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Lumbar Puncture in HIV-infected Patients with Syphilis
Abstract & Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University, School of Medicine, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Synopsis: In this study, 202 patients with HIV infection and syphilis and no neurologic symptoms were studied, and 61 underwent either immediate or delayed lumbar puncture (LP). Using a combination of rapid plasma reagin (RPR) titer ≥: 32 and CD4+ lymphocyte count ≥ 350 cells/uL or serologic response to treatment improved the ability to identify asymptomatic neurosyphilis (ANS).
Source: Ghanem KG, et al. Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms. Clin Infect Dis. 2009;48:816-821.
Eligible subjects in this study included all patients with concurrent HIV infection and syphilis in a prospective cohort who had no neurologic symptoms at time of lumbar puncture. Retrospective stratification was applied as follows: 1) LP in patients with late latent syphilis or syphilis of unknown duration regardless of CD4 count or RPR titer, 2) LP if CD4 ≥ 350 cells/uL and/or RPR titer ≥: 1:32 regardless of syphilis stage, and 3) LP in the context of serologic nonresponse to syphilis therapy (lack of ≥: 4-fold decrease in RPR titer ≥: 12 months after receipt of appropriate treatment or ≥: 4-fold increase in RPR titer ≥: 30 days after receipt of therapy).
The results showed that 202 patients with syphilis and HIV did not have neurologic symptoms. Immediate LP was performed in 48 patients, and 10 cases (22%) were found to have ANS using standard CSF analysis criteria (any of: WBC > 10/uL, protein > 50 mg/dL, CSF VDRL reactive). With use of criterion 1, two (14%) of 10 cases of ANS would have been missed. With use of criterion 2, no cases of ANS would have been missed but would have required an LP be performed in 88% of all patients. Performance of LP in 13 patients meeting criterion 3 (serologic nonresponse to treatment) yielded four cases (31%) of ANS.
From an historical perspective, following the advent of the use of penicillin for treatment of syphilis following World War II, the rates of neurologic complications of syphilis declined dramatically and resulted in the abandonment of routine LP for staging of patients with syphilis in the absence of neurologic symptoms. By the 1980s, a number of case reports of neurