Syphilis
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Case 1: A 35-year-old man with no past medical history presents with a painless ulcer in his right groin following a reported unprotected sexual encounter one week prior with a new partner. The patient reported a history of treated syphilis five years ago. FTA Ab is positive, and RPR is negative. What is your diagnostic approach?
Explanation :
Correct Answer: D) Both B and C
This is likely a false early positive RPR. Recommend empiric treatment versus repeat RPR in a couple of weeks. In cases of early syphilis, the time to positivity of Rapid Plasma Reagin (RPR) and Fluorescent Treponemal Antibody Absorption (FTA-ABS) tests can vary based on the stage of the infection and the individual's immune response.
RPR test is a non-treponemal test that detects antibodies produced by the body in response to the syphilis infection. It typically becomes positive within 3 to 6 weeks after the initial infection, but it can sometimes show false-negative results in very early stages (primary syphilis). This is because the antibody levels may not have reached detectable levels yet.
On the other hand, FTA-ABS is a treponemal test that detects specific antibodies against the bacterium that causes syphilis. It usually becomes positive a bit later in the course of the infection compared to RPR, around 4 to 8 weeks after infection. FTA-ABS is more specific than RPR and remains positive even after successful treatment of syphilis.
In some cases of early syphilis, there can be a discrepancy between the timing of RPR and FTA-ABS positivity, leading to a possible false early negative RPR result. This emphasizes the importance of considering both tests together and, in some cases, conducting additional confirmatory tests if there is clinical suspicion of syphilis despite initial negative results.
Correct Answer: D) Both B and C
This is likely a false early positive RPR. Recommend empiric treatment versus repeat RPR in a couple of weeks. In cases of early syphilis, the time to positivity of Rapid Plasma Reagin (RPR) and Fluorescent Treponemal Antibody Absorption (FTA-ABS) tests can vary based on the stage of the infection and the individual's immune response.
RPR test is a non-treponemal test that detects antibodies produced by the body in response to the syphilis infection. It typically becomes positive within 3 to 6 weeks after the initial infection, but it can sometimes show false-negative results in very early stages (primary syphilis). This is because the antibody levels may not have reached detectable levels yet.
On the other hand, FTA-ABS is a treponemal test that detects specific antibodies against the bacterium that causes syphilis. It usually becomes positive a bit later in the course of the infection compared to RPR, around 4 to 8 weeks after infection. FTA-ABS is more specific than RPR and remains positive even after successful treatment of syphilis.
In some cases of early syphilis, there can be a discrepancy between the timing of RPR and FTA-ABS positivity, leading to a possible false early negative RPR result. This emphasizes the importance of considering both tests together and, in some cases, conducting additional confirmatory tests if there is clinical suspicion of syphilis despite initial negative results.
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Case 2: A 20-year-old man with past medical history HIV, well controlled on B/F/TAF, presents with a rash on palms and soles of hands and feet, fevers, and generalized fatigue for three days. RPR is negative. FTA ab is positive. The patient denies any known history of syphilis. What is your diagnostic approach?
Explanation :
Correct Answer: C) Recommend dilution of serum sample to rule out prozone effect
The prozone effect, also known as the "hook effect," can occur in syphilis testing when there is an excess of antibody present in the serum sample. This excess of antibody can lead to a false-negative result in tests like the Rapid Plasma Reagin (RPR) test.
In the prozone effect, the high concentration of antibodies overwhelms the test system, preventing the formation of visible antigen-antibody complexes. As a result, the traditional agglutination reaction that the RPR test relies on for detection is inhibited, leading to a negative result even when the patient is actually infected with syphilis.
To address the prozone effect in syphilis testing, dilution of the serum sample can be performed to reduce the antibody concentration and allow for the formation of antigen-antibody complexes for proper detection. It's essential to be aware of the prozone effect and consider dilution steps when interpreting syphilis test results, especially if there is a high clinical suspicion of syphilis despite a negative RPR result.
Correct Answer: C) Recommend dilution of serum sample to rule out prozone effect
The prozone effect, also known as the "hook effect," can occur in syphilis testing when there is an excess of antibody present in the serum sample. This excess of antibody can lead to a false-negative result in tests like the Rapid Plasma Reagin (RPR) test.
In the prozone effect, the high concentration of antibodies overwhelms the test system, preventing the formation of visible antigen-antibody complexes. As a result, the traditional agglutination reaction that the RPR test relies on for detection is inhibited, leading to a negative result even when the patient is actually infected with syphilis.
