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{{Syphilis}}
{{Syphilis}}
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==Overview==
==Overview==
Syphilis is a curable [[sexually transmitted disease]] caused by the ''[[Treponema pallidum]]'' [[spirochete]]. The route of transmission of syphilis is almost always by [[sexual]] contact, although there are examples of [[congenital syphilis]] via transmission from mother to child [[in utero]]. The signs and [[symptoms]] of syphilis are numerous; before the advent of [[serological testing]], precise [[diagnosis]] was very difficult. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Syphilis (unless [[antibiotic resistance|antibiotic-resistant]]) can be easily treated with [[antibiotics]] including [[penicillin]]. The oldest and still most effective method is an [[intramuscular injection]] of [[Penicillin#Benzathine benzylpenicillin|benzathine penicillin]]. If not treated, syphilis can cause serious effects such as damage to the [[heart]], [[aorta]], [[brain]], [[eyes]], and [[bones]]. In some cases these effects can be fatal. In 1998, the complete [[genetic sequence]] of ''T. pallidum'' was published which may aid understanding of the [[pathogenesis]] of syphilis.
Syphilis is a curable [[sexually transmitted disease]] caused by the ''[[Treponema pallidum]]'' [[spirochete]]. The route of transmission of syphilis is almost always by [[sexual]] contact, although there are examples of [[congenital syphilis]] via transmission from mother to child [[in utero]]. The signs and [[symptoms]] of syphilis are numerous; before the advent of [[serological testing]], precise [[diagnosis]] was very difficult. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Syphilis (unless [[antibiotic resistance|antibiotic-resistant]]) can be easily treated with [[antibiotics]] including [[penicillin]]. The oldest and still most effective method is an [[intramuscular injection]] of [[Penicillin#Benzathine benzylpenicillin|benzathine penicillin]]. If not treated, syphilis can cause serious effects such as damage to the [[heart]], [[aorta]], [[brain]], [[eyes]], and [[bones]]. In some cases these effects can be fatal. In 1998, the complete [[genetic sequence]] of ''T. pallidum'' was published which may aid understanding of the [[pathogenesis]] of syphilis.
==Historical Perspective==
The name "syphilis" was coined by the Italian physician and poet [[Girolamo Fracastoro]] in his epic noted poem, written in Latin, entitled ''Syphilis sive morbus gallicus'' (Latin for "Syphilis or The French Disease") in 1530. The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's ''Metamorphoses'').  Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him. From this character Fracastoro derived a new name for the disease, which he also used in his medical text ''De Contagionibus'' ("On Contagious Diseases"). Until that time, as Fracastoro notes, syphilis had been called the "French disease" in Italy and Germany, and the "Italian disease" in France. In addition, the Dutch called it the "Spanish disease", the Russians called it the "Polish disease", the Turks called it the "Christian disease" or "Frank disease" (''frengi'') and the Tahitians called it the "British disease". These 'national' names are due to the disease often being present among invading armies or sea crews, due to their high amount of unprotected sexual contacts with prostitutes. It's interesting to notice how the invaders named it after the invaded country and vice versa. It was also called "Great pox" in the 16th century to distinguish it from [[smallpox]]. In its early stages, the Great pox produced a rash similar to smallpox (also known as [[variola]]). However, the name is misleading, as smallpox was a far more deadly disease. The terms "[http://www.merriam-webster.com/dictionary/lues Lues]" (or ''Lues venerea'', Latin for "venereal plague") and "Cupid's disease" have also been used to refer to syphilis. In Scotland, Syphilis was referred to as the ''Grandgore''. It was also called [http://www.antiquusmorbus.com/English/EnglishB.htm The Black Lion].


