Syphilis natural history, complications and prognosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Syphilis}}
{{Syphilis}}
{{CMG}}; {{AE}}{{AA}}
{{CMG}}; {{AE}}{{AA}}; {{NRM}}


== Overview ==
== Overview ==
 
Syphilis initially presents with the appearance of a painless [[chancre]] after 3-4 weeks of exposure. If left untreated, the [[chancre]] self resolves and the patient may progress to develop [[constitutional sypmtoms|constitutional symptoms]] and a 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|gummatous lesions]] involving [[skin]], [[bone]] and [[joints]] which is associated with significant [[morbidity]] and [[mortality]]. 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 involvement 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><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>


==Natural history==
==Natural history==
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 sypmtoms]] and generalised 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(80-85%, [[aortic aneurysm]], [[aortic regurgitation]], [[angina]], [[heart failure]]), neurologic infection (5-10%, cranial nerve dysfunction, [[meningitis]], [[stroke]], acute or chronic altered mental status, loss of vibration sense, and auditory or ophthalmic abnormalities) and gummatous lesions involving skin, bone and joints which is associated with significant [[morbidity]] and [[mortality]].<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><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>
* Painless [[chancre]] appears 3-4 weeks after exposure.
* [[Chancre]] typically resolves, after which the patient may develop [[constitutional symptoms]] and generalized symmetric [[rash]] in 4 to 8 weeks.
** In less than 10% of individuals, complications such as [[hepatitis]], [[iritis]], [[nephritis]], and neurological problems may develop at this stage.
* This stage is typically self limited to 4 to 8 weeks without treatment and patient enters into asymptomatic latent phase.
* Approximately 25% of patients develop recurrent symptoms in one year.
* Approximately 35% of patients develop tertiary syphilis, which includes the following complications:
** Cardiovascular involvement after 15-30 years (80-85% of patients) including [[aortic aneurysm]], [[aortic regurgitation]], [[angina]], and [[heart failure]]
** Neurologic infection in 10-15 years (5-10% of patients) including cranial nerve dysfunction, [[meningitis]], [[stroke]], acute or chronic [[altered mental status]], loss of vibration sense, and auditory or ophthalmic abnormalities
** [[Gummatous]] lesions involving skin, bone and joints, associated with significant [[morbidity]] and [[mortality]]<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><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>


==Complications==
==Complications==
Complications that can develop as a result of syphilis are:
Complications that can develop as a result of syphilis include:


