Leprosy other diagnostic studies: Difference between revisions

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==Overview==
==Overview==
Although there are no laboratory studies to help in the [[diagnosis]] of leprosy, other studies such as [[biopsy]] of [[skin lesions]] and [[skin]] smear tests have an important contribution for the [[diagnosis]] of leprosy in patients, whose [[diagnosis]] is suspected from the clinical presentation.
[[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.


==Other Diagnostic Studies==
==Other Diagnostic Studies==


===Smear test===
===Smear test===
May be obtained from any [[skin lesion]], from the [[nasal mucosa]] and/or the [[ear lobe]]. This test has a [[sensitivity]] of 50% and a [[specificity]] of 100%. After collection of the [Laboratory specimen|specimen]], in order to visualize the [[bacteria]], the ''Ziehl-Neelsen'' stain should be used. According to the ''Global Initiative'' from the [[WHO]], in countries where leprosy is [[endemic]], the [[diagnosis]] should be made based on the clinical signs and the results of the smear test, despite the availability of more sophisticated tests, such as [[serology]] tests.<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="pmid7570870">{{cite journal| author=Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY, Klatser PR| title=Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia. | journal=Trans R Soc Trop Med Hyg | year= 1995 | volume= 89 | issue= 4 | pages= 381-5 | pmid=7570870 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7570870  }} </ref><ref name="pmid20966523">{{cite journal| author=Aggarwal A, Pandey A| title=Inverse sampling to study disease burden of leprosy. | journal=Indian J Med Res | year= 2010 | volume= 132 | issue=  | pages= 438-41 | pmid=20966523 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20966523  }} </ref><ref name="pmid9503866">{{cite journal| author=Ramaprasad P, Fernando A, Madhale S, Rao JR, Edward VK, Samson PD et al.| title=Transmission and protection in leprosy: indications of the role of mucosal immunity. | journal=Lepr Rev | year= 1997 | volume= 68 | issue= 4 | pages= 301-15 | pmid=9503866 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9503866  }} </ref>
May be obtained from any [[skin lesion]], [[nasal mucosa]] and/or [[ear lobe]].  
This test has [[sensitivity]] of 50% and [[specificity]] of 100%. After collection of the [[Laboratory specimen|specimen]], to visualize the [[bacteria]], the ''Ziehl-Neelsen'' stain should be used. Developing countries with low resources and innovative techniques should base the [[diagnosis]] on clinical [[signs]], and results from the smear test.<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="pmid7570870">{{cite journal| author=Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY, Klatser PR| title=Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia. | journal=Trans R Soc Trop Med Hyg | year= 1995 | volume= 89 | issue= 4 | pages= 381-5 | pmid=7570870 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7570870  }} </ref><ref name="pmid20966523">{{cite journal| author=Aggarwal A, Pandey A| title=Inverse sampling to study disease burden of leprosy. | journal=Indian J Med Res | year= 2010 | volume= 132 | issue=  | pages= 438-41 | pmid=20966523 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20966523  }} </ref><ref name="pmid9503866">{{cite journal| author=Ramaprasad P, Fernando A, Madhale S, Rao JR, Edward VK, Samson PD et al.| title=Transmission and protection in leprosy: indications of the role of mucosal immunity. | journal=Lepr Rev | year= 1997 | volume= 68 | issue= 4 | pages= 301-15 | pmid=9503866 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9503866  }} </ref>


===Skin Biopsy===
===Skin Biopsy===
A [[biopsy]] of the [[skin lesion]] should be performed and [[stained]] according to the ''Fite-Faraco'' technique (a especially designed protocol for [[staining]] the leprosy ''[[bacilli]]'').
A [[biopsy]] of the [[skin lesion]] should be performed and [[stained]] according to the ''Fite-Faraco'' technique (a especially designed protocol for [[staining]] the leprosy ''[[bacilli]]'').
According to the pole of leprosy in that patient, typical findings include:<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="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>
* '''Tuberculoid pole''':
:* ''[[Bacilli]]'' are commonly not observed.
:* [[Granulomas]] commonly found, containing:
::* [[Epithelioid]] [[cells]].
::* [[Lymphocytic]] infiltrate.
::* [[Langerhans cells]].
:* Common [[nerve]] involvement.
 
* '''Lepromatous pole''':
:* [[Inflammatory]] infiltrate.
:* Virchow cells loaded with ''[[bacilli]]''.
:* Loss of adnexal structures.


