Leprosy pathophysiology: Difference between revisions
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==Pathogenesis== | ==Pathogenesis== | ||
[[Mycobacterium leprae]] has predisposition to [[infect]] [[macrophages]]. It is usually collected inside these, in [[intracellular]] groups, also called ''globi''. This [[organism]] has an ideal growth temperature of 27-30ºC, which explains why it usually [[infection|infects]] areas such as the [[skin]], [[upper respiratory]] [[mucosa]] and [[peripheral nerves]]. It is able to [[infect]] [[cells]], particularly due to 2 structures:<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="pmid23870850">{{cite journal| author=Eichelmann K, González González SE, Salas-Alanis JC, Ocampo-Candiani J| title=Leprosy. An update: definition, pathogenesis, classification, diagnosis, and treatment. | journal=Actas Dermosifiliogr | year= 2013 | volume= 104 | issue= 7 | pages= 554-63 | pmid=23870850 | doi=10.1016/j.adengl.2012.03.028 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23870850 }} </ref> | [[Mycobacterium leprae]] has predisposition to [[infect]] [[macrophages]]. It is usually collected inside these, in [[intracellular]] groups, also called ''globi''. This [[organism]] has an ideal growth temperature of 27-30ºC, which explains why it usually [[infection|infects]] areas such as the [[skin]], [[upper respiratory]] [[mucosa]] and [[peripheral nerves]]. It is able to [[infect]] [[cells]], particularly due to 2 structures:<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="pmid23870850">{{cite journal| author=Eichelmann K, González González SE, Salas-Alanis JC, Ocampo-Candiani J| title=Leprosy. An update: definition, pathogenesis, classification, diagnosis, and treatment. | journal=Actas Dermosifiliogr | year= 2013 | volume= 104 | issue= 7 | pages= 554-63 | pmid=23870850 | doi=10.1016/j.adengl.2012.03.028 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23870850 }} </ref><ref name="BrittonLockwood2004">{{cite journal|last1=Britton|first1=Warwick J|last2=Lockwood|first2=Diana NJ|title=Leprosy|journal=The Lancet|volume=363|issue=9416|year=2004|pages=1209–1219|issn=01406736|doi=10.1016/S0140-6736(04)15952-7}}</ref><ref name="GuliaFried2010">{{cite journal|last1=Gulia|first1=Andrea|last2=Fried|first2=Isabella|last3=Massone|first3=Cesare|title=New insights in the pathogenesis and genetics of leprosy|journal=F1000 Medicine Reports|volume=2|year=2010|issn=17575931|doi=10.3410/M2-30}}</ref> | ||
* [[Capsule]] - target of | * [[Capsule]] - target of intense humoral immune response (immunoglobulin M-mediated). | ||
* [[Cell wall]] - | * [[Cell wall]] - | ||
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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
Pathogenesis
Mycobacterium leprae has predisposition to infect macrophages. It is usually collected inside these, in intracellular groups, also called globi. This organism has an ideal growth temperature of 27-30ºC, which explains why it usually infects areas such as the skin, upper respiratory mucosa and peripheral nerves. It is able to infect cells, particularly due to 2 structures:[1][2][3][4]
- Capsule - target of intense humoral immune response (immunoglobulin M-mediated).
Genetics
The infection by the mycobacterium leprae and the course of the disease are influenced by certain genetic factors of the host.[5][6] Some single-nucleotide polymorphism have been associated with a higher incidence of leprosy. These include:[5][7][8][9][10]
- Low occurrence of a lymphotoxin-α-producing allele.
- Vitamin D receptor gene.
- TNF-α gene.
- IL-10 gene.
- IFN-γ gene.
- TLR 1 gene.
Another study has also suggested a possible relationship between genetic variants of the NOD2 gene and increased susceptibility to leprosy and the development of type I and II reactions.[11]
Associated Conditions
Gross Pathology
Immunologic Reactions
Systemic inflammatory reactions may occur before, during or after the treatment of leprosy.[12] There are two different types of reactions, which are thought to have different underlying immunologic mechanisms.
Tipe 1 (T1R) or Reversal Reaction (RR)
- Predominant in borderline disease.
- Red patches developing in previous skin lesions, commonly on the face or nerve trunks.
- Erythema of previous skin lesions.
- Inflammation may lead to nerve lesion and paralysis.
- Edema of hands and feet.
- Arthralgia, predominantly of small joints.
- Ulcerated lesions.* Pain or tenderness on lesions.
Type 2 (T2R) or Erythema Nodosum Leprosum (ENL)
- Predominant in lepromatous disease.
- Sudden occurrence of painful nodules.
