Syphilis pathophysiology: Difference between revisions

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__NOTOC__
__NOTOC__
{{CMG}}
{{CMG}} {{AE}} {{AA}}; {{NRM}}
{{Syphilis}}
{{Syphilis}}
==Overview==
==Overview==
Syphilis is caused by a spirochete, treponema pallidum. It has an incubation period of 3 - 12 weeks. Spirochete penetrates intact mucous membrane or microscopic dermal abrasions and rapidly enters systemic circulation with the central nervous system being invaded during the early phase of infection. The meninges and blood vessels are initially involved with the brain parenchyma and spinal cord being involved in the later stages of the disease. The histopathological hallmark findings are endarteritis and plasma cell-rich infiltrates reflecting a delayed-type of hypersensitivity to the spirochete
Syphilis is caused by a [[spirochete]], [[Treponema pallidum|''Treponema pallidum'']]. It has an average incubation period of 3 - 12 weeks. However, it may vary according to the size of innoculum. Spirochete penetrates intact mucous membrane or microscopic dermal abrasions and rapidly enters systemic circulation with the [[central nervous system]] being invaded during the early phase of infection. The histopathological hallmark findings are endarteritis and plasma cell-rich infiltrates reflecting a delayed-type of hypersensitivity reaction to the spirochete.<ref name="pmid21694502">{{cite journal| author=Carlson JA, Dabiri G, Cribier B, Sell S| title=The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. | journal=Am J Dermatopathol | year= 2011 | volume= 33 | issue= 5 | pages= 433-60 | pmid=21694502 | doi=10.1097/DAD.0b013e3181e8b587 | pmc=3690623 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21694502  }} </ref><ref name="pmid1386838">{{cite journal| author=Fitzgerald TJ| title=The Th1/Th2-like switch in syphilitic infection: is it detrimental? | journal=Infect Immun | year= 1992 | volume= 60 | issue= 9 | pages= 3475-9 | pmid=1386838 | doi= | pmc=257347 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1386838  }} </ref><ref name="pmid10194456">{{cite journal| author=Singh AE, Romanowski B| title=Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. | journal=Clin Microbiol Rev | year= 1999 | volume= 12 | issue= 2 | pages= 187-209 | pmid=10194456 | doi= | pmc=88914 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10194456  }} </ref><ref name="pmid1911961">{{cite journal| author=Engelkens HJ, ten Kate FJ, Vuzevski VD, van der Sluis JJ, Stolz E| title=Primary and secondary syphilis: a histopathological study. | journal=Int J STD AIDS | year= 1991 | volume= 2 | issue= 4 | pages= 280-4 | pmid=1911961 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1911961  }} </ref><ref name="pmid3285346">{{cite journal| author=Thomas DD, Navab M, Haake DA, Fogelman AM, Miller JN, Lovett MA| title=Treponema pallidum invades intercellular junctions of endothelial cell monolayers. | journal=Proc Natl Acad Sci U S A | year= 1988 | volume= 85 | issue= 10 | pages= 3608-12 | pmid=3285346 | doi= | pmc=280263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3285346  }} </ref><ref name="pmid18800002">{{cite journal| author=Quatresooz P, Piérard GE| title=Skin homing of Treponema pallidum in early syphilis: an immunohistochemical study. | journal=Appl Immunohistochem Mol Morphol | year= 2009 | volume= 17 | issue= 1 | pages= 47-50 | pmid=18800002 | doi=10.1097/PAI.0b013e3181788186 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18800002  }} </ref><ref name="pmid3734178">{{cite journal| author=Tanabe JL, Huntley AC| title=Granulomatous tertiary syphilis. | journal=J Am Acad Dermatol | year= 1986 | volume= 15 | issue= 2 Pt 2 | pages= 341-4 | pmid=3734178 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3734178  }} </ref>
 
