0:04

This is Dr. Samantha Shapiro, executive

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editor of Harrison's Principles of Internal

0:09

Medicine. Harrison's Podglass

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is brought to you by McGraw-Hill's Access Medicine,

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the online medical resource that

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delivers the latest trusted content from the

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best minds in medicine. And now,

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on to the episode.

0:28

Hi, everyone. Welcome back to Harrison's Podglass.

0:30

We're your co-hosts. I'm Dr. Kathy Handy.

0:33

And I'm Dr. Charlie Weiner, and we're joining you from

0:35

the Johns Hopkins School of Medicine. Welcome

0:38

to episode 107 of 43-Year-Olds with

0:41

Eye Pain and Visual Changes. Kathy,

0:44

today's patient is a 43-year-old man who's

0:47

known he has HIV for the last year. He

0:50

is on highly active antiretroviral treatment,

0:52

and recent labs revealed a CD4 count

0:55

of 263. Today

0:57

he presents to the clinic and reports visual changes

1:00

in eye pain over the last month. On

1:02

examination, his vitals are normal,

1:04

but his visual acuity is diminished and

1:06

he has bilateral red eyes. His

1:09

neurological examination shows normal temperature

1:11

sensation, proprioception, deep

1:14

pain sensation, normal reflexes,

1:16

and normal gait. So the only abnormalities are in

1:18

his eyes. This is somebody

1:20

who I would refer to ophthalmology for a more

1:23

in-depth examination, given those are

1:25

his only symptoms. Okay.

1:27

Well, your ophthalmology colleague does

1:30

examine him and tells you that he has uveitis.

1:33

So let's stop here for a minute and tell me a little

1:35

bit about uveitis.

1:37

Great. Just to do a brief review of the eye,

1:39

there are three layers. The outer layer

1:41

is the sclera and the cornea. The

1:44

inner layer is the retina and

1:46

the middle layer is the uvia. The

1:49

uvia contains the iris, ciliary

1:51

body, and choroid. Uveitis

1:54

is inflammation of the uvia and most commonly

1:56

occurs in the anterior portion between

1:59

the back of the cornea

1:59

and in front of the lens. Symptoms

2:02

of this form of uveitis can include eye

2:05

pain, red eyes, blurred vision,

2:07

and sensitivity to light which this

2:09

patient is experiencing. So

2:11

it sounds like our patient has anterior uveitis

2:15

and presumably our

2:17

ophthalmology colleague did a slit lamp examination

2:19

to diagnose that. What's

2:22

on your differential of anterior uveitis?

2:24

Yeah there are a number of systemic illnesses that can

2:26

present with anterior uveitis and

2:29

these include inflammatory diseases. So

2:31

examples of this are sarcoidosis,

2:34

ankylosing spondylitis, juvenile

2:36

idiopathic arthritis, inflammatory

2:38

bowel disease, psoriasis,

2:40

reactive arthritis, and Bichette's disease.

2:43

Anterior uveitis can also be associated

2:46

with some infections. So on

2:48

that list I would think of herpes

2:50

infections, syphilis, Lyme

2:52

disease, oncorrhoceriasis,

2:55

tuberculosis, and leprosy. Now

2:58

although anterior uveitis can occur in conjunction

3:00

with many diseases, no cause

3:02

is found to explain the majority of cases. So

3:05

that's a great review and I have not realized that

3:07

the differential of anterior uveitis is so

3:09

wide. Let's go to the question. So

3:12

the question asks in this patient

3:15

with the findings of anterior uveitis, which

3:17

of the following tests should you do next? Option

3:21

A is a lumbar puncture for bacterial cultures,

3:23

cell count, protein, and glucose. Option

3:26

B is a lumbar puncture for RPR,

3:28

cell counts, protein, glucose, and serum

3:31

for RPR. Option

3:33

C is a lumbar puncture for VDRL,

3:35

cell count, protein, glucose,

3:38

and serum for RPR. Option

3:41

D is an MRI of the brain and

3:43

option E is serum for RPR and

3:45

VDRL. Okay,

3:48

so first let's recall that this patient has

3:50

well controlled HIV. We don't know his history

3:52

or prior lapse, but

3:55

I'm sure we're worried about syphilis, which I mentioned

3:57

was on the differential as a potential infectious

4:00

cause of anterior uveitis. Now

4:03

the presentation here could be

4:05

a manifestation of neurosyphilis. So

4:08

the question is really asking about what

4:10

diagnostic procedures you need for that.

4:13

So the answer is B, he needs

4:15

a lumbar puncture with testing for RPR,

4:19

cell count, protein, and glucose,

4:21

and then he should also have a serum RPR.

4:25

Okay, well there's lots to talk about. The

4:27

only difference between B and C, options

4:30

B and C, is whether or not to get a CSFRPR

4:33

or a CSFVDRL. So

4:35

you're gonna have to tell me that. A little bit more about

4:37

that. So all

4:40

patients who suspect are infected with

4:42

treponema pallidum or syphilis

4:45

or potentially infected who have

4:47

signs or symptoms either of neurologic disease,

4:49

so that would include like meningitis

4:52

symptoms or hearing loss, or if

4:54

they have any evidence of eye disease like

4:56

in this patient, which would include uveitis,

4:59

they should have a CSF examination

5:01

regardless of the disease stage. So

5:04

how do you detect it? You need to look at the CSF

5:06

for mononuclear pleocytosis. So

5:08

that would be more than five white blood cells.

5:11

Increased protein concentration, which would

5:13

be more than 45 milligrams per deciliter,

5:16

or CSFVDRL reactivity.

5:19

Elevated CSF cell count and protein

5:21

concentration are not specific for neurosyphilis

5:24

and may be confounded by HIV co-infection.