To address the prozone effect in syphilis testing, dilution of the serum sample can be performed to reduce the antibody concentration and allow for the formation of antigen-antibody complexes for proper detection. It's essential to be aware of the prozone effect and consider dilution steps when interpreting syphilis test results, especially if there is a high clinical suspicion of syphilis despite a negative RPR result.
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Case 3: A 28-year-old woman who is 13 weeks pregnant, asymptomatic, presents with positive FTA-Ab, RPR 1:2. She is penicillin allergic. She reports that the penicillin reaction was hives ten years ago. She had a history of syphilis five years ago and was treated with 14 days of doxycycline. RPR initial titer was 1:64, and her last known titer was 1:1 three years ago. What is your next diagnostic approach?
Explanation :
Correct Answer: B) Repeat RPR titer in 2-4 weeks, this is likely serofast state
Titers may not seroconvert to nonreactive result and remain persistently reactive, consistent with serofast state. Since this is a one-dilution change, this would not be considered a failure or necessarily a reinfection. Because of her pregnancy, it would be reasonable to test for PCN allergy and, if negative, retreat or desensitize to PCN and treat empirically.
An alternative approach would be to repeat titers in 2-4 weeks to see if there is any change.
Serofast state in syphilis refers to a condition where the serological tests for syphilis remain positive even after appropriate treatment has been administered, and the patient's clinical symptoms have resolved. This can happen especially in cases of treated late syphilis.
In the serofast state, the Rapid Plasma Reagin (RPR) levels may not change or may show only minimal fluctuations. This lack of decline in RPR titers does not necessarily indicate treatment failure or active infection. Instead, it could be due to persistent levels of non-treponemal antibodies in the blood, which may remain detectable even after successful treatment.
Correct Answer: B) Repeat RPR titer in 2-4 weeks, this is likely serofast state
Titers may not seroconvert to nonreactive result and remain persistently reactive, consistent with serofast state. Since this is a one-dilution change, this would not be considered a failure or necessarily a reinfection. Because of her pregnancy, it would be reasonable to test for PCN allergy and, if negative, retreat or desensitize to PCN and treat empirically.
An alternative approach would be to repeat titers in 2-4 weeks to see if there is any change.
Serofast state in syphilis refers to a condition where the serological tests for syphilis remain positive even after appropriate treatment has been administered, and the patient's clinical symptoms have resolved. This can happen especially in cases of treated late syphilis.
In the serofast state, the Rapid Plasma Reagin (RPR) levels may not change or may show only minimal fluctuations. This lack of decline in RPR titers does not necessarily indicate treatment failure or active infection. Instead, it could be due to persistent levels of non-treponemal antibodies in the blood, which may remain detectable even after successful treatment.
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Case 4: An 85-year-old woman with past medical history of diabetes, hypertension, coronary artery disease is referred to you after workup for acute worsening mental status over the past year. Laboratory testing reveals positive FTA-Ab and RPR 1:1. She does not recall ever being treated for syphilis in the past, but she is confused and unable to provide an adequate history. What is your diagnostic approach?
Explanation :
Correct Answer: B) Treat empirically for neurosyphilis or pursue lumbar puncture
A lumbar puncture in an elderly patient with altered mental status would be indicated if the FTA antibody test was positive and the RPR (rapid plasma reagin) test was 1:1 in order to confirm or rule out neurosyphilis. These test results suggest a prior diagnosis of syphilis, based on the positive FTA antibody test.
Given the potentially severe consequences of untreated neurosyphilis, prompt diagnosis and treatment are essential in this scenario. The results of the lumbar puncture, along with clinical evaluation, will help determine the appropriate management plan for the patient.
Correct Answer: B) Treat empirically for neurosyphilis or pursue lumbar puncture
A lumbar puncture in an elderly patient with altered mental status would be indicated if the FTA antibody test was positive and the RPR (rapid plasma reagin) test was 1:1 in order to confirm or rule out neurosyphilis. These test results suggest a prior diagnosis of syphilis, based on the positive FTA antibody test.
Given the potentially severe consequences of untreated neurosyphilis, prompt diagnosis and treatment are essential in this scenario. The results of the lumbar puncture, along with clinical evaluation, will help determine the appropriate management plan for the patient.
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Case 4, Part 2: Lumbar puncture shows 2 WBCs, normal glucose, protein 68, and negative CSF VDRL negative. What is the next diagnostic step?
Explanation :
Correct Answer: D) Either A or C
Based on the normal WBCs and negative CSF VDRL, it is unlikely to be neurosyphilis.
If there is still suspicion for neurosyphilis despite the initial negative CSF VDRL test, given the elevated protein in CSF findings, a Fluorescent Treponemal Antibody Absorption (FTA-ABS) test in the CSF can be performed to improve the sensitivity of the diagnosis.
