Leprosy pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Line 81: Line 81:
==Microscopic Pathology==
==Microscopic Pathology==
===Histopathology===
===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:<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><ref name="pmid6219136">{{cite journal| author=Modlin RL, Hofman FM, Taylor CR, Rea TH| title=T lymphocyte subsets in the skin lesions of patients with leprosy. | journal=J Am Acad Dermatol | year= 1983 | volume= 8 | issue= 2 | pages= 182-9 | pmid=6219136 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6219136  }} </ref><ref name="pmid6332791">{{cite journal| author=Wallach D, Flageul B, Bach MA, Cottenot F| title=The cellular content of dermal leprous granulomas: an immuno-histological approach. | journal=Int J Lepr Other Mycobact Dis | year= 1984 | volume= 52 | issue= 3 | pages= 318-26 | pmid=6332791 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6332791  }} </ref>
The clinical manifestations of leprosy depend on the host's [[immune response]] towards the [[mycobacteria]]. Therefore, ''tuberculoid'' and ''lepromatous'' patients will show different [[histopathologic]] findings:<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><ref name="pmid6219136">{{cite journal| author=Modlin RL, Hofman FM, Taylor CR, Rea TH| title=T lymphocyte subsets in the skin lesions of patients with leprosy. | journal=J Am Acad Dermatol | year= 1983 | volume= 8 | issue= 2 | pages= 182-9 | pmid=6219136 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6219136  }} </ref><ref name="pmid6332791">{{cite journal| author=Wallach D, Flageul B, Bach MA, Cottenot F| title=The cellular content of dermal leprous granulomas: an immuno-histological approach. | journal=Int J Lepr Other Mycobact Dis | year= 1984 | volume= 52 | issue= 3 | pages= 318-26 | pmid=6332791 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6332791  }} </ref>
====Tuberculoid patients====
====Tuberculoid patients====
These patients will show a strong [[immune response]] towards the [[bacteria]], with:
These patients will show a strong [[immune response]] towards the [[bacteria]], with:
* Production of IFN-γ  
* Production of [[IFN-γ]]
* [[Inflammatory]] infiltrate with multiple [[granulomas]]
* [[Inflammatory]] infiltrate with multiple [[granulomas]]
* [[Granulomas]] containing [[giant cells]], differentiated macrophages and epithelioid cells
* [[Granulomas]] containing [[giant cells]], differentiated [[macrophage]]s and epithelioid cells
* Predominance of [[CD4]] cells
* Predominance of [[CD4]] cells
* Low [[bacterial]] index.
* Low [[bacterial]] index
* Commonly positive [[lepromin]] [[skin test]]
* Commonly positive [[lepromin]] [[skin test]]


Revision as of 16:57, 8 July 2014

Leprosy Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Leprosy from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Tertiary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Leprosy pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Leprosy pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Leprosy pathophysiology

CDC on Leprosy pathophysiology

Leprosy pathophysiology in the news

Blogs on Leprosy pathophysiology

Directions to Hospitals Treating Leprosy

Risk calculators and risk factors for Leprosy pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

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.

Pathogenesis

Mycobacterium leprae has predisposition to infect macrophages. It is usually collected inside these, in intracellular groups, 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).

The bacillus is known to target Schwann cells, specifically the G domain of the laminin-α2 chain. This domain is predominantly expressed in the basal lamina of peripheral nerves, thereby explaining the neuropathy felt in this condition. The pathogen then penetrates the cell, at which time it will multiply, until the infected cell is finally recognized by the immune system and a an inflammatory reaction is started.[1][5]

This mechanism explains the reason why the clinical manifestations of the disease will depend on the immunologic status of the patient and the intensity of the response developed following the infection of the host cells.[1]

Genetics

The infection by the mycobacterium leprae and the course of the disease are influenced by genetic factors in the host.[6][7] Some single-nucleotide polymorphism have been associated with a higher incidence of leprosy. These include:[6][8][9][10][11]

Another study has suggested a possible relationship between genetic variants of the NOD2 gene, increased susceptibility to leprosy and the development of type I and II reactions.[12]

It has also been suggested an association between leprosy and a locus in chromosome 10p13, in the proximity of the mannose receptor 1 gene. Since the mannose receptors are located on the macrophage's surface, they play an important role in phagocytosis.[13]

Additionally, the subtype of leprosy developed in a patient has been associated with genes of the class II HLA/major histocompatibility complex, at chromosome 6. Accordingly:

  • HLA-DR2 and HLA-DR3 are considered to be linked with the tuberculoid class.
  • HLA-DQ1 is considered to be linked with the lepromatous class.

Associated Conditions

Leprosy Among Patients with HIV

There is no increased susceptibility to Mycobacterium leprae in HIV patients, nor are the clinical features altered. After initiation of antiretroviral therapy, latent leprosy can become clinically apparent in an HIV patient once the immune response is reestablished.[14][15]

Gross Pathology

Type of Leprosy

Tuberculoid Leprosy

Lepromatous Leprosy

Immunologic Reactions

Systemic inflammatory reactions may occur before, during or after the treatment of leprosy.[16] These are thought to be related to changes in the immune system, such as following stress situations, pregnancy or leprosy medications.[1] There are two different types of reactions, which are thought to have different underlying immunologic mechanisms:

Tipe 1 (T1R) or Reversal Reaction (RR)

Type 2 (T2R) or Erythema Nodosum Leprosum (ENL)

Microscopic Pathology

Histopathology

The clinical manifestations of leprosy depend on the host's immune response towards the mycobacteria. Therefore, tuberculoid and lepromatous patients will show different histopathologic findings:[6][16][18]

Tuberculoid patients

These patients will show a strong immune response towards the bacteria, with:

Lepromatous patients

These patients will show a weaker immune response, with:

Histopathology Image Gallery

References

  1. ↑ 1.0 1.1 1.2 1.3 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. ↑ 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.
  3. ↑ 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.
  4. ↑ 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. ↑ Shimoji Y, Ng V, Matsumura K, Fischetti VA, Rambukkana A (1999). "A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion". Proc Natl Acad Sci U S A. 96 (17): 9857–62. PMC 22300. PMID 10449784.
  6. ↑ 6.0 6.1 6.2 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Alter A, Grant A, Abel L, Alcaïs A, Schurr E (2011). "Leprosy as a genetic disease". Mamm Genome. 22 (1–2): 19–31. doi:10.1007/s00335-010-9287-1. PMID 20936290.
  14. ↑ 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.
  15. ↑ Ustianowski AP, Lawn SD, Lockwood DN (2006). "Interactions between HIV infection and leprosy: a paradox". Lancet Infect Dis. 6 (6): 350–60. doi:10.1016/S1473-3099(06)70493-5. PMID 16728321.
  16. ↑ 16.0 16.1 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.
  17. ↑ Balagon, M. V. F.; Gelber, R. H.; Abalos, R. M.; Cellona, R. V. (2010). "Reactions Following Completion of 1 and 2 Year Multidrug Therapy (MDT)". American Journal of Tropical Medicine and Hygiene. 83 (3): 637–644. doi:10.4269/ajtmh.2010.09-0586. ISSN 0002-9637.
  18. ↑ 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.
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 19.6 19.7 19.8 "Public Health Image Library (PHIL), Centers for Disease Control and Prevention".


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Leprosy_pathophysiology&oldid=990331"