Syphilis

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Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[5]

Sexually transmitted diseases Main Page

Syphilis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Syphilis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Primary and Secondary Syphilis
Latent Syphilis
Tertiary Syphilis
Neurosyphilis
HIV-Infected Patients
Pregnancy
Management of Sexual Partners

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Syphilis On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Syphilis

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Syphilis

CDC on Syphilis

Syphilis in the news

Blogs on Syphilis

Directions to Hospitals Treating Syphilis

Risk calculators and risk factors for Syphilis

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.[6]

References

  1. 1.0 1.1 French P (2007). "Syphilis". BMJ. 334 (7585): 143–7. doi:10.1136/bmj.39085.518148.BE. PMC 1779891. PMID 17235095.
  2. Chakraborty R, Luck S (2008). "Syphilis is on the increase: the implications for child health". Arch Dis Child. 93 (2): 105–9. doi:10.1136/adc.2006.103515. PMID [uid 18208988[uid]] Check |pmid= value (help).
  3. http://www.cdc.gov/std/stats10/app-casedef.htm Accessed on September 19, 2016
  4. 4.0 4.1 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.
  5. Fitzgerald TJ (1992). "The Th1/Th2-like switch in syphilitic infection: is it detrimental?". Infect Immun. 60 (9): 3475–9. PMC 257347. PMID 1386838.
  6. 6.0 6.1 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.
  7. Antal GM, Lukehart SA, Meheus AZ (January 2002). "The endemic treponematoses". Microbes Infect. 4 (1): 83–94. doi:10.1016/S1286-4579(01)01513-1. PMID 11825779.
  8. Fatahzadeh M, Schwartz RA (2007). "Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management". J. Am. Acad. Dermatol. 57 (5): 737–63, quiz 764–6. doi:10.1016/j.jaad.2007.06.027. PMID 17939933.
  9. O'Farrell N (2002). "Donovanosis". Sexually Transmitted Infections. 78 (6): 452–7. PMC 1758360. PMID 12473810.
  10. Coovadia YM, Kharsany A, Hoosen A (1985). "The microbial aetiology of genital ulcers in black men in Durban, South Africa". Genitourin Med. 61 (4): 266–9. PMC 1011828. PMID 2991120.
  11. Mabey D, Peeling RW (2002). "Lymphogranuloma venereum". Sexually Transmitted Infections. 78 (2): 90–2. PMC 1744436. PMID 12081191.
  12. 12.0 12.1 https://www.cdc.gov/std/stats14/surv-2014-print.pdf Accessed on September 16, 2016
  13. Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M, Low N; et al. (2015). "Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting". PLoS One. 10 (12): e0143304. doi:10.1371/journal.pone.0143304. PMC 4672879. PMID 26646541.
  14. Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan R, Ocfemia MC; et al. (2013). "Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008". Sex Transm Dis. 40 (3): 187–93. doi:10.1097/OLQ.0b013e318286bb53. PMID 23403598.
  15. http://apps.who.int/iris/bitstream/10665/85376/1/9789241505895_eng.pdf?=1 Accessed on September 16, 2016
  16. Purcell DW, Johnson CH, Lansky A, Prejean J, Stein R, Denning P; et al. (2012). "Estimating the population size of men who have sex with men in the United States to obtain HIV and syphilis rates". Open AIDS J. 6: 98–107. doi:10.2174/1874613601206010098. PMC 3462414. PMID 23049658.
  17. Heffelfinger JD, Swint EB, Berman SM, Weinstock HS (2007). "Trends in primary and secondary syphilis among men who have sex with men in the United States". Am J Public Health. 97 (6): 1076–83. doi:10.2105/AJPH.2005.070417. PMC 1874206. PMID 17463387.
  18. Judson FN, Penley KA, Robinson ME, Smith JK (1980). "Comparative prevalence rates of sexually transmitted diseases in heterosexual and homosexual men". Am J Epidemiol. 112 (6): 836–43. PMID 6893897.
  19. Rolfs RT, Goldberg M, Sharrar RG (1990). "Risk factors for syphilis: cocaine use and prostitution". Am J Public Health. 80 (7): 853–7. PMC 1404975. PMID 2356911.
  20. Zhou H, Chen XS, Hong FC, Pan P, Yang F, Cai YM; et al. (2007). "Risk factors for syphilis infection among pregnant women: results of a case-control study in Shenzhen, China". Sex Transm Infect. 83 (6): 476–80. doi:10.1136/sti.2007.026187. PMC 2598725. PMID 17675391.
  21. 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.
  22. Hook EW, Peeling RW (2004). "Syphilis control--a continuing challenge". N Engl J Med. 351 (2): 122–4. doi:10.1056/NEJMp048126. PMID 15247352.
  23. Buchacz K, Greenberg A, Onorato I, Janssen R (2005). "Syphilis epidemics and human immunodeficiency virus (HIV) incidence among men who have sex with men in the United States: implications for HIV prevention". Sex Transm Dis. 32 (10 Suppl): S73–9. PMID 16205297.
  24. https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-nonpregnant-adults-and-adolescents?ds=1&s=syphilis Accessed on September 19, 2016
  25. http://www.cdc.gov/std/treatment/2010/specialpops.htm Accessed on September 19, 2016
  26. https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-pregnancy-screening?ds=1&s=syphilis Accessed on September 19, 2016
  27. 27.0 27.1 Thomas SB, Quinn SC (1991). "The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community". Am J Public Health. 81 (11): 1498–505. PMC 1405662. PMID 1951814.
  28. 28.0 28.1 GJESTLAND T (1955). "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". Acta Derm Venereol Suppl (Stockh). 35 (Suppl 34): 3–368, Annex I-LVI. PMID 13301322.
  29. http://www.cdc.gov/std/tg2015/syphilis.htm Accessed on September 26, 2016
  30. Ghanem KG, Erbelding EJ, Cheng WW, Rompalo AM (2006) Doxycycline compared with benzathine penicillin for the treatment of early syphilis. Clin Infect Dis 42 (6):e45-9. DOI:10.1086/500406 PMID: 16477545
  31. "Sexually Transmitted Diseases Treatment Guidelines, 2010". Retrieved 2012-12-19.
  32. 32.0 32.1 http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016
  33. Stamm LV (2010). "Global challenge of antibiotic-resistant Treponema pallidum". Antimicrobial Agents and Chemotherapy. 54 (2): 583–9. doi:10.1128/AAC.01095-09. PMC 2812177. PMID 19805553. Retrieved 2012-02-21. Unknown parameter |month= ignored (help)


