Leprosy overview: Difference between revisions
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{{Leprosy}} | {{Leprosy}} | ||
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==Overview== | ==Overview== | ||
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==Historical Perspective== | ==Historical Perspective== | ||
''[[Mycobacterium leprae]]'', the causative agent of leprosy, was discovered by [[Gerhard Armauer Hansen|G. H. Armauer Hansen]] in Norway in 1873, making it the first [[bacterium]] to be identified as causing [[disease]] in man.<ref name=Hansen_1874>{{cite journal | author = Hansen GHA | title = Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy) | journal = Norsk Mag. Laegervidenskaben | year = 1874 | volume = 4| pages = pp. 1–88 | language = Norwegian }}</ref><ref name=Irgens_2002>{{cite journal |author=Irgens L |title=The discovery of the leprosy bacillus |journal=Tidsskr Nor Laegeforen |volume=122 |issue=7 |pages=708-9 |year=2002 |pmid=11998735}}</ref> | ''[[Mycobacterium leprae]]'', the causative agent of leprosy, was discovered by [[Gerhard Armauer Hansen|G. H. Armauer Hansen]] in Norway in 1873, making it the first [[bacterium]] to be identified as causing [[disease]] in man.<ref name=Hansen_1874>{{cite journal | author = Hansen GHA | title = Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy) | journal = Norsk Mag. Laegervidenskaben | year = 1874 | volume = 4| pages = pp. 1–88 | language = Norwegian }}</ref><ref name=Irgens_2002>{{cite journal |author=Irgens L |title=The discovery of the leprosy bacillus |journal=Tidsskr Nor Laegeforen |volume=122 |issue=7 |pages=708-9 |year=2002 |pmid=11998735}}</ref> Historically, individuals with leprosy have been known as ''lepers'', however, this term is falling into disuse due the pejorative connotation of the term. | ||
==Classification== | ==Classification== | ||
The ''Ridley Jopling classification'' and the ''WHO classification'' are the two most widely used systems to classify Leprosy. These classification systems are based on [[clinical]], [[microbiological]] and [[histopathological]] features, and are used to determine the patient's [[prognosis]] and the [[Therapy|treatment]] regimen.<ref name="WalkerLockwood2007">{{cite journal|last1=Walker|first1=Stephen L.|last2=Lockwood|first2=Dina N.J.|title=Leprosy|journal=Clinics in Dermatology|volume=25|issue=2|year=2007|pages=165–172|issn=0738081X|doi=10.1016/j.clindermatol.2006.05.012}}</ref><ref name="EichelmannGonzález González2013">{{cite journal|last1=Eichelmann|first1=K.|last2=González González|first2=S.E.|last3=Salas-Alanis|first3=J.C.|last4=Ocampo-Candiani|first4=J.|title=Leprosy. An Update: Definition, Pathogenesis, Classification, Diagnosis, and Treatment|journal=Actas Dermo-Sifiliográficas (English Edition)|volume=104|issue=7|year=2013|pages=554–563|issn=15782190|doi=10.1016/j.adengl.2012.03.028}}</ref><ref name="BhatPrakash2012">{{cite journal|last1=Bhat|first1=Ramesh Marne|last2=Prakash|first2=Chaitra|title=Leprosy: An Overview of Pathophysiology|journal=Interdisciplinary Perspectives on Infectious Diseases|volume=2012|year=2012|pages=1–6|issn=1687-708X|doi=10.1155/2012/181089}}</ref> | The ''Ridley Jopling classification'' and the ''WHO classification'' are the two most widely used systems to classify Leprosy. These classification systems are based on [[clinical]], [[microbiological|microbiologic]] and [[histopathological]] features, and are used to determine the patient's [[prognosis]] and the [[Therapy|treatment]] regimen.<ref name="WalkerLockwood2007">{{cite journal|last1=Walker|first1=Stephen L.|last2=Lockwood|first2=Dina N.J.|title=Leprosy|journal=Clinics in Dermatology|volume=25|issue=2|year=2007|pages=165–172|issn=0738081X|doi=10.1016/j.clindermatol.2006.05.012}}</ref><ref name="EichelmannGonzález González2013">{{cite journal|last1=Eichelmann|first1=K.|last2=González González|first2=S.E.|last3=Salas-Alanis|first3=J.C.|last4=Ocampo-Candiani|first4=J.|title=Leprosy. An Update: Definition, Pathogenesis, Classification, Diagnosis, and Treatment|journal=Actas Dermo-Sifiliográficas (English Edition)|volume=104|issue=7|year=2013|pages=554–563|issn=15782190|doi=10.1016/j.adengl.2012.03.028}}</ref><ref name="BhatPrakash2012">{{cite journal|last1=Bhat|first1=Ramesh Marne|last2=Prakash|first2=Chaitra|title=Leprosy: An Overview of Pathophysiology|journal=Interdisciplinary Perspectives on Infectious Diseases|volume=2012|year=2012|pages=1–6|issn=1687-708X|doi=10.1155/2012/181089}}</ref> | ||