===Lepromin Test===
===Lepromin Test===
Although not a [[diagnostic test]], the [[lepromin skin test]] is used to classify and determine the [[prognosis]] of the condition. For this test it is used the inactivated form of ''[[Mycobacterium leprae]]'', extracted from lepromas, as follows:<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>
Although not a [[diagnostic test]], the [[lepromin skin test]] is used to classify and determine the [[prognosis]] of the condition. For this test it is used the inactivated form of ''[[Mycobacterium leprae]]'', extracted from lepromas:<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>
* [[Intradermal]] injection of [[lepromin skin test|lepromin]] (the [[antigen]]) on the [[forearm]].
* [[Intradermal]] injection of [[lepromin skin test|lepromin]] ([[antigen]]) on the [[forearm]]
* The result will then be interpreted at 2 moments:
* The result will then be interpreted at 2 moments:
: '''1. Early reaction (Fernandez reaction):'''
: '''1. Early reaction (Fernandez reaction):'''
::* Good [[sensitivity]].
::* Good [[sensitivity]]
::* Cross reactivity with other [[mycobacteria]].
::* Cross reactivity with other [[mycobacteria]]
::* May be read at 24 or 48h.
::* May be read at 24 or 48h
: '''2. Later reaction (Mitsuda reaction):'''
: '''2. Later reaction (Mitsuda reaction):'''
::* Read at the 21st day.
::* Read at the 21st day
::* Positive result is expressed by a [[nodule]] measuring more than 5 mm.
::* Positive result is expressed by a [[nodule]] measuring more than 5 mm
::* Indicative of [[resistance]] to the ''[[mycobacterium leprae]]''.
::* Indicative of [[resistance]] to the ''[[mycobacterium leprae]]''


===Serology===
===Serology===
The [[serology]] test using the PGL-1 [[antibody titer]] (Phenolic Glycolipid 1) is a useful [[diagnostic]] tool, particularly for ''multibacillary'' cases. However, it is not a good test for ''paucibacillary'' cases.<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="pmid18076551">{{cite journal| author=Silva EA, Iyer A, Ura S, Lauris JR, Naafs B, Das PK et al.| title=Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions. | journal=Trop Med Int Health | year= 2007 | volume= 12 | issue= 12 | pages= 1450-8 | pmid=18076551 | doi=10.1111/j.1365-3156.2007.01951.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18076551  }} </ref><ref name="pmid20735843">{{cite journal| author=Banerjee S, Sarkar K, Gupta S, Mahapatra PS, Gupta S, Guha S et al.| title=Multiplex PCR technique could be an alternative approach for early detection of leprosy among close contacts--a pilot study from India. | journal=BMC Infect Dis | year= 2010 | volume= 10 | issue=  | pages= 252 | pmid=20735843 | doi=10.1186/1471-2334-10-252 | pmc=PMC2942881 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20735843  }} </ref><ref name="pmid20963340">{{cite journal| author=Martins AC, Miranda A, Oliveira ML, Bührer-Sékula S, Martinez A| title=Nasal mucosa study of leprosy contacts with positive serology for the phenolic glycolipid 1 antigen. | journal=Braz J Otorhinolaryngol | year= 2010 | volume= 76 | issue= 5 | pages= 579-87 | pmid=20963340 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20963340  }} </ref>
The [[serology]] test using the PGL-1 [[antibody titer]] (Phenolic Glycolipid 1) is particularly indicated for ''multibacillary'' cases. Yet, it is not a good test for ''paucibacillary'' leprosy. Because of its lack of [[sensitivity]] the test is not available in the United States.<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="pmid18076551">{{cite journal| author=Silva EA, Iyer A, Ura S, Lauris JR, Naafs B, Das PK et al.| title=Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions. | journal=Trop Med Int Health | year= 2007 | volume= 12 | issue= 12 | pages= 1450-8 | pmid=18076551 | doi=10.1111/j.1365-3156.2007.01951.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18076551  }} </ref><ref name="pmid20735843">{{cite journal| author=Banerjee S, Sarkar K, Gupta S, Mahapatra PS, Gupta S, Guha S et al.| title=Multiplex PCR technique could be an alternative approach for early detection of leprosy among close contacts--a pilot study from India. | journal=BMC Infect Dis | year= 2010 | volume= 10 | issue=  | pages= 252 | pmid=20735843 | doi=10.1186/1471-2334-10-252 | pmc=PMC2942881 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20735843  }} </ref><ref name="pmid20963340">{{cite journal| author=Martins AC, Miranda A, Oliveira ML, Bührer-Sékula S, Martinez A| title=Nasal mucosa study of leprosy contacts with positive serology for the phenolic glycolipid 1 antigen. | journal=Braz J Otorhinolaryngol | year= 2010 | volume= 76 | issue= 5 | pages= 579-87 | pmid=20963340 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20963340 }} </ref><ref name="pmid9465156">{{cite journal| author=Butlin CR, Soares D, Neupane KD, Failbus SS, Roche PW| title=IgM anti-phenolic glycolipid-I antibody measurements from skin-smear sites: correlation with venous antibody levels and the bacterial index. | journal=Int J Lepr Other Mycobact Dis | year= 1997 | volume= 65 | issue= 4 | pages= 465-8 | pmid=9465156 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9465156 }} </ref>


