Leprosy is an ancient disease, which only has lost in significance recently due to better medications that are available. Originally it was known as Hansen’s Disease; in Europe it is known more under the name “Lepra”.
Despite some success with medication 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.
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 (thanks to upload.wikimedia.org for this image).
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
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 (thanks to web.stanford.edu for this image) 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 super-infected deep forearm and lower leg ulcers. Often only amputation can rescue the patient, who otherwise would die from septicemia of other bacteria or fungi.
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 (thanks to jdtr.pagesperso-orange.fr for this image). 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”).
There is another form of leprosy in the middle of the two extremes of leprosy, borderline 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
Lepra type 1 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.
Lepra type 2 reactions
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.
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 (thanks to www.healthfinder.gov for this link).
1.The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 265.
2.James Chin et al., Editors: Control of Communicable Diseases Manual, 17th edition, 2000, American Public Health Association
3.The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 112.
4. The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 115.
5. The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 113.
6. Suzanne Somers: “Breakthrough” Eight Steps to Wellness– Life-altering Secrets from Today’s Cutting-edge Doctors”, Crown Publishers, 2008