===Ocular===
===Ocular===
*[[Interstitial keratitis]]<ref name="pmid16282150">{{cite journal| author=Kiss S, Damico FM, Young LH| title=Ocular manifestations and treatment of syphilis. | journal=Semin Ophthalmol | year= 2005 | volume= 20 | issue= 3 | pages= 161-7 | pmid=16282150 | doi=10.1080/08820530500232092 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16282150  }} </ref><ref name="pmid16651059">{{cite journal| author=Balba GP, Kumar PN, James AN, Malani A, Palestine AG, Welch JN et al.| title=Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy. | journal=Am J Med | year= 2006 | volume= 119 | issue= 5 | pages= 448.e21-5 | pmid=16651059 | doi=10.1016/j.amjmed.2005.11.016 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16651059  }} </ref><ref name="pmid17707328">{{cite journal| author=Westeneng AC, Rothova A, de Boer JH, de Groot-Mijnes JD| title=Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis. | journal=Am J Ophthalmol | year= 2007 | volume= 144 | issue= 5 | pages= 781-5 | pmid=17707328 | doi=10.1016/j.ajo.2007.06.034 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17707328  }} </ref>
*[[Interstitial keratitis]]<ref name="pmid16282150">{{cite journal| author=Kiss S, Damico FM, Young LH| title=Ocular manifestations and treatment of syphilis. | journal=Semin Ophthalmol | year= 2005 | volume= 20 | issue= 3 | pages= 161-7 | pmid=16282150 | doi=10.1080/08820530500232092 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16282150  }} </ref><ref name="pmid16651059">{{cite journal| author=Balba GP, Kumar PN, James AN, Malani A, Palestine AG, Welch JN et al.| title=Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy. | journal=Am J Med | year= 2006 | volume= 119 | issue= 5 | pages= 448.e21-5 | pmid=16651059 | doi=10.1016/j.amjmed.2005.11.016 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16651059  }} </ref><ref name="pmid17707328">{{cite journal| author=Westeneng AC, Rothova A, de Boer JH, de Groot-Mijnes JD| title=Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis. | journal=Am J Ophthalmol | year= 2007 | volume= 144 | issue= 5 | pages= 781-5 | pmid=17707328 | doi=10.1016/j.ajo.2007.06.034 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17707328  }} </ref>
*Anterior, intermediate, and posterior [[uveitis] <ref name="pmid7072806">{{cite journal| author=Schlaegel TF, Kao SF| title=A review (1970-1980) of 28 presumptive cases of syphilitic uveitis. | journal=Am J Ophthalmol | year= 1982 | volume= 93 | issue= 4 | pages= 412-4 | pmid=7072806 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7072806  }} </ref>
*Anterior, intermediate, and posterior [[uveitis]]<ref name="pmid7072806">{{cite journal| author=Schlaegel TF, Kao SF| title=A review (1970-1980) of 28 presumptive cases of syphilitic uveitis. | journal=Am J Ophthalmol | year= 1982 | volume= 93 | issue= 4 | pages= 412-4 | pmid=7072806 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7072806  }} </ref>
*[[Episcleritis]] <ref name="pmid1590633">{{cite journal| author=Deschenes J, Seamone CD, Baines MG| title=Acquired ocular syphilis: diagnosis and treatment. | journal=Ann Ophthalmol | year= 1992 | volume= 24 | issue= 4 | pages= 134-8 | pmid=1590633 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1590633  }} </ref>
*[[Episcleritis]] <ref name="pmid1590633">{{cite journal| author=Deschenes J, Seamone CD, Baines MG| title=Acquired ocular syphilis: diagnosis and treatment. | journal=Ann Ophthalmol | year= 1992 | volume= 24 | issue= 4 | pages= 134-8 | pmid=1590633 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1590633  }} </ref>
*[[Scleritis]]  
*[[Scleritis]]  
*[[Iritis]]<ref name=ocular>Moore, Joseph Earle. "Syphilitic iritis: a study of 249 patients." American Journal of Ophthalmology 14.2 (1931): 110-126.</ref>
*[[Iritis]]<ref name=ocular>Moore, Joseph Earle. "Syphilitic iritis: a study of 249 patients." American Journal of Ophthalmology 14.2 (1931): 110-126.</ref>
*[[Iridocyclitis]]
*[[Vitritis]]
*[[Chorioretinitis]]
*[[Chorioretinitis]]
*[[Retinitis]]
*[[Retinitis]]
*Retinal [[vasculitis]]
*Retinal [[vasculitis]]
*[[Optic neuropathy]]
*[[Optic neuropathy]]
*[[optic neuritis]]
*[[Optic neuritis]]


===Auditory===
===Auditory===
*[[Sensorineural deafness]]<ref name="pmid1487268">{{cite journal| author=Morrison AW| title=On syphilis and the ear--an otologist's view. | journal=Genitourin Med | year= 1992 | volume= 68 | issue= 6 | pages= 420-2 | pmid=1487268 | doi= | pmc=1194985 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1487268  }} </ref>
*[[Sensorineural deafness]]<ref name="pmid1487268">{{cite journal| author=Morrison AW| title=On syphilis and the ear--an otologist's view. | journal=Genitourin Med | year= 1992 | volume= 68 | issue= 6 | pages= 420-2 | pmid=1487268 | doi= | pmc=1194985 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1487268  }} </ref>


