Treponema pallidum pallidum: Difference between revisions
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Treponema pallidum pallidum
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*Not seen on standard microscopy; requires darkfield microscopy |
*Not seen on standard microscopy; requires darkfield microscopy |
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− | ==Clinical |
+ | ==Clinical Manifestations== |
− | ===Stages=== |
+ | ===Overview of Stages=== |
*Primary syphilis (incubation period [[Usual incubation period::3 weeks]] [range [[Incubation period range::3 to 90 days]]]) |
*Primary syphilis (incubation period [[Usual incubation period::3 weeks]] [range [[Incubation period range::3 to 90 days]]]) |
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===Latent Syphilis=== |
===Latent Syphilis=== |
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+ | *Defined as asymptomatic and untreated but with positive serology |
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+ | **Can be early latent (<1 year) or late latent (≥1 year) |
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+ | **If unknown duration, late latent is assumed |
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*High rate of relapse of secondary syphilis within the first 1-2 years following infection (but especially within the first year) |
*High rate of relapse of secondary syphilis within the first 1-2 years following infection (but especially within the first year) |
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*Isolated auditory syphilis |
*Isolated auditory syphilis |
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*Isolated optic syphilis |
*Isolated optic syphilis |
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+ | |||
+ | === Congenital Syphilis === |
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+ | |||
+ | * May be either early (<2 years old) or late (≥2 years old) |
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+ | * Classic Hutchison triad is interstitial [[keratitis]], cranial nerve VIII deafness, and abnormal teeth |
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+ | * See [[Congenital syphilis]] for more information |
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==Diagnosis== |
==Diagnosis== |
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− | === |
+ | ===Lumbar Puncture for CSF=== |
− | * |
+ | *Should be done routinely when: |
− | ** |
+ | **Neurological (including optic and auditory) signs or symptoms |
− | ** |
+ | **Failure of serologic response |
− | ** |
+ | **Tertiary syphilis |
− | ** |
+ | **Congenital syphilis |
− | ** |
+ | **In patients with HIV: |
− | *** |
+ | ***CD4 ≤350 |
− | *** |
+ | ***RPR ≥1:32 |
− | * |
+ | *The sample should be sent for cell count and differential, protein, and either VDRL (not RPR) or FTA-Abs |
==Management== |
==Management== |
Revision as of 07:42, 27 August 2020
Background
- Causes syphilis
Microbiology
- Small, slow-growing spirochete
- Not seen on standard microscopy; requires darkfield microscopy
Clinical Manifestations
Overview of 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 (≥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
- Defined as asymptomatic and untreated but with positive serology
- Can be early latent (<1 year) or late latent (≥1 year)
- If unknown duration, late latent is assumed
- 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
Congenital Syphilis
- May be either early (<2 years old) or late (≥2 years old)
- Classic Hutchison triad is interstitial keratitis, cranial nerve VIII deafness, and abnormal teeth
- See Congenital syphilis for more information
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 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 | — | — | 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 |
Lumbar Puncture for CSF
- Should be done routinely when:
- Neurological (including optic and auditory) signs or symptoms
- Failure of serologic response
- Tertiary syphilis
- Congenital syphilis
- In patients with HIV:
- CD4 ≤350
- RPR ≥1:32
- The sample should be sent for cell count and differential, protein, and either VDRL (not RPR) or FTA-Abs
Management
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