagated by a specific microorganism.

      The route of transmission of leprosy remained a matter of debate. The prevailing opinion for many years was that the illness spread via prolonged skin-to-skin contact. Then the theory of respiratory transmission became popular; it posited that the bacillus entered the human body through the lining of the nose. For a time scientists even entertained the possibility of transmission by insect bites. In the late 20th century, experiments with a mouse model of the disease showed that transmission is indeed possible through the intact lining of the nose and through breaks in the skin but not via the mouth, lungs, or digestive tract or through unbroken skin. And, although leprosy can be produced in mice by exposing them to the bacillus, the disease cannot be transmitted from an infected to an uninfected mouse.

Course of the disease

      The body's first reaction to the leprosy bacillus takes place in the deep layers of the skin in one of two ways. In one type of reaction, immune cells crowd into the area in an attempt to seal off the bacterium, and in these areas very few bacilli can be found. This gives rise to a form of leprosy known as tuberculoid leprosy because of the hard nodules, or tubercles, that form in the skin. The intense cellular reaction involves all of the thicknesses of the skin and the tissues under it, the sweat glands, the hair follicles, and the nerve fibres that end in the skin. This reaction manifests on the infected person's skin as a firm, dry patch in which there is no sense of heat, cold, or touch. The cellular reaction continues to spread into the main trunk of the involved nerve, so that nerve impulses cannot be transmitted, which thereby causes loss of sensation and decreased circulation in the affected part. This is most commonly seen in the forearm or lower leg, and it leads to claw hand and gross deformity of the foot. Paralysis of muscles of the face, eye, and neck may also occur. The patient is unable to feel pain, and minor injuries remain unnoticed. Large eroding ulcers can form, causing loss of fingers and toes; sometimes the condition of the limb is so bad that amputation is necessary. It is ironic that this form of leprosy occurs in people whose tissues resist the disease, for the intense cellular response is a reaction of resistance—successful insofar as it prevents local multiplication of the leprosy bacillus and its spread throughout the body but unsuccessful in that it destroys vital tissues in the invaded areas.

      In the second type of reaction, giving rise to what is called lepromatous leprosy, there is very little cellular response, and the bacilli can multiply freely. The organisms are found in enormous numbers in the deep layers of the affected skin, and they spread widely through the skin's lymphatic channels. The disease spreads via the nerves but does not adhere to them as in the tuberculoid form. It spreads very often to the skin of the face, where it causes thickening and corrugation of the skin and a typical leonine appearance. Soft nodules appear on the ears, nose, and cheeks and sometimes erode into discharging sores. The nose often is teeming with bacilli, and this sometimes leads to destruction of the septum of the nose and the palate.

      The progress of leprosy is slow. It may be years before a child infected by a parent shows the first sign of disease, frequently a vague, scarcely noticed patch on the skin. Often the child has grown to an adult before the disease is recognized. Persons with leprosy have occasional bouts of fever, but the course of the disease is mainly one of increasing disability and disfigurement, slowly progressing through the years even though it does not usually cut life short.

Therapy (therapeutics)

      The current treatment of leprosy is extremely effective, halting the progress of the disease. The bacilli can be killed rapidly, and multidrug therapy—the use of two or more antileprosy drugs in combination—prevents the development of drug-resistant strains. Indeed, multidrug therapy—a practice widely adopted in the treatment of tuberculosis and AIDS—was first proposed after scientists observed that some cases of leprosy were becoming resistant to sulfones, the earliest class of antileprosy drugs. A multidrug regimen developed by the World Health Organization (WHO) is the current standard of treatment.

      For patients with localized forms of leprosy and relatively few leprosy bacilli in their bodies, two drugs, dapsone and rifampicin, are given for a total of six months. For patients with more widespread disease and relatively large numbers of bacilli, three drugs—dapsone, clofazimine, and rifampicin—are given for 24 months. Most patients are able to tolerate the drugs well, but a few experience undesirable side effects or even exacerbations of the symptoms. Relapses, in general, are rare, occurring in fewer than 1 per 1,000 treated patients. Occasionally the infection persists despite continued therapy.

