Harrison's PodClass provides engaging, high-yield discussions of key topics commonly found on rotational and board exams in internal and family medicine.
Harrison's PodClass provides engaging, high-yield discussions of key topics commonly found on rotational and board exams in internal and family medicine.
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[Dr. Shapiro] This is Dr. Samantha Shapiro, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. And now, onto the episode.
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[Dr. Handy] Hi everyone, welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy.
[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine.
[Dr. Handy] Welcome to episode 107, a 43-year-old with eye pain and visual changes.
[Dr. Wiener] Cathy, today's patient is a 43-year-old man, who has known he has HIV for the last year. He is on highly active antiretroviral treatment, and recent labs revealed a CD4 count of 263. Today, he presents to the clinic and reports visual changes and eye pain over the last month. On examination, his vitals are normal, but his visual acuity is diminished, and he has bilateral red eyes. His neurological examination shows normal temperature sensation, proprioception, deep pain sensation, normal reflexes, and normal gait. So, the only abnormalities are in his eyes.
[Dr. Handy] This is somebody who I would refer to ophthalmology for a more in-depth examination, given those are his only symptoms.
[Dr. Wiener] Okay, well, your ophthalmology colleague does examine him and tells you that he has uveitis. So, let's stop here for a minute and tell me a little bit about uveitis.
[Dr. Handy] Right, just to do a brief review of the eye, there are three layers. The outer layer is the sclera and the cornea, the inner layer is the retina, and the middle layer is the uvea. The uvea contains the iris, ciliary body, and choroid. Uveitis is inflammation of the uvea, and most commonly occurs in the anterior portion between the back of the cornea and in front of the lens. Symptoms of this form of uveitis can include eye pain, red eyes, blurred vision, and sensitivity to light, which this patient is experiencing.
[Dr. Wiener] So, it sounds like our patient has anterior uveitis, and presumably, our ophthalmology colleague did a slit lamp examination to diagnose that. What's on your differential of anterior uveitis?
[Dr. Handy] Yeah, there are a number of systemic illnesses that can present with anterior uveitis, and these include inflammatory diseases, so examples of this are sarcoidosis, ankylosing spondylitis, juvenile idiopathic arthritis, inflammatory bowel disease, psoriasis, reactive arthritis, and Behcet's disease. Anterior uveitis can also be associated with some infections, so on that list, I would think of herpes infections, syphilis, Lyme disease, onchocerciasis, tuberculosis, and leprosy. Now, although anterior uveitis can occur in conjunction with many diseases, no cause is found to explain the majority of cases.
[Dr. Wiener] So, that's a great review, and I have not realized that the differential of anterior uveitis is so wide. Let's go to the question. So, the question asks, in this patient with the findings of anterior uveitis, which of the following tests should you do next? Option A. is a lumbar puncture for bacterial cultures, cell count, protein, and glucose; option B. is a lumbar puncture for RPR, cell counts, protein, glucose, and serum for RPR; option C. is a lumbar puncture for VDRL, cell count, protein, glucose, and serum for RPR; option D. is an MRI of the brain; and option E. is serum for RPR and VDRL.
[Dr. Handy] Okay, so first, let's recall that this patient has well-controlled HIV. We don't know his history or prior labs, but I'm sure we're worried about syphilis, which I mentioned was on the differential as a potential infectious cause of anterior uveitis. Now, the presentation here could be a manifestation of neurosyphilis. So, the question is really asking about like what diagnostic procedures you need for that. So, the answer is B., he needs a lumbar puncture with testing for RPR, cell count, protein, and glucose, and then he should also have a serum RPR.
[Dr. Wiener] Okay, well, there's lots to talk about. The only difference between B. and C., options B. and C. is whether or not to get a CSF-RPR or CSF-VDRL. So, you're going to have to tell me that, a little bit more about that.
[Dr. Handy] So all patients who you suspect are infected with treponema pallidum or syphilis, or potentially infected, who have signs or symptoms either of neurologic disease, so that would include like meningitis symptoms or hearing loss, or if they have any evidence of eye disease like in this patient, which would include uveitis, they should have a CSF examination regardless of the disease stage. So, how do you detect it? You need to look at the CSF for mononuclear pleocytosis, so that would be more than five white blood cells, increased protein concentration, which would be more than 45 mg/dL, or a CSF-VDRL reactivity. Elevated CSF cell count and protein concentration are not specific for neurosyphilis and may be confounded by HIV co-infection. Because CSF pleocytosis may also be due to HIV, some studies have suggested using a CSF white cell cut-off of 20 cells per microliter as a diagnostic of neurosyphilis in HIV-infected patients with syphilis.