==Classification==
==Classification==
===Congenital syphilis===
Syphilis may be classified according to the development of disease into 2 groups: congenital and acquired. Acquired syphilis may be classified further into 4 subtypes: primary, secondary, latent and tertiary syphilis.<ref name="pmid17235095">{{cite journal| author=French P| title=Syphilis. | journal=BMJ | year= 2007 | volume= 334 | issue= 7585 | pages= 143-7 | pmid=17235095 | doi=10.1136/bmj.39085.518148.BE | pmc=1779891 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17235095  }} </ref><ref name="pmid18208988[uid]">{{cite journal| author=Chakraborty R, Luck S| title=Syphilis is on the increase: the implications for child health. | journal=Arch Dis Child | year= 2008 | volume= 93 | issue= 2 | pages= 105-9 | pmid=18208988[uid] | doi=10.1136/adc.2006.103515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18208988  }} </ref><ref name=abc>http://www.cdc.gov/std/stats10/app-casedef.htm Accessed on September 19, 2016</ref>
Further sub-classified depending on the different manifestations that occur depending on the stage of the disease.
 
*Early
==Pathophysiology==
*Late
Syphilis is caused by the [[spirochete]], [[Treponema pallidum]]. It has an incubation period of 3 - 12 weeks. The [[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 obliterans|endarteritis]] and plasma cell-rich infiltrates reflecting a [[Type IV hypersensitivity|delayed-type of hypersensitivity]] 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>
*Stigmata
 
==Causes==
Syphilis is caused by a [[spirochete]], [[Treponema pallidum]]. The spirochete rapidly penetrates via intact mucosal membranes or microscopic dermal abrasions. It is spread through intimate sexual contact, [[blood transfusion]] or [[vertical transmission]] from infected mother to [[fetus]].<ref name="pmid11825779">{{cite journal |author=Antal GM, Lukehart SA, Meheus AZ |title=The endemic treponematoses |journal=Microbes Infect. |volume=4 |issue=1 |pages=83–94 |date=January 2002 |pmid=11825779 |doi= 10.1016/S1286-4579(01)01513-1|url=http://linkinghub.elsevier.com/retrieve/pii/S1286457901015131}}</ref>
 
==Differentiating Syphilis from other Diseases==
Syphilis is a curable [[sexually transmitted disease]] caused by the ''[[Treponema pallidum]]'' [[spirochete]]. The route of transmission of syphilis is almost always by [[sexual]] contact, although there are examples of [[congenital syphilis]] via transmission from mother to child [[in utero]]. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Hence, patients with tertiary syphilis should also be tested for other [[STD|sexually transmitted diseases]] such as [[chlamydia]], [[gonorrhea]], [[trichomoniasis]], [[bacterial vaginosis]] and [[HIV|HIV infection]].<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="pmid17939933">{{cite journal |author=Fatahzadeh M, Schwartz RA |title=Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management |journal=J. Am. Acad. Dermatol. |volume=57 |issue=5 |pages=737–63; quiz 764–6 |year=2007 |pmid=17939933 |doi=10.1016/j.jaad.2007.06.027}}</ref><ref name="pmid12473810">{{cite journal |vauthors=O'Farrell N |title=Donovanosis |journal=Sexually Transmitted Infections |volume=78 |issue=6 |pages=452–7 |year=2002 |pmid=12473810 |pmc=1758360 |doi= |url=}}</ref><ref name="pmid2991120">{{cite journal |vauthors=Coovadia YM, Kharsany A, Hoosen A |title=The microbial aetiology of genital ulcers in black men in Durban, South Africa |journal=Genitourin Med |volume=61 |issue=4 |pages=266–9 |year=1985 |pmid=2991120 |pmc=1011828 |doi= |url=}}</ref><ref name="pmid12081191">{{cite journal |vauthors=Mabey D, Peeling RW |title=Lymphogranuloma venereum |journal=Sexually Transmitted Infections |volume=78 |issue=2 |pages=90–2 |year=2002 |pmid=12081191 |pmc=1744436 |doi= |url=}}</ref>
 
