Treponema pallidum pallidum: Difference between revisions

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Treponema pallidum pallidum
(added further reading)
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Line 1: Line 1:
βˆ’
* Causes '''syphilis'''
 +
*Causes '''syphilis'''
   
βˆ’
== Background ==
 +
==Background==
βˆ’
=== Microbiology ===
 +
===Microbiology===
βˆ’
* Small, slow-growing spirochete
  
βˆ’
* Not seen on standard microscopy; requires darkfield microscopy
  
   
  +
*Small, slow-growing spirochete
βˆ’
== Clinical Presentation ==
  
  +
*Not seen on standard microscopy; requires darkfield microscopy
βˆ’
=== Stages ===
  
βˆ’
* Primary syphilis (incubation period 3 weeks [range 3 to 90 days])
  
βˆ’
* Secondary syphilis (incubation period 2 weeks to 3 months [range 2 weeks to 6 months])
  
βˆ’
* Latent
  
βˆ’
** Early latent (<1 year)
  
βˆ’
** Late latent (β‰₯1 year)
  
βˆ’
* Tertiary syphilis (incubation period years to decades)
  
βˆ’
** Cardiovascular (incubation period 10 to 30 years)
  
βˆ’
** Gummatous (incubation period 15 years [range 1 to 46 years])
  
βˆ’
** Neurosyphilis (incubation period 2 to 20 years)
  
βˆ’
*** Meningovascular
  
βˆ’
*** Parenchymatous
  
βˆ’
*** Tabes dorsalis
  
βˆ’
* Congenital
  
βˆ’
** Early (< 2 years)
  
βˆ’
** Late (≥ 2 years)
  
   
  +
==Clinical Presentation==
βˆ’
=== Primary syphilis ===
  
  +
===Stages===
βˆ’
* Incubation period is about 3 weeks
  
βˆ’
* Chancre
  
βˆ’
* Ulcerative lesion
  
βˆ’
** Clean borders
  
βˆ’
** Indurated
  
βˆ’
** Not painful unless secondarily infected
  
βˆ’
** Lasts 2 to 6 weeks
  
βˆ’
* May present with regional lymphadenopathy
  
βˆ’
* Diagnosis with darkfield microscopy, fluorescent antibody smear, or (most commonly) serology
  
βˆ’
* Serology often negative in early syphilis
  
   
  +
*Primary syphilis (incubation period 3 weeks [range 3 to 90 days])
βˆ’
=== Secondary syphilis ===
  
βˆ’
* Incubation period 3 weeks to 3 months
 +
*Secondary syphilis (incubation period 2 weeks to 3 months [range 2 weeks to 6 months])
  +
*Latent
βˆ’
* Often no history of chancre
  
  +
**Early latent (<1 year)
βˆ’
* Diffuse maculopapular rash that involves palms and soles
  
  +
**Late latent (β‰₯1 year)
βˆ’
** Typically begins on trunk
  
  +
*Tertiary syphilis (incubation period years to decades)
βˆ’
** Start as pinkish-reddish macular lesions that evolve into brownish-reddish papules that may have scaling
  
  +
**Cardiovascular (incubation period 10 to 30 years)
βˆ’
** May progress to pustular lesions (pustular syphilids)
  
  +
**Gummatous (incubation period 15 years [range 1 to 46 years])
βˆ’
** May be itchy
  
  +
**Neurosyphilis (incubation period 2 to 20 years)
βˆ’
** Can be isolated to palms and soles
  
  +
***Meningovascular
βˆ’
* Generalized lymphadenopathy
  
  +
***Parenchymatous
βˆ’
* Fever, chills, arthralgias
  
  +
***Tabes dorsalis
βˆ’
* Less common: condyloma lata, aseptic meningitis, iritis, mucosal white patches, glomerulonephritis, paroxysmal nocturnal hemoglobinuria, hepatitis
  
