Lepromin

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The lepromin skin test is used to determine what type of leprosy a person is infected with. It involves the injection of a standardized extract of the inactivated "leprosy bacillus" ( Mycobacterium leprae or "Hansen's bacillus") under the skin. It is not recommended as a primary mode of diagnosis. [1]

Contents

Method

Positive reaction means: A) 10 mm (0.39 in) or more induration after 48hrs B) 5 mm (0.20 in) 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 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 or other skin irritations should have the test performed on an unaffected part of the body.[ citation needed ] 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. The more familiar the child is with what will happen and why the less anxiety he or she will feel.[ citation needed ] When the antigen is injected, there may be a slight stinging or burning sensation. There may also be mild itching at the site of injection afterwards.

Normal values

People who don't have clinical leprosy (Hansen's disease, or HD) may have little or no skin reaction to the antigen, 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 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 (T-cell mediated) rather than a humoral response (B-cell/antibody). 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 containing bacterial cell wall, 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" 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. [2] 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 [3] 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 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 reactions. 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. [4] 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. [5] 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 that may include itching and rarely hives.[ citation needed ]

History

Aldo Castellani was the first to prepare a substance similar to lepromin while attempting to produce a leprosy vaccine. [6] [7] Kensuke Mitsuda worked with lepromin starting in 1916 and published the first paper on it in 1919 [8] However, he retained Ernest Reinhold Rost'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. [9] Working on Java in the Dutch East Indies, Paul Bargehr published his findings on a similar process in 1926, giving his modified serum the name "lepromin". [10] Mitsuda had stored his own materials in refrigeration and finally found Fumio Hayashi to continue his work. The Mitsuda Test was at last completed by Hayashi in 1933. [11]

Sources

Related Research Articles

<span class="mw-page-title-main">Leprosy</span> Chronic infection caused by mycobacteria leprae or lepromatosis

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 damage may result in a lack of ability to feel pain, which can lead to the loss of parts of a person's extremities from repeated injuries or infection through unnoticed wounds. An infected person may also experience muscle weakness and poor eyesight. Leprosy symptoms may begin within one year, but, for some people, symptoms may take 20 years or more to occur.

<span class="mw-page-title-main">Mantoux test</span> Immunological method to test for tuberculosis

The Mantoux test or Mendel–Mantoux test is a tool for screening for tuberculosis (TB) and for tuberculosis diagnosis. It is one of the major tuberculin skin tests used around the world, largely replacing multiple-puncture tests such as the tine test. The Heaf test, a form of tine test, was used until 2005 in the UK, when it was replaced by the Mantoux test. The Mantoux test is endorsed by the American Thoracic Society and Centers for Disease Control and Prevention. It was also used in the USSR and is now prevalent in most of the post-Soviet states, although Soviet mantoux produced many false positives due to children's allergic reaction.

<span class="mw-page-title-main">Hypersensitivity</span> Medical condition

Hypersensitivity is an abnormal physiological condition in which there is an undesirable and adverse immune response to antigen. It is an abnormality in the immune system that causes immune diseases including allergies and autoimmunity. It is caused by many types of particles and substances from the external environment or from within the body that are recognized by the immune cells as antigens. The immune reactions are usually referred to as an over-reaction of the immune system and they are often damaging and uncomfortable.

<i>Mycobacterium leprae</i> Bacterium that causes leprosy

Mycobacterium leprae 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 targets the skin, eyes, nose, and muscles.

The Heaf test, a diagnostic skin test, was long performed to determine whether or not children had been exposed to tuberculosis infection. The test was named after F. R. G. Heaf. Also known as the Sterneedle test, it was administered by a Heaf gun, a spring-loaded instrument with six needles arranged in a circular formation which was inserted in the wrist or shoulder.

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<span class="mw-page-title-main">Neuritis</span> Inflammation of a nerve or generally any part of the nervous system

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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 antigens found in Mycobacterium leprae, the bacteria that causes leprosy. The reaction occurs via a delayed-type hypersensitivity mechanism. This reaction occurs within 48 hours of injection of lepromin and is seen in only tuberculoid forms of leprosy. This represents a delayed-type hypersensitivity reaction. In contrast, the Mitsuda reaction occurs 3–4 weeks after injection of lepromin and is only seen in patients with the tuberculoid form of leprosy. In terms of mechanism of action and appearance, the reaction is similar to the tuberculin reaction of a positive Mantoux test for tuberculosis.