==Epidemiology and Demographics==
In 2012, the incidence of syphilis was estimated to be 6 million cases worldwide. From year 2005 to 2014, the incidence of syphilis in the United States increased from 2.9 to 6.3 cases/100,000/year. The rate of reported cases increased by 15.1% between 2013 and 2014 in the United States.<ref name=CDC>https://www.cdc.gov/std/stats14/surv-2014-print.pdf Accessed on September 16, 2016</ref> Syphilis incidence increased in every region of the Untied States in 2014, with the highest rate in the West and lowest rate in the Midwest. In 2012, the [[prevalence]] of syphilis was estimated to be approximately 18 million cases in men and women aged 15-29 worldwide.<ref name="pmid26646541">{{cite journal| author=Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M, Low N et al.| title=Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting. | journal=PLoS One | year= 2015 | volume= 10 | issue= 12 | pages= e0143304 | pmid=26646541 | doi=10.1371/journal.pone.0143304 | pmc=4672879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26646541  }} </ref> The incidence and prevalence of syphilis may be affected by age, gender, race, sexual behavior and geographical distribution.<ref name=CDC>https://www.cdc.gov/std/stats14/surv-2014-print.pdf Accessed on September 16, 2016</ref><ref name="pmid23403598">{{cite journal| author=Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan R, Ocfemia MC et al.| title=Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008. | journal=Sex Transm Dis | year= 2013 | volume= 40 | issue= 3 | pages= 187-93 | pmid=23403598 | doi=10.1097/OLQ.0b013e318286bb53 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23403598  }} </ref><ref name=WHO2012>http://apps.who.int/iris/bitstream/10665/85376/1/9789241505895_eng.pdf?=1 Accessed on September 16, 2016</ref><ref name="pmid23049658">{{cite journal| author=Purcell DW, Johnson CH, Lansky A, Prejean J, Stein R, Denning P et al.| title=Estimating the population size of men who have sex with men in the United States to obtain HIV and syphilis rates. | journal=Open AIDS J | year= 2012 | volume= 6 | issue=  | pages= 98-107 | pmid=23049658 | doi=10.2174/1874613601206010098 | pmc=3462414 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23049658  }} </ref><ref name="pmid17463387">{{cite journal| author=Heffelfinger JD, Swint EB, Berman SM, Weinstock HS| title=Trends in primary and secondary syphilis among men who have sex with men in the United States. | journal=Am J Public Health | year= 2007 | volume= 97 | issue= 6 | pages= 1076-83 | pmid=17463387 | doi=10.2105/AJPH.2005.070417 | pmc=1874206 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17463387  }} </ref><ref name="pmid6893897">{{cite journal| author=Judson FN, Penley KA, Robinson ME, Smith JK| title=Comparative prevalence rates of sexually transmitted diseases in heterosexual and homosexual men. | journal=Am J Epidemiol | year= 1980 | volume= 112 | issue= 6 | pages= 836-43 | pmid=6893897 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6893897  }} </ref>
 
==Risk Factors==
The risk factors of syphilis include [[unprotected sex]], IV [[drug abuse]] and occupational risk for health care professionals.<ref name="pmid2356911">{{cite journal| author=Rolfs RT, Goldberg M, Sharrar RG| title=Risk factors for syphilis: cocaine use and prostitution. | journal=Am J Public Health | year= 1990 | volume= 80 | issue= 7 | pages= 853-7 | pmid=2356911 | doi= | pmc=1404975 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2356911  }} </ref><ref name="pmid17675391">{{cite journal| author=Zhou H, Chen XS, Hong FC, Pan P, Yang F, Cai YM et al.| title=Risk factors for syphilis infection among pregnant women: results of a case-control study in Shenzhen, China. | journal=Sex Transm Infect | year= 2007 | volume= 83 | issue= 6 | pages= 476-80 | pmid=17675391 | doi=10.1136/sti.2007.026187 | pmc=2598725 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17675391  }} </ref><ref>Newell, J., et al. "A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour." Genitourinary medicine 69.6 (1993): 421-426.</ref><ref name="pmid15247352">{{cite journal| author=Hook EW, Peeling RW| title=Syphilis control--a continuing challenge. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 2 | pages= 122-4 | pmid=15247352 | doi=10.1056/NEJMp048126 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15247352  }} </ref><ref name="pmid16205297">{{cite journal| author=Buchacz K, Greenberg A, Onorato I, Janssen R| title=Syphilis epidemics and human immunodeficiency virus (HIV) incidence among men who have sex with men in the United States: implications for HIV prevention. | journal=Sex Transm Dis | year= 2005 | volume= 32 | issue= 10 Suppl | pages= S73-9 | pmid=16205297 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16205297  }} </ref>
 
