Syphilis Affects Central Nervous System in Patients With HIV

Daniel M. Keller, PhD

October 21, 2013

BRUSSELS — A large number of HIV-infected men with early syphilis may have neurosyphilis, despite low serum titers and no symptoms, according to a new study.

"We were surprised that 92% of the patients in the study showed positive for neurosyphilis by cerebrospinal fluid examination," study author Pawel Swiecki, MD, from the Hospital of Infectious Diseases, AIDS Diagnosis and Therapy Center, in Warsaw, Poland, told Medscape Medical News.

Dr. Swiecki presented the results of the study here at the 14th European AIDS Conference.

Dr. Swiecki and his team looked at 73 HIV-positive patients diagnosed with early syphilis who also underwent a lumbar puncture. The patients were all male, ranging in age from 23 to 58 years.

Neurosyphilis was confirmed in 67 of these patients by positive fluorescent treponemal antibody-absorption or Venereal Disease Research Laboratory (VDRL) test and by an increase in cerebrospinal fluid mononuclear cells.

 
We were surprised that 92% of the patients in the study showed positive for neurosyphilis by cerebrospinal fluid examination. Dr. Pawel Swiecki
 

Although the number of patients with early syphilis who received a lumbar puncture rose fairly steadily from year to year, the proportion of confirmed neurosyphilis cases remained about the same at around 7% to 11%.

But because a number of patients refused lumbar punctures, the true incidence of neurosyphilis could be even higher, Dr. Swiecki speculated.

Researchers reported a statistically significant association between pleocytosis and serum HIV load >1000 copies/mL (P = .045) and between pleocytosis and combination antiretroviral treatment (P = .033). However, they noted that pleocytosis can result from a cerebrospinal fluid viral load alone, which was not tested for.

There was no association between CD4 counts and any cerebrospinal fluid parameter.

Table. Early Syphilis and Neurosyphilis Cases by Year

Cases

2008 2009 2010 2011 2012

Early syphilis (n)

21 27 45 37 61

Lumbar puncture (n)

7 9 18 14 25

Neurosyphilis (%)

0 11 11 7 8

 

European guidelines of the International Union Against Sexually Transmitted Infections suggest that HIV-infected patients with syphilis are at risk for early asymptomatic neurologic involvement and recommend examination of the cerebrospinal fluid of anyone who is infected with HIV and who has a serum VDRL titer of 1:32 or greater. But in this study, some patients had central nervous system involvement even if they had low serum VDRL titers.

"We had several patients with VDRL titers below 1:32 who had neurological symptoms," said Dr. Swiecki. He concluded that it may be prudent to examine the cerebrospinal fluid of all HIV-positive patients diagnosed with syphilis in light of the high proportion of patients with confirmed neurosyphilis, including those with low titers.

Alternatively, he advised using antibiotic treatments with good penetration into the central nervous system when cerebrospinal fluid examination is not possible. He told Medscape Medical News that his treatment of choice is crystalline penicillin for up to 3 weeks, sometimes with doxycline.

A member of the audience at the presentation questioned whether Dr. Swiecki might have overdiagnosed neurosyphilis among his patients.

Asked for a comment, session chair Lut Lyten, MD, from the Institute of Tropical Medicine in Antwerp, Belgium, told Medscape Medical News, "I think it's exaggerated to say that all abnormal cerebrospinal fluid findings are confirmed syphilis. If they all have neurosyphilis, you wouldn't have to do a lumbar puncture. You could just go for a long-term treatment, which I think is going to be unacceptable to patients because you have to put them in hospital for 2 weeks with an IV drip."

She said that in her institute, the clinical picture often presents a conundrum when the VDRL titer is not going down. "Is it because they do have neurosyphilis, or is it because they were reinfected?" she questions. "This is a very difficult population to follow up with and figure out what is going on."

Better diagnostic tests on cerebrospinal fluid and on serum are needed to define neurosyphilis, says Dr. Lyten, because VDRL or rapid plasma reagin flutuations are "too difficult to interpret in patients who have continuous at-risk behaviors."

The take-home message from the study for Dr. Lyten is that clinicians should consider neurosyphilis in patients who have unexplained increases of VDRL after treatment. She recommends follow-up with regular measurements of VDRL or rapid plasma reagin titers, and if there is no decrease in these measurements, she would urge the patient to have a lumbar puncture to check.

Dr. Lyten says, however, that in her experience, anyone who had neurologic symptoms and a positive serum VDRL whom she has sent for lumbar puncture did not have a positive cerebrospinal fluid VDRL. But she treated them with IV penicillin anyway on the basis of the presence of neurologic symptoms. In her opinion, to treat asymptomatic patients with IV penicillin is "going too far."

This study received no commercial support. Dr. Swiecki reports no relevant financial relationships. Dr. Lyten was not involved in the study and reports no relevant financial relationships.

14th European AIDS Conference. Abstract BPD2/2. Presented October 18, 2013.

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