      Killing the bacillus has no effect on body tissues that have already been damaged or destroyed. Up to a point, nerve function can be restored by antileprosy drugs, but once the disease has progressed beyond that point, the loss of function is permanent. Nerve impairment—of which leprosy is the leading cause worldwide—leads to paralysis, loss of sensation, and changes in the individual's physical appearance. About 7 percent of newly diagnosed leprosy patients today have visible deformity or damage to their hands or feet or impaired vision. These disabilities can interfere with their ability to earn a living and otherwise lead a normal life. If the damage is unsightly, and it frequently is, then they also must cope with loss of social acceptance.

History

      People tend to think of leprosy as a tropical disease, because most cases today are found in less-developed countries, which are mainly in the tropics. This has not always been the case. In AD 1200 an estimated 19,000 leprosy hospitals existed all over Europe. The disease is much older than that, however. There are many difficulties in interpreting ancient medical writings, and the descriptive terms used by ancient authors for clinical conditions are often misleading, but an illness that fits the description of leprosy almost certainly appears in the Sushruta-samhita, a medical work from India that dates to about 600 BC. A similar ailment is described in a Chinese medical text from 400 BC. Several Greek (ancient Greek civilization) writers, including Galen (Galen Of Pergamum) (2nd–3rd century AD), described a disease that may have been leprosy, though the Greeks did not apply to this disease the term lepra (“scaly”), from which the modern term leprosy is derived; instead, they referred to it as elephantiasis græcorum. In a similar vein, the “leprosy” referred to in the Bible—both the tzaraath of the Hebrew Bible and the lepra of the Greek New Testament—is not described in a clinically recognizable manner and probably was any of a number of severe, chronic skin diseases.

      Tradition has it that members of the army of Alexander the Great contracted the illness when they invaded India in the 4th century BC and carried it into the Middle East and then throughout the eastern Mediterranean upon their return home. It is also traditionally believed that Roman soldiers in the army of Pompey (Pompey the Great) took the disease from Egypt to Italy in the 1st century BC and that Roman legionnaires later took the disease as far as the British Isles. On the other hand, genetic analysis of the leprosy bacillus indicates that Mycobacerium leprae may have evolved some 100,000 years ago in eastern Africa or southwestern Asia. From there it seems to have migrated eastward and westward, developing one distinct subtype in Asia and another subtype in Europe and North Africa. Leprosy appears to have been introduced by Europeans or North Africans into western Africa, where the bacillus evolved yet another distinct subtype. The disease was brought to the Americas by European colonists and western African slaves.

 Between the 11th and 13th centuries AD, leprosy spread along trade routes in Europe and also in places in the Holy Land occupied by European Crusaders and pilgrims—its most prominent victim being Baldwin IV, the “leper king” of Jerusalem. So acute was the suffering of those infected by leprosy that the disease was thought to be highly contagious. Persons with leprosy not wealthy enough to live at home in isolation were segregated in what came to be called lazarets or leprosaria. Outside these hospices they were feared and ostracized, frequently condemned to wander the roads wearing signs and ringing bells to warn healthy people of their approach. Leprosy came to be referred to as the “living death,” and often its victims were treated as if they had already died. Funeral services were conducted to declare those living with the disease “dead” to society, and relatives were allowed to claim their inheritance. Like many diseases, leprosy was considered to be a form of divine punishment for worldly sins, and the outward signs of the disease were taken as proof that leprosy victims were utterly embroiled in sin. Special laws required the use of separate seats in churches, separate holy-water fonts, and in some cases a “lepers' window” or slot in the church wall through which the afflicted could view the mass without contaminating the congregation or the ceremony.

      Rather abruptly and for unknown reasons, the incidence of leprosy began to decline in Europe—with the exception of Scandinavia—between 1200 and 1300. In Norway the disease persisted until the 20th century but has now disappeared. It was taken to what is now Louisiana, in the southern United States, by French Canadians (Acadians) who were expelled from Canada in 1755. Another immigrant group known to include people with leprosy moved to the United States from Scandinavia, mainly Norway, in the middle of the 19th century and settled principally in Minnesota. The disease was transmitted and has persisted in Louisiana, where occasional new cases appear even today among people of Acadian descent, but the disease was not transmitted in Minnesota and has completely disappeared there.