==Screening==
Screening guidelines for syphilis include all high risk non pregnant individuals aged 15-65, all pregnant females, men who have sex with men, women who have sex with women, [[HIV]] positive individuals.<ref name= sypilis>https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-nonpregnant-adults-and-adolescents?ds=1&s=syphilis Accessed on September 19, 2016</ref> Routine screening of adolescents who are asymptomatic for syphilis is not recommended <ref name=cdc5>http://www.cdc.gov/std/treatment/2010/specialpops.htm Accessed on September 19, 2016</ref><ref name=USPTF4> https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-pregnancy-screening?ds=1&s=syphilis Accessed on September 19, 2016</ref>
 
==Natural History, Complications and Prognosis==
Initial presentation of syphilis is appearance of painless chancre after 3-4 weeks of exposure. If left untreated, [[chancre]] self resolves and may progress to develop constitutional symptoms and generalized symmetric rash in four to eight weeks. In less than 10% of individuals, complications such as [[hepatitis]], [[iritis]], [[nephritis]], and neurological problems may develop at this stage. However, it resolves in four to eight weeks without treatment and patient enters into asymptomatic latent phase. About a quarter of patients may develop recurrence of similar symptoms in one year. If left untreated, 35% of patients may develop tertiary syphilis which include complications such as cardiovascular involvement, neurologic infection and [[gummatous]] lesions involving skin, bone and joints which is associated with significant [[morbidity]] and [[mortality]].<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="pmid17235095">{{cite journal| author=French P| title=Syphilis. | journal=BMJ | year= 2007 | volume= 334 | issue= 7585 | pages= 143-7 | pmid=17235095 | doi=10.1136/bmj.39085.518148.BE | pmc=1779891 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17235095  }} </ref><ref name="pmid1951814">{{cite journal| author=Thomas SB, Quinn SC| title=The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community. | journal=Am J Public Health | year= 1991 | volume= 81 | issue= 11 | pages= 1498-505 | pmid=1951814 | doi= | pmc=1405662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1951814  }} </ref><ref name="pmid13301322">{{cite journal| author=GJESTLAND T| title=The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. | journal=Acta Derm Venereol Suppl (Stockh) | year= 1955 | volume= 35 | issue= Suppl 34 | pages= 3-368; Annex I-LVI | pmid=13301322 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13301322  }} </ref> The prognosis of syphilis varies by stage of disease.Prognosis of primary and secondary syphilis is good with treatment. For tertiary syphilis, prognosis varies by site of involvememnt and duration of disease. 90% of patients with neurosyphilis respond to treatment. However, mortality rates are high with cardiovascular complications.<ref name="pmid1951814">{{cite journal| author=Thomas SB, Quinn SC| title=The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community. | journal=Am J Public Health | year= 1991 | volume= 81 | issue= 11 | pages= 1498-505 | pmid=1951814 | doi= | pmc=1405662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1951814  }} </ref><ref name="pmid13301322">{{cite journal| author=GJESTLAND T| title=The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. | journal=Acta Derm Venereol Suppl (Stockh) | year= 1955 | volume= 35 | issue= Suppl 34 | pages= 3-368; Annex I-LVI | pmid=13301322 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13301322  }} </ref>
 