  +
*Congenital
  +
**Early (< 2 years)
  +
**Late (≥ 2 years)
   
βˆ’
=== Latent syphilis ===
 +
===Primary syphilis===
βˆ’
* High rate of relapse of secondary syphilis within the first 1-2 years following infection (but especially within the first year)
  
   
  +
*Incubation period is about 3 weeks
βˆ’
=== Tertiary syphilis ===
  
  +
*Chancre
βˆ’
* Eventually occurs in about 30% of untreated cases
  
  +
*Ulcerative lesion
  +
**Clean borders
  +
**Indurated
  +
**Not painful unless secondarily infected
  +
**Lasts 2 to 6 weeks
  +
*May present with regional lymphadenopathy
  +
*Diagnosis with darkfield microscopy, fluorescent antibody smear, or (most commonly) serology
  +
*Serology often negative in early syphilis
   
βˆ’
==== Neurosyphilis ====
 +
===Secondary syphilis===
βˆ’
* Of the 25-60% of people who have CNS invasion, 95% are asymptomatic during the early stage and 80% of those spontaneously clear it
  
βˆ’
* Incubation period is 7-15 years
  
βˆ’
* Three major presentations: meningovascular syphilis, parenchymous syphilis, and tabse dorsalis
  
   
  +
*Incubation period 3 weeks to 3 months
βˆ’
===== Meningovascular =====
  
  +
*Often no history of chancre
βˆ’
* Possibly the most common neurosyphilis
  
  +
*Diffuse maculopapular rash that involves palms and soles
βˆ’
* Subdivided into cerebromeningeal (diffuse or focal) and cerebrovascular
  
  +
**Typically begins on trunk
βˆ’
* Stroke-like symptoms, especially MCA or basilar territory
  
  +
**Start as pinkish-reddish macular lesions that evolve into brownish-reddish papules that may have scaling
βˆ’
* Can present as a sudden change, as syphilitic apoplexy
  
  +
**May progress to pustular lesions (pustular syphilids)
βˆ’
* Can present following a prodrome of weeks to months of non-specific headaches, vertigo, irritability, insomnia, and personality changes
  
  +
**May be itchy
  +
**Can be isolated to palms and soles
  +
*Generalized lymphadenopathy
  +
*Fever, chills, arthralgias
  +
*Less common: condyloma lata, aseptic meningitis, iritis, mucosal white patches, glomerulonephritis, paroxysmal nocturnal hemoglobinuria, hepatitis
   
βˆ’
===== Parenchymatous =====
 +
===Latent syphilis===
βˆ’
* Previously known as "generalized paresis of the insane"
  
βˆ’
* Occurs in 2-5% of cases of untreated syphilis
  
βˆ’
* Commonly found on psychiatric wards
  
βˆ’
* Causes psychosis and dementia
  
βˆ’
* Later, coarse tremors, Argyll-Robinson pupil, paresis
  
   
  +
*High rate of relapse of secondary syphilis within the first 1-2 years following infection (but especially within the first year)
βˆ’
===== Tabes dorsalis =====
  
βˆ’
* Occurs in 2-9% of cases of untreated syphilis
  
βˆ’
* Isolated posterior cord degeneration leading to a loss of proprioception in the lower extremities
  
βˆ’
* Stomp the ground when walking to use intact pain/pressure sensation
  
βˆ’
* Loss of sensation in the Hitzig zones (tip of nose, band including nipple area, medial forearms, and lateral leg)
  
βˆ’
* Can present with Charcot foot and, rarely, recurrent abdominal pain
  
βˆ’
* Diagnosed by serum CMIA, but RPR may be negative
  
   
βˆ’
===== Others =====
 +
===Tertiary syphilis===
βˆ’
* Isolated ocular neurosyphilis
  
βˆ’
* Meningitis: can present at any time during the course of disease
  
βˆ’
* Others
  
   
  +
*Eventually occurs in about 30% of untreated cases
βˆ’
==== Cardiovascular syphilis ====
  