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Historical Perspective

Sexually transmitted diseases Main Page

Syphilis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Syphilis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Primary and Secondary Syphilis
Latent Syphilis
Tertiary Syphilis
Neurosyphilis
HIV-Infected Patients
Pregnancy
Management of Sexual Partners

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Syphilis On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Syphilis

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Syphilis

CDC on Syphilis

Syphilis in the news

Blogs on Syphilis

Directions to Hospitals Treating Syphilis

Risk calculators and risk factors for Syphilis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [7]

Overview

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.

Historical Perspective

Origin

Public Domain, https://commons.wikimedia.org/w/index.php?curid=1819475 - In this medical illustration attributed to Albrecht Dürer (1496), the disease is believed to have astrological causes.

There have been three theories on the origin of syphilis which formed an ongoing debate in anthropological and historical fields.

The pre-Columbian theory holds that syphilis symptoms are described by Hippocrates in Classical Greece in its venereal/tertiary form. There are other suspected syphilis findings for pre-contact Europe, including at a 13–14th century Augustinian friary in the northeastern English port of Kingston upon Hull. This city's maritime history is thought to have been a key factor in the transmission of syphilis.[1] Carbon dated skeletons of monks who lived in the friary showed bone lesions typical of venereal syphilis. Skeletons in pre-Columbus Pompeii and Metaponto in Italy demonstrating signs of congenital syphilis have also been found[2], although the interpretation of the evidence has been disputed.[3]

The Columbian Exchange theory holds that syphilis was a New World disease brought back by Columbus and Martin Alonzo Pinzon. Supporters of the Columbian theory find syphilis lesions on pre-contact Native Americans and cite documentary evidence linking crewmen of Columbus's voyages to the Naples outbreak of 1494.[4] A recent study of the genes of venereal syphilis and related bacteria have supported this theory, by locating an intermediate disease between yaws and syphilis in Guyana, South America.[5][6]

Historian Alfred Crosby suggests both theories are correct in a combination theory. Crosby's argument is built on the similarities of the species of bacteria which cause yaws and syphilis. The bacteria that causes syphilis belongs to the same phylogenetic family as the bacteria which cause yaws and several other diseases. Despite a tradition of assigning yaws's homeland to sub-Saharan Africa, Crosby notes that there is no unequivocal evidence of any related disease being present in pre-Columbian Europe, Africa, or Asia, while there is indisputable evidence of syphilis' presence in the pre-Columbian Americas. Conceding this point, Crosby writes, "It is not impossible that the organisms causing treponematosis arrived from America in the 1490s...and evolved into both venereal and non-venereal syphilis and yaws."[7]

However, Crosby considers it somewhat more likely that a highly contagious ancestral species of bacteria moved with early human ancestors across the land bridge of the Bering Straits many thousands of years ago without dying out in the original source population. He hypothesizes that "the differing ecological conditions produced different types of treponematosis and, in time, closely related but different diseases".[8] Thus, a weak, non-syphilitic bacteria survived in the Old World to eventually give rise to yaws or bejel, while a New World version evolved into the milder pinta and the more aggressive syphilis.

Going further than Crosby in arguing for worldwide incidence of syphilis prior to Columbus, Douglas Owsley, the famed physical anthropologist at the Smithsonian Institute, has written that many medieval European cases of leprosy, colloquially called "lepra," were actually cases of syphilis. Although folklore claimed that syphilis was unknown in Europe until the return of the diseased sailors of the Columbian voyages,

. . . syphilis probably cannot be "blamed"—as it often is—on any geographical area or specific race. The evidence suggests that the disease existed in both hemispheres from prehistoric times. It is only coincidental with the Columbus expeditions that the syphilis previously thought of as "lepra" flared into virulence at the end of the fifteenth century.[9]
Owsley noted that a Chinese medical case recorded in 2637 B.C.E. seems to be describing a case of syphilis, and that a European writer who recorded an outbreak of "lepra" in 1303 C.E. is "clearly describing syphilis".[9]

While working at the Rockefeller Institute in 1913, Hideyo Noguchi, a Japanese scientist, demonstrated the presence of the spirochete Treponema pallidum in the brain of a progressive paralysis patient, proving that Treponema pallidum was the cause of the disease. [8] Prior to Noguchi's discovery, syphilis had been a burden to humanity in many lands, sometimes misdiagnosed and often misattributed to political enemies.

The insanity caused by late-stage syphilis was once one of the more common forms of dementia; this was known as the general paresis of the insane. One suspected example is the insanity of noted composer Robert Schumann, although the precise cause of his death is still disputed by scholars.

European outbreak

The first well-recorded European outbreak of what is now known as syphilis occurred in 1494 when it broke out among French troops besieging Naples.[10] The French may have caught it via Spanish mercenaries serving King Charles of France in that siege.[9] From this centre, the disease swept across Europe. As Jared Diamond describes it, "when syphilis was first definitely recorded in Europe in 1495, its pustules often covered the body from the head to the knees, caused flesh to fall from people's faces, and led to death within a few months." In addition, the disease was more frequently fatal than it is today. Diamond concludes that "by 1546, the disease had evolved into the disease with the symptoms so well known to us today."[11] The epidemiology of this first syphilis epidemic shows that the disease was either new or a mutated form of an earlier disease.

Syphilis in art and literature

Art

The artist Kees van Dongen produced a series of illustrations for the anarchist publication L'Assiette au Beurre showing the descent of a young prostitute from poverty to her death from syphilis as a criticism of the social order at the end of the 19th century.