==Treatment==
===Medical Therapy===
[[Penicillin#Benzylpenicillin (penicillin G)|Penicillin G]], administered parenterally, is the preferred drug for treating all stages of syphilis. If allergic, then [[tetracycline]] or [[doxycycline]] may also be used. During pregnancy, [[Penicillin#Benzylpenicillin (penicillin G)|parenteral penicillin G]] is the only therapy with documented efficacy for syphilis.<ref name=cdcsyphilis>http://www.cdc.gov/std/tg2015/syphilis.htm Accessed on September 26, 2016</ref>
 
===Management of Primary and Secondary Stages===
[[Penicillin#Benzylpenicillin (penicillin G)|Parenteral penicillin G]] has been used effectively for more than 50 years to achieve clinical resolution (i.e., the healing of lesions and prevention of sexual transmission) and to prevent late sequelae. However, no comparative trials have been adequately conducted to guide the selection of an optimal penicillin regimen (i.e., the dose, duration, and preparation). Substantially fewer data are available for non-penicillin regimens.<ref name="pmid16477545">Ghanem KG, Erbelding EJ, Cheng WW, Rompalo AM (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16477545 Doxycycline compared with benzathine penicillin for the treatment of early syphilis.] Clin Infect Dis 42 (6):e45-9. [http://dx.doi.org/10.1086/500406 DOI:10.1086/500406] PMID: [http://pubmed.gov/16477545 16477545]</ref>
 
===Tertiary Syphilis===
[[Syphilis pathophysiology#Tertiary syphilis|Tertiary syphilis]] refers to [[Syphilis physical examination#Tertiary syphilis: Gumma|gumma and cardiovascular syphilis]] but not to all [[Neurosyphilis#Clinical presentation: Four clinical types|neurosyphilis]]. Patients who are not [[Syphilis medical therapy#Pencillin allergy|allergic to penicillin]] and have no evidence of [[neurosyphilis]] should be treated with the following regimen.<ref name="urlSexually Transmitted Diseases Treatment Guidelines, 2010">{{cite web |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm |title=Sexually Transmitted Diseases Treatment Guidelines, 2010 |format= |work= |accessdate=2012-12-19}}</ref><ref name=cdc2015>http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016</ref>
 
===Neurosyphilis===
[[CNS]] involvement can occur during any stage of syphilis. However, [[CSF]] laboratory abnormalities are common in persons with [[Syphilis pathophysiology#Primary syphilis|early syphilis]], even in the absence of clinical neurological findings. No evidence exists to support variation from recommended treatment for early syphilis for patients found to have such abnormalities. If clinical evidence of neurologic involvement is observed (e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of [[meningitis]]), a [[CSF]] examination should be performed. [[uveitis|Syphilitic uveitis]] or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis. Patients who have neurosyphilis or syphilitic eye disease (e.g., [[uveitis]], [[neuroretinitis]], and [[optic neuritis]]) should be treated with the recommended regimen for neurosyphilis; those with [[eye]] disease should be managed in collaboration with an ophthalmologist. A [[Syphilis laboratory tests#CSF analysis|CSF examination]] should be performed for all patients with syphilitic eye disease to identify those with abnormalities; patients found to have abnormal [[CSF]] test results should be provided follow-up [[CSF]] examinations to assess treatment response.<ref name=cdc2015>http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016</ref>


===Acquired syphilis===
===Primary Prevention===
*Primary syphilis
As of 2010, there is no vaccine effective for prevention.<ref name="pmid19805553">{{cite journal |author=Stamm LV |title=Global challenge of antibiotic-resistant Treponema pallidum |journal=[[Antimicrobial Agents and Chemotherapy]] |volume=54 |issue=2 |pages=583–9 |year=2010 |month=February |pmid=19805553 |pmc=2812177 |doi=10.1128/AAC.01095-09 |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=19805553 |accessdate=2012-02-21}}</ref>
*Secondary syphilis
===Secondary Prevention===
*Latent syphilis
While abstinence from intimate physical contact with an infected person is very effective at reducing the transmission of syphilis, it should be noted that ''T. pallidum'' readily crosses intact [[mucosa]] and cut skin, including areas not covered by a condom. Proper and consistent use of a latex [[condom]] can reduce, but not eliminate, the spread of syphilis.[http://www.cdc.gov/std/syphilis/STDFact-Syphilis.htm#protect]
*Late/tertiary syphilis