==Pathogenesis==
==Pathogenesis==
The pathogenesis of syphilis may be described  in the following steps:<ref name="pmid21694502">{{cite journal| author=Carlson JA, Dabiri G, Cribier B, Sell S| title=The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. | journal=Am J Dermatopathol | year= 2011 | volume= 33 | issue= 5 | pages= 433-60 | pmid=21694502 | doi=10.1097/DAD.0b013e3181e8b587 | pmc=3690623 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21694502  }} </ref><ref name="pmid1386838">{{cite journal| author=Fitzgerald TJ| title=The Th1/Th2-like switch in syphilitic infection: is it detrimental? | journal=Infect Immun | year= 1992 | volume= 60 | issue= 9 | pages= 3475-9 | pmid=1386838 | doi= | pmc=257347 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1386838  }} </ref><ref name="pmid10194456">{{cite journal| author=Singh AE, Romanowski B| title=Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. | journal=Clin Microbiol Rev | year= 1999 | volume= 12 | issue= 2 | pages= 187-209 | pmid=10194456 | doi= | pmc=88914 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10194456  }} </ref><ref name="pmid1911961">{{cite journal| author=Engelkens HJ, ten Kate FJ, Vuzevski VD, van der Sluis JJ, Stolz E| title=Primary and secondary syphilis: a histopathological study. | journal=Int J STD AIDS | year= 1991 | volume= 2 | issue= 4 | pages= 280-4 | pmid=1911961 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1911961  }} </ref><ref name="pmid3285346">{{cite journal| author=Thomas DD, Navab M, Haake DA, Fogelman AM, Miller JN, Lovett MA| title=Treponema pallidum invades intercellular junctions of endothelial cell monolayers. | journal=Proc Natl Acad Sci U S A | year= 1988 | volume= 85 | issue= 10 | pages= 3608-12 | pmid=3285346 | doi= | pmc=280263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3285346  }} </ref><ref name="pmid18800002">{{cite journal| author=Quatresooz P, Piérard GE| title=Skin homing of Treponema pallidum in early syphilis: an immunohistochemical study. | journal=Appl Immunohistochem Mol Morphol | year= 2009 | volume= 17 | issue= 1 | pages= 47-50 | pmid=18800002 | doi=10.1097/PAI.0b013e3181788186 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18800002  }} </ref><ref name="pmid3734178">{{cite journal| author=Tanabe JL, Huntley AC| title=Granulomatous tertiary syphilis. | journal=J Am Acad Dermatol | year= 1986 | volume= 15 | issue= 2 Pt 2 | pages= 341-4 | pmid=3734178 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3734178  }} </ref><ref name="pmid7001910">{{cite journal| author=Baker-Zander S, Sell S| title=A histopathologic and immunologic study of the course of syphilis in the experimentally infected rabbit. Demonstration of long-lasting cellular immunity. | journal=Am J Pathol | year= 1980 | volume= 101 | issue= 2 | pages= 387-414 | pmid=7001910 | doi= | pmc=1903600 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7001910  }} </ref><ref name="pmid18008231">{{cite journal| author=Sheffield JS, Wendel GD, McIntire DD, Norgard MV| title=Effect of genital ulcer disease on HIV-1 coreceptor expression in the female genital tract. | journal=J Infect Dis | year= 2007 | volume= 196 | issue= 10 | pages= 1509-16 | pmid=18008231 | doi=10.1086/522518 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18008231  }} </ref><ref name="pmid1191529">{{cite journal| author=Abell E, Marks R, Jones EW| title=Secondary syphilis: a clinico-pathological review. | journal=Br J Dermatol | year= 1975 | volume= 93 | issue= 1 | pages= 53-61 | pmid=1191529 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1191529  }} </ref><ref name="pmid26100683">{{cite journal| author=Pastuszczak M, Jakiela B, Jaworek AK, Wypasek E, Zeman J, Wojas-Pelc A| title=Association of Interleukin-10 promoter polymorphisms with neurosyphilis. | journal=Hum Immunol | year= 2015 | volume= 76 | issue= 7 | pages= 469-72 | pmid=26100683 | doi=10.1016/j.humimm.2015.06.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26100683  }} </ref>