βˆ’
* Occurs in 10% of people with untreated syphilis
  
βˆ’
* Incubation period is 20-25 years
  
βˆ’
* Aortic root involvement leading to aortitis and dilatation
  
βˆ’
* May result in aneurysm, aortic insufficiency, or angina secondary to stenosis at the aortic root
  
βˆ’
* Diagnosed by RPR +/- CMIA
  
   
βˆ’
==== Gummatous syphilis ====
 +
====Neurosyphilis====
βˆ’
* Gummas are necrotizing granulomatous lesions
  
βˆ’
* Occurs in 15% of people with untreated syphilis
  
βˆ’
* Incubation period 6-8 years
  
βˆ’
* Gummas may appear anywhere, in any organ, but most commonly on the skin, on mucosa, and in bones
  
βˆ’
* CNS lesions look like toxo, so beware in HIV patients
  
   
  +
*Of the 25-60% of people who have CNS invasion, 95% are asymptomatic during the early stage and 80% of those spontaneously clear it
βˆ’
=== Other presentations ===
  
  +
*Incubation period is 7-15 years
βˆ’
* Isolated auditory syphilis
  
  +
*Three major presentations: meningovascular syphilis, parenchymous syphilis, and tabse dorsalis
βˆ’
* Isolated optic syphilis
  
   
  +
=====Meningovascular=====
βˆ’
== Diagnosis ==
  
βˆ’
* Often done as non-treponemal test to screen, followed by treponemal test to confirm
  
βˆ’
* In Ontario, we do a treponemal test to screen (CMIA), then repeat it with a more specific treponemal test (TPPA) alongside RPR
  
   
  +
*Possibly the most common neurosyphilis
βˆ’
=== Direct visualization ===
  
  +
*Subdivided into cerebromeningeal (diffuse or focal) and cerebrovascular
βˆ’
* Darkfield microscopy
  
  +
*Stroke-like symptoms, especially MCA or basilar territory
βˆ’
** Chancre cleaned and smear obtained
  
  +
*Can present as a sudden change, as syphilitic apoplexy
βˆ’
** Smear must be visualized immediately
  
  +
*Can present following a prodrome of weeks to months of non-specific headaches, vertigo, irritability, insomnia, and personality changes
βˆ’
** Sensitivity decreases with duration
  
βˆ’
* Smear for fluorescent monoclonal antibody
  
βˆ’
** Best to use in primary syphilis
  
   
  +
=====Parenchymatous=====
βˆ’
=== Non-treponemal tests (VDRL/RPR) ===
  
βˆ’
* Veneral Diseases Research Laboratory (VDRL) has been replaced by the [[rapid plasma reagin]] (RPR) test
  
βˆ’
** Quantitative tests for a non-specific anti-cardiolipin antibody that is produced in syphilitic (and other) infections
  
βˆ’
* False positives in pregnancy, autoimmune disorders (lupus, APLA), and chronic infections (leishmaniasis, leprosy, ...)
  
βˆ’
* 50% sensitive in primary, 100% sensitive in secondary
  
βˆ’
* Tests will eventually become nonreactive
  
   
  +
*Previously known as "generalized paresis of the insane"
βˆ’
=== Treponemal tests ===
  
  +
*Occurs in 2-5% of cases of untreated syphilis
βˆ’
* More specific and sensitive, but more expensive
  
  +
*Commonly found on psychiatric wards
βˆ’
* False positive in lupus and Lyme disease
  
  +
*Causes psychosis and dementia
βˆ’
* Remain positive for life
  
  +
*Later, coarse tremors, Argyll-Robinson pupil, paresis
βˆ’
* Four main tests:
  
βˆ’
** '''Fluorescent treponemal antibody absorption (FTA-Abs):''' Essentially the gold standard
  
βˆ’
** '''Chemoluminescnence microparticle immunoassay (CMIA or CLIA)''': the screening test used in Ontario. Often used as a screening test as it is an easily-automated immunoassay and is more sensitive and specific than RPR.
  