==References==
==References==
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[[Category:Disease]]
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[[Category:Infectious disease]]
[[Category:Infectious disease]]
[[Category:Urology]]
[[Category:Neurology]]

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Overview

Syphilis is a curable sexually transmitted disease caused by the Treponema pallidum spirochete. The route of transmission of syphilis is almost always by sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero. The signs and symptoms of syphilis are numerous; before the advent of serological testing, precise diagnosis was very difficult. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Syphilis (unless antibiotic-resistant) can be easily treated with antibiotics including penicillin. The oldest and still most effective method is an intramuscular injection of benzathine penicillin. If not treated, syphilis can cause serious effects such as damage to the heart, aorta, brain, eyes, and bones. In some cases these effects can be fatal. In 1998, the complete genetic sequence of T. pallidum was published which may aid understanding of the pathogenesis of syphilis.

Historical Perspective

The name "syphilis" was coined by the Italian physician and poet Girolamo Fracastoro in his epic noted poem, written in Latin, entitled Syphilis sive morbus gallicus (Latin for "Syphilis or The French Disease") in 1530. The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's Metamorphoses). Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him. From this character Fracastoro derived a new name for the disease, which he also used in his medical text De Contagionibus ("On Contagious Diseases"). Until that time, as Fracastoro notes, syphilis had been called the "French disease" in Italy and Germany, and the "Italian disease" in France. In addition, the Dutch called it the "Spanish disease", the Russians called it the "Polish disease", the Turks called it the "Christian disease" or "Frank disease" (frengi) and the Tahitians called it the "British disease". These 'national' names are due to the disease often being present among invading armies or sea crews, due to their high amount of unprotected sexual contacts with prostitutes. It's interesting to notice how the invaders named it after the invaded country and vice versa. It was also called "Great pox" in the 16th century to distinguish it from smallpox. In its early stages, the Great pox produced a rash similar to smallpox (also known as variola). However, the name is misleading, as smallpox was a far more deadly disease. The terms "Lues" (or Lues venerea, Latin for "venereal plague") and "Cupid's disease" have also been used to refer to syphilis. In Scotland, Syphilis was referred to as the Grandgore. It was also called The Black Lion.

Classification

Syphilis may be classified according to the development of disease into 2 groups: congenital and acquired. Acquired syphilis may be classified further into 4 subtypes: primary, secondary, latent and tertiary syphilis.[1][2][3]

Pathophysiology

Syphilis is caused by the spirochete, Treponema pallidum. It has an incubation period of 3 - 12 weeks. The 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.[4][5][6]

Causes

Syphilis is caused by a spirochete, Treponema pallidum. The spirochete rapidly penetrates via intact mucosal membranes or microscopic dermal abrasions. It is spread through intimate sexual contact, blood transfusion or vertical transmission from infected mother to fetus.[7]

Differentiating Syphilis from other Diseases

Syphilis is a curable sexually transmitted disease caused by the Treponema pallidum spirochete. The route of transmission of syphilis is almost always by sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Hence, patients with tertiary syphilis should also be tested for other sexually transmitted diseases such as chlamydia, gonorrhea, trichomoniasis, bacterial vaginosis and HIV infection.[4][8][9][10][11]