===Neurological ===  
===Neurological ===
*[[Neurosyphilis]]
*[[Meningitis]]<ref name="pmid24365430">{{cite journal| author=Berger JR, Dean D| title=Neurosyphilis. | journal=Handb Clin Neurol | year= 2014 | volume= 121 | issue=  | pages= 1461-72 | pmid=24365430 | doi=10.1016/B978-0-7020-4088-7.00098-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24365430  }} </ref>
*[[Meningitis]]<ref name="pmid24365430">{{cite journal| author=Berger JR, Dean D| title=Neurosyphilis. | journal=Handb Clin Neurol | year= 2014 | volume= 121 | issue=  | pages= 1461-72 | pmid=24365430 | doi=10.1016/B978-0-7020-4088-7.00098-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24365430  }} </ref>
*Meningiovascular syphilis<ref name="pmid3890813">{{cite journal| author=Simon RP| title=Neurosyphilis. | journal=Arch Neurol | year= 1985 | volume= 42 | issue= 6 | pages= 606-13 | pmid=3890813 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3890813  }} </ref><ref name="pmid3056164">{{cite journal| author=Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH| title=Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. | journal=Ann Intern Med | year= 1988 | volume= 109 | issue= 11 | pages= 855-62 | pmid=3056164 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3056164  }} </ref>
*Meningiovascular syphilis<ref name="pmid3890813">{{cite journal| author=Simon RP| title=Neurosyphilis. | journal=Arch Neurol | year= 1985 | volume= 42 | issue= 6 | pages= 606-13 | pmid=3890813 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3890813  }} </ref><ref name="pmid3056164">{{cite journal| author=Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH| title=Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. | journal=Ann Intern Med | year= 1988 | volume= 109 | issue= 11 | pages= 855-62 | pmid=3056164 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3056164  }} </ref>
*[[Argyll-Robertson pupil]]<ref name="pmid19093312">{{cite journal| author=Loewenfeld IE| title=The Argyll Robertson pupil 1869-1969. A critical survey of the literature. | journal=Surv Ophthalmol | year= 1969 | volume= 14 | issue= 3 | pages= 199-299 | pmid=19093312 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19093312  }} </ref>
*[[Argyll-Robertson pupil]]<ref name="pmid19093312">{{cite journal| author=Loewenfeld IE| title=The Argyll Robertson pupil 1869-1969. A critical survey of the literature. | journal=Surv Ophthalmol | year= 1969 | volume= 14 | issue= 3 | pages= 199-299 | pmid=19093312 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19093312  }} </ref>
*[[Stroke]]<ref name="pmid7340118">{{cite journal| author=Hotson JR| title=Modern neurosyphilis: a partially treated chronic meningitis. | journal=West J Med | year= 1981 | volume= 135 | issue= 3 | pages= 191-200 | pmid=7340118 | doi= | pmc=1273113 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7340118  }} </ref>
*[[Stroke]]<ref name="pmid7340118">{{cite journal| author=Hotson JR| title=Modern neurosyphilis: a partially treated chronic meningitis. | journal=West J Med | year= 1981 | volume= 135 | issue= 3 | pages= 191-200 | pmid=7340118 | doi= | pmc=1273113 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7340118  }} </ref>
*Cranial nerve neuropathies <ref name=syphilisCNS>Musher, Daniel M., Richard J. Hamill, and Robert E. Baughn. "Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment." Annals of Internal Medicine 113.11 (1990): 872-881.</ref>
*[[Cranial nerves|Cranial nerve]] [[Neuropathy|neuropathies]] <ref name=syphilisCNS>Musher, Daniel M., Richard J. Hamill, and Robert E. Baughn. "Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment." Annals of Internal Medicine 113.11 (1990): 872-881.</ref>
*Parenchymal syphilis<ref name=neurosyphilis>Katz, Debra A., Joseph R. Berger, and Robert C. Duncan. "Neurosyphilis: a comparative study of the effects of infection with human immunodeficiency virus." Archives of neurology 50.3 (1993): 243-249.</ref>
*Parenchymal syphilis<ref name=neurosyphilis>Katz, Debra A., Joseph R. Berger, and Robert C. Duncan. "Neurosyphilis: a comparative study of the effects of infection with human immunodeficiency virus." Archives of neurology 50.3 (1993): 243-249.</ref>
:*[[General paresis of the insane|Generalized paresis of the insane]]   
:*[[General paresis of the insane|Generalized paresis of the insane]]   
Line 53: Line 60:
*[[Acute renal failure]]
*[[Acute renal failure]]
*[[Membranous glomerulonephritis]]  
*[[Membranous glomerulonephritis]]  
*Diffuse endocapillary glomerulonephritis
*Diffuse endocapillary [[glomerulonephritis]]