<span class="mw-page-title-main">Type III hypersensitivity</span> Type of allergic reaction

Type III hypersensitivity, in the Gell and Coombs classification of allergic reactions, occurs when there is accumulation of immune complexes that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response and attraction of leukocytes. There are three steps that lead to this response. The first step is immune complex formation, which involves the binding of antigens to antibodies to form mobile immune complexes. The second step is immune complex deposition, during which the complexes leave the plasma and are deposited into tissues. Finally, the third step is the inflammatory reaction, during which the classical pathway is activated and macrophages and neutrophils are recruited to the affected tissues. Such reactions may progress to immune complex diseases.

A leprostatic agent is a drug that interferes with proliferation of the bacterium that causes leprosy.

This page is currently under construction.

<span class="mw-page-title-main">Lepromatous leprosy</span> Medical condition

Lepromatous leprosy is a form of leprosy characterized by pale macules in the skin.

Mycobacterium lepromatosis is an aerobic, acid-fast bacillus (AFB), and the second known causative agent of Hansen's disease (leprosy). It was discovered in 2008. Analysis of the 16S rRNA gene confirms that the species is distinct from Mycobacterium leprae.

William Jopling was an Italian-born British leprologist who together with D. S. Ridley proposed the Ridley-Jopling classification of leprosy (1962), and wrote the widely read textbook of "Handbook of Leprosy" which had a fifth edition. He had a wide understanding of leprosy problems based on his experiences as the director of Jordan hospital, a leprosy hospital (1950–1967) in England and wrote various articles including "leprosy stigma".

<span class="mw-page-title-main">Kensuke Mitsuda</span>

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 (1951) and Damien-Dutton Award (1961). He has been the cause of admiration from one side, and the target of criticism from the other.

Mosuke Murata was a Japanese dermatologist and was the designator of erythema nodosum leprosum (ENL)(1912), the type 2 lepra reaction.

Fumio Hayashi was a Japanese physician and leprologist. He worked in Tama Zenshoen Sanatorium, Nagashima Aiseien Sanatorium, Hoshizuka Keiaien Sanatorium and Ooshima Seishoen Sanatorium. He helped with Kensuke Mitsuda, and completed the first lepromin test or Mitsuda skin test.

Lucio's phenomenon is an unusual reaction seen almost exclusively in patients from the Caribbean and Mexico with diffuse lepromatous leprosy, especially in untreated cases. It is characterised by recurrent crops of large, sharply demarcated, ulcerative lesions, affecting mainly the lower extremities, but may generalise and become fatal as a result of secondary bacterial infection and sepsis.

Paul Bargehr was an Austrian medical doctor and writer mostly known for his work treating Hansen's disease (leprosy) in the Dutch East Indies. Although the Japanese researcher Kensuke Mitsuda receives credit for first developing the modern lepromin test for distinguishing between different forms of Hansen's disease, Bargehr's work was responsible for coining and popularizing its current name.

References

  1. ↑ "Leprosy". The Lecturio Medical Concept Library. Retrieved 1 August 2021.
  2. ↑ Dermatologic Manifestations of Leprosy~workup at eMedicine
  3. ↑ "Ridley Jopling" . Retrieved 11 December 2014.
  4. ↑ "Mitsuda Reaction" . Retrieved 11 December 2014.
  5. ↑ "Lepromin test & Dharmendra antigen". 2008-10-23. Retrieved 11 December 2014.
  6. ↑ Feldman & al. (1951), p. 53.
  7. ↑ Castellani, Aldo (1948), "The Relative Importance in Practice of Various Laboratory Methods in the Diagnosis of Leprosy", Memoria del V Congreso Internacional de la Lepra.
  8. ↑ Mitsuda, K (1919). "On the Value of Skin Reaction with Emulsion of Leproma". Japanese Journal of Dermatology. 19: 697–708.
  9. ↑ Outlook of the 3rd International Leprosy Conference(1950) Sato S. Papers of Kensuke Mitsuda, 2nd edition, Okayama, Japan
  10. ↑ Feldman, William H.; Karlson, Alfred G.; Grindlay, John H. (March 1951), "Lepromin: Mitsuda's Reaction with Experimental Observations in Dogs", Annals of the New York Academy of Sciences, New York City: NYAS, 54 (1): 53–72, Bibcode:1951NYASA..54...53F, doi:10.1111/j.1749-6632.1951.tb45832.x, PMID   14819908 .
  11. ↑ Hayashi, F (1933). "Mitsuda's Skin Reaction in Leprosy". Int J Leprosy. 1: 31–8.
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