==Pathophysiology== | ==Pathophysiology== | ||
The clinical manifestations of leprosy largely reflect the [[immune response]] of the host towards the [[infection]]. Once the [[bacterial]] [[cells]] penetrate and multiply within the hosts [[skin]] and [[peripheral nerve]] cells, the [[immune system]] mounts a response toward the [[infected]] [[cells]], which results in clinical [[symptoms]]. Several [[single-nucleotide polymorphism]]s such as [[TNF-α]], [[IL-10]], [[IFN-γ]], [[TLR 1]] have been associated with a greater susceptibility to leprosy as have other genetic markers. | |||
==Causes== | ==Causes== | ||
''[[Mycobacterium leprae]]'' is a [[gram-positive]] [[Obligate intracellular parasite|obligate intracellular]], [[acid-fast bacillus]], responsible for the development of leprosy, or Hansen's disease. This [[organism]] has a very slow growth and | ''[[Mycobacterium leprae]]'' is a [[gram-positive]] [[Obligate intracellular parasite|obligate intracellular]], [[acid-fast bacillus]], responsible for the development of leprosy, or Hansen's disease. This [[organism]] has a very slow growth and has a predilection to affect colder parts of the [[body]], such as the [[skin]], superficial [[nerves]] and [[upper respiratory tract|upper respiratory]] [[mucous membranes]]. Although a route of [[transmission]] has not been absolutely defined yet, studies are pointing to a colonization of the [[dermis]] and [[respiratory]] [[mucosa]] of the [[infected]] patients. It is an uncommon [[bacteria]], since it has only been noticed to [[infect]] and grow in some [[species]] of primates and in the nine-banded armadillo.<ref name="BhatPrakash2012">{{cite journal|last1=Bhat|first1=Ramesh Marne|last2=Prakash|first2=Chaitra|title=Leprosy: An Overview of Pathophysiology|journal=Interdisciplinary Perspectives on Infectious Diseases|volume=2012|year=2012|pages=1–6|issn=1687-708X|doi=10.1155/2012/181089}}</ref> | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
Leprosy | Leprosy must be differentiated from other diseases that cause [[skin lesions]], [[nodules]], [[plaques]] [[paresthesias]] and [[nerve pain]], such as [[autoimmune diseases]], [[SLE]], [[parasitic infections]], [[vitiligo]] or [[tuberculosis|cutaneous tuberculosis]]. | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
Current [[prevalence]] rate of leprosy per 100,000 is 3.7. The disease is more prevalent in [[endemic]] areas, which represent a potential source of spread of the disease to the rest of the world. | |||
==Risk Factors== | ==Risk Factors== | ||
Risk factors for contracting leprosy include close contact with an untreated, active [[bacilli|multibacillary]] disease patient with the subtype of lepromatous leprosy, living in an endemic region (Angola, Brazil, Central African Republic, Democratic Republic of Congo, Federated States of Micronesia, India, Kiribati, Madagascar, Mozambique, Nepal, Republic of Marshall Islands, United Republic of Tanzania), age between 5 and 15 as well as over 30, Armadillo contact, tattoos, and genetic variants of the [[NOD2]]-mediated signaling pathway. | |||
==Natural History, Complications and Prognosis== | |||
Leprosy may lead to severe [[complications]] if not [[diagnosis|diagnosed]] and treated early, which will affect the [[prognosis]]. | |||
==Diagnosis== | ==Diagnosis== | ||
===Diagnostic Criteria=== | |||
The [[diagnosis]] of leprosy requires at least 1 of 3 criteria to be present: 1) [[loss of sensation]] of a [[Hypopigmentation|hipopigmented]] [[skin]] patch, 2) a thickened [[peripheral nerve]] concomitantly with [[weakness]] or [[loss of sensation]] of the area, and/or 3) confirmation of [[mycobacterium leprae]] in a [[skin]] smear. | |||