βˆ’
** '''''Treponema pallidum'' Particulate Agglutination assay (TPPA)''': a modification of the TPHA. Used as the confirmatory test (alongside RPR) used in Ontario.
  
βˆ’
** '''''T. pallidum'' hemagglutination assay (TPHA)''': very old test.
  
βˆ’
** '''''T. pallidum'' enzyme immunassay (TP-EIA)'''
  
   
  +
=====Tabes dorsalis=====
βˆ’
=== Interpretation of serology ===
  
  +
  +
*Occurs in 2-9% of cases of untreated syphilis
  +
*Isolated posterior cord degeneration leading to a loss of proprioception in the lower extremities
  +
*Stomp the ground when walking to use intact pain/pressure sensation
  +
*Loss of sensation in the Hitzig zones (tip of nose, band including nipple area, medial forearms, and lateral leg)
  +
*Can present with Charcot foot and, rarely, recurrent abdominal pain
  +
*Diagnosed by serum CMIA, but RPR may be negative
  +
  +
=====Others=====
  +
  +
*Isolated ocular neurosyphilis
  +
*Meningitis: can present at any time during the course of disease
  +
*Others
  +
  +
====Cardiovascular syphilis====
  +
  +
*Occurs in 10% of people with untreated syphilis
  +
*Incubation period is 20-25 years
  +
*Aortic root involvement leading to aortitis and dilatation
  +
*May result in aneurysm, aortic insufficiency, or angina secondary to stenosis at the aortic root
  +
*Diagnosed by RPR +/- CMIA
  +
  +
====Gummatous syphilis====
  +
  +
*Gummas are necrotizing granulomatous lesions
  +
*Occurs in 15% of people with untreated syphilis
  +
*Incubation period 6-8 years
  +
*Gummas may appear anywhere, in any organ, but most commonly on the skin, on mucosa, and in bones
  +
*CNS lesions look like toxo, so beware in HIV patients
  +
  +
===Other presentations===
  +
  +
*Isolated auditory syphilis
  +
*Isolated optic syphilis
  +
  +
==Diagnosis==
  +
  +
*Often done as non-treponemal test to screen, followed by treponemal test to confirm
  +
*In Ontario, we do a treponemal test to screen (CMIA), then repeat it with a more specific treponemal test (TPPA) alongside RPR
  +
  +
===Direct visualization===
  +
  +
*Darkfield microscopy
  +
**Chancre cleaned and smear obtained
  +
**Smear must be visualized immediately
  +
**Sensitivity decreases with duration
  +
*Smear for fluorescent monoclonal antibody
  +
**Best to use in primary syphilis
  +
  +
===Non-treponemal tests (VDRL/RPR)===
  +
  +
*Veneral Diseases Research Laboratory (VDRL) has been replaced by the [[rapid plasma reagin]] (RPR) test
  +
**Quantitative tests for a non-specific anti-cardiolipin antibody that is produced in syphilitic (and other) infections
  +
*False positives:
  +
**Acute biologic false positive: [[malaria]], [[brucellosis]], and [[mononucleosis]]; maybe [[pregnancy]]
  +
**Chronic biologic false positive: [[lupus]] and other autoimmune disorders, [[HIV]], intravenous drug use, and [[leprosy]]
  +
*Only 50% sensitive in primary, 100% sensitive in secondary
  +
*Tests will eventually become nonreactive
  +
  +
===Treponemal tests===
  +
  +
*More specific and sensitive, but more expensive
  +
*False positives: [[lupus]] and other autoimmune disorders, [[Lyme disease]], and other [[Treponema species|treponemal infections]]
  +
*Remain positive for life
  +
*Four main tests:
  +
**'''Fluorescent treponemal antibody absorption (FTA-Abs):''' Essentially the gold standard
  +
**'''Chemoluminescnence microparticle immunoassay (CMIA or CLIA)''': the screening test used in Ontario. Often used as a screening test as it is an easily-automated immunoassay and is more sensitive and specific than RPR.
  +
**'''''Treponema pallidum'' Particulate Agglutination assay (TPPA)''': a modification of the TPHA. Used as the confirmatory test (alongside RPR) used in Ontario.
  +
**'''''T. pallidum'' hemagglutination assay (TPHA)''': very old test.
  +
**'''''T. pallidum'' enzyme immunassay (TP-EIA)'''
  +
  +
===Interpretation of serology===
 