5:27

Because CSF pleocytosis may also

5:30

be due to HIV some

5:31

studies have suggested

5:32

using a CSF white cell cutoff

5:35

of 20 cells per microliter as a diagnostic

5:37

of neurosyphilis in HIV infected

5:39

patients with syphilis. What

5:41

about the VDRL versus the RPR and

5:43

the CSF? You mentioned VDRL.

5:46

Yeah, sorry. So CSFVDRL

5:49

test is highly specific and when reactive

5:51

is considered diagnostic of neurosyphilis.

5:54

However, this test is insensitive and maybe

5:56

non-reactive even in cases of symptomatic

5:58

neurosyphilis. The RPR

6:01

is the better test and should not be substituted

6:03

by the VDRL test for CSF examination.

6:06

In addition, he should have a serum tested for

6:08

syphilis, partially as the RPR

6:10

can be followed clinically as a sign of appropriate

6:13

response to treatment. The

6:15

RPR test is easier to perform and uses

6:17

unheated serum or plasma and it's a

6:19

test of choice for rapid serologic diagnosis

6:22

in the clinical setting. So

6:24

again, we've already established that this patient needs

6:27

the CSF RPR, not

6:29

VDRL, and then all the usual studies

6:31

we do with an LP. But this is

6:33

a two-part question. It goes on to ask,

6:36

assuming the test you ordered is positive

6:39

and you've diagnosed neurosyphilis, which

6:41

of the following is the appropriate treatment for his

6:43

condition? Option

6:45

A is aqueous crystalline penicillin

6:47

G, 24 million units daily

6:50

for 14 days. Option

6:53

B is benzothenin penicillin G, 24 million

6:56

units IV daily for 14 days. Option

6:59

C is benzothenin penicillin G, 2.4

7:02

million units IM weekly

7:04

for four weeks. Option

7:07

D is cestriaxone, 2 grams IV

7:09

daily for seven days. And option

7:11

E is doxycycline, 100 milligrams PO

7:13

twice daily for 14 days. Okay,

7:17

so just to tell you the answer,

7:19

it's A. He should get aqueous crystalline

7:21

penicillin G, 24 million

7:24

units IV daily, which is

7:26

a continuous infusion, and you do that

7:28

for 14 days. What's wrong with

7:30

the other options? So the hard part

7:32

of treatment is picking a drug that will kill the treponema

7:35

in the nervous system. So benzothenin

7:37

penicillin G, even at high doses,

7:40

does not produce treponemicidal

7:42

concentrations of penicillin G in

7:45

the CSF. So that should not be used

7:47

for treatment of neurosyphilis. Neurosyphilis

7:50

may relapse as symptomatic disease after

7:53

treatment with benzotene penicillin,

7:55

and the risk of relapse may be higher in

7:57

HIV-infected patients. symptomatic

8:00

and asymptomatic neurosyphilis should be treated

8:03

with aqueous penicillin. Administration

8:06

of either IV aqueous penicillin G or

8:09

of IM aqueous protein penicillin

8:11

G plus oral probit

8:14

Benicid in recommended doses is

8:16

thought to ensure trepeneumicidal concentrations

8:19

of penicillin G in the CSF. And

8:22

what about the clinical response to these therapies?

8:24

The clinical response to penicillin therapy

8:26

for meningeal syphilis is dramatic, but

8:29

the treatment of neurosyphilis with existing parenchymal

8:32

damage may only arrest disease progression.

8:35

No data suggests that additional therapy is

8:37

beneficial after treatment for neurosyphilis.

8:40

Okay, so you mentioned a couple of other penicillins,

8:42

the benzethene, etc., etc. Let's

8:44

just review briefly about how you

8:47

use them for the various stages of syphilis.

8:50

All right, so although early syphilis,

8:53

which when I say that I mean like primary

8:55

syphilis or secondary syphilis without neurologic

8:57

involvement and early latent syphilis, so

9:00

that's effectively treated with a single dose

9:02

of intramuscular benzethene penicillin

9:05

G and latent cardiovascular

9:08

or benign tertiary syphilis are

9:10

effectively treated with three weekly doses

9:13

of IM benzethene penicillin

9:15

G. This does not produce detectable

9:17

concentrations of penicillin in the CSF

9:20

like I mentioned, so it's not recommended

9:22

for the treatment of neurosyphilis like we

9:24

think this patient has. So many patients

9:27

report allergies to penicillin. What do

9:29

you do in that situation? In patients

9:31

with confirmed penicillin allergy, desensitization

9:34

and treatment with penicillin are still recommended.

9:37

The use of antibiotics other than penicillin

9:39

for the treatment of neurosyphilis has not been studied,

9:42

although limited data suggests that cetriaxone

9:44

may be used, but again, old-fashioned

9:47

penicillin is the answer. Okay,

9:50

so there's a lot of teaching points in this case. First

9:52

off, let's remember that anterior uveitis,

9:54

which has a broad differential, requires a slit

9:57

lamp examination to really diagnose

9:59

definitively. UVitis

10:01

or anterior uveitis may be a manifestation

10:04

of neurosyphilis and that requires a

10:06

lumbar puncture and serum

10:08

RPR testing to diagnose. The

10:10

treatment of neurosyphilis remains aqueous

10:13

penicillin and remembering the various

10:15

stages of syphilis and the appropriate treatments

10:17

for syphilis is important for

10:19

your patient care. And if you

10:21

want to learn more about this or review everything

10:23

we've talked about, you can check out the chapter on syphilis

10:26

and also the chapter on disorders

10:28

of the eye.

10:30

Thanks for listening to Harrison's Pod Class.

10:33

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Review Questions which complement and expand

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upon the questions in this episode and much

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more. accessmedicine.com

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may already be available to you via your

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academic institution. Check it out.