The pathogenesis of syphilis may be described  in the following steps:<ref name="pmid21694502">{{cite journal| author=Carlson JA, Dabiri G, Cribier B, Sell S| title=The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. | journal=Am J Dermatopathol | year= 2011 | volume= 33 | issue= 5 | pages= 433-60 | pmid=21694502 | doi=10.1097/DAD.0b013e3181e8b587 | pmc=3690623 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21694502  }} </ref><ref name="pmid1386838">{{cite journal| author=Fitzgerald TJ| title=The Th1/Th2-like switch in syphilitic infection: is it detrimental? | journal=Infect Immun | year= 1992 | volume= 60 | issue= 9 | pages= 3475-9 | pmid=1386838 | doi= | pmc=257347 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1386838  }} </ref><ref name="pmid10194456">{{cite journal| author=Singh AE, Romanowski B| title=Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. | journal=Clin Microbiol Rev | year= 1999 | volume= 12 | issue= 2 | pages= 187-209 | pmid=10194456 | doi= | pmc=88914 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10194456  }} </ref><ref name="pmid1911961">{{cite journal| author=Engelkens HJ, ten Kate FJ, Vuzevski VD, van der Sluis JJ, Stolz E| title=Primary and secondary syphilis: a histopathological study. | journal=Int J STD AIDS | year= 1991 | volume= 2 | issue= 4 | pages= 280-4 | pmid=1911961 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1911961  }} </ref><ref name="pmid3285346">{{cite journal| author=Thomas DD, Navab M, Haake DA, Fogelman AM, Miller JN, Lovett MA| title=Treponema pallidum invades intercellular junctions of endothelial cell monolayers. | journal=Proc Natl Acad Sci U S A | year= 1988 | volume= 85 | issue= 10 | pages= 3608-12 | pmid=3285346 | doi= | pmc=280263 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3285346  }} </ref><ref name="pmid18800002">{{cite journal| author=Quatresooz P, Piérard GE| title=Skin homing of Treponema pallidum in early syphilis: an immunohistochemical study. | journal=Appl Immunohistochem Mol Morphol | year= 2009 | volume= 17 | issue= 1 | pages= 47-50 | pmid=18800002 | doi=10.1097/PAI.0b013e3181788186 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18800002  }} </ref><ref name="pmid3734178">{{cite journal| author=Tanabe JL, Huntley AC| title=Granulomatous tertiary syphilis. | journal=J Am Acad Dermatol | year= 1986 | volume= 15 | issue= 2 Pt 2 | pages= 341-4 | pmid=3734178 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3734178  }} </ref><ref name="pmid7001910">{{cite journal| author=Baker-Zander S, Sell S| title=A histopathologic and immunologic study of the course of syphilis in the experimentally infected rabbit. Demonstration of long-lasting cellular immunity. | journal=Am J Pathol | year= 1980 | volume= 101 | issue= 2 | pages= 387-414 | pmid=7001910 | doi= | pmc=1903600 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7001910  }} </ref><ref name="pmid18008231">{{cite journal| author=Sheffield JS, Wendel GD, McIntire DD, Norgard MV| title=Effect of genital ulcer disease on HIV-1 coreceptor expression in the female genital tract. | journal=J Infect Dis | year= 2007 | volume= 196 | issue= 10 | pages= 1509-16 | pmid=18008231 | doi=10.1086/522518 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18008231  }} </ref><ref name="pmid1191529">{{cite journal| author=Abell E, Marks R, Jones EW| title=Secondary syphilis: a clinico-pathological review. | journal=Br J Dermatol | year= 1975 | volume= 93 | issue= 1 | pages= 53-61 | pmid=1191529 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1191529  }} </ref><ref name="pmid26100683">{{cite journal| author=Pastuszczak M, Jakiela B, Jaworek AK, Wypasek E, Zeman J, Wojas-Pelc A| title=Association of Interleukin-10 promoter polymorphisms with neurosyphilis. | journal=Hum Immunol | year= 2015 | volume= 76 | issue= 7 | pages= 469-72 | pmid=26100683 | doi=10.1016/j.humimm.2015.06.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26100683  }} </ref>
      