{| class="wikitable sortable"
  
{| class="wikitable sortable"
βˆ’
! CMIA screen
 +
!CMIA screen
βˆ’
! RPR
 +
!RPR
βˆ’
! TPPA
 +
!TPPA
βˆ’
! Interpretation
 +
!Interpretation
 
|-
  
|-
βˆ’
| Non-reactive
 +
|Non-reactive
βˆ’
| β€”
 +
|β€”
βˆ’
| β€”
 +
|β€”
βˆ’
| Negative result; or early syphilis (consider repeat in 4 weeks)
 +
|Negative result; or early syphilis (consider repeat in 4 weeks)
 
|-
  
|-
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Recent or prior syphilis infection
 +
|Recent or prior syphilis infection
 
|-
  
|-
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Non-reactive
 +
|Non-reactive
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Recent or prior syphilis infection
 +
|Recent or prior syphilis infection
 
|-
  
|-
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Non-reactive
 +
|Non-reactive
βˆ’
| Non-reactive
 +
|Non-reactive
βˆ’
| False positive; or early syphilis, previously treated, or late latent (repeat in 4 weeks)
 +
|False positive; or early syphilis, previously treated, or late latent (repeat in 4 weeks)
 
|-
  
|-
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Non-reactive
 +
|Non-reactive
βˆ’
| Indeterminate
 +
|Indeterminate
βˆ’
| Inconclusive result; false positive, early syphilis, old treated syphilis, or old untreated syphilis (repeat in 4 weeks)
 +
|Inconclusive result; false positive, early syphilis, old treated syphilis, or old untreated syphilis (repeat in 4 weeks)
 
|-
  
|-
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Non-reactive
 +
|Non-reactive
βˆ’
| Inconclusive result; false positive, early syphilis, old treated syphilis, or untreated syphilis (repeat in 4 weeks)
 +
|Inconclusive result; false positive, early syphilis, old treated syphilis, or untreated syphilis (repeat in 4 weeks)
 
|-
  
|-
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Reactive
 +
|Reactive
βˆ’
| Indeterminate
 +
|Indeterminate
βˆ’
| Recent or prior syphilis infection
 +
|Recent or prior syphilis infection
 
|}
  
|}
   
βˆ’
== Treatment ==
 +
==Treatment==
βˆ’
=== Primary, secondary, and early latent ===
 +
===Primary, secondary, and early latent===
βˆ’
* [[Is treated by::Benzathine penicillin G]] 2.4 million units IM once, divided between two buttocks
  
βˆ’
* Alternative (penicillin allergy): [[Is treated by::doxycycline]] 100mg BID for 2 weeks
  
βˆ’
* Alternative (penicillin allergy and pregnancy): penicillin desensitization or [[Is treated by::azithromycin]]
  
   
  +
*[[Is treated by::Benzathine penicillin G]] 2.4 million units IM once, divided between two buttocks
βˆ’
=== Late latent and tertiary (excluding neurosyphilis) ===
  
βˆ’
* [[Is treated by::Benzathine penicillin G]] 2.4 million units IM q1week for 3 weeks
 +
*Alternative (penicillin allergy): [[Is treated by::doxycycline]] 100mg BID for 2 weeks
βˆ’
* Alternative (penicillin allergy): [[Is treated by::doxycycline]] for 30 days
 +
*Alternative (penicillin allergy and pregnancy): penicillin desensitization or [[Is treated by::azithromycin]]
βˆ’
* Monitor response with RPR titres, which should drop 4-fold within 6 months
  