      It was in Norway that Hansen identified the leprosy bacillus in 1873. (At that time leprosy affected about 2.5 percent of the population of Bergen, where Hansen did his work.) This great discovery made possible the modern era of treating the disease itself, rather than merely containing it or treating the symptoms. Even into the 20th century, the only effective control applied to prevent the spread of the disease was compulsory segregation of the patient, frequently in large “leper colonies.” Perhaps the most famous colony was at Kalaupapa (Kalaupapa Peninsula), on the island of Molokai, Hawaii, where the Belgian priest Father Damien (Damien, Father) served leprosy patients who had been forcibly relocated to the isolated community. In 1894 the Louisiana Leper Home was established near Carville, Louisiana, on the Mississippi River near New Orleans. Early in the 20th century, the Carville home was transferred to U.S. federal control and became officially known as the Gillis W. Long Hansen's Disease Center. The new name Hansen's disease was part of a determined effort by health authorities to rid leprosy of its old social stigma and to focus attention on the fact that leprosy was finally becoming a treatable disease.

      For centuries an oil derived from the seeds of the chaulmoogra tree (genus Hydnocarpus) had been used to treat leprosy and other skin conditions in India and China. In 1854 Frederic John Mouat, an English doctor working in Calcutta (Kolkata), reported the possible utility of chaulmoogra oil in treating leprosy, and by the 1920s the oil or derivatives of the oil were the principal medication available. However, the drug was not effective when applied locally to affected areas, produced nausea when taken orally, and caused pain upon injection. Its real value was never fully accepted by authorities, and it was finally abandoned upon introduction of the sulfones, the first truly effective leprosy drug, in the 1940s.

      Diaminodiphenyl sulfone, or DDS, was synthesized in Germany in 1908, but it was not until the 1930s that researchers began to investigate its possible antibacterial properties. In 1941 doctors at Carville began to test a derivative of the compound, called promin, on patients. Promin had drawbacks—it had to be given intravenously, on a regular schedule, and for a long period of time—but it reversed the course of the disease in enough cases to be heralded as the “miracle at Carville.” Over the following decade researchers produced sulfone drugs that could be taken orally. The most effective one was a medicinal form of DDS called dapsone, which quickly replaced chaulmoogra oil as the standard medication for leprosy.

      The sulfones are bacteriostatic; that is, they interfere with the growth of Mycobacterium leprae by preventing it from synthesizing the essential vitamin folic acid. In the 1960s rifampicin, a truly bactericidal (i.e., bacteria-killing) drug, was shown to be very effective against the leprosy bacillus. About the same time, clofazimine, another bacteriostatic drug that also had anti-inflammatory properties, was introduced. With these drugs it was possible to treat people with leprosy as outpatients and to cease the practice of isolating them from the general population.

      No sooner was leprosy finally treatable than the problem of drug resistance arose. Resistance to the sulfones was first described in the mid-1960s and resistance to rifampicin in the early 1970s. When some strains of M. leprae were shown in the laboratory to be resistant to both the sulfones and rifampicin, the spectre was raised of a return to untreatable leprosy. In the early 1980s experts assembled by WHO issued the recommendation that all leprosy patients receive combination multidrug therapy and that all leprosy treatment be strictly limited in duration. Patients with localized leprosy would be treated for only six months, and the most advanced cases would receive treatment for only two years. Initially, these methods were highly controversial, but, as they were shown to be successful, they became the standard of treatment.

      The prospect of improved treatment led public health authorities to embrace the slogan “Leprosy is curable.” Leprosy patients who completed multidrug-therapy regimens were counted as cured and were taken off the lists of those with the disease. This had the effect of reducing the official numbers of people with leprosy from millions to only hundreds of thousands. Such was the situation when WHO, in the 1990s, launched an ambitious campaign to eliminate leprosy worldwide by the year 2000. The goal could not be reached in some parts of the world (notably India and Brazil) because of the difficulty of mounting health campaigns in populous and poor regions, the sheer numbers of affected people, and the peculiarly long incubation time of the leprosy bacillus.

Susannah C.J. Kearns June E. Nash

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