===Musculoskeletal ===
===Musculoskeletal ===
Line 63: Line 70:


===Dermatological ===
===Dermatological ===
*Syphilidis(macular, maculopapular scaly lesions)<ref name="pmid17560432">{{cite journal| author=Wöhrl S, Geusau A| title=Clinical update: syphilis in adults. | journal=Lancet | year= 2007 | volume= 369 | issue= 9577 | pages= 1912-4 | pmid=17560432 | doi=10.1016/S0140-6736(07)60895-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17560432  }} </ref>
*Syphilidis (macular, maculopapular scaly lesions)<ref name="pmid17560432">{{cite journal| author=Wöhrl S, Geusau A| title=Clinical update: syphilis in adults. | journal=Lancet | year= 2007 | volume= 369 | issue= 9577 | pages= 1912-4 | pmid=17560432 | doi=10.1016/S0140-6736(07)60895-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17560432  }} </ref>
*[[Pustular]] syphilis
*[[Pustular rash|Pustular]] syphilis
*[[Condyloma lata]]<ref name="pmid7455863">{{cite journal| author=Chapel TA| title=The signs and symptoms of secondary syphilis. | journal=Sex Transm Dis | year= 1980 | volume= 7 | issue= 4 | pages= 161-4 | pmid=7455863 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7455863  }} </ref>
*[[Condyloma latum|Condyloma lata]]<ref name="pmid7455863">{{cite journal| author=Chapel TA| title=The signs and symptoms of secondary syphilis. | journal=Sex Transm Dis | year= 1980 | volume= 7 | issue= 4 | pages= 161-4 | pmid=7455863 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7455863  }} </ref>
*[[lues maligna]]<ref name=syphilisCNS>Musher, Daniel M., Richard J. Hamill, and Robert E. Baughn. "Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment." Annals of Internal Medicine 113.11 (1990): 872-881.</ref><ref>http://medical-dictionary.thefreedictionary.com/Lues+maligna</ref> <ref name="pmid19035775">{{cite journal| author=Pleimes M, Hartschuh W, Kutzner H, Enk AH, Hartmann M| title=Malignant syphilis with ocular involvement and organism-depleted lesions. | journal=Clin Infect Dis | year= 2009 | volume= 48 | issue= 1 | pages= 83-5 | pmid=19035775 | doi=10.1086/594127 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19035775  }} </ref><ref name="pmid5761808">{{cite journal| author=Fisher DA, Chang LW, Tuffanelli DL| title=Lues maligna. Presentation of a cas and a review of the literature. | journal=Arch Dermatol | year= 1969 | volume= 99 | issue= 1 | pages= 70-3 | pmid=5761808 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5761808  }} </ref>
*Lues maligna<ref name=syphilisCNS>Musher, Daniel M., Richard J. Hamill, and Robert E. Baughn. "Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment." Annals of Internal Medicine 113.11 (1990): 872-881.</ref><ref>http://medical-dictionary.thefreedictionary.com/Lues+maligna</ref> <ref name="pmid19035775">{{cite journal| author=Pleimes M, Hartschuh W, Kutzner H, Enk AH, Hartmann M| title=Malignant syphilis with ocular involvement and organism-depleted lesions. | journal=Clin Infect Dis | year= 2009 | volume= 48 | issue= 1 | pages= 83-5 | pmid=19035775 | doi=10.1086/594127 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19035775  }} </ref><ref name="pmid5761808">{{cite journal| author=Fisher DA, Chang LW, Tuffanelli DL| title=Lues maligna. Presentation of a cas and a review of the literature. | journal=Arch Dermatol | year= 1969 | volume= 99 | issue= 1 | pages= 70-3 | pmid=5761808 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5761808  }} </ref>
*[[Alopecia]]<ref name="pmid7455863">{{cite journal| author=Chapel TA| title=The signs and symptoms of secondary syphilis. | journal=Sex Transm Dis | year= 1980 | volume= 7 | issue= 4 | pages= 161-4 | pmid=7455863 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7455863  }} </ref>
*[[Alopecia]]<ref name="pmid7455863">{{cite journal| author=Chapel TA| title=The signs and symptoms of secondary syphilis. | journal=Sex Transm Dis | year= 1980 | volume= 7 | issue= 4 | pages= 161-4 | pmid=7455863 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7455863  }} </ref>