      
===Transmission===
===Transmission===
[[Treponema pallidum]] is usually transmitted via direct contact with the infected lesion (sexual contact) or blood transfusion (rare).
[[Treponema pallidum|''Treponema pallidum'']] is usually transmitted via direct contact with the infected lesion (sexual contact) or blood transfusion (rare).


===Incubation===
===Incubation===
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===Dissemination===
===Dissemination===
*Following transmission, the [[Trepenoma pallidum]] uses the intact or abraded [[mucous membrane]] to enter the body.  
*Following transmission, [[Treponema pallidum|''Treponema pallidum'']] uses the intact or abraded [[mucous membrane]] to enter the body.  
*It then disseminates to the [[lymphatics]] and blood stream to gain access to any organ of the body.
*It then disseminates to the [[lymphatics]] and blood stream to gain access to any organ of the body.


===Seeding===
===Seeding===
*Syphilis uses [[fibronectin]] molecules to attach to the [[endothelial]] surface of the vessels in organs resulting in inflammation and obliteration of the small blood vessels causing [[vasculitis]] (end arteritis obliterans).
*Syphilis uses [[fibronectin]] molecules to attach to the [[endothelial]] surface of the vessels in organs resulting in inflammation and obliteration of the small blood vessels causing [[vasculitis]] ([[endarteritis obliterans]]).
*Organism has slow replication rate (30-33 hrs) and evades the initial host immune response.
*Organism has slow replication rate (30-33 hrs) and evades the initial host immune response.
*It may seed to different organs of the body esp cardiovascular system and central nervous system resulting in tertiary syphilis.
*It may seed to different organs of the body especially the [[cardiovascular system]] and [[central nervous system]] resulting in tertiary syphilis.


===Immune response===
===Immune response===
Different stages of syphilis results from the interaction between the [[antigen]] and the [[host immune response]].
Different stages of syphilis results from the interaction between the [[antigen]] and the [[host immune response]].<ref name="pmid21694502">{{cite journal| author=Carlson JA, Dabiri G, Cribier B, Sell S| title=The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. | journal=Am J Dermatopathol | year= 2011 | volume= 33 | issue= 5 | pages= 433-60 | pmid=21694502 | doi=10.1097/DAD.0b013e3181e8b587 | pmc=3690623 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21694502  }} </ref><ref name="pmid1386838">{{cite journal| author=Fitzgerald TJ| title=The Th1/Th2-like switch in syphilitic infection: is it detrimental? | journal=Infect Immun | year= 1992 | volume= 60 | issue= 9 | pages= 3475-9 | pmid=1386838 | doi= | pmc=257347 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1386838  }} </ref>


'''Acute response'''
'''Acute response'''
*The initial infection in primary syphilis is limited due to [[Th1 response]] and lack of the [[antibody]] response.
*The initial infection in primary syphilis is limited due to [[Th1 response]] and lack of the [[antibody]] response.
*It is speculated that there is a shift from Th1 to Th2 response during the secondary syphilis.
*It is speculated that there is a shift from Th1 to [[Th2 response]] during secondary syphilis.
'''Chronic  
'''Chronic  
*Cyototxic T cells and incomplete humoral response is mainly responsible for persistence of infection and tissue damage in the tertiary syphilis.
*[[Cytotoxic T cells]] and an incomplete humoral response is mainly responsible for persistence of infection and tissue damage in tertiary syphilis.
*Ineffective type 4 delayed hypersensitivity reaction containing [[macrophages]] and sensitized [[T cells]] is mainly responsible for the [[gumma]] formation in various organs.
*Ineffective [[Type IV hypersensitivity|type 4 delayed hypersensitivity]] reaction containing [[macrophages]] and sensitized [[T cells]] is mainly responsible for the [[gumma]] formation in various organs.