===History and Symptoms=== | ===History and Symptoms=== | ||
Common [[symptoms]] of leprosy include [[hypopigmentation|hypopigmented]], [[anesthetic]], red [[skin lesions]], that are hard to heal, [[nodular]] growths on the [[skin]], [[muscle weakness]] and [[paresthesia]] of the extremities and [[eye]] problems. If left untreated [[blindness]] and [[paralysis]] may occur. | |||
===Physical Examination=== | ===Physical Examination=== | ||
Although the findings on [[physical examination]] may vary depending upon the subytpe of leprosy, common findings include [[Hypopigmentation|hypopigmented]] [[skin lesions]], thickened [[dermis]], and [[loss of sensation]]. | |||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
There are no laboratory tests that diagnose leprosy. | |||
===X Ray=== | ===X Ray=== | ||
[[Osteoporosis]] is a common finding in leprosy patients | [[Osteoporosis]] is a common finding in leprosy patients which along with the [[loss of sensation]] may lead to [[fractures]]. | ||
===Other Imaging Findings=== | ===Other Imaging Findings=== | ||
There are no other imaging studies that diagnose leprosy. | |||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
[[Biopsy]] of [[skin lesions]] and [[skin]] smear tests are important for the [[diagnosis]] of leprosy in patients whose clinical examination is suspicious of the disease. | |||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
The [[medical treatment]] of leprosy is made with a multiple [[drug]] regimen, | The [[medical treatment]] of leprosy is made with a multiple [[drug]] regimen, for 6 to 12 months. This [[drug]] regimen may include 2 or 3 drugs: [[rifampicin]], [[dapsone]] and [[clofazimine]], or [[rifampicin]] and [[dapsone]], depending on the class of the disease. | ||
===Surgery=== | ===Surgery=== | ||
[[Surgery]] is not indicated in the [[Therapy|treatment]] of leprosy, yet it may treat or decrease the impact of some of the [[complications]] that may arise from the [[disease]]. | |||
===Primary prevention=== | ===Primary prevention=== | ||
[[Primary prevention]] of leprosy includes [[immunoprophylaxis]], [[chemoprophylaxis]] and education of the populations to prevent [[infection]] by the ''[[Mycobacterium leprae]]''. | |||
===Secondary Prevention=== | ===Secondary Prevention=== | ||
There is no [[secondary prevention]] of leprosy available because it is not possible to know if contact with leprosy will lead to the development of the disease, until first [[symptoms]] appear. | |||
===Tertiary prevention=== | ===Tertiary prevention=== | ||
After | After [[Therapy|treatment]] has been initiated, other measures to minimize further damage to the patient include: education of the individual and family members to monitor and treat [[skin]] [[ulcers]] and other lesions, primary care facilities to provide help to the populations and to direct patients to a specialist, whenever necessary.<ref name=WHO>{{cite web | title = Enhanced global strategy for further reducing the disease burden due to leprosy (2011-2015) | url = http://www.searo.who.int/entity/global_leprosy_programme/documents/enhanced_global_strategy_2011_2015_operational_guidelines.pdf }}</ref> | ||
===Cost-effectiveness of Therapy=== | ===Cost-effectiveness of Therapy=== | ||
| Line 68: | Line 72: | ||
===Future or Investigational Therapies=== | ===Future or Investigational Therapies=== | ||
Ongoing [[research]] focuses on the the mechanism of leprosy transmission as well as the identification of patients at high risk of infection in order to improve disease prevention and to treat infected individuals earlier. <ref name=WHO>{{cite web | title = Enhanced Global Strategy for Further Reducing the Disease Burden due to Leprosy | url = http://www.searo.who.int/entity/global_leprosy_programme/documents/enhanced_global_strategy_2011_2015_operational_guidelines.pdf }}</ref> Identification of alternatives to existing [[drugs]], such as [[rifampicin]] is also critical in so far as these agents may be [[contraindicated]] either because of [[toxicity]] or [[resistance]]. <ref name=WHO>{{cite web | title = Enhanced Global Strategy for Further Reducing the Disease Burden due to Leprosy | url = http://www.searo.who.int/entity/global_leprosy_programme/documents/enhanced_global_strategy_2011_2015_operational_guidelines.pdf }}</ref> | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