Correct Answer: D) Either A or C
Based on the normal WBCs and negative CSF VDRL, it is unlikely to be neurosyphilis.
If there is still suspicion for neurosyphilis despite the initial negative CSF VDRL test, given the elevated protein in CSF findings, a Fluorescent Treponemal Antibody Absorption (FTA-ABS) test in the CSF can be performed to improve the sensitivity of the diagnosis.
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Case 5: A 28-year-old man with past medical history of newly diagnosed HIV, recently started on DTG/TDF/FTC, presents with secondary syphilis and RPR titer of 1:32. He is treated with one dose of Benzathine PCN 2.4 million units. Six months later, he comes for a follow-up, and the RPR titer is now 1:128. The patient is adamant that he was not reexposed and has not had any sexual encounters since he was last treated for syphilis. His only complaint at the follow-up visit was a headache. Denies any fevers, rash, hearing, or visual changes. What is your diagnostic approach?
Explanation :
Correct Answer: C) Recommend lumbar puncture to rule out neurosyphilis versus empiric treatment with 14 days of IV penicillin for neurosyphilis
A 4-fold increase in titer post treatment indicates that the initial treatment was not effective in clearing the infection and any neurological symptoms should prompt the workup to rule out neurosyphilis. Asymptomatic or symptomatic CNS infavsion can occur in patients with primary, secondary, latent, or tertiary disease, so presence of any neurological symptoms should prompt workup to rule out CNS disease.
Correct Answer: C) Recommend lumbar puncture to rule out neurosyphilis versus empiric treatment with 14 days of IV penicillin for neurosyphilis
A 4-fold increase in titer post treatment indicates that the initial treatment was not effective in clearing the infection and any neurological symptoms should prompt the workup to rule out neurosyphilis. Asymptomatic or symptomatic CNS infavsion can occur in patients with primary, secondary, latent, or tertiary disease, so presence of any neurological symptoms should prompt workup to rule out CNS disease.
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Case 6: A 45-year-old man with past medical history of newly diagnosed HIV, recently started on B/F/TAF five weeks ago, presents to the office with fevers, rash, headache, and intermittent blurry vision with associated floaters in his left eye for the past two days. His baseline RPR was negative one month ago. He has been compliant with his ARV. His CD4 count is 458, and his HIV viral load is now undetectable. Physical exam is notable for temperature of 100.8, diffuse maculopapular rash on the palms of his hands and the soles of his feet. He has reduced visual acuity in the L eye. His alkaline phosphatase is elevated at 350. FTA-Ab is positive and RPR is 1:256. Ophthalmology is consulted and left-sided posterior uveitis is reported. Lumbar puncture shows 4 WBCs, protein is normal, and CSF VDRL is negative. How do you approach treatment in this patient?
Explanation :
Correct Answer: A) Treat with 14 days of IV penicillin
The patient presents with findings consistent with secondary syphilis. In cases of serological or clinical evidence of syphilis, clinicians must assess for potential neurological, ocular, and otic manifestations. If ocular or otic symptoms are present without neurological manifestations, a lumbar puncture may not be necessary. However, patients exhibiting neurological signs should be promptly referred for a lumbar puncture. It is noted that a considerable proportion of individuals with ocular syphilis (up to 40%) and an even higher percentage of those with otic syphilis (>90%) may have a normal cerebrospinal fluid (CSF) examination. The hepatic profile in classic syphilitic hepatitis typically reveals a modest elevation in alkaline phosphatase levels while aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels remain within normal limits. He has a positive RPR, rash, and fever consistent with secondary syphilis. With optic or otic syphilis (even in the absence of neurosyphilis), patients should be treated with 14 days of intravenous penicillin.
Correct Answer: A) Treat with 14 days of IV penicillin
The patient presents with findings consistent with secondary syphilis. In cases of serological or clinical evidence of syphilis, clinicians must assess for potential neurological, ocular, and otic manifestations. If ocular or otic symptoms are present without neurological manifestations, a lumbar puncture may not be necessary. However, patients exhibiting neurological signs should be promptly referred for a lumbar puncture. It is noted that a considerable proportion of individuals with ocular syphilis (up to 40%) and an even higher percentage of those with otic syphilis (>90%) may have a normal cerebrospinal fluid (CSF) examination. The hepatic profile in classic syphilitic hepatitis typically reveals a modest elevation in alkaline phosphatase levels while aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels remain within normal limits. He has a positive RPR, rash, and fever consistent with secondary syphilis. With optic or otic syphilis (even in the absence of neurosyphilis), patients should be treated with 14 days of intravenous penicillin.
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