The artist Jan van der Straet, also known as Johannes Stradanus or simply Stradanus, painted a scene of a wealthy man receiving treatment of syphilis with the tropical wood guaiacum sometime around 1580.[12] The title of the work is "Preparation and Use of Guayaco for Treating Syphilis." That the artist chose to include this image in a series of works celebrating the New World indicates how important a "cure" (however ineffective) for syphilis was to the European elite at that time. The richly colored and detailed work depicts four servants preparing the concoction while a physician looks on, hiding something behind his back while the hapless patient drinks.[13]

Classic and antique literature

Delicado also featured the effects of syphilis in his Portrait of Lozana: The Lusty Andalusian Woman (1528).

There are references to syphilis in William Shakespeare's play Measure for Measure, particularly in a number of early passages spoken by the character Lucio. For example, Lucio says "[...] thy bones are hollow"; this is a reference to the brittleness of bones engendered by the use of mercury which was then widely used to treat syphilis.

In Shakespeare's play Othello, the clown at the beginning of Act III makes jest of Cassio, who is leading a musician troupe for Othello, by asking him if he had just arrived from Naples and playing with his nose. (Alluding to the reputation of Naples of being a likely place to contract syphilis, which eats away at the bridge of the nose.)

Francisco de Quevedo puns in his Buscón[14] about a nose entre Roma y Francia meaning both "between Rome and France" and "between dull and eaten by the French illness".

Jonathan Swift's poetry mentions syphilis as a condition of prostitution which reaches the highest ranks of society. See, for example, "A Beautiful Young Nymph Going To Bed" and "The Progress of Beauty".

Moll dies of syphillis, Hogarth's A Harlot's Progress.

William Hogarth's works frequently show his subject's infection with syphilis. Two examples are A Harlot's Progress and Marriage à-la-mode. In both instances it is used to indicate the moral profligacy of the infected.

Some critics have argued that the character of Edward Rochester's first wife, Bertha, in Charlotte Brontë's novel Jane Eyre, suffers from the advanced stages of syphilitic infection, general paresis of the insane, and point to corroborative evidence within the text to substantiate this view.

The novel Candide by Voltaire describes Candide's mentor and teacher, Pangloss, as having contracted syphilis from a maidservant he slept with; the syphilis has ravaged and deformed his body. Pangloss explains to Candide that syphilis is 'necessary in the best of worlds' because the line of infection - which he explains - leads back to Christopher Columbus. If Columbus had not sailed to America and brought back syphilis, Pangloss states, the Europeans would not have been able to enjoy 'New World wonders' such as chocolate. (One of the purposes of the novel was to satirize Leibniz's philosophy as Pangloss's disingenuous rose-tinted viewpoint.) Pangloss eventually loses an eye and an ear to the syphilis before he is cured.

Also, in Charles Dickens' novel Tale of Two Cities, references are made that allude to the main character, Sydney Carton, having syphilis.

In Eça de Queiroz's novel written in 1870, "The Mystery of the Sintra Road", some of the characters have syphilis, and it plays an important role in the plot of a recent movie adaptation.[15]

Henrik Ibsen's once-controversial play Ghosts has a young man who is suffering from a mysterious unnamed disease. Though it is never named, the events of the play make it plain that this is syphilis, an inheritance from his dissolute father. However, the young man's mother remains unaffected - this is because it is possible for a woman to carry syphillis and transmit it to her child in the womb without exhibiting any noticeable symptoms. Dr. Rank in Ibsen's play A Doll's House also has inherited syphilis.

Modern literature

Unnamed American medical students described syphilis in a series of early 20th-century American limericks, using medical terminology to ghastly comic effect in the Journal of the American Medical Association January 1942.[16]

Thomas Disch in his novel Camp Concentration describe a fictional strain of syphilis that enhances intelligence but is lethal.

In Thomas Mann's novel Doktor Faustus, the Faust character, Adrian Leverkühn, acquires his genius for musical composition from the neurological effects of syphilis.

In Dick Francis' novel, Bonecrack the character Enso Rivera is suffering from megalomania caused by syphilis.

Neal Stephenson's trilogy The Baroque Cycle has multiple characters and historical figures who have syphilis, most notably James II of England and Jack Shaftoe; the latter is cured of the disease by running a high fever.

In Leonard Cohen's second novel Beautiful Losers, the character F. is described in detail as having the terminal stages of syphilis.

In Christina Garcia's novel "Dreaming in Cuban," Felica contracts syphilis from her unfaithful husband. The syphilis and her family history lead Felica down a path towards insanity.

In Ken Follett's novel "A Dangerous Fortune," the wealthy Edward Pilaster contracts syphilis from his frequency of using brothels. When Edward's cohort Micky Miranda finds out, it looks as though his diabolical plans may have a snag.

In Josilyn Jackson's novel "Between, Georgia", the protagonist Nonny Frett suffers from syphilis from a cheating husband she can't seem to rid herself of.

Film, Television and Stage

Syphilis is used as a plot device in many dramatic films, television shows, and plays. While some, such as Warner Bros.' 1940 film, Dr. Ehrlich's The Magic Bullet, focus on the history of the disease, most involve late-stage syphilis because the neurological damage common to late-stage syphilis provides an excuse for strange behaviors. In recent years, syphilis has been mentioned on Grey's Anatomy, House M.D., Law & Order: SVU, Buffy the Vampire Slayer, Angel and other television shows. A few particularly notable appearances include:

  • Miss Evers' Boys is a 1992 stage play written by Dr. David Feldshuh based on the true story of the decades-long Tuskegee syphillis experiment. The play was subsequently adapted into a 1997 HBO TV movie directed by Joseph Sargent and starring Alfre Woodard and Laurence Fishburne. The film was nominated for eleven Emmy Awards and won in four categories, including Outstanding Made for Television Movie.
  • In Akira Kurosawa's Japanese movie "The Quiet Duel" (1949) Toshirô Mifune plays a doctor who gets infected with syphilis while operating on a soldier.
  • In big budget Spanish film Alatriste, the main character finds the love of his life, actress María de Castro, dying in a hospital for syphilitics. It is implied that she caught the disease from an affair with Philip IV of Spain.
  • In the Masterpiece Theatre version of Bram Stoker's "Dracula", Arthur Holmwood, whose father dies of syphilitic insanity, enlists the services of Count Dracula in hopes of curing his congenital syphilis.