Line 72: Line 79:
*[[Hepatitis]]<ref name="pmid1401840,">{{cite journal| author=Young MF, Sanowski RA, Manne RA| title=Syphilitic hepatitis. | journal=J Clin Gastroenterol | year= 1992 | volume= 15 | issue= 2 | pages= 174-6 | pmid=1401840, | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1401840  }} </ref>
*[[Hepatitis]]<ref name="pmid1401840,">{{cite journal| author=Young MF, Sanowski RA, Manne RA| title=Syphilitic hepatitis. | journal=J Clin Gastroenterol | year= 1992 | volume= 15 | issue= 2 | pages= 174-6 | pmid=1401840, | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1401840  }} </ref>
*[[Hepatosplenomegaly]]<ref name="pmid17560432">{{cite journal| author=Wöhrl S, Geusau A| title=Clinical update: syphilis in adults. | journal=Lancet | year= 2007 | volume= 369 | issue= 9577 | pages= 1912-4 | pmid=17560432 | doi=10.1016/S0140-6736(07)60895-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17560432  }} </ref><ref name="pmid426583">{{cite journal| author=Campisi D, Whitcomb C| title=Liver disease in early syphilis. | journal=Arch Intern Med | year= 1979 | volume= 139 | issue= 3 | pages= 365-6 | pmid=426583 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=426583  }} </ref>  
*[[Hepatosplenomegaly]]<ref name="pmid17560432">{{cite journal| author=Wöhrl S, Geusau A| title=Clinical update: syphilis in adults. | journal=Lancet | year= 2007 | volume= 369 | issue= 9577 | pages= 1912-4 | pmid=17560432 | doi=10.1016/S0140-6736(07)60895-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17560432  }} </ref><ref name="pmid426583">{{cite journal| author=Campisi D, Whitcomb C| title=Liver disease in early syphilis. | journal=Arch Intern Med | year= 1979 | volume= 139 | issue= 3 | pages= 365-6 | pmid=426583 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=426583  }} </ref>  
*Non specific gastritis <ref name="pmid8113584">{{cite journal| author=Greenstein DB, Wilcox CM, Schwartz DA| title=Gastric syphilis. Report of seven cases and review of the literature. | journal=J Clin Gastroenterol | year= 1994 | volume= 18 | issue= 1 | pages= 4-9 | pmid=8113584 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8113584  }} </ref>
*Non specific [[gastritis]] <ref name="pmid8113584">{{cite journal| author=Greenstein DB, Wilcox CM, Schwartz DA| title=Gastric syphilis. Report of seven cases and review of the literature. | journal=J Clin Gastroenterol | year= 1994 | volume= 18 | issue= 1 | pages= 4-9 | pmid=8113584 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8113584  }} </ref>
*Gastric ulcers<ref name="pmid1733388">{{cite journal| author=Winters HA, Notar-Francesco V, Bromberg K, Rawstrom SA, Vetrano J, Prego V et al.| title=Gastric syphilis: five recent cases and a review of the literature. | journal=Ann Intern Med | year= 1992 | volume= 116 | issue= 4 | pages= 314-9 | pmid=1733388 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1733388  }} </ref>
*Gastric [[ulcers]]<ref name="pmid1733388">{{cite journal| author=Winters HA, Notar-Francesco V, Bromberg K, Rawstrom SA, Vetrano J, Prego V et al.| title=Gastric syphilis: five recent cases and a review of the literature. | journal=Ann Intern Med | year= 1992 | volume= 116 | issue= 4 | pages= 314-9 | pmid=1733388 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1733388  }} </ref>
===Gummatous lesions===
===Gummatous lesions===
*CNS<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="pmid17560432">{{cite journal| author=Wöhrl S, Geusau A| title=Clinical update: syphilis in adults. | journal=Lancet | year= 2007 | volume= 369 | issue= 9577 | pages= 1912-4 | pmid=17560432 | doi=10.1016/S0140-6736(07)60895-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17560432  }} </ref><ref name="pmid27088540">{{cite journal| author=Zhang L, Zhou Y, Chen J, Yan W, Kong Q, Chen P et al.| title=A case of a cerebral syphilitic gumma developed in a few months mimicking a brain tumor in a human immunodeficiency virus-negative patient. | journal=Br J Neurosurg | year= 2016 | volume=  | issue=  | pages= 1-3 | pmid=27088540 | doi=10.3109/02688697.2016.1173190 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27088540  }} </ref>
*[[CNS]]<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="pmid17560432">{{cite journal| author=Wöhrl S, Geusau A| title=Clinical update: syphilis in adults. | journal=Lancet | year= 2007 | volume= 369 | issue= 9577 | pages= 1912-4 | pmid=17560432 | doi=10.1016/S0140-6736(07)60895-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17560432  }} </ref><ref name="pmid27088540">{{cite journal| author=Zhang L, Zhou Y, Chen J, Yan W, Kong Q, Chen P et al.| title=A case of a cerebral syphilitic gumma developed in a few months mimicking a brain tumor in a human immunodeficiency virus-negative patient. | journal=Br J Neurosurg | year= 2016 | volume=  | issue=  | pages= 1-3 | pmid=27088540 | doi=10.3109/02688697.2016.1173190 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27088540  }} </ref>
*Bone
*[[Bone]]
*skin
*[[Skin]]


