What is leprosy?

 Leprosy is a disease caused by the bacteria Mycobacterium leprae, which causes damage
to the skin and the peripheral nervous system. The disease develops slowly (from six months to
40 years!) and results in skin lesions and deformities, most often affecting the cooler places on
the body (for example, eyes, nose, earlobes, hands, feet, and testicles). The skin lesions and
deformities can be very disfiguring and are the reason that infected individuals historically were
considered outcasts in many cultures. Although human-to-human transmission is the primary
source of infection, three other species can carry and (rarely) transfer M. leprae to humans:
chimpanzees, mangabey monkeys, and nine-banded armadillos. The disease is termed a chronic
granulomatous disease, similar to tuberculosis, because it produces inflammatory nodules
(granulomas) in the skin and nerves over time.

What causes leprosy?

 Leprosy is caused mainly by Mycobacterium leprae, a rod-shaped bacillus that is an

obligate intracellular (only grows inside of certain human and animal cells)
bacterium. M. leprae is termed an "acid fast" bacterium because of its chemical
characteristics. When special stains are used for microscopic analysis, it stains red on a
blue background due to mycolic acid content in its cell walls. The Ziehl-Neelsen stain is
an example of the special staining techniques used to view the acid-fast organisms under
the microscope.
 The bacteria take an extremely long time to reproduce inside of cells (about 12-14 days
as compared to minutes to hours for most bacteria). The bacteria grow best at 80.9 F-86
F, so cooler areas of the body tend to develop the infection. The bacteria grow very well
in the body's macrophages and Schwann cells (cells that cover and protect nerve
axons). M. leprae is genetically related to M. tuberculosis (the type of bacteria that cause
tuberculosis) and other mycobacteria that infect humans. Patients with leprosy produce
anti-endothelial antibodies (antibodies against the lining tissues of blood vessels)

What are leprosy symptoms and signs?

 The early signs and symptoms of leprosy are very subtle and occur slowly (usually over
years). The symptoms are similar to those that may occur with syphilis, tetanus,
and leptospirosis. Numbness and loss of temperature sensation (cannot sense very hot or
cold temperatures) are some of the first symptoms that patients experience. As the disease
progresses, the sensations of touch, then pain, and eventually deep pressure are decreased
or lost. Signs that occur, such as relatively painless ulcers, skin lesions of hypo
pigmented macules (flat, pale areas of skin), and eye damage (dryness, reduced blinking)
are experienced before the large ulcerations, loss of digits, and facial disfigurement
develop. This long-term developing sequence of events begins and continues on the
cooler areas of the body (for example, hands, feet, face, and knees).
 What is the treatment for leprosy?

 The majority of cases (mainly clinically diagnosed) are treated with antibiotics. The
recommended antibiotics, their dosages, and length of time of administration are based on the
form or classification of the disease and whether or not the patient is supervised by a medical
professional.
 In general, paucibacillary leprosy is treated with two antibiotics, dapsone and rifampicin, while
multibacillary leprosy is treated with the same two plus a third antibiotic, clofazimine. Usually,
the antibiotics are given for at least six to 12 months or more.
 Antibiotics can treat paucibacillary leprosy with little or no residual effects on the patient.
Multibacillary leprosy can be kept from advancing, and living M. leprae can be essentially
eliminated from the person by antibiotics, but the damage done before antibiotics are administered
is usually not reversible. Recently, the WHO suggested that single-dose treatment of patients with
only one skin lesion with rifampicin, minocycline (Minocin), or ofloxacin (Floxin) is effective.
Studies of other antibiotics are ongoing. Each patient, depending on the above criteria, has a
schedule for their individual treatment, so treatment schedules should be planned by a clinician
knowledgeable about that patient's initial diagnostic classification.

How is leprosy transmitted?

 Researchers suggest that M. leprae are spread person to person by nasal secretions or droplets.
They speculate that infected droplets reach other peoples' nasal passages and begin the infection
there. Some investigators suggest the infected droplets can infect others by entering breaks in the
skin. M. leprae apparently cannot infect intact skin. Rarely, humans get leprosy from the few
animal species mentioned above. Occurrence in animals makes it difficult to eradicate leprosy
from these endemic sources. Routes of transmission are still being researched for leprosy. Recent
genetic studies have demonstrated that several genes (about seven) are associated with an
increased susceptibility to leprosy; some researchers now conclude that susceptibility to leprosy
may be partially inheritable.

How is leprosy diagnosed?

 The majority of cases of leprosy are diagnosed by clinical findings, especially since most current
cases are diagnosed in areas that have limited or no laboratory equipment available.
Hypopigmented patches of skin or reddish skin patches with loss of sensation, thickened
peripheral nerves, or both clinical findings together often comprise the clinical diagnosis.
 Skin smears or biopsy material that show acid-fast bacilli with the Ziehl-Neelsen stain or the
Fite stain (biopsy) can diagnose multibacillary leprosy, or if bacteria are absent, diagnose
paucibacillary leprosy. Other tests can be done, but most of these are done by specialized labs and
may help a clinician to place the patient in the more detailed Ridley-Jopling classification and are
not routinely done (lepromin test, phenolic glycolipid-1 test, PCR, lymphocyte migration
inhibition test or LMIT). Other tests such as CBC test, liver function tests, creatinine test, or
a nerve biopsy may be done to help determine if other organ systems have been affected.

How is leprosy prevented?