===Genetics===
===Genetics===
There is no known genetic association of syphilis. However, [[neurosyphilis]] may be associated with the gene polymorphism for IL 10 production with increased levels seen in the patients with neurosyphilis.<ref name="pmid26100683">{{cite journal| author=Pastuszczak M, Jakiela B, Jaworek AK, Wypasek E, Zeman J, Wojas-Pelc A| title=Association of Interleukin-10 promoter polymorphisms with neurosyphilis. | journal=Hum Immunol | year= 2015 | volume= 76 | issue= 7 | pages= 469-72 | pmid=26100683 | doi=10.1016/j.humimm.2015.06.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26100683  }} </ref>
There is no known genetic association of syphilis. However, [[neurosyphilis]] may be associated with the gene polymorphism for [[IL-10]] production with increased levels seen in the patients with neurosyphilis.<ref name="pmid26100683">{{cite journal| author=Pastuszczak M, Jakiela B, Jaworek AK, Wypasek E, Zeman J, Wojas-Pelc A| title=Association of Interleukin-10 promoter polymorphisms with neurosyphilis. | journal=Hum Immunol | year= 2015 | volume= 76 | issue= 7 | pages= 469-72 | pmid=26100683 | doi=10.1016/j.humimm.2015.06.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26100683  }} </ref>


===Associated conditions===
===Associated conditions===
Syphilis is associated with the increased transmission of [[HIV]]. The underlying mechanism may be related to the accumulation of [[dendritic cells]] containing [[CCR5 co receptors]] at the site of infection, the same receptor entity binding the HIV.
Syphilis is associated with increased transmission of [[HIV]]. The underlying mechanism may be related to the accumulation of [[dendritic cells]] containing [[CCR5]] co-receptors at the site of infection, the same receptor entity binding the HIV.<ref name="pmid18008231">{{cite journal| author=Sheffield JS, Wendel GD, McIntire DD, Norgard MV| title=Effect of genital ulcer disease on HIV-1 coreceptor expression in the female genital tract. | journal=J Infect Dis | year= 2007 | volume= 196 | issue= 10 | pages= 1509-16 | pmid=18008231 | doi=10.1086/522518 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18008231  }} </ref>
 
===Gross pathology===
Gross pathology


===Microscopic pathology===
===Microscopic pathology===
Line 51: Line 47:
'''Secondary syphilis'''
'''Secondary syphilis'''
*Swelling and dilatation of blood vessels in the [[dermis]]
*Swelling and dilatation of blood vessels in the [[dermis]]
*[[Epidermal hyperplasia]] and neutrophilic infiltration
*Epidermal [[hyperplasia]] and neutrophilic infiltration
*Inflammatory cell infiltrate predominantly [[plasma cell]]  
*Inflammatory cell infiltrate, predominantly [[plasma cell]]  


'''Tertiary syphilis'''
'''Tertiary syphilis'''
*Small vessel inflammation (end arteritis obliterans)
*Small vessel inflammation ([[endarteritis obliterans]])
*Granulomatous lesions ([[gumma]]) containing central necrosis, inflammatory cells such as lymphocytes, macrophages, plasma cells and fibroblasts.
*Granulomatous lesions ([[gumma]]) containing central necrosis, inflammatory cells, such as [[lymphocytes]], [[macrophages]], [[plasma cells]] and [[Fibroblast|fibroblasts]].
 