==Prognosis==
==Prognosis==
The prognosis of syphilis varies by stage of disease:
The prognosis of syphilis depends on the stage of disease:<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><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>
 
===Primary and secondary syphilis===
'''Primary and secondary syphilis'''
Prognosis is good with appropriate [[antimicrobial]] treatment and most patients will have full resolution of symptoms.
Good prognosis with treatment.
===Tertiary syphilis===
 
Prognosis varies by site of involvement and duration of disease:
'''Tertiary syphilis'''
Prognosis varies by site of involvememnt and duration of disease:
*90% of patients with neurosyphilis respond to treatment.
*90% of patients with neurosyphilis respond to treatment.
*Gummatous lesions reverse with treatment.
*[[Gummatous]] lesions reverse with treatment.
*Mortality rates are high with cardiovascular complications.  
*Mortality rates are high with cardiovascular complications.  
*20% of patients with tertiary syphilis die of complications.
*20% of patients with [[tertiary syphilis]] die of complications.


== References ==
== References ==
{{reflist|2}}
{{reflist|2}}
[[category: Infectious disease]]
[[category: Gynaecology]]
[[category: Primary care]]
{{WH}}
{{WH}}


{{WS}}
{{WS}}
[[Category:Infectious disease]]
[[Category:Gynaecology]]

Latest revision as of 00:23, 30 July 2020

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

Overview

Syphilis initially presents with the appearance of a painless chancre after 3-4 weeks of exposure. If left untreated, the chancre self resolves and the patient may progress to develop constitutional symptoms and a 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. 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 involvement and duration of disease. 90% of patients with neurosyphilis respond to treatment. However, mortality rates are high with cardiovascular complications.[1][2][3][4]