Diagnosis

Early 20th century

In 1906, the first effective test for syphilis, the Wassermann test, was developed. Although it had some false positive results, it was a major advance in the prevention of syphilis. By allowing testing before the acute symptoms of the disease had developed, this test allowed the prevention of transmission of syphilis to others, even though it did not provide a cure for those infected.

In the 1930s the Hinton test, developed by William Augustus Hinton, and based on flocculation, was shown to have fewer false positive reactions than the Wassermann test. Both of these early tests have been superseded by newer analytical methods.

Modern diagnostic tests

It was only in the 20th century that effective tests and treatments for syphilis were developed. Microscopy of fluid from the primary or secondary lesion using darkfield illumination can diagnose treponemal disease with high accuracy. As there are other treponemes that may be confused with T. pallidum, care must be taken in evaluating with microscopy to correlate symptoms with the correct disease.

Treatment

There were originally no effective treatments for syphilis. The Spanish priest Francisco Delicado wrote El modo de adoperare el legno de India (Rome, 1525) about the use of Guaiacum in the treatment of syphilis. He himself suffered from syphilis. Another common remedy was mercury: the use of which gave rise to the saying "A night in the arms of Venus leads to a lifetime on Mercury".[17] It was administered multiple ways including by mouth and by rubbing it on the skin. One of the more curious methods was fumigation, in which the patient was placed in a closed box with his head sticking out. Mercury was placed in the box and a fire was started under the box which caused the mercury to vaporize. It was a grueling process for the patient and the least effective for delivering mercury to the body.

As the disease became better understood, more effective treatments were found. The first antibiotic to be used for treating disease was the arsenic-containing drug Salvarsan, developed in 1908 by Sahachiro Hata while working in the laboratory of Nobel prize winner Paul Ehrlich. This was later modified into Neosalvarsan. Unfortunately, these drugs were not 100% effective, especially in late disease. It had been observed that some who develop high fevers could be cured of syphilis. Thus, for a brief time malaria was used as treatment for tertiary syphilis because it produced prolonged and high fevers. This was considered an acceptable risk because the malaria could later be treated with quinine which was available at that time. This discovery was championed by Julius Wagner-Jauregg, who won the 1927 Nobel Prize for Medicine for his work in this area. Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvant therapy. These treatments were finally rendered obsolete by the discovery of penicillin, and its widespread manufacture after World War II allowed syphilis to be effectively and reliably cured.[18]

References

  1. Keys, David (2007). "English syphilis epidemic pre-dated European outbreaks by 150 years". Independent News and Media Limited.
  2. Henneberg M, Henneberg RJ, 1994, Treponematosis in an Ancient Greek colony of Metaponto, Southern Italy 580-250 BCE [in:] O Dutour, G Palfi, J Berato, J-P Brun (eds), The Origin of Syphilis in Europe, Before or After 1493?, Centre Archeologique du Var, Editions Errance Toulon-Paris, pp. 92-98, Henneberg M, Henneberg RJ, 2002 Reconstructing Medical Knowledge in Ancient Pompeii from the Hard Evidence of Bones and Teeth. In: J Renn, G Castagnetti (eds) Homo Faber: Studies on Nature. Technology and Science at the Time of Pompeii, “L’ERMA” di Bretschneider, Rome, pp.169-187.
  3. Origins of Syphilis
  4. Baker, et al.
  5. http://www.newscientist.com/article/dn13186-columbus-blamed-for-spread-of-syphilis-.html
  6. http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000148
  7. ref:225 Crosby
  8. ref:225 Crosby
  9. 9.0 9.1 9.2 [1] John Lobdell and Douglas Owsley, Journal of Sex Research, August 1974, Vol. 10:1 pp. 76-79. Accessed via JSTOR August 5, 2007.
  10. Oriel, J.D. (1994). The Scars of Venus: A History of Venereology. London: Springer-Verlag.
  11. Diamond, Jared (1997). Guns, Germs and Steel. New York: W.W. Norton. p. 210.
  12. Johannes Stradanus undated brief review of works hosted at the University of York in the United Kingdom. Accessed August 6, 2007.
  13. Jan van der Straet's "Preparation..." at commercial art site. Accessed August 6, 2007.
  14. :wikisource:es:Historia de la vida del Buscón: Libro Primero: Capítulo III: continues with [...] porque se le había comido de unas búas de resfriado, que aun no fueron de vicio porque cuestan dinero;: "[...] because it had been eaten by the bubons of a cold, which were not of vice because they cost money;".
  15. "O Misterio da Estrada de Sintra".
  16. http://www.ucolick.org/~randi/aecom/syphilis.txt
  17. "The magical properties of Mercury, the metal the EU wants to ban". Text " the Daily Mail " ignored (help)
  18. Brown, Kevin (2006). The Pox: The Life and Near Death of a Very Social Disease. Stroud: WSutton. pp. 85–111, 185–91.


Template:WikiDoc Sources

Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [9] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[10]; Nate Michalak, B.A.

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Diagnosis

History and Symptoms

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Treatment

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Cost-Effectiveness of Therapy

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Risk calculators and risk factors for Syphilis

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.


Template:WikiDoc Sources

Epidemiology and Demographics

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [11] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[12]; Nate Michalak, B.A.