- Nodules may lead to pustules or ulcers.
- Pustules may discharge pus containing polymorphonuclear cells and degenerating mycobacteria.
- After lesions resolve, brawn skin lesions may remain.
- Occasionally may occur: orchitis, muscle and lymphadenopathy tenderness and/or swollen joints.
- Without treatment usually lasts for 2 weeks.
Microscopic Pathology
Histopathology
The manifestations of leprosy depend on the host's immune response towards the mycobacteria. Therefore, tuberculoid and lepromatous patients will show different histopathologic findings:[5][12][13]
- Tuberculoid patients - These patients will show a strong immune response towards the bacteria, with production of IFN-γ and commonly showing a positive lepromin skin test.
- Inflammatory infiltrate with multiple granulomas.
- Granulomas containing giant cells, differentiated macrophages and epithelioid cells.
- Predominance of CD4 cells.
- Low bacterial index.
- Lepromatous patients - These patients will show a weaker immune response towards the bacteria, particularly a weak cell-mediated response.
- Absence of granulomas.
- Straightened skin.
- Predominance of CD8 cells.
- High bacterial index.
References
- ↑ 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.
- ↑ Eichelmann K, González González SE, Salas-Alanis JC, Ocampo-Candiani J (2013). "Leprosy. An update: definition, pathogenesis, classification, diagnosis, and treatment". Actas Dermosifiliogr. 104 (7): 554–63. doi:10.1016/j.adengl.2012.03.028. PMID 23870850.
- ↑ Britton, Warwick J; Lockwood, Diana NJ (2004). "Leprosy". The Lancet. 363 (9416): 1209–1219. doi:10.1016/S0140-6736(04)15952-7. ISSN 0140-6736.
- ↑ Gulia, Andrea; Fried, Isabella; Massone, Cesare (2010). "New insights in the pathogenesis and genetics of leprosy". F1000 Medicine Reports. 2. doi:10.3410/M2-30. ISSN 1757-5931.
- ↑ 5.0 5.1 5.2 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.
- ↑ Alter A, Alcaïs A, Abel L, Schurr E (2008). "Leprosy as a genetic model for susceptibility to common infectious diseases". Hum Genet. 123 (3): 227–35. doi:10.1007/s00439-008-0474-z. PMID 18247059.
- ↑ Alcaïs A, Alter A, Antoni G, Orlova M, Nguyen VT, Singh M; et al. (2007). "Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy". Nat Genet. 39 (4): 517–22. doi:10.1038/ng2000. PMID 17353895.
- ↑ Mira MT, Alcais A, di Pietrantonio T, Thuc NV, Phuong MC, Abel L; et al. (2003). "Segregation of HLA/TNF region is linked to leprosy clinical spectrum in families displaying mixed leprosy subtypes". Genes Immun. 4 (1): 67–73. doi:10.1038/sj.gene.6363911. PMID 12595904.
- ↑ Correa-Oliveira, Rodrigo; Misch, Elizabeth A.; Macdonald, Murdo; Ranjit, Chaman; Sapkota, Bishwa R.; Wells, Richard D.; Siddiqui, M. Ruby; Kaplan, Gilla; Hawn, Thomas R. (2008). "Human TLR1 Deficiency Is Associated with Impaired Mycobacterial Signaling and Protection from Leprosy Reversal Reaction". PLoS Neglected Tropical Diseases. 2 (5): e231. doi:10.1371/journal.pntd.0000231. ISSN 1935-2735.
- ↑ Cardoso CC, Pereira AC, Brito-de-Souza VN, Dias-Baptista IM, Maniero VC, Venturini J; et al. (2010). "IFNG +874 T>A single nucleotide polymorphism is associated with leprosy among Brazilians". Hum Genet. 128 (5): 481–90. doi:10.1007/s00439-010-0872-x. PMID 20714752.
- ↑ Berrington WR, Macdonald M, Khadge S, Sapkota BR, Janer M, Hagge DA; et al. (2010). "Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states". J Infect Dis. 201 (9): 1422–35. doi:10.1086/651559. PMC 2853728. PMID 20350193.
- ↑ 12.0 12.1 Modlin RL, Hofman FM, Taylor CR, Rea TH (1983). "T lymphocyte subsets in the skin lesions of patients with leprosy". J Am Acad Dermatol. 8 (2): 182–9. PMID 6219136.
- ↑ Wallach D, Flageul B, Bach MA, Cottenot F (1984). "The cellular content of dermal leprous granulomas: an immuno-histological approach". Int J Lepr Other Mycobact Dis. 52 (3): 318–26. PMID 6332791.