[Dr. Wiener] What about the VDRL versus the RPR in the CSF? You mentioned VDRL.
[Dr. Handy] Yeah, sorry. So, CSF-VDRL test is highly specific, and when reactive, is considered diagnostic of neurosyphilis. However, this test is insensitive and may be non-reactive even in cases of symptomatic neurosyphilis. The RPR is the better test and should not be substituted by the VDRL test for CSF examination. In addition, he should have his serum tested for syphilis, partially as the RPR can be followed clinically as a sign of appropriate response to treatment. The RPR test is easier to perform and uses unheated serum or plasma, and it's the test of choice for rapid serologic diagnosis in the clinical setting.
[Dr. Wiener] So again, we've already established that this patient needs the CSF-RPR, not VDRL, and then all the usual studies we do with an LP, but this is a two-part question. It goes on to ask, assuming the test you ordered is positive, and you've diagnosed neurosyphilis, which of the following is the appropriate treatment for his condition? Option A. is aqueous crystalline penicillin G, 24 million units daily for 14 days; option B. is benzathine penicillin G, 24 million units IV daily for 14 days; option C. is benzathine penicillin G, 2.4 million units, IM weekly for four weeks; option D. is ceftriaxone, 2 grams IV daily for seven days; and option E. is doxycycline, 100 milligrams PO twice daily for 14 days.
[Dr. Handy] Okay, so just to tell you the answer, it's A. He should get aqueous crystalline penicillin G, 24 million units IV daily, which is a continuous infusion, and you do that for 14 days.
[Dr. Wiener] What's wrong with the other options?
[Dr. Handy] So the hard part of treatment is picking a drug that will kill the treponema in the nervous system. So, benzathine penicillin G, even at high doses, does not produce treponemacidal concentrations of penicillin G in the CSF. So that should not be used for treatment of neurosyphilis. Asymptomatic neurosyphilis may relapse as symptomatic disease after treatment with benzathine penicillin, and the risk of relapse may be higher in HIV-infected patients. Both symptomatic and asymptomatic neurosyphilis should be treated with aqueous penicillin. Administration of either IV aqueous penicillin G or of IM aqueous procaine penicillin G, plus oral probenecid in recommended doses is thought to ensure treponemacidal concentrations of penicillin G in the CSF.
[Dr. Wiener] And what about the clinical response to these therapies?
[Dr. Handy] The clinical response to penicillin therapy for meningeal syphilis is dramatic but the treatment of neurosyphilis with existing parenchymal damage may only arrest disease progression. No data suggests that additional therapy is beneficial after treatment for neurosyphilis.
[Dr. Wiener] Okay, so you mentioned a couple of other penicillins, the benzathine, et cetera, et cetera, let's just review briefly about how you use them for the various stages of syphilis.
[Dr. Handy] All right, so although early syphilis, which, when I say that, I mean like primary syphilis or secondary syphilis without neurologic involvement in early latent syphilis, so that's effectively treated with a single dose of intramuscular benzathine penicillin G, and late latent cardiovascular or benign tertiary syphilis are effectively treated with three weekly doses of IM benzathine penicillin G. This has not produced detectable concentrations of penicillin in the CSF, like I mentioned, so it's not recommended for the treatment of neurosyphilis like we think this patient has.
[Dr. Weiener] So, many of our patients report allergies to penicillin, what do you do in that situation?
[Dr. Handy] In patients with confirmed penicillin allergy, desensitization and treatment with penicillin are still recommended. The use of antibiotics other than penicillin for the treatment of neurosyphilis has not been studied. Although limited data suggests that ceftriaxone may be used but again, old-fashioned penicillin is the answer.
[Dr. Wiener] Okay, so there are a lot of teaching points in this case. First off, let's remember that anterior uveitis, which has a broad differential, requires a slit lamp examination to really diagnose definitively. Uveitis, or anterior uveitis may be a manifestation of neurosyphilis, and that requires a lumbar puncture and serum RPR testing to diagnose. The treatment of neurosyphilis remains aqueous penicillin, and remembering the various stages of syphilis and the appropriate treatments for syphilis is important for your patient care.
[Dr. Handy] And if you want to learn more about this or review everything we've talked about, you can check out the chapter on syphilis and also the chapter on disorders of the eye.
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[Dr. Shapiro] Thanks for listening to Harrison's Podclass. You can listen to this episode and more on AccessMedicine.com, which includes the complete Harrison's Principles of Internal Medicine text, Harrison's Review Questions, which complement and expand upon the questions in this episode, and much more. AccessMedicine.com may already be available to you via your academic institution. Check it out!
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