Epidemiology and Demographics

In 2012, the incidence of syphilis was estimated to be 6 million cases worldwide. From year 2005 to 2014, the incidence of syphilis in the United States increased from 2.9 to 6.3 cases/100,000/year. The rate of reported cases increased by 15.1% between 2013 and 2014 in the United States.[12] Syphilis incidence increased in every region of the Untied States in 2014, with the highest rate in the West and lowest rate in the Midwest. In 2012, the prevalence of syphilis was estimated to be approximately 18 million cases in men and women aged 15-29 worldwide.[13] The incidence and prevalence of syphilis may be affected by age, gender, race, sexual behavior and geographical distribution.[12][14][15][16][17][18]

Risk Factors

The risk factors of syphilis include unprotected sex, IV drug abuse and occupational risk for health care professionals.[19][20][21][22][23]

Screening

Screening guidelines for syphilis include all high risk non pregnant individuals aged 15-65, all pregnant females, men who have sex with men, women who have sex with women, HIV positive individuals.[24] Routine screening of adolescents who are asymptomatic for syphilis is not recommended [25][26]

Natural History, Complications and Prognosis

Initial presentation of syphilis is appearance of painless chancre after 3-4 weeks of exposure. If left untreated, chancre self resolves and may progress to develop constitutional symptoms and generalized symmetric rash in four to eight weeks. In less than 10% of individuals, complications such as hepatitis, iritis, nephritis, and neurological problems may develop at this stage. However, it resolves in four to eight weeks without treatment and patient enters into asymptomatic latent phase. About a quarter of patients may develop recurrence of similar symptoms in one year. If left untreated, 35% of patients may develop tertiary syphilis which include complications such as cardiovascular involvement, neurologic infection and gummatous lesions involving skin, bone and joints which is associated with significant morbidity and mortality.[6][1][27][28] The prognosis of syphilis varies by stage of disease.Prognosis of primary and secondary syphilis is good with treatment. For tertiary syphilis, prognosis varies by site of involvememnt and duration of disease. 90% of patients with neurosyphilis respond to treatment. However, mortality rates are high with cardiovascular complications.[27][28]

Treatment

Medical Therapy

Penicillin G, administered parenterally, is the preferred drug for treating all stages of syphilis. If allergic, then tetracycline or doxycycline may also be used. During pregnancy, parenteral penicillin G is the only therapy with documented efficacy for syphilis.[29]

Management of Primary and Secondary Stages

Parenteral penicillin G has been used effectively for more than 50 years to achieve clinical resolution (i.e., the healing of lesions and prevention of sexual transmission) and to prevent late sequelae. However, no comparative trials have been adequately conducted to guide the selection of an optimal penicillin regimen (i.e., the dose, duration, and preparation). Substantially fewer data are available for non-penicillin regimens.[30]

Tertiary Syphilis

Tertiary syphilis refers to gumma and cardiovascular syphilis but not to all neurosyphilis. Patients who are not allergic to penicillin and have no evidence of neurosyphilis should be treated with the following regimen.[31][32]

Neurosyphilis

CNS involvement can occur during any stage of syphilis. However, CSF laboratory abnormalities are common in persons with early syphilis, even in the absence of clinical neurological findings. No evidence exists to support variation from recommended treatment for early syphilis for patients found to have such abnormalities. If clinical evidence of neurologic involvement is observed (e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of meningitis), a CSF examination should be performed. Syphilitic uveitis or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis. Patients who have neurosyphilis or syphilitic eye disease (e.g., uveitis, neuroretinitis, and optic neuritis) should be treated with the recommended regimen for neurosyphilis; those with eye disease should be managed in collaboration with an ophthalmologist. A CSF examination should be performed for all patients with syphilitic eye disease to identify those with abnormalities; patients found to have abnormal CSF test results should be provided follow-up CSF examinations to assess treatment response.[32]

Primary Prevention

As of 2010, there is no vaccine effective for prevention.[33]

Secondary Prevention

While abstinence from intimate physical contact with an infected person is very effective at reducing the transmission of syphilis, it should be noted that T. pallidum readily crosses intact mucosa and cut skin, including areas not covered by a condom. Proper and consistent use of a latex condom can reduce, but not eliminate, the spread of syphilis.[3]

References

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