 
 
 
 
 
 
 
 
*Syphilis can not be contracted through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.<ref>{{cite web  | last = Centers for Disease Control (CDC) | authorlink = Centers for Disease Control and Prevention  | title =STD Facts - Syphilis  | publisher = [[Centers for Disease Control]] | date = 05-2004  | url = http://www.cdc.gov/std/syphilis/STDFact-Syphilis.htm }}</ref>
.
:*There may be a symmetrical reddish-pink non-itchy rash on the trunk and extremities.<ref name=2darySyphilis>{{cite journal | author=Dylewski J, Duong M | title=The rash of secondary syphilis | journal=CMAJ. | date= 2007 Jan 2 | volume=176 | issue=1 | pages=33-5 | doi= 10.1503/cmaj.060665}}</ref>
 
 
<gallery perRow="5">
Image:Secondary Syphilis on palms CDC 6809 lores rsh.jpg|Typical presentation of secondary syphilis rash on the palms of the hands and usually also seen on soles of feet
 
Image:condyoma lata (syphilis secondary).jpg|Condyoma lata (syphilis secondary)
 
Image:TreponemaPallidum.jpg|Electron micrograph of Treponema pallidum
 
Image:Syphilis lesions on back.jpg|Syphilis lesions on a patient's back
 
Image:Syphilis lesions on chest.jpg|Syphilis lesions on a patient's chest
 
Image:Penis syphilis.png|Chancres on the penile shaft due to a primary syphilitic infection
 
Image:Vaginal syphilis (disturbing image).jpg|Secondary syphilis manifested perineal condylomata lata lesions, which presented as gray, raised papules that sometimes appear on the vulva or near the anus, or in any other warm intertriginous region.
Image:Gumma of nose due to a long standing tertiary syphilitic Treponema pallidum infection 5330 lores.jpg|Gumma of the nose due to long standing tertiary syphilis
</gallery>
 
 
:::*General paresis<ref name=AMN>{{cite journal | author = Richard B. Jamess, MD, PhD | title = [http://www.health.am/sex/syphilis/ Syphilis- Sexually Transmitted Infections], 2006. | journal =Sexually transmitted diseases treatment guidelines | volume = | issue = | pages = | year = 2002}}</ref>, otherwise known as general paresis of the insane, is a severe manifestation of neurosyphilis.
 
 
:::*Imaging of the brain usually shows atrophy.
 
===Microscopic Pathology===
 
====Brain: Gumma of Syphilis====
 
{{#ev:youtube|Cd60sjchsN8}}
 
==== Brain: Paresis (syphilis)====
 
{{#ev:youtube|1Ibu71qHznA}}


==References==
==References==
Line 113: Line 61:


[[Category:Gynecology]]
[[Category:Gynecology]]
[[Category:Emergency mdicine]]
[[Category:Disease]]
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Infectious disease]]
[[Category:Primary care]]
[[Category:Urology]]
[[Category:Neurology]]

Latest revision as of 00:23, 30 July 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]; Nate Michalak, B.A.

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Overview

Syphilis is caused by a spirochete, Treponema pallidum. It has an average incubation period of 3 - 12 weeks. However, it may vary according to the size of innoculum. Spirochete penetrates intact mucous membrane or microscopic dermal abrasions and rapidly enters systemic circulation with the central nervous system being invaded during the early phase of infection. The histopathological hallmark findings are endarteritis and plasma cell-rich infiltrates reflecting a delayed-type of hypersensitivity reaction to the spirochete.[1][2][3][4][5][6][7]

Pathogenesis

The pathogenesis of syphilis may be described in the following steps:[1][2][3][4][5][6][7][8][9][10][11]

Transmission

Treponema pallidum is usually transmitted via direct contact with the infected lesion (sexual contact) or blood transfusion (rare).

Incubation

The incubation period varies with the size of innoculum (9-90 days).

Dissemination

Seeding

Immune response

Different stages of syphilis results from the interaction between the antigen and the host immune response.[1][2]

Acute response

  • The initial infection in primary syphilis is limited due to Th1 response and lack of the antibody response.
  • It is speculated that there is a shift from Th1 to Th2 response during secondary syphilis.