 Prevention of contact with droplets from nasal and other secretions from patients with
untreated M. leprae infection currently is a way recommended to avoid the disease.
Treatment of patients with appropriate antibiotics stops the person from spreading the
disease. People who live with individuals who have untreated leprosy are about eight
times as likely to develop the disease, because investigators speculate that family
members have close proximity to infectious droplets. Leprosy is not hereditary, but recent
findings suggest susceptibility to the disease may have a genetic basis.
 There is no commercially available vaccine available to prevent leprosy. However, there
are reports of using BCG vaccine, the BCG vaccine along with heat-killed M. leprae organisms,
and other preparations that may be protective or help to clear the infection or to shorten
treatment. Except for BCG in some countries, these preparations are not readily available.

Are there different forms (classifications) of leprosy?

 There are multiple forms of leprosy described in the literature. The forms of leprosy are
based on the person's immune response to M. leprae. A good immune response can produce the
so-called tuberculoid form of the disease, with limited skin lesions and some asymmetric nerve
involvement. A poor immune response can result in the lepromatous form, characterized by
extensive skin and symmetric nerve involvement. Some patients may have aspects of both forms.
Currently, two classification systems exist in the medical literature: the WHO system and the
Ridley-Jopling system. The Ridley-Jopling system is composed of six forms or classifications,
listed below according to increasing severity of symptoms:
• Indeterminate leprosy:

 a few hypopigmented macules; can heal spontaneously, persists or advances to other

forms.

• Tuberculoid leprosy:

 a few hypopigmented macules, some are large and some become anesthetic (lose pain
sensation); some neural involvement in which nerves become enlarged; spontaneous resolution
in a few years, persists or advances to other forms.

• Borderline tuberculoid leprosy:

 lesions like tuberculoid leprosy but smaller and more numerous with less nerve
enlargement; this form may persist, revert to tuberculoid leprosy, or advance to other forms.
 • Mid-borderline leprosy:

 many reddish plaques that are asymmetrically distributed, moderately anesthetic, with
regional adenopathy (swollen lymph nodes); the form may persist, regress to another form, or
progress.

• Borderline lepromatous leprosy:

 many skin lesions with macules (flat lesions) papules (raised bumps), plaques, and
nodules, sometimes with or without anesthesia; the form may persist, regress or progress to
lepromatous leprosy.

• Lepromatous leprosy:

 Early lesions are pale macules (flat areas) that are diffuse and symmetric; later many M.
leprae organisms can be found in them. Alopecia (hair loss) occurs; often patients have no
eyebrows or eyelashes. As the disease progresses, nerve involvement leads to anesthetic areas
and limb weakness; progression leads to aseptic necrosis (tissue death from lack of blood to
area), lepromas (skin nodules), and disfigurement of many areas including the face. The
lepromatous form does not regress to the other less severe forms. Histoid leprosy is a clinical
variant of lepromatous leprosy that presents with clusters of histiocytes (a type of cell involved
in the inflammatory response) and a grenz zone (an area of collagen separating the lesion from
normal tissue) seen in microscopic tissue sections.
 As partial fulfillment for

our requirements in

Related Learning Experience III

LEPROSY
(HANSEN’S DISEASE)

Presented by:

ABLOG, ARRON PAUL B.

CB – 09
What is the history of leprosy (Hansen's disease)?

 The history of leprosy and its interaction with man is one of suffering and
misunderstanding. The newest research suggests that at least as early as 4000 B.C.
individuals had been infected with M. leprae, while the first known written reference to
the disease was found on Egyptian papyrus in about 1550 B.C. The disease was well
recognized in ancient China, Egypt, and India, and there are several references to the
disease in the Bible. Because the disease was poorly understood, very disfiguring, slow to
show symptoms, and had no known treatment, many cultures thought the disease was a
curse or punishment from the gods. Consequently, leprosy was left to be "treated" by
priests or holy men, not physicians.

 Consequently, some cultures considered infected people (and occasionally their close
relatives) as "unclean" or as "lepers" and ruled they could not associate with uninfected
people. Often infected people had to wear special clothing and ring bells so uninfected
people could avoid them.
 The Romans and the Crusaders brought the disease to Europe, and the Europeans brought
it to the Americas. In 1873, Dr. Hansen discovered bacteria in leprosy lesions, suggesting
leprosy was an infectious disease, not a hereditary disease or a punishment from the gods.
However, patients with the disease were still ostracized by many societies and cared for
only at missions by religious personnel. Patients with leprosy were encouraged or forced
to live in seclusion up to the 1940s, even in the U.S. (for example, the leper colony on
Molokai, Hawaii, and at Carville, La.), often because no effective treatments were
available.
 Because of Hansen's discovery of M. leprae, efforts were made to find treatments that
would stop or eliminate M. leprae; in the early 1900s to about 1940, oil from Chaulmoogra nuts
was used with questionable efficacy by injecting it into patients' skin. At Carville in 1941,
promin, a sulfone drug, showed efficacy but required many painful injections. Dapsone pills
were found to be effective in the 1950s, but soon (1960s-1970s), M. leprae developed resistance
to dapsone. Fortunately, drug trials on the island of Malta in the 1970s showed that a three-drug
combination (dapsone, rifampicin [Rifadin], and clofazimine [Lamprene]) was very effective in
killing M. leprae. This multi-drug treatment (MDT) was recommended by the WHO in 1981 and
remains, with minor changes, the therapy of choice. MDT, however, does not alter the damage
done to an individual by M. leprae before MDT is started.

 Leprosy is often termed "Hansen's disease" by many clinicians in an attempt to have

patients forgo the stigmas attached to being diagnosed with leprosy.