Sexually transmitted diseases Main Page

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Overview

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Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Ultrasound

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Other Diagnostic Studies

Treatment

Medical Therapy

Primary and Secondary Syphilis
Latent Syphilis
Tertiary Syphilis
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Risk calculators and risk factors for Syphilis

Overview

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.[1] 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.[2] The incidence and prevalence of syphilis may be affected by age, gender, race, sexual behavior and geographical distribution.[1][3][4][5][6][7]

Epidemiology

Incidence

  • Worldwide incidence of syphilis:
    • 2004: approximately 12 million cases[8]
    • 2008: approximately 10.9 million cases[9][10][11]
    • 2012: approximately 6 million cases[2]
  • Incidence of syphilis in the United States:
    • From 2005 to 2014, the incidence of primary and secondary syphilis increased from 2.9 to 6.3 cases/100,000/year.
    • From 2009 to 2014, the incidence of late and latent syphilis increased from 5.6 to 7.4 cases/100,000/year.
    • The rate of reported cases increased by 15.1% between 2013 and 2014.[1]
    • 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.
Source: https://www.cdc.gov/

Prevalence

  • In 2008, the prevalence of syphilis was estimated to be 36.4 million cases worldwide.[9]
  • In 2012, the prevalence of syphilis is estimated to be 18 million cases in men and women aged 15-29 worldwide.[2]
  • In 2014, the prevalence of syphilis in the United States was estimated to be 20 cases/100,000 individuals.[1]

Demographics

The incidence and prevalence of syphilis may be affected by the following demographic factors:[1][4]

Age

In 2014, the highest rate of primary and secondary syphilis in the United States was seen in age groups 20-24 years and 25-29 years.[1][3]

Source: https://www.cdc.gov/

Gender

  • There is increased incidence of primary and secondary syphilis in men who have sex with men (MSM).
    • In 2014, 61% of 19,999 total reported cases of primary and secondary syphilis were estimated to be among MSM.[1][4][5][6][7]

Primary and Secondary Syphilis — Reported Cases by Stage, Sex, and Sexual Behavior, 2014

Source: https://www.cdc.gov/

Race

  • Syphilis is more prevalent in the African American population as compared to other racial groups.[2]
  • In 2014, the highest incidence of primary and secondary syphilis in the United States was reported to be in the African American population and the lowest incidence was observed in Caucasisans, Asians and multiracial groups.[1]

Primary and Secondary Syphilis — Reported Cases by Sex, Sexual Behavior, and Race/Ethnicity, United States, 2014

Source: https://www.cdc.gov/

Geographical distribution

Worldwide, the highest incidence and prevalence of syphilis was seen in Africa and South East Asia, while the lowest was seen in Europe and the Eastern Mediterranean region in 2012.[2]

United States

  • Rates of reported cases of primary and secondary syphilis by state for 2014 is shown in the map below:
Source: https://www.cdc.gov/
  • Rates of reported cases of primary and secondary syphilis by region for 2014 is shown in the map below:
Source: https://www.cdc.gov/

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 https://www.cdc.gov/std/stats14/surv-2014-print.pdf Accessed on September 16, 2016
  2. 2.0 2.1 2.2 2.3 2.4 Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M, Low N; et al. (2015). "Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting". PLoS One. 10 (12): e0143304. doi:10.1371/journal.pone.0143304. PMC 4672879. PMID 26646541.
  3. 3.0 3.1 Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan R, Ocfemia MC; et al. (2013). "Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008". Sex Transm Dis. 40 (3): 187–93. doi:10.1097/OLQ.0b013e318286bb53. PMID 23403598.
  4. 4.0 4.1 4.2 http://apps.who.int/iris/bitstream/10665/85376/1/9789241505895_eng.pdf?=1 Accessed on September 16, 2016
  5. 5.0 5.1 Purcell DW, Johnson CH, Lansky A, Prejean J, Stein R, Denning P; et al. (2012). "Estimating the population size of men who have sex with men in the United States to obtain HIV and syphilis rates". Open AIDS J. 6: 98–107. doi:10.2174/1874613601206010098. PMC 3462414. PMID 23049658.
  6. 6.0 6.1 Heffelfinger JD, Swint EB, Berman SM, Weinstock HS (2007). "Trends in primary and secondary syphilis among men who have sex with men in the United States". Am J Public Health. 97 (6): 1076–83. doi:10.2105/AJPH.2005.070417. PMC 1874206. PMID 17463387.
  7. 7.0 7.1 Judson FN, Penley KA, Robinson ME, Smith JK (1980). "Comparative prevalence rates of sexually transmitted diseases in heterosexual and homosexual men". Am J Epidemiol. 112 (6): 836–43. PMID 6893897.
  8. Hook EW, Peeling RW (2004). "Syphilis control--a continuing challenge". N Engl J Med. 351 (2): 122–4. doi:10.1056/NEJMp048126. PMID 15247352.
  9. 9.0 9.1 http://apps.who.int/iris/bitstream/10665/75181/1/9789241503839_eng.pdf Accessed on September 16, 2016
  10. Herbert LJ, Middleton SI (2012). "An estimate of syphilis incidence in Eastern Europe". J Glob Health. 2 (1): 010402. doi:10.7189/jogh.02.010402. PMC 3484754. PMID 23198131.
  11. Kenyon CR, Osbak K, Tsoumanis A (2016). "The Global Epidemiology of Syphilis in the Past Century - A Systematic Review Based on Antenatal Syphilis Prevalence". PLoS Negl Trop Dis. 10 (5): e0004711. doi:10.1371/journal.pntd.0004711. PMC 4864207. PMID 27167068.


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Risk Factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [13]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[14]

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History and Symptoms

Physical Examination

Laboratory Findings

X Ray

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Treatment

Medical Therapy

Primary and Secondary Syphilis
Latent Syphilis
Tertiary Syphilis
Neurosyphilis
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Risk calculators and risk factors for Syphilis

Overview

Common risk factors in the development of syphilis include unprotected sexual intercourse, intravenous drug abuse, men who have sex with men and healthcare occupations.[1][2][3][4][5][6][7]

Risk Factors

Risk factors include:[1][2][4][5][6][7][8]