Natural history

  • Painless chancre appears 3-4 weeks after exposure.
  • Chancre typically resolves, after which the patient may develop constitutional symptoms and generalized symmetric rash in 4 to 8 weeks.
    • In less than 10% of individuals, complications such as hepatitis, iritis, nephritis, and neurological problems may develop at this stage.
  • This stage is typically self limited to 4 to 8 weeks without treatment and patient enters into asymptomatic latent phase.
  • Approximately 25% of patients develop recurrent symptoms in one year.
  • Approximately 35% of patients develop tertiary syphilis, which includes the following complications:

Complications

Complications that can develop as a result of syphilis include:

Ocular

Auditory

Neurological

Cardiovascular

Renal

Musculoskeletal

Dermatological

Gastrintestinal

Gummatous lesions

Prognosis

The prognosis of syphilis depends on the stage of disease:[1][2][3]

Primary and secondary syphilis

Prognosis is good with appropriate antimicrobial treatment and most patients will have full resolution of symptoms.

Tertiary syphilis

Prognosis varies by site of involvement and duration of disease:

  • 90% of patients with neurosyphilis respond to treatment.
  • Gummatous lesions reverse with treatment.
  • Mortality rates are high with cardiovascular complications.
  • 20% of patients with tertiary syphilis die of complications.