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[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Dermatology]] | [[Category:Dermatology]] | ||
[[Category:Tropical disease]] | [[Category:Tropical disease]] | ||
[[Category:Leprosy]] | [[Category:Leprosy]] | ||
Latest revision as of 18:10, 18 September 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Leprosy is a chronic infectious disease caused by the bacterium Mycobacterium leprae.[1] Leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the primary external symptom. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs, and eyes.
Historical Perspective
Mycobacterium leprae, the causative agent of leprosy, was discovered by G. H. Armauer Hansen in Norway in 1873, making it the first bacterium to be identified as causing disease in man.[2][3] Historically, individuals with leprosy have been known as lepers, however, this term is falling into disuse due the pejorative connotation of the term.
Classification
The Ridley Jopling classification and the WHO classification are the two most widely used systems to classify Leprosy. These classification systems are based on clinical, microbiologic and histopathological features, and are used to determine the patient's prognosis and the treatment regimen.[4][5][6]
Pathophysiology
The clinical manifestations of leprosy largely reflect the immune response of the host towards the infection. Once the bacterial cells penetrate and multiply within the hosts skin and peripheral nerve cells, the immune system mounts a response toward the infected cells, which results in clinical symptoms. Several single-nucleotide polymorphisms such as TNF-α, IL-10, IFN-γ, TLR 1 have been associated with a greater susceptibility to leprosy as have other genetic markers.
Causes
Mycobacterium leprae is a gram-positive obligate intracellular, acid-fast bacillus, responsible for the development of leprosy, or Hansen's disease. This organism has a very slow growth and has a predilection to affect colder parts of the body, such as the skin, superficial nerves and upper respiratory mucous membranes. Although a route of transmission has not been absolutely defined yet, studies are pointing to a colonization of the dermis and respiratory mucosa of the infected patients. It is an uncommon bacteria, since it has only been noticed to infect and grow in some species of primates and in the nine-banded armadillo.[6]
Differential Diagnosis
Leprosy must be differentiated from other diseases that cause skin lesions, nodules, plaques paresthesias and nerve pain, such as autoimmune diseases, SLE, parasitic infections, vitiligo or cutaneous tuberculosis.
Epidemiology and Demographics
Current prevalence rate of leprosy per 100,000 is 3.7. The disease is more prevalent in endemic areas, which represent a potential source of spread of the disease to the rest of the world.
Risk Factors
Risk factors for contracting leprosy include close contact with an untreated, active multibacillary disease patient with the subtype of lepromatous leprosy, living in an endemic region (Angola, Brazil, Central African Republic, Democratic Republic of Congo, Federated States of Micronesia, India, Kiribati, Madagascar, Mozambique, Nepal, Republic of Marshall Islands, United Republic of Tanzania), age between 5 and 15 as well as over 30, Armadillo contact, tattoos, and genetic variants of the NOD2-mediated signaling pathway.
Natural History, Complications and Prognosis
Leprosy may lead to severe complications if not diagnosed and treated early, which will affect the prognosis.
Diagnosis
Diagnostic Criteria
The diagnosis of leprosy requires at least 1 of 3 criteria to be present: 1) loss of sensation of a hipopigmented skin patch, 2) a thickened peripheral nerve concomitantly with weakness or loss of sensation of the area, and/or 3) confirmation of mycobacterium leprae in a skin smear.
