Flashcards in syphilis: 2nd time's a charm Deck (35):
Congenital syphilis (CS, a severe mutilating form of the disease):
when most likely??
Fetal response to infection
detected when ??
via placenta *at any time during pregnancy*, but fetal infection in utero occurs most frequently with mother in *early stage of infection*.
-fetal response detected 18-20th wk of development when fetal immune system becomes operational.
CS infected fetus mostly likely will be ??
stillborn (significant mortality).
if live birth: symptomatic, or Perinatal/infantile/early congenital form (asymptomatic, most)
life birth CS: if Symptomatic newborns are??
-are often born premature and usually die shortly after birth.
-Manifest with hepatosplenomegaly, skeletal abnormalities, pneumonia, pemphigus syphiliticus (a bullous skin disease)
Perinatal/infantile/early congenital form: most are born without clinical evidence of disease but would be ??
STORCH test positive
-inf. involves multiple organs with lesions present in virtually any organ (esp. skin, bone, CNS, liver, kidney).
-Symptoms appear before age 2 (usually 34m post birth), are similar to secondary syphilis in adults, and include: macpap., desquam. rash, condylomata lata, persistent mucopurulent rhinitis/AKA snuffles (infection of the nasal mucosa) and S&S consistent with lesions involving one or more organs
CS: Latent period: ??
If the patient survives the first 6-12 months after birth, enters the latent period (usually 5-15 y), then late congenital syphilis occurs
Late congenital form (aka stigmata): which occurs ?? after birth. Appearance is somewhat like ??
tertiary syphilis in adults
Late congenital form: Stigmata AKA "Hutchinson‘s triad"
-VIIIth nerve deafness
-Corneal ulcers and opacities and Interstitial keratitis.
-Hutchinson‘s teeth (centrally notched and widely spaced, peg-shaped, upper central incisors).
Late congenital form: Other Stigmata:
Parrot’s Frontal Bossing (skull), Bulldog jaw (prominent mandible), Higoumenakia sign (unilateral irregular enlargement of the sternoclavicular portion of the clavicle secondary to periostitis), Mulberry molars (6th year molars with multiple poorly developed cusps), Saddle nose (depression of nasal bridge due to destruction of the
nasal septum & palate - gumma), perforation of palate, saber shins (anterior tibial bowing), Clutton's joints (due to inflammation of the knee joints).
Late congenital form: Other Stigmata: 2
Skin rhagades (radial scars) plus petechiae, haemorrhagic vesicles, bullae (pemphygis syphiliticus), erythematous macular, papulosquamous, annular, or polymorphous eruptions, optic nerve atrophy, neurosyphilis (tabes dorsalis and general paresis may develop as in adults) but rarely CV involvement.
syphilis dx: often on ??
clinical findings (S/S) and a history of sexual contact with
a known infected individual in conjunction with laboratory test
-The organism is extremely fastidious and cannot be cultured in vitro or in vivo.
Diagnosis by microscopic detection of T. pallidum cells in the primary and/or secondary lesions (scrapings, lesion material, or exudate):
-*not observable in the blood* due to low level spirochetemia.
-*Darkfield microscopy – Direct observation of the spirochete*
-*Fluorescent microscopic examination of specimens with DFA for Treponema pallidum (DFA-TP; a fluorescein-labeled-T. pallidum specific- monoclonal antibody)*
*Used to dx 1o and 2o syphilis*
how can T. pallidum be misdx??
If lesions are in mouth, mucous membranes, anus, etc., normal spirochetal flora may contaminate lesion material collected from the site leading to misdiagnose if the normal spirochetal flora are mistaken for T. pallidum
Two types of antibodies are produced in response to infection that both are the basis of the serological assays for T. pallidum
Treponemal-specific and Non-treponemal-specific Ab
Non-treponemal antibody tests (NTT) detect ??
*Reagin (both IgM and IgG antibodies)* in the serum of persons infected with T. pallidum. These antiphospholipid antibodies serologically/immunologically cross reacts with cardiolipin (a phospholipid extracted
from beef heart)
Reagin (both IgM and IgG antibodies) used in these screening tests:
-Venereal Disease Research Lab (VDRL)
-Rapid Plasma Reagin (RPR)
-Enzyme Immunoassay (EIA) is replacing the VDRL/RPR tests.
characteristics of NTT Reagin screening tests
when do titers decline??
All 3 tests possess ??
-flocculation (agglutination) slide tests that are easy to perform, cheap, and widely used
-100% positive by end 4 week after chancre first appears (during 1o syphilis). Titers peak during 2o stage, then may gradually decline and even become negative in late latent syphilis but can persist for years in untx persons.