   
  +
===Late latent and tertiary (excluding neurosyphilis)===
βˆ’
=== Tertiary neurosyphilis ===
  
βˆ’
* [[Is treated by::Penicillin G]] 4 million units IV q4h for 10 to 14 days
  
βˆ’
* Often followed by at least one dose of IM benzathine penicillin, sometimes weekly for 2-3 weeks
  
   
  +
*[[Is treated by::Benzathine penicillin G]] 2.4 million units IM q1week for 3 weeks
βˆ’
=== Congenital syphilis ===
  
  +
*Alternative (penicillin allergy): [[Is treated by::doxycycline]] for 30 days
βˆ’
* If <1 month of age: [[Is treated by::crystalline penicillin G]] 50 kU/kg IV q12h for the first week of life and q8h thereafter, for a total of 10 days
  
  +
*Monitor response with RPR titres, which should drop 4-fold within 6 months
βˆ’
* If ≥1 month of age: [[Is treated by::crystalline penicillin G]] 50,000 units/kg IV every 6 hours for 10-14 days
  
  +
βˆ’
** If there is no neurological involvement, then you can consider [[Is treated by::benzathine penicillin G]] 50 kU/kg (max 2.4 MU) IM weekly for 3 weeks
  
  +
===Tertiary neurosyphilis===
  +
  +
*[[Is treated by::Penicillin G]] 4 million units IV q4h for 10 to 14 days
  +
*Often followed by at least one dose of IM benzathine penicillin, sometimes weekly for 2-3 weeks
  +
  +
===Congenital syphilis===
  +
  +
*If <1 month of age: [[Is treated by::crystalline penicillin G]] 50 kU/kg IV q12h for the first week of life and q8h thereafter, for a total of 10 days
  +
*If ≥1 month of age: [[Is treated by::crystalline penicillin G]] 50,000 units/kg IV every 6 hours for 10-14 days
  +
**If there is no neurological involvement, then you can consider [[Is treated by::benzathine penicillin G]] 50 kU/kg (max 2.4 MU) IM weekly for 3 weeks
   
 
==Further Reading==
  
==Further Reading==
  +
βˆ’
* [https://www.toronto.ca/wp-content/uploads/2018/02/8528-tph-syphilis-lab-interpretation-guideline-Jan-2018.pdf Toronto Public Health Syphilis Laboratory Interpretation and Treatment] (2-page PDF)
  
  +
*[https://www.toronto.ca/wp-content/uploads/2018/02/8528-tph-syphilis-lab-interpretation-guideline-Jan-2018.pdf Toronto Public Health Syphilis Laboratory Interpretation and Treatment] (2-page PDF)
   
 
{{DISPLAYTITLE:''Treponema pallidum pallidum''}}
  
{{DISPLAYTITLE:''Treponema pallidum pallidum''}}

Revision as of 21:01, 25 July 2020

  • Causes syphilis

Background

Microbiology

  • Small, slow-growing spirochete
  • Not seen on standard microscopy; requires darkfield microscopy

Clinical Presentation

Stages

  • Primary syphilis (incubation period 3 weeks [range 3 to 90 days])
  • Secondary syphilis (incubation period 2 weeks to 3 months [range 2 weeks to 6 months])
  • Latent
    • Early latent (<1 year)
    • Late latent (β‰₯1 year)
  • Tertiary syphilis (incubation period years to decades)
    • Cardiovascular (incubation period 10 to 30 years)
    • Gummatous (incubation period 15 years [range 1 to 46 years])
    • Neurosyphilis (incubation period 2 to 20 years)
      • Meningovascular
      • Parenchymatous
      • Tabes dorsalis
  • Congenital
    • Early (< 2 years)
    • Late (≥ 2 years)