References

  1. 1.0 1.1 Rolfs RT, Goldberg M, Sharrar RG (1990). "Risk factors for syphilis: cocaine use and prostitution". Am J Public Health. 80 (7): 853–7. PMC 1404975. PMID 2356911.
  2. 2.0 2.1 Zhou H, Chen XS, Hong FC, Pan P, Yang F, Cai YM; et al. (2007). "Risk factors for syphilis infection among pregnant women: results of a case-control study in Shenzhen, China". Sex Transm Infect. 83 (6): 476–80. doi:10.1136/sti.2007.026187. PMC 2598725. PMID 17675391.
  3. 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.
  4. 4.0 4.1 Hook EW, Peeling RW (2004). "Syphilis control--a continuing challenge". N Engl J Med. 351 (2): 122–4. doi:10.1056/NEJMp048126. PMID 15247352.
  5. 5.0 5.1 Buchacz K, Greenberg A, Onorato I, Janssen R (2005). "Syphilis epidemics and human immunodeficiency virus (HIV) incidence among men who have sex with men in the United States: implications for HIV prevention". Sex Transm Dis. 32 (10 Suppl): S73–9. PMID 16205297.
  6. 6.0 6.1 Solomon MM, Mayer KH (2015). "Evolution of the syphilis epidemic among men who have sex with men". Sex Health. 12 (2): 96–102. doi:10.1071/SH14173. PMC 4470884. PMID 25514173.
  7. 7.0 7.1 Hakre S, Arteaga GB, Núñez AE, Arambu N, Aumakhan B, Liu M; et al. (2014). "Prevalence of HIV, syphilis, and other sexually transmitted infections among MSM from three cities in Panama". J Urban Health. 91 (4): 793–808. doi:10.1007/s11524-014-9885-4. PMC 4134449. PMID 24927712.
  8. 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.


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Screening

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [15] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[16]

Sexually transmitted diseases Main Page

Syphilis Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Syphilis from other Diseases

Epidemiology and Demographics

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Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Primary and Secondary Syphilis
Latent Syphilis
Tertiary Syphilis
Neurosyphilis
HIV-Infected Patients
Pregnancy
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Secondary Prevention

Cost-Effectiveness of Therapy

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Case #1

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Risk calculators and risk factors for Syphilis

Overview

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, and HIV positive individuals.[1] Routine screening of adolescents who are asymptomatic for syphilis is not recommended.[2][3]

Screening

Screening guidelines for syphilis are:

Non-pregnant adults and adolescents (age 15-65)

  • All individuals who are at increased risk for syphilis should be screened for syphilis Grade A recommendation.[1][4]
  • Routine screening of adolescents who are asymptomatic for syphilis is not recommended.[2]

Pregnant women

  • Uninsured women
  • Women living in poverty
  • Sex workers
  • Illicit drug users
  • Presence of other sexually transmitted diseases (STDs)
  • Other women living in communities with high syphilis morbidity

Men who have sex with men

  • Annually for sexually active men who have sex with men[5]
  • Every 3 to 6 months if increased risk

Women who have sex with women

  • Routine screening is recommended[2]

HIV positive individuals

  • At first HIV evaluation for sexually active individuals[5][6]
  • Annually after first evaluation
  • More frequent testing for individuals who are at increased risk or are residing in highly prevalent areas of syphilis

Screening tests

Screening tests recommended for syphilis include the following:[7]

Screening non-treponemal tests

Confirmatory treponemal tests

References

  1. 1.0 1.1 https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-nonpregnant-adults-and-adolescents?ds=1&s=syphilis Accessed on September 19, 2016
  2. 2.0 2.1 2.2 http://www.cdc.gov/std/treatment/2010/specialpops.htm Accessed on September 19, 2016
  3. 3.0 3.1 3.2 https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-pregnancy-screening?ds=1&s=syphilis Accessed on September 19, 2016
  4. US Preventive Services Task Force (USPSTF). Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW; et al. (2016). "Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: US Preventive Services Task Force Recommendation Statement". JAMA. 315 (21): 2321–7. doi:10.1001/jama.2016.5824. PMID 27272583.
  5. 5.0 5.1 5.2 http://www.cdc.gov/std/tg2015/screening-recommendations.htm#modalIdString_CDCTable_2 Accessed on September 19, 2016
  6. http://hivprevent.thelancet.com/content/guidelines-and-recommendations Accesed on September 19, 2016
  7. https://www.uspreventiveservicestaskforce.org/Page/Document/ClinicalSummaryFinal/syphilis-infection-in-pregnancy-screening Accessed on September 19, 2016
  8. 8.0 8.1 Ratnam S (2005). "The laboratory diagnosis of syphilis". Can J Infect Dis Med Microbiol. 16 (1): 45–51. PMC 2095002. PMID 18159528.
  9. 9.0 9.1 Larsen SA, Steiner BM, Rudolph AH (1995). "Laboratory diagnosis and interpretation of tests for syphilis". Clin Microbiol Rev. 8 (1): 1–21. PMC 172846. PMID 7704889.


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Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [17]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [18] Aysha Anwar, M.B.B.S[19]

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Overview

Syphilis is named as the "Great Imitator" because the symptomatology and physical exam findings of syphilis in different stages mimicks large variety of other diseases. Syphilis must be differentiated from other common diseases that cause rash such as measles, rubella, Kawasaki disease , and mononucleosis. Syphilis also has overlapping symptoms with the other genital infections such as chancroid, condyloma acuminata, genital warts, herpes simplex, and herpes zoster.[1][2][3][4][5]

Differentiating Syphilis from other Diseases

Syphilis is named as a "great imitator" because symptomatology and physical exam findings of syphilis in different stages mimicks large variety of other diseases.[1][2][3][4][5][6][7][8][9][10][8][11][12][13][14][15][16][17]