History and Symptoms
Common symptoms of leprosy include hypopigmented, anesthetic, red skin lesions, that are hard to heal, nodular growths on the skin, muscle weakness and paresthesia of the extremities and eye problems. If left untreated blindness and paralysis may occur.
Physical Examination
Although the findings on physical examination may vary depending upon the subytpe of leprosy, common findings include hypopigmented skin lesions, thickened dermis, and loss of sensation.
Laboratory Findings
There are no laboratory tests that diagnose leprosy.
X Ray
Osteoporosis is a common finding in leprosy patients which along with the loss of sensation may lead to fractures.
Other Imaging Findings
There are no other imaging studies that diagnose leprosy.
Other Diagnostic Studies
Biopsy of skin lesions and skin smear tests are important for the diagnosis of leprosy in patients whose clinical examination is suspicious of the disease.
Treatment
Medical Therapy
The medical treatment of leprosy is made with a multiple drug regimen, for 6 to 12 months. This drug regimen may include 2 or 3 drugs: rifampicin, dapsone and clofazimine, or rifampicin and dapsone, depending on the class of the disease.
Surgery
Surgery is not indicated in the treatment of leprosy, yet it may treat or decrease the impact of some of the complications that may arise from the disease.
Primary prevention
Primary prevention of leprosy includes immunoprophylaxis, chemoprophylaxis and education of the populations to prevent infection by the Mycobacterium leprae.
Secondary Prevention
There is no secondary prevention of leprosy available because it is not possible to know if contact with leprosy will lead to the development of the disease, until first symptoms appear.
Tertiary prevention
After treatment has been initiated, other measures to minimize further damage to the patient include: education of the individual and family members to monitor and treat skin ulcers and other lesions, primary care facilities to provide help to the populations and to direct patients to a specialist, whenever necessary.[7]
Cost-effectiveness of Therapy
After the results of the campaign of the WHO to eradicate leprosy, the treatment of this disease may be considered cost-effective.
Future or Investigational Therapies
Ongoing research focuses on the the mechanism of leprosy transmission as well as the identification of patients at high risk of infection in order to improve disease prevention and to treat infected individuals earlier. [7] Identification of alternatives to existing drugs, such as rifampicin is also critical in so far as these agents may be contraindicated either because of toxicity or resistance. [7]
References
- ↑ Sasaki S, Takeshita F, Okuda K, Ishii N (2001). "Mycobacterium leprae and leprosy: a compendium". Microbiol Immunol. 45 (11): 729–36. PMID 11791665.
- ↑ Hansen GHA (1874). "Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy)". Norsk Mag. Laegervidenskaben (in Norwegian). 4: pp. 1–88.
- ↑ Irgens L (2002). "The discovery of the leprosy bacillus". Tidsskr Nor Laegeforen. 122 (7): 708–9. PMID 11998735.
- ↑ Walker, Stephen L.; Lockwood, Dina N.J. (2007). "Leprosy". Clinics in Dermatology. 25 (2): 165–172. doi:10.1016/j.clindermatol.2006.05.012. ISSN 0738-081X.
- ↑ Eichelmann, K.; González González, S.E.; Salas-Alanis, J.C.; Ocampo-Candiani, J. (2013). "Leprosy. An Update: Definition, Pathogenesis, Classification, Diagnosis, and Treatment". Actas Dermo-Sifiliográficas (English Edition). 104 (7): 554–563. doi:10.1016/j.adengl.2012.03.028. ISSN 1578-2190.
- ↑ 6.0 6.1 Bhat, Ramesh Marne; Prakash, Chaitra (2012). "Leprosy: An Overview of Pathophysiology". Interdisciplinary Perspectives on Infectious Diseases. 2012: 1–6. doi:10.1155/2012/181089. ISSN 1687-708X.
- ↑ 7.0 7.1 7.2 "Enhanced global strategy for further reducing the disease burden due to leprosy (2011-2015)" (PDF).