Primary syphilis

  • Incubation period is about 3 weeks
  • Chancre
  • Ulcerative lesion
    • Clean borders
    • Indurated
    • Not painful unless secondarily infected
    • Lasts 2 to 6 weeks
  • May present with regional lymphadenopathy
  • Diagnosis with darkfield microscopy, fluorescent antibody smear, or (most commonly) serology
  • Serology often negative in early syphilis

Secondary syphilis

  • Incubation period 3 weeks to 3 months
  • Often no history of chancre
  • Diffuse maculopapular rash that involves palms and soles
    • Typically begins on trunk
    • Start as pinkish-reddish macular lesions that evolve into brownish-reddish papules that may have scaling
    • May progress to pustular lesions (pustular syphilids)
    • May be itchy
    • Can be isolated to palms and soles
  • Generalized lymphadenopathy
  • Fever, chills, arthralgias
  • Less common: condyloma lata, aseptic meningitis, iritis, mucosal white patches, glomerulonephritis, paroxysmal nocturnal hemoglobinuria, hepatitis

Latent syphilis

  • High rate of relapse of secondary syphilis within the first 1-2 years following infection (but especially within the first year)

Tertiary syphilis

  • Eventually occurs in about 30% of untreated cases

Neurosyphilis

  • Of the 25-60% of people who have CNS invasion, 95% are asymptomatic during the early stage and 80% of those spontaneously clear it
  • Incubation period is 7-15 years
  • Three major presentations: meningovascular syphilis, parenchymous syphilis, and tabse dorsalis
Meningovascular
  • Possibly the most common neurosyphilis
  • Subdivided into cerebromeningeal (diffuse or focal) and cerebrovascular
  • Stroke-like symptoms, especially MCA or basilar territory
  • Can present as a sudden change, as syphilitic apoplexy
  • Can present following a prodrome of weeks to months of non-specific headaches, vertigo, irritability, insomnia, and personality changes
Parenchymatous
  • Previously known as "generalized paresis of the insane"
  • Occurs in 2-5% of cases of untreated syphilis
  • Commonly found on psychiatric wards
  • Causes psychosis and dementia
  • Later, coarse tremors, Argyll-Robinson pupil, paresis
Tabes dorsalis
  • Occurs in 2-9% of cases of untreated syphilis
  • Isolated posterior cord degeneration leading to a loss of proprioception in the lower extremities
  • Stomp the ground when walking to use intact pain/pressure sensation
  • Loss of sensation in the Hitzig zones (tip of nose, band including nipple area, medial forearms, and lateral leg)
  • Can present with Charcot foot and, rarely, recurrent abdominal pain
  • Diagnosed by serum CMIA, but RPR may be negative
Others
  • Isolated ocular neurosyphilis
  • Meningitis: can present at any time during the course of disease
  • Others

Cardiovascular syphilis

  • Occurs in 10% of people with untreated syphilis
  • Incubation period is 20-25 years
  • Aortic root involvement leading to aortitis and dilatation
  • May result in aneurysm, aortic insufficiency, or angina secondary to stenosis at the aortic root
  • Diagnosed by RPR +/- CMIA

Gummatous syphilis

  • Gummas are necrotizing granulomatous lesions
  • Occurs in 15% of people with untreated syphilis
  • Incubation period 6-8 years
  • Gummas may appear anywhere, in any organ, but most commonly on the skin, on mucosa, and in bones
  • CNS lesions look like toxo, so beware in HIV patients

Other presentations

  • Isolated auditory syphilis
  • Isolated optic syphilis

Diagnosis

  • Often done as non-treponemal test to screen, followed by treponemal test to confirm
  • In Ontario, we do a treponemal test to screen (CMIA), then repeat it with a more specific treponemal test (TPPA) alongside RPR

