A.
Positive nontreponemal/Positive treponemal test
The combination of a positive screening nontreponemal test and a
positive treponemal confirmatory test supports a diagnosis of syphilis. For
patients without a history of syphilis, these results are consistent with a new
infection that must be treated. However, for patients with a history of treated
syphilis in the past, the interpretation is sometimes less clear, and the need
for treatment depends upon the patient's clinical presentation and the
nontreponemal titer. On rare occasion, both nontreponemal and treponemal tests
can be falsely positive. This can result from a different infectious etiology
(eg, endemic treponematoses such as yaws, bejel, and pinta), or a noninfectious
condition affecting immune function.
1.
Patients without
a history of syphilis
A diagnosis of syphilis is made when both
nontreponemal and treponemal tests are reactive. To determine the appropriate
treatment, patients should be assessed for the stage of disease.
l
Symptomatic persons can be
staged as having primary, secondary, or tertiary syphilis.
l
Asymptomatic persons have
either early latent or late latent syphilis
2.
Patients with a
history of treated syphilis
Although treponemal tests usually remain positive
after infection, titers of nontreponemal assays decline following successful
therapy, and usually revert to nonreactive over time. Thus, for patients with a
history of treated syphilis, the presence of a positive nontreponemal test
indicates a new infection, an evolving response to recent treatment, treatment
failure, or the presence of a serofast state.
To properly interpret the results of the serologic
test, titers should be compared with the patient's prior post-treatment titer.
If possible, titers should be compared using the same test methodology.
l
A new syphilis infection is
diagnosed when quantitative testing using a nontreponemal test reveals a
fourfold or greater increase in titer from the individual's prior
post-treatment test, provided the same test type was used.
l
Patients are considered to be
serofast if they have a persistently reactive nontreponemal test despite
adequate treatment, generally at a low titer.
l
All others would be considered
treatment failures. The appropriate management of such patients is discussed
elsewhere.
For patients
who were treated and were lost to follow-up, distinguishing new from old
infection must be based upon clinical as well as serologic findings. We
consider a patient to have a new infection if the patient with reactive
serologic tests has any of the following:
l
A history of being previously
treated with an appropriate regimen and a documented response to that treatment.
l
Clinical manifestations of
either primary or secondary syphilis.
l
History of new risk factors.
l
An adequate response following
treatment of the possible reinfection (eg, a fourfold decline in RPR titer)
※ ※ ※
B. Positive nontreponemal/Negative treponemal
In laboratories using the nontreponemal test for screening, patients
who have a positive nontreponemal test followed by a negative treponemal test
are generally considered to have a false positive syphilis result. Although
false positive test results tend to be of low titer, the level of the titer
alone does not reliably help the clinician differentiate between a true or
false positive result. Thus, a reactive nontreponemal test must be followed
with specific treponemal testing to rule out active syphilis.
False positive tests are particularly common during pregnancy. In
addition, false positive nontreponemal test results can be related to an acute
event, such as an acute febrile illness (eg, endocarditis, rickettsial disease)
or recent immunization. Test abnormalities attributed to these conditions are
usually transitory and typically last for six months or less. Other etiologies
include chronic conditions, such as autoimmune disorders (particularly systemic
lupus erythematosus); intravenous drug use; chronic liver disease; and
underlying HIV disease.
※ ※ ※
C. Positive treponemal/Negative nontreponemal test
Patients who are tested for syphilis using an initial
treponemal-specific screening strategy can have discordant results, ie, a
positive treponemal test followed by a negative nontreponemal test. This
scenario is typically seen in patients with a history of successfully treated
syphilis, and no further evaluation or treatment of such patients is needed.
For patients without a history of treated syphilis, discordant
results can lead to confusion regarding patient management. For such patients,
we first perform a directed history and physical examination to evaluate for risk
factors and evidence of early syphilis since these patients may have a false
negative nontreponemal test.
l
If a chancre or rash is
present, a nontreponemal test should be repeated to assess for seroconversion,
and empiric treatment should be administered at the same patient encounter. The
response to treatment should be monitored clinically and serologically.
l
If no signs or symptoms of
syphilis are present, we counsel patients regarding a possible diagnosis of
late latent syphilis.
We then perform a second treponemal test, preferably one that
targets different antigens than the initial screening test.
ü
If the repeat treponemal test
is also positive, we recommend treatment for late latent syphilis.
ü
If a repeat treponemal test is
negative, we do not suggest any further evaluation, and we consider the original
test a false positive.
※ ※ ※
D. Negative
nontreponemal test in early syphilis
For most patients who are tested for syphilis using an initial
nontreponemal test, a negative result excludes the diagnosis of active syphilis
and no further testing is needed. However, patients with clinical signs and
symptoms of early syphilis (eg, ulcer, rash) may have a false negative test
result. For such patients, a false negative test is typically the result of
testing prior to antibody formation or secondary to a prozone effect. A false
negative test can also be seen in those who received early empiric therapy.
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