Lepromin
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The lepromin skin test is used to determine what type of
leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...
a person is infected with. It involves the injection of a standardized extract of the inactivated "''leprosy bacillus''" (''
Mycobacterium leprae ''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus), is one of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and ...
'' or "Hansen's bacillus") under the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
. It is not recommended as a primary mode of
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
.


Method

Positive reaction means: A) or more induration after 48hrs B) or above nodule after 21 days. An extract sample of inactivated Hansen's bacillus is injected just under the skin, usually on the forearm, so that a small lump pushes the skin upward. The lump indicates that the
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
has been injected at the correct depth. The injection site is labeled and examined at 48hours and 21 days later to see if there is a reaction. People with
dermatitis Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can v ...
or other skin irritations should have the test performed on an unaffected part of the body. If a child needs to have this test performed, it may be helpful to explain how the test will feel, and even practice or demonstrate on a
doll A doll is a physical model, model typically of a human or humanoid character, often used as a toy for children. Dolls have also been used in traditional religious rituals throughout the world. Traditional dolls made of materials such as clay and ...
. The more familiar the child is with what will happen and why the less
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
he or she will feel. When the antigen is injected, there may be a slight stinging or burning sensation. There may also be mild
itching Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasan ...
at the site of injection afterwards.


Normal values

People who don't have clinical
leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...
(
Hansen's disease Monster Beverage Corporation is an American beverage company that manufactures energy drinks including Monster Energy, Relentless and Burn. The company was originally founded as Hansen's in 1935 in Southern California, originally selling juice ...
, or HD) may have little or no skin reaction to the
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
, or may have a strong reaction to it. This is because lepromin only tests for infection, not for ongoing disease. It is believed that most people exposed to ''
Mycobacterium leprae ''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus), is one of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and ...
'' are not infected and thus would not respond, or are infected but self-resolve or never manifest overt symptoms and therefore would respond to the lepromin skin test. Paradoxically, however, patients with "lepromatous" (Virchowian) HD, the most severe and transmissible form, have no skin reaction to the antigen. This is because an effective immune response to the bacterium is a result of a
cellular immune response Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...
(
T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...
mediated) rather than a humoral response (
B-cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
/
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
). Lepromatous HD, the more severe and disfiguring form is a result of the patient's immune response being mainly humoral in nature. Antibodies, the main effectors of a humoral response, are ineffective against ''M. leprae'' because of the unusually dense and waxy nature of the
mycolic acid Mycolic acids are long fatty acids found in the cell walls of the Mycolata taxon, a group of bacteria that includes ''Mycobacterium tuberculosis'', the causative agent of the disease tuberculosis. They form the major component of the cell wall of ...
containing
bacterial cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...
, and so the bacterium proliferates, causing the cutaneous disfigurements and peripheral neuropathologies characteristic of the disease. The reason there is little or no response to the lepromin test is that a positive response to lepromin is due to "
delayed type hypersensitivity Delay (from Latin: dilatio) may refer to: Arts, entertainment, and media * ''Delay 1968'', a 1981 album by German experimental rock band Can * ''The Delay'', a 2012 Uruguayan film People * B. H. DeLay (1891–1923), American aviator and act ...
" that is T-cell mediated, and it is the failure of a robust T-cell response that results in the onset of lepromatous leprosy in the first place. However, given the severe nature of lepromatous leprosy, a skin test is unnecessary, and the definitive test, a biopsy, readily reveals the bacterium within lesions as well as the characteristic histopathology of HD. Moreover, lepromatous HD is typically diagnosed on clinical presentation alone. By contrast, two forms of positive reactions are seen when tuberculoid or borderline cases of HD are assessed by the lepromin test. (There are three borderline diagnoses possible as well as the tuberculoid and lepromatous diagnoses in the Ridley-Jopling classification system. The severity of disease and thus assignment to one of the five diagnoses is related to the strength of the cell mediated immune response.) The Fernandez (early) reaction appears within two days and is roughly equivalent in nature and underlying mechanism to the response seen in
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
patients reacting positively to the tuberculin test. Induration of 5mm or more with erythema (redness), or 10mm without, 48 hours post-injection are positive
Fernandez reaction The Fernandez reaction is a reaction that occurs to signal a positive result in the lepromin skin test for leprosy. The reaction occurs in the skin at the site of injection if the body possesses antibodies to the Dharmendra antigen, one of the ant ...
s. Unlike the tuberculin test, however, another reaction occurs in lepromatous patients at the injection site 21 days post-injection, also appearing as induration and possible ulceration. This late positive reaction is known as the Mitsuda reaction. These reactions differ dependent on the type of lepromin antigen used. There are two types of lepromin antigen in use that differ in the method of preparation. The Dharmendra antigen evokes a stronger early positive reaction than the Mitsuda antigen, which provokes a stronger late reaction. A strong Mitsuda reaction indicates a strong cell mediated immune response and a milder tuberculoid disease. Thus the strength of the reaction to lepromin can be used to help classify the extent of the disease as defined by within the Ridley-Jopling classification system. Strong positive Fernandez responses represent strong cell mediated responses that suppress the bacterium and result in tuberculoid HD. Progressively weaker responses are consistent with diagnoses moving through borderline diagnoses to lepromatous HD.


