Leprosy
( Hansen's Disease)Introduction Leprosy is an ancient
disease, which only has lost in significance recently due to better medications
that are available. However, this skin deforming disease is still a
serious health threat in many development countries because of poverty and the
inability of the masses to afford effective anti-leprosy medication. The cause
for leprosy is the Mycobacterium leprae, an acid-fast bacillus similar to the
one that causes tuberculosis. It is also known as "Hansen's Disease". There
are more than 10 million people in the world that suffer from leprosy, which is
affecting mainly skin nerves, skin and mucous membranes (=the moist skin inside
the mouth,nose, the anogenital area, the tip of the penis and the vagina). There
is still no consensus how exactly leprosy is transmitted, but we do know that
it can be transmitted through nasal secretions that contain leprosy bacteria.
But there are also some animals like armadillos in Louisiana and non human primates
that can harbor leprosy bacteria. Household members of a leprosy patient are a
a higher risk to also come down with leprosy. Signs and symptoms: Here
is a link
to a leprosy picture . There are two extremes of leprosy depending
on the state of the immune system as is pointed out in more detail in the table
below. The one form is tuberculoid leprosy and the other form is lepromatous leprosy.
| Two Forms of
Leprosy Explained: |
Tuberculoid
leprosy: In a patient with a healthy immune system who is highly sensitized,
leprosy manifests itself as tuberculoid leprosy. The patient will have
a few depigmented
spots of skin that have altered or missing sensitivity. There is no sense
of heat, cold or touch. The cellular reaction, which penetrates the skin destroys
the sweat glands, hair follicles and nerve endings. Nerves adjacent to affected
skin spots can get damaged and enlarged. There is no itch associated with this
type of rash and the presentation is asymmetrical. There is hardly any or no Mycobacterium
leprae present in the affected skin or nerve tissue. However, untreated the infectious
process eats its way backwards through lymphatic connections and along the nerve
pathways more into the center of the extremities. Eventually it affects the circulation
in the periphery leading to loss of muscle power, loss of pain perception(because
of damaged nerves) and huge, ugly ulcers that are often diagnosed too late to
rescue the tissue. Loss of toes and fingers are the result as well as hopeless
superinfected deep forearm and lower leg ulcers. Often only amputation can rescue
the patient, who otherwise would die from septicemia of other bacteria or fungi.
Lepromatous
leprosy: If the immune system is weak, the Mycobacterium leprae is present
abundantly in plaques and nodules of disfigured skin, which is affected symmetrically.
These are the images that are shown on television and that we are familiar with.
As the whole skin thickness is affected, much disfigurement is associated with
this form, which can lead to the loss of the nasal septum and palate. Soft
nodules appear on ears, the nose and cheeks. They can break down and give
way to discharging sores. Progress of leprosy is slow: it takes years to develop
from a sore to a full blown case of leprosy. In Latin
America and Mexico patients often have a diffuse infiltration of the skin, which
leads to hair loss and loss of skin appendices (nails, ears,part of nose; affecting
also testicles and scrotum). This is called diffuse lepromatosis (or "lepra
bonita"). |
Borderline
leprosy: There is another form of leprosy in the middle of the
two extremes of leprosy. However, this type is not stable and wants to shift into
the direction of tuberculoid leprosy or lepromatous leprosy. What seems
to be happening behind the scene is that either the immune system gets overpowered
resulting in lepromatous leprosy. On the other hand the immune system might get
stimulated containing leprosy more and resulting in tuberculoid leprosy. It remains
a mystery how the immune system is triggered to react this way. The way
the immune system reacts is also deciding how the physician has to treat the disease.
Before the physician treats, the type of leprosy (in Latin "lepra")
reaction has to be determined, see table for details on this.
| There are two
types of lepra reactions | Borderline leprosy patients may develop a flare-up
of inflammation in existing leprosy skin lesions or newly infected skin and/or
nerves(neuritis). This is associated with a fever and pain of the affected region.
This reaction commonly happens during therapy and is then also called "reversal
reaction". It is due to T helper cells that produce large quantities of cytokines
such as interferon-gamma. Corticosteroids have to be taken for several months
to mitigate this reaction. | Approximately 50% of patients with lepromatous leprosy
will develop a painful condition called erythema nodosum leprosum (ENL) in the
first years of successful leprosy therapy. ENL is due to circulating immune complexes
and vasculitis involving inflammatory cells, T helper cells and tumor necrosis
factor released by these cells. This inflammatory process eventually leads to
skin ulceration and also to inflammation of lymph glands (lymphadenitis), arthritis,
glomerulonephritis (an inflammatory kidney disease) and orchitis (=inflammation
of testicles). Other target tissues are the bone marrow and the liver, which leads
to hemolytic anemia and abnormal liver function tests. Milder cases are treated
with aspirin, more severe cases with a brief course of corticosteroid medication.
If there are recurrent lepra type 2 reactions the treatment of choice is thalidomide
(although this cannot be given to pregnant women or if pregnancy is a possibility
because of fetal malformations from the drug). |
Diagnostic Tests for Leprosy One of the problems
has been that the Mycobacterium leprae cannot be cultured in the conventional
sense in the lab, as the bacterium needs to have living skin or nerve cells to
multiply. However, it can be grown in a mouse footpad in cases where the clinical
diagnosis is not certain. In this case body fluids suspicious of leprosy
would be injected into the footpad of an experimental mouse using a fine needle.
After a certain incubation period the animal is sacrificed and a histological
diagnosis of the injection site is obtained. There are characteristic histological
signs and the acid-fast bacillus can be demonstrated, if the case is positive.
This testing model can also be utilized for drug sensitivity testing as the mouse
can be treated with the same antibiotic that is later given to the leprosy patient.
The regular diagnosis is done clinically by identifying the typical skin
lesions and the patches of loss of skin sensitivity (peripheral neuropathy). The
physician then takes a skin biopsy from the active edge of a tuberculoid lesion.
In patients with lepromatous leprosy a biopsy of one of the nodules or plaques
is taken. There are very characteristic foam cells and also the acid fast bacilli
that the histopathologist can identify and that are only seen in leprosy. This
histological "blueprint" is then used along with the other clinical
features to identify the presence or absence of leprosy. Leprosy
Treatment In the past only dapsone (a sulfur containing antibiotic)
was available, but often leprosy is resistant to this when used alone. Multidrug
antibiotic therapy is the method of choice for all forms of leprosy. Drug sensitivity
testing in mice is recommended for all newly diagnosed patients as this way one
knows whether or not the Mycobacterium leprae is resistant or not and at the same
time an effective combination of drugs can be established. Long term treatment
is recommended by the WHO and depends on the bacillus load when tests with skin
biopsies are done. When lots of bacilli are present in biopsies, a combination
of dapsone, clofacimine and rifampin is given for between 2 and 5 years. Multiple
skin biopsies have to be negative before treatment is stopped. For cases
with a paucity of bacilli on biopsies (tuberculoid leprosy) dapsone and rifampin
are given for 6 months to 12 months. In the US, where dapsone resistant
strains are rare, lepromatous leprosy is treated with dapsone for life, but during
the first 2-3 years rifampin is added. With tuberculoid leprosy dapsone is used
as a single drug for 5 years. Details can be obtained from the Gillis
W.Long Hansen's Disease Center, Carville, LA, Tel. 504-642-4755.
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