Direct visualization

  • Darkfield microscopy
    • Chancre cleaned and smear obtained
    • Smear must be visualized immediately
    • Sensitivity decreases with duration
  • Smear for fluorescent monoclonal antibody
    • Best to use in primary syphilis

Non-treponemal tests (VDRL/RPR)

  • Veneral Diseases Research Laboratory (VDRL) has been replaced by the rapid plasma reagin (RPR) test
    • Quantitative tests for a non-specific anti-cardiolipin antibody that is produced in syphilitic (and other) infections
  • False positives:
  • Only 50% sensitive in primary, 100% sensitive in secondary
  • Tests will eventually become nonreactive

Treponemal tests

  • More specific and sensitive, but more expensive
  • False positives: lupus and other autoimmune disorders, Lyme disease, and other treponemal infections
  • Remain positive for life
  • Four main tests:
    • Fluorescent treponemal antibody absorption (FTA-Abs): Essentially the gold standard
    • Chemoluminescnence microparticle immunoassay (CMIA or CLIA): the screening test used in Ontario. Often used as a screening test as it is an easily-automated immunoassay and is more sensitive and specific than RPR.
    • Treponema pallidum Particulate Agglutination assay (TPPA): a modification of the TPHA. Used as the confirmatory test (alongside RPR) used in Ontario.
    • T. pallidum hemagglutination assay (TPHA): very old test.
    • T. pallidum enzyme immunassay (TP-EIA)

Interpretation of serology

CMIA screen RPR TPPA Interpretation
Non-reactive β€” β€” Negative result; or early syphilis (consider repeat in 4 weeks)
Reactive Reactive Reactive Recent or prior syphilis infection
Reactive Non-reactive Reactive Recent or prior syphilis infection
Reactive Non-reactive Non-reactive False positive; or early syphilis, previously treated, or late latent (repeat in 4 weeks)
Reactive Non-reactive Indeterminate Inconclusive result; false positive, early syphilis, old treated syphilis, or old untreated syphilis (repeat in 4 weeks)
Reactive Reactive Non-reactive Inconclusive result; false positive, early syphilis, old treated syphilis, or untreated syphilis (repeat in 4 weeks)
Reactive Reactive Indeterminate Recent or prior syphilis infection

Treatment

Primary, secondary, and early latent

  • Benzathine penicillin G 2.4 million units IM once, divided between two buttocks
  • Alternative (penicillin allergy): doxycycline 100mg BID for 2 weeks
  • Alternative (penicillin allergy and pregnancy): penicillin desensitization or azithromycin

Late latent and tertiary (excluding neurosyphilis)

  • Benzathine penicillin G 2.4 million units IM q1week for 3 weeks
  • Alternative (penicillin allergy): doxycycline for 30 days
  • Monitor response with RPR titres, which should drop 4-fold within 6 months

Tertiary neurosyphilis

  • Penicillin G 4 million units IV q4h for 10 to 14 days
  • Often followed by at least one dose of IM benzathine penicillin, sometimes weekly for 2-3 weeks

Congenital syphilis

  • If <1 month of age: crystalline penicillin G 50 kU/kg IV q12h for the first week of life and q8h thereafter, for a total of 10 days
  • If ≥1 month of age: crystalline penicillin G 50,000 units/kg IV every 6 hours for 10-14 days
    • If there is no neurological involvement, then you can consider benzathine penicillin G 50 kU/kg (max 2.4 MU) IM weekly for 3 weeks

Further Reading

References

  1. ^  NicolΓ² Girometti, Muhammad H Junejo, Diarmuid Nugent, Alan McOwan, Gary Whitlock, Keerti Gedela, Sheel Patel, Tara Suchak, Victoria Tittle. Clinical and serological outcomes in patients treated with oral doxycycline for early neurosyphilis. Journal of Antimicrobial Chemotherapy. 2021;76(7):1916-1919. doi:10.1093/jac/dkab100.

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