Syphilis pathophysiology: Difference between revisions
Jump to navigation
Jump to search
Aysha Aslam (talk | contribs) No edit summary |
m (Bot: Removing from Primary care) |
||
| (35 intermediate revisions by 5 users not shown) | |||
| Line 1: | Line 1: | ||
__NOTOC__ | __NOTOC__ | ||
{{CMG}} | {{CMG}} {{AE}} {{AA}}; {{NRM}} | ||
{{Syphilis}} | {{Syphilis}} | ||
==Overview== | ==Overview== | ||
Syphilis is caused by a 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> | |||
===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=== | ||
[[ | The [[incubation period]] varies with the size of innoculum (9-90 days). | ||
===Dissemination=== | ===Dissemination=== | ||
*Following transmission, | *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. | ||
===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]] ([[endarteritis obliterans]]). | ||
*It may seed to different organs of the body | *Organism has slow replication rate (30-33 hrs) and evades the initial host immune response. | ||
*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]].<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''' | |||
*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 | ||
* | *[[Cytotoxic T cells]] and an incomplete humoral response is mainly responsible for persistence of infection and tissue damage in tertiary syphilis. | ||
*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 gene polymorphism for IL 10 production with increased levels seen in 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 increased transmission of [[HIV]]. The underlying mechanism may be related to accumulation of [[dendritic cells]] containing [[CCR5 co receptors | 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> | ||
=== | |||
===Microscopic pathology=== | ===Microscopic pathology=== | ||
| Line 56: | 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 | ||
*Inflammatory cell infiltrate predominantly [[plasma cell]] | *Inflammatory cell infiltrate, predominantly [[plasma cell]] | ||
'''Tertiary syphilis''' | '''Tertiary syphilis''' | ||
*Small vessel inflammation ( | *Small vessel inflammation ([[endarteritis obliterans]]) | ||
*Granulomatous lesions ([[gumma]]) containing central necrosis, inflammatory cells such as lymphocytes, macrophages, plasma cells and | *Granulomatous lesions ([[gumma]]) containing central necrosis, inflammatory cells, such as [[lymphocytes]], [[macrophages]], [[plasma cells]] and [[Fibroblast|fibroblasts]]. | ||
==References== | ==References== | ||
| Line 118: | Line 61: | ||
[[Category:Gynecology]] | [[Category:Gynecology]] | ||
[[Category:Emergency mdicine]] | |||
[[Category:Disease]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Infectious disease]] | [[Category:Infectious disease]] | ||
[[Category: | [[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.
|
Syphilis Microchapters | |
|
Diagnosis | |
|
Treatment | |
|
Case Studies | |
|
Syphilis pathophysiology On the Web | |
|
American Roentgen Ray Society Images of Syphilis pathophysiology | |
|
Risk calculators and risk factors for Syphilis pathophysiology | |
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
- Following transmission, 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.
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 (endarteritis obliterans).
- Organism has slow replication rate (30-33 hrs) and evades the initial host immune response.
- It may seed to different organs of the body especially the cardiovascular system and central nervous system resulting in tertiary syphilis.
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
- 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.
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
- Small vessel inflammation (endarteritis obliterans)
- Granulomatous lesions (gumma) containing central necrosis, inflammatory cells, such as lymphocytes, macrophages, plasma cells and fibroblasts.
References
- ↑ 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.
- ↑ 2.0 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.
- ↑ 3.0 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.
- ↑ 4.0 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.
- ↑ 5.0 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.
- ↑ 6.0 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.
- ↑ 7.0 7.1 Tanabe JL, Huntley AC (1986). "Granulomatous tertiary syphilis". J Am Acad Dermatol. 15 (2 Pt 2): 341–4. PMID 3734178.
- ↑ 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.
- ↑ 9.0 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.
- ↑ Abell E, Marks R, Jones EW (1975). "Secondary syphilis: a clinico-pathological review". Br J Dermatol. 93 (1): 53–61. PMID 1191529.
- ↑ 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.