References

  1. ↑ 1.0 1.1 1.2 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.
  2. ↑ 2.0 2.1 2.2 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.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 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 French P (2007). "Syphilis". BMJ. 334 (7585): 143–7. doi:10.1136/bmj.39085.518148.BE. PMC 1779891. PMID 17235095.
  5. ↑ Kiss S, Damico FM, Young LH (2005). "Ocular manifestations and treatment of syphilis". Semin Ophthalmol. 20 (3): 161–7. doi:10.1080/08820530500232092. PMID 16282150.
  6. ↑ Balba GP, Kumar PN, James AN, Malani A, Palestine AG, Welch JN; et al. (2006). "Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy". Am J Med. 119 (5): 448.e21–5. doi:10.1016/j.amjmed.2005.11.016. PMID 16651059.
  7. ↑ Westeneng AC, Rothova A, de Boer JH, de Groot-Mijnes JD (2007). "Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis". Am J Ophthalmol. 144 (5): 781–5. doi:10.1016/j.ajo.2007.06.034. PMID 17707328.
  8. ↑ Schlaegel TF, Kao SF (1982). "A review (1970-1980) of 28 presumptive cases of syphilitic uveitis". Am J Ophthalmol. 93 (4): 412–4. PMID 7072806.
  9. ↑ Deschenes J, Seamone CD, Baines MG (1992). "Acquired ocular syphilis: diagnosis and treatment". Ann Ophthalmol. 24 (4): 134–8. PMID 1590633.
  10. ↑ Moore, Joseph Earle. "Syphilitic iritis: a study of 249 patients." American Journal of Ophthalmology 14.2 (1931): 110-126.
  11. ↑ Morrison AW (1992). "On syphilis and the ear--an otologist's view". Genitourin Med. 68 (6): 420–2. PMC 1194985. PMID 1487268.
  12. ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  13. ↑ Simon RP (1985). "Neurosyphilis". Arch Neurol. 42 (6): 606–13. PMID 3890813.
  14. ↑ Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH (1988). "Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment". Ann Intern Med. 109 (11): 855–62. PMID 3056164.
  15. ↑ Loewenfeld IE (1969). "The Argyll Robertson pupil 1869-1969. A critical survey of the literature". Surv Ophthalmol. 14 (3): 199–299. PMID 19093312.
  16. ↑ Hotson JR (1981). "Modern neurosyphilis: a partially treated chronic meningitis". West J Med. 135 (3): 191–200. PMC 1273113. PMID 7340118.
  17. ↑ 17.0 17.1 Musher, Daniel M., Richard J. Hamill, and Robert E. Baughn. "Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment." Annals of Internal Medicine 113.11 (1990): 872-881.
  18. ↑ Katz, Debra A., Joseph R. Berger, and Robert C. Duncan. "Neurosyphilis: a comparative study of the effects of infection with human immunodeficiency virus." Archives of neurology 50.3 (1993): 243-249.
  19. ↑ Sapira JD (1981 Apr). ""Quincke, de Musset, Duroziez, and Hill: some aortic regurgitations"". South Med J. 74 (4): 459–67. Check date values in: |date= (help)
  20. ↑ Pugh PJ, Grech ED (2002). "Images in clinical medicine. Syphilitic aortitis". N Engl J Med. 346 (9): 676. doi:10.1056/NEJMicm010343. PMID 11870245.
  21. ↑ Kennedy JL, Barnard JJ, Prahlow JA (2006). "Syphilitic coronary artery ostial stenosis resulting in acute myocardial infarction and death". Cardiology. 105 (1): 25–9. doi:10.1159/000088337. PMID 16179782.
  22. ↑ "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1998. A 46-year-old man with chest pain and coronary ostial stenosis". N Engl J Med. 338 (13): 897–903. 1998. doi:10.1056/NEJM199803263381308. PMID 9518283.
  23. ↑ Burch, George E., and Travis Winsor. "Syphilitic coronary stenosis, with myocardial infarction." American Heart Journal 24.6 (1942): 740-751.
  24. ↑ Hunte W, al-Ghraoui F, Cohen RJ (1993). "Secondary syphilis and the nephrotic syndrome". J Am Soc Nephrol. 3 (7): 1351–5. PMID 8439646.
  25. ↑ Reginato AJ (1993). "Syphilitic arthritis and osteitis". Rheum Dis Clin North Am. 19 (2): 379–98. PMID 8502778.
  26. ↑ Mindel A, Tovey SJ, Timmins DJ, Williams P (1989). "Primary and secondary syphilis, 20 years' experience. 2. Clinical features". Genitourin Med. 65 (1): 1–3. PMC 1196177. PMID 2921046.
  27. ↑ 27.0 27.1 27.2 Wöhrl S, Geusau A (2007). "Clinical update: syphilis in adults". Lancet. 369 (9577): 1912–4. doi:10.1016/S0140-6736(07)60895-2. PMID 17560432.
  28. ↑ 28.0 28.1 Chapel TA (1980). "The signs and symptoms of secondary syphilis". Sex Transm Dis. 7 (4): 161–4. PMID 7455863.
  29. ↑ http://medical-dictionary.thefreedictionary.com/Lues+maligna
  30. ↑ Pleimes M, Hartschuh W, Kutzner H, Enk AH, Hartmann M (2009). "Malignant syphilis with ocular involvement and organism-depleted lesions". Clin Infect Dis. 48 (1): 83–5. doi:10.1086/594127. PMID 19035775.
  31. ↑ Fisher DA, Chang LW, Tuffanelli DL (1969). "Lues maligna. Presentation of a cas and a review of the literature". Arch Dermatol. 99 (1): 70–3. PMID 5761808.
  32. ↑ Young MF, Sanowski RA, Manne RA (1992). "Syphilitic hepatitis". J Clin Gastroenterol. 15 (2): 174–6. PMID 1401840, Check |pmid= value (help).
  33. ↑ Campisi D, Whitcomb C (1979). "Liver disease in early syphilis". Arch Intern Med. 139 (3): 365–6. PMID 426583.
  34. ↑ Greenstein DB, Wilcox CM, Schwartz DA (1994). "Gastric syphilis. Report of seven cases and review of the literature". J Clin Gastroenterol. 18 (1): 4–9. PMID 8113584.
  35. ↑ Winters HA, Notar-Francesco V, Bromberg K, Rawstrom SA, Vetrano J, Prego V; et al. (1992). "Gastric syphilis: five recent cases and a review of the literature". Ann Intern Med. 116 (4): 314–9. PMID 1733388.
  36. ↑ Zhang L, Zhou Y, Chen J, Yan W, Kong Q, Chen P; et al. (2016). "A case of a cerebral syphilitic gumma developed in a few months mimicking a brain tumor in a human immunodeficiency virus-negative patient". Br J Neurosurg: 1–3. doi:10.3109/02688697.2016.1173190. PMID 27088540.

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