Chronic

Genetics

There is no known genetic association of syphilis. However, neurosyphilis may be associated with the gene polymorphism for IL-10 production with increased levels seen in the patients with neurosyphilis.[11]

Associated conditions

Syphilis is associated with increased transmission of HIV. The underlying mechanism may be related to the accumulation of dendritic cells containing CCR5 co-receptors at the site of infection, the same receptor entity binding the HIV.[9]

Microscopic pathology

On microscopic histopathological analysis, characteristic findings of syphilis depends on the stage of the disease:

Primary syphilis

  • Mononuclear leukocytic infiltration, macrophages, and lymphocytes
  • Swelling and proliferation of small blood vessels

Secondary syphilis

  • Swelling and dilatation of blood vessels in the dermis
  • Epidermal hyperplasia and neutrophilic infiltration
  • Inflammatory cell infiltrate, predominantly plasma cell

Tertiary syphilis

References

  1. ↑ 1.0 1.1 1.2 Carlson JA, Dabiri G, Cribier B, Sell S (2011). "The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity". Am J Dermatopathol. 33 (5): 433–60. doi:10.1097/DAD.0b013e3181e8b587. PMC 3690623. PMID 21694502.
  2. ↑ 2.0 2.1 2.2 Fitzgerald TJ (1992). "The Th1/Th2-like switch in syphilitic infection: is it detrimental?". Infect Immun. 60 (9): 3475–9. PMC 257347. PMID 1386838.
  3. ↑ 3.0 3.1 Singh AE, Romanowski B (1999). "Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features". Clin Microbiol Rev. 12 (2): 187–209. PMC 88914. PMID 10194456.
  4. ↑ 4.0 4.1 Engelkens HJ, ten Kate FJ, Vuzevski VD, van der Sluis JJ, Stolz E (1991). "Primary and secondary syphilis: a histopathological study". Int J STD AIDS. 2 (4): 280–4. PMID 1911961.
  5. ↑ 5.0 5.1 Thomas DD, Navab M, Haake DA, Fogelman AM, Miller JN, Lovett MA (1988). "Treponema pallidum invades intercellular junctions of endothelial cell monolayers". Proc Natl Acad Sci U S A. 85 (10): 3608–12. PMC 280263. PMID 3285346.
  6. ↑ 6.0 6.1 Quatresooz P, Piérard GE (2009). "Skin homing of Treponema pallidum in early syphilis: an immunohistochemical study". Appl Immunohistochem Mol Morphol. 17 (1): 47–50. doi:10.1097/PAI.0b013e3181788186. PMID 18800002.
  7. ↑ 7.0 7.1 Tanabe JL, Huntley AC (1986). "Granulomatous tertiary syphilis". J Am Acad Dermatol. 15 (2 Pt 2): 341–4. PMID 3734178.
  8. ↑ Baker-Zander S, Sell S (1980). "A histopathologic and immunologic study of the course of syphilis in the experimentally infected rabbit. Demonstration of long-lasting cellular immunity". Am J Pathol. 101 (2): 387–414. PMC 1903600. PMID 7001910.
  9. ↑ 9.0 9.1 Sheffield JS, Wendel GD, McIntire DD, Norgard MV (2007). "Effect of genital ulcer disease on HIV-1 coreceptor expression in the female genital tract". J Infect Dis. 196 (10): 1509–16. doi:10.1086/522518. PMID 18008231.
  10. ↑ Abell E, Marks R, Jones EW (1975). "Secondary syphilis: a clinico-pathological review". Br J Dermatol. 93 (1): 53–61. PMID 1191529.
  11. ↑ 11.0 11.1 Pastuszczak M, Jakiela B, Jaworek AK, Wypasek E, Zeman J, Wojas-Pelc A (2015). "Association of Interleukin-10 promoter polymorphisms with neurosyphilis". Hum Immunol. 76 (7): 469–72. doi:10.1016/j.humimm.2015.06.010. PMID 26100683.


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