Stage of Syphilis Differential diagnosis Findings
Primary Herpes simplex(1,2) Presents as multiple, round, superficial oral and genital ulcers which are painful.[2] Adults with non-typical presentation are more difficult to diagnose. However, prodromal symptoms that occur before the appearance of herpetic lesions helps to differentiate HSV from other conditions with similar symptoms like allergic stomatitis. Genital herpes can be more difficult to diagnose than oral herpes since most genital herpes/HSV-2-infected persons have no classical signs and symptoms.[2]
Granuloma inguinale Commonly characterized as painless, progressive ulcerative lesions without regional lymphadenopathy. The lesions are highly vascular and bleed easily on contact.[3]
Chancroid Characterized by painful sores on the genitalia.[4]
Lymphogranuloma venereum Self-limited genital ulcer or papule with tender inguinal or femoral lymphadenopathy.[5][6]
Condyloma acuminatum Presents as warty lesions in the form of clusters and can be very tiny or can spread into large masses in the genital or penile area.[7][18][19]
Urethritis Discharge (milky or pus-like) from the penis, stinging or burning during urination, itching, tingling, burning or irritation inside the penis.
Cystitis Presents as abnormal urine color (cloudy), blood in the urine, frequent urination or urgent need to urinate, painful or burning urination, pressure in the lower pelvis or back, flank pain, back pain, nausea, vomiting, and chills
Candidiasis Presents as redness, itching and discomfort of affected area.[20][21]
Other STIs Such as Chlamydia, Gonorrhea, and Trichomonas vaginalis
Secondary HIV Acute illness present with fever, lymphadenopathy, rash, fatigue, and myalgia. AIDS classically presents with weight loss, night sweats, fatigue, diarrhea, mucosal sores, cough, and cognitive and neurological deficits.
Pityriasis rosea Pink and flaky oval-shaped rash followed by clusters of smaller, more numerous patches of rash. May be accompanied by headache, fever, nausea and fatigue.
Viral exanthem Such as measles, mumps, chicken pox, cytomegalovirus, coxsackie virus, rubella. Findings may include fever, rash, and constitutional symptoms.[22]
Scarlet fever Presenting symptoms include fever, punctate red macules on the hard and soft palate and uvula (Forchheimer's spots), bright red tongue with a "strawberry" appearance, sore throat and headache and lymphadenopathy.
Insect bite Immediate skin reaction often resulting in a rash and swelling in the injured area, often with formation of vesicles.
Mononucleosis Common symptoms include low-grade fever without chills, sore throat, white patches on tonsils and back of the throat, muscle weakness and sometime extreme fatigue, tender lymphadenopathy, petechial hemorrhage and skin rash.
Rocky mountain spotted fever Symptoms may include maculopapular rash, petechial rash, abdominal pain and joint pain.
Rickettsialpox Overlapping symptoms with secondary syphilis may include flu-like illness including fever, chills, weakness and muscle pain but the most distinctive symptom is the rash that breaks out, spanning the person's entire body.
Kawasaki disease Commonly presents with high and persistent fever, red mucous membranes in mouth, "strawberry tongue", swollen lymph nodes and skin rash in early disease, with peeling off of the skin of the hands, feet and genital area
Yaws Tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pertenue
Stevens-Johnson syndrome Symptoms may include fever, sore throat and fatigue. Commonly presents ulcers and other lesions in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions.
Tertiary Brain tumour Findings which may overlap with neurosyphilis include headache,seizures, visual changes and personality changes.[8]
Other causes of seizures Neurosyphilitic disease can present with seizures and must be differentiated from other causes of seizures.
Other causes of stroke[9] Presents as weakness, sensory loss, gait abnormality and cranial nerve damage.
Meningococcemia Rash, petechiae, headache, confusion, and stiff neck, high fever, mental status changes, nausea and vomiting.[10]
Multiple sclerosis May presents as changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty in moving, difficulties with coordination and balance (ataxia), problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology (mainly depression).[23]
Other causes of meningitis][8][11] Such as bacterial, fungal and viral meningitis. It commonly presents with headache, nuchal rigidity, fever, petechiae and altered mental status.
Psychosis Presents as hallucinations, delusions, auditory hallucinations, and flat or blunted affect and emotion, poverty of speech (alogia), anhedonia, and lack of motivation.[24]
Vasculitides Cardiovasular syphilis may present as aortitis and aortic aneurysm. Overlapping symptoms with other vasculitis may include back pain, fever, abdominal pain, chest pain, shortness of breath, fatigue, arm and leg weakness, lightheadedness, dizziness, fainting, and headaches.[25][13][14]
Other causes of congestive heart failure Presenting symptoms include dizziness, dyspnea on ordinary exertion or greater shortness of breath with usual activities, fainting, fatigue, hemoptysis or frothy sputum, nocturia or urination during the night, nocturnal cough, orthopnea or sleeping on pillows, palpitations or extra heart beats, paroxysmal nocturnal dyspnea or awakening at night with shortness of breath, shortness of breath, syncope or passing out and weakness.
Other causes of glomerulonephritis May presents as blood in the urine (dark, rust-colored, or brown urine), foamy urine (due to excess protein in the urine), swelling (edema) of the face, eyes, ankles, feet, legs, or abdomen.
Other causes of arthritis Gummatous lesions of syphilis in joints may present as joint pains and stiffness.
Other causes of lymphadenitis May present as fever, myalgia, weight loss, and lymph node enlargement.[15]
Other causes of hepatitis Common presenting symptoms may include dark urine, fatigue, weight loss, fever usually low-grade, itching, jaundice (yellowing of the skin or eyes), loss of appetite, nausea and vomiting.[16]
Other causes of nephrotic syndrome Presents as proteinuria, edema, weight gain, fatigue and dyspnea.
Other causes of uveitis Symptoms of uveitis include eye pain, eye redness, and photophobia. Intermediate, posterior, and panuveitis commonly present with floaters, blurry vision, and impaired vision.[15][17]