===Polymerase Chain Reaction===
===Polymerase Chain Reaction===
The detection of the bacillus with PCR has high sensitivity and specificity, however, it is a very expensive procedure, which limits its use, particularly in developing countries with very little resources and infrastructures.<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>
High [[sensitivity]] and [[specificity]] test, particularly useful when [[histologic]] results are inconclusive. Because it is an expensive test it is rarely used in developing countries.<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>


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Dermatology]]
[[Category:Dermatology]]
[[Category:Infectious disease]]
 
[[Category:Tropical disease]]
[[Category:Tropical disease]]
[[Category:Leprosy]]
[[Category:Leprosy]]

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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

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.

Other Diagnostic Studies

Smear test

May be obtained from any skin lesion, nasal mucosa and/or ear lobe. This test has sensitivity of 50% and specificity of 100%. After collection of the specimen, to visualize the bacteria, the Ziehl-Neelsen stain should be used. Developing countries with low resources and innovative techniques should base the diagnosis on clinical signs, and results from the smear test.[1][2][3][4]

Skin Biopsy

A biopsy of the skin lesion should be performed and stained according to the Fite-Faraco technique (a especially designed protocol for staining the leprosy bacilli). [1]

Lepromin Test

Although not a diagnostic test, the lepromin skin test is used to classify and determine the prognosis of the condition. For this test it is used the inactivated form of Mycobacterium leprae, extracted from lepromas:[1]

1. Early reaction (Fernandez reaction):
2. Later reaction (Mitsuda reaction):

Serology

The serology test using the PGL-1 antibody titer (Phenolic Glycolipid 1) is particularly indicated for multibacillary cases. Yet, it is not a good test for paucibacillary leprosy. Because of its lack of sensitivity the test is not available in the United States.[1][5][6][7][8]

Polymerase Chain Reaction

High sensitivity and specificity test, particularly useful when histologic results are inconclusive. Because it is an expensive test it is rarely used in developing countries.[1]

References

  1. 1.0 1.1 1.2 1.3 1.4 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.
  2. Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY, Klatser PR (1995). "Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia". Trans R Soc Trop Med Hyg. 89 (4): 381–5. PMID 7570870.
  3. Aggarwal A, Pandey A (2010). "Inverse sampling to study disease burden of leprosy". Indian J Med Res. 132: 438–41. PMID 20966523.
  4. Ramaprasad P, Fernando A, Madhale S, Rao JR, Edward VK, Samson PD; et al. (1997). "Transmission and protection in leprosy: indications of the role of mucosal immunity". Lepr Rev. 68 (4): 301–15. PMID 9503866.
  5. Silva EA, Iyer A, Ura S, Lauris JR, Naafs B, Das PK; et al. (2007). "Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions". Trop Med Int Health. 12 (12): 1450–8. doi:10.1111/j.1365-3156.2007.01951.x. PMID 18076551.
  6. Banerjee S, Sarkar K, Gupta S, Mahapatra PS, Gupta S, Guha S; et al. (2010). "Multiplex PCR technique could be an alternative approach for early detection of leprosy among close contacts--a pilot study from India". BMC Infect Dis. 10: 252. doi:10.1186/1471-2334-10-252. PMC 2942881. PMID 20735843.
  7. Martins AC, Miranda A, Oliveira ML, Bührer-Sékula S, Martinez A (2010). "Nasal mucosa study of leprosy contacts with positive serology for the phenolic glycolipid 1 antigen". Braz J Otorhinolaryngol. 76 (5): 579–87. PMID 20963340.
  8. Butlin CR, Soares D, Neupane KD, Failbus SS, Roche PW (1997). "IgM anti-phenolic glycolipid-I antibody measurements from skin-smear sites: correlation with venous antibody levels and the bacterial index". Int J Lepr Other Mycobact Dis. 65 (4): 465–8. PMID 9465156.


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