Risks

There is an extremely small risk of an
allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
that may include itching and rarely
hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...
.


History

Aldo Castellani Aldo Castellani, KCMG (8 September 1874 – 3 October 1971) was an Italian pathologist and bacteriologist A bacteriologist is a microbiologist, or similarly trained professional, in bacteriology -- a subdivision of microbiology that studies b ...
was the first to prepare a substance similar to lepromin while attempting to produce a leprosy
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
.
Kensuke Mitsuda was a Japanese leprologist and director of the Tama Zenshoen Sanatorium (1914–1931) and the National Sanatorium Nagashima Aiseien (1931–1957). He had been at the frontier of leprosy policy of Japan. He was given the Order of Cultural Merits (1 ...
worked with lepromin starting in 1916 and published the first paper on it in 1919 However, he retained
Ernest Reinhold Rost Lieutenant-colonel Ernest Reinhold Rost (22 August 1872 – 23 June 1930) O.B.E. was an English physician and Buddhist writer. Biography Rost was born at Ealing on 22 August 1872. He was the son of Reinhold Rost. He was educated at Highgate S ...
's earlier name leprolin and his original idea was to find a test that distinguishes leprosy patients from non-leprosy persons. During his study, he found that the test results differed depending on the types of leprosy. He reported it at the 3rd International Leprosy Congress in France in 1923 but it received little attention. Working on
Java Java (; id, Jawa, ; jv, ꦗꦮ; su, ) is one of the Greater Sunda Islands in Indonesia. It is bordered by the Indian Ocean to the south and the Java Sea to the north. With a population of 151.6 million people, Java is the world's List ...
in the
Dutch East Indies The Dutch East Indies, also known as the Netherlands East Indies ( nl, Nederlands(ch)-Indië; ), was a Dutch colony consisting of what is now Indonesia. It was formed from the nationalised trading posts of the Dutch East India Company, which ...
,
Paul Bargehr Paul Bargehr (18 March 1889 31 December 1951) was an Austrian medical doctor and writer mostly known for his work treating Hansen's disease (leprosy) in the Dutch East Indies (now Indonesia). Although the Japanese researcher Kensuke Mitsuda re ...
published his findings on a similar process in 1926, giving his modified serum the name "lepromin". Mitsuda had stored his own materials in refrigeration and finally found
Fumio Hayashi is a Japanese economist. He is a professor at the National Graduate Institute for Policy Studies (GRIPS) in Tokyo. Hayashi received his Bachelor of Arts from the University of Tokyo and his Ph.D. from Harvard University in 1980. He has taught ...
to continue his work. The Mitsuda Test was at last completed by Hayashi in 1933.


Sources

*


References


External links

* {{MeshName, Lepromin Skin tests Leprosy