Differentiating secondary syphilis from other diseases

  • Secondary siphilis should be differentiated from other diseases causing erythamosquamous rash. the differentials include the following:
Disease Rash Characteristics Signs and Symptoms Associated Conditions Images
Cutaneous T cell lymphoma/Mycosis fungoides[26]
courtesy of wikipedia.org - By Bobjgalindo - Own work, GFDL, https://commons.wikimedia.org/w/index.php?curid=7139812
Pityriasis rosea[27]
  • Pink or salmon in color, which may be scaly; referred to as "herald patch"
  • Oval shape
  • Long axis oriented along the cleavage lines
  • Distributed on the trunk and proximal extremities
  • Squamous marginal collarette and a “fir-tree” or “Christmas tree” distribution on posterior trunk
  • Secondary to viral infections
  • Resolves spontaneously after 6-8 weeks
By James Heilman,MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16305230
Pityriasis lichenoides chronica
  • Recurrent lesions are usually less evenly scattered than in cases of psoriasis
  • Brownish red or orange-brown in color
  • Lesions are capped by a single detachable, opaque, mica-like scale
  • Often leave hypopigmented macules
courtesy of http://www.regionalderm.com
Nummular dermatitis[30]
  • Lesions commonly relapse after occasional remission or may persist for long periods
  • Pruritus
courtesy of your-doctor.net dermatology atlas
Secondary syphilis[31]
  • Round, coppery, red colored lesions on palms and soles
  • Papules with collarette of scales
Source: https://www.cdc.gov/
Bowen’s disease[32]
  • Erythematous, small, scaly plaque, which enlarges erratically over time
  • Scale is usually yellow or white and it is easily detachable without any bleeding
  • Well-defined margins
By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11509003
Exanthematous pustulosis[34]
Acute generalized exanthematous pustulosis: an unusual side effect of meropenem". Indian J Dermatol 55 (2): 176–7. DOI:10.4103/0019-5154.62759. PMID 20606889. PMC: 2887524., CC BY 1.0, https://commons.wikimedia.org/w/index.php?curid=52979729
Hypertrophic lichen planus[36]

courtesy of wikipedia.org

Sneddon–Wilkinson disease[38]
  • Flaccid pustules that are often generalized and have a tendency to involve the flexural areas
  • Annular configuration
courtesy http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=427
Small plaque parapsoriasis[42]
  • Erythematous plaques with fine scaly surface
  • May present with elongated, finger-like patches
  • Symmetrical distribution on the flanks
  • Known as digitate dermatosis
  • Lesions may be asymptomatic
  • May be mildly pruritic
  • May fade or disappear after sun exposure during the summer season, but typically recur during the winter
courtesy http://www.regionalderm.com
Intertrigo[44]
courtesy of cdc.gov
Langerhans cell histiocytosis[45]
  • Scaling and crusting of scalp
courtesy http://www.regionalderm.com
Tinea manuum/pedum/capitis[49]
  • Scaling, flaking, and sometimes blistering of the affected areas
  • Hair loss with a black dot on scalp in case of tinea capitis
courtesy regionalderm.com
Seborrheic dermatitis
By Roymishali - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=27267929

Syphilitic oral lesions must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.

Disease Presentation Risk Factors Diagnosis Affected Organ Systems Important features Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis
  • Denture users
  • As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication.
  • Clinical diagnosis
  • Confirmatory tests rarely needed
Localized candidiasis

Invasive candidasis

Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions
  • Stress
  • Recent URTI
  • Female sex
  • The symptoms of primary HSV infection generally resolve within two weeks
Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers
  • Painful, red spot or bump that develops into an open ulcer
  • Physical examination
  • Diagnosis of exclusion
  • Oral cavity
  • Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks
Apthous ulcer on the lower surface of the tongue - By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma
Squamous cell carcinoma - By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia
  • Vulvar lesions occur independent of oral lesions
courtesy of http://www.regionalderm.com
]
Melanoma
Oral melanoma - By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis - Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots
Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome
Torus palatinus
Torus palatinus - By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet's disease
Behcet's disease - By Ahmet Altiner MD, Rajni Mandal MD - http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn's disease
Agranulocytosis
Syphilis[54]
oral syphilis - By CDC/Susan Lindsley - http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus
  • Symptomatic treatment
Coxsackie virus stomatitis - Adapted from Dermatology Atlas.[55]
Chicken pox
Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles
  • Unvaccinated individuals[56][57]
  • Crowded and/or unsanitary conditions
  • Traveling to less developed and developing countries
  • Immunocompromized
  • Winter and spring seasons
  • Born after 1956 and never fully vaccinated
  • Health care workers
Koplick spots (Measles) - By CDC - http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483

Secondary syphilis must be differentiated from other causes of rash and arthritis[58][59][60]

Disease Findings
Nongonococcal septic arthritis
  • Presents with an acute onset of joint swelling and pain (usually monoarticular)
  • Culture of joint fluid reveals organisms
Acute rheumatic fever
  • Presents with polyarthritis and rash (rare presentation) in young adults. Microbiologic or serologic evidence of a recent streptococcal infection confirm the diagnosis.
  • Poststreptococcal arthritis have a rapid response to salicylates or other antiinflammatory drugs.
Syphilis
  • Presents with acute secondary syphilis usually presents with generalized, pustular lesions at the palms and soles with generalized lymphadenopathy
  • Rapid plasma reagin (RPR), Venereal Disease Research Laboratory (VDRL) and Fluorescent treponemal antibody absorption (FTA-ABS) tests confirm the presence of the causative agent.
Reactive arthritis (Reiter syndrome)
  • Musculoskeletal manifestation include arthritis, tenosynovitis, dactylitis, and low back pain.
  • Extraarticular manifestation include conjunctivitis, urethritis, and genital and oral lesions.
  • Reactive arthritis is a clinical diagnosis based upon the pattern of findings and there is no definitive diagnostic test
Hepatitis B virus (HBV) infection
  • Presents with fever, chills, polyarthritis, tenosynovitis, and urticarial rash
  • Synovial fluid analysis usually shows noninflammatory fluid
  • Elevated serum aminotransaminases and evidence of acute HBV infection on serologic testing confirm the presence of the HBV.
Herpes simplex virus (HSV)
  • Genital and extragenital lesions can mimic the skin lesions that occur in disseminated gonococcal infection
  • Viral culture, polymerase chain reaction (PCR), and direct fluorescence antibody confirm the presence of the causative agent.
HIV infection
  • Present with generalized rash with mucus membrane involvement, fever, chills, and arthralgia. Joint effusions are uncommon
Gout and other crystal-induced arthritis
  • Presents with acute monoarthritis with fever and chills
  • Synovial fluid analysis confirm the diagnosis.
Lyme disease
  • Present with erythema chronicum migrans rash and monoarthritis as a later presentation.
  • Clinical characteristics of the rash and and serologic testing confirm the diagnosis.

References

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Natural History, Complications & Prognosis

Natural History

 complications and prognosis

Diagnosis

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Treatment

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