-high sensitivity but low specificity
Uses of screening tests:
To diagnose primary -> early latent syphilis.
-RPR (only) is routinely used to monitor efficacy of tx (In most pts after the initiation of effective tx, RPR usually reverts to negative or near-negative values in 1-2 y)
-VDRL (only) to dx neurosyphilis
Treponemal-specific antibody tests detect the presence of ??
Used in ??
IgM and/or IgG antibodies (specific for a T. pallidum Ag) in the serum of persons infected with T. pallidum
confirming test for syphilis
Treponemal-specific antibody tests include:
-Fluorescent Treponemal Antibody test after Absorption (FTA-Ab). Pt.'s adsorbed serum is mixed with non-viable pathogenic treponemes and then fluorescein-labeled-anti-human IgG is added, observed microscopically.
-Microhemagglutination assay for T. pallidum [MHA-TP] and hemagglutination assay for T. pallidum [TP-HA] /hemagglutination treponemal test for Syphilis [HATTS]
-Enzyme Immunoassay (EIA) is replacing other confirming tests.
Treponemal-specific antibody tests are ??
highly specific, sensitive, reliable and are positive early in 1o syphilis
Uses of (Treponemal-specific) confirming tests:
-confirm screening tests RPR, EIA + rxns (to rule out BFP)
-to dx neurosyphilis (FTA-ABS CSF), esp. if VDRL is neg
-Used to dx late latent or tertiary syphilis because the NTT results may be negative
-Not used to assess therapy because treponemal specific-Ab are present in all 3 stages of disease regardless of tx; Ab titers are unaffected by tx.
Congenital syphilis is extremely difficult to dx and may incorporate ??
clinical findings with specialized serological tests and comparing infant and maternal antibody titers
tx of choice for all stages and conditions of syphilis: ??
a long-acting Benzathine penicillin G administered IM.
Tx is based on stage of disease:
length of Benzathine PCN G tx regimen is ??
Prognosis for 1o or 2o syphillis with tx?? w.out??
3o syphilis px?
extended in latter stages of the disease (e.g. late-
excellent w. tx, w.out: 33% of all pts with 2o syphillis will progress to late/3o syphilis and die. (Late/3o is notoriously refractory to abx therapy)
-In the absence of adequate treatment, pt may progress to further stages
what is used in patients with hypersensitivity to penicillin??
Macrolide (erythromycin, azithromycin), Tetracyclines (tetracycline, doxycycline), and ceftriaxone
(but treatment failures occur)
how does resistance develop to alternative T. pallidum abx??
An A → G mutation in the 23S ribosomal RNA genes confers azithromycin resistance in clinical strains in localities in the US and Europe.
-occurs by spontaneous mutation, not by spread of a single resistant strain.
tx of Congenital syphilis:
Prognosis for a patient with congenital syphilis ??
tx the gravid female with benzathine penicillin for *more than 1 month prior to birth* is adequate for fetal infection if the appropriate serologic response is observed in the mother.
-Prognosis for a patient with congenital syphilis is poor unless treated early enough
-endotoxic shock-like response, probably the result of dead or dying
treponemes released into the peripheral blood
-Often occur during tx, warn pt!
-Occurs 2-12 (1 -4)h post initiation of tx.
-s/s include: fever, chills or rigors, malaise, headache, myalgia and tachycardia
more Jarisch-Herxheimer reaction characteristics
-Rarely severe or fatal with syphilis tx
-response does not affect efficacy or tx course
-does not predict if tx will or will not be effective
-nature of tx (antibiotics or which antibiotic or even if using an arsenical) is irrelevant to if response occurs or not
A more significant systemic response (Jarisch-Herxheimer reaction) occurs when treating persons in early stages of syphilis but response can result in ?? if person tx is in late stages of syphilis
CNS or cardiovascular damage
The Jarisch-Herxheimer reaction in relapsing fever has been controlled anti-TNF-α antibodies??
-tx or prevented with NSAIDs for 24-48h starting with administration of
-Severe reactions respond well to prednisone
Syphilis Treatment follow-up is essential. Do serology (RPR) when ??
3, 6, 12, 24 months post treatment.
Expect declining antibody titers over a 1-2 year period following tx
congenital syphilis px
Poor prognosis unless very early treatment. Untx: 25-50% mortality and 50% of survivors have serious sequelae (which may occur even with effective treatment)
Sexually transmitted syphilis px
With tx prognosis is excellent.
Without: about 33% of all
syphilis patients develop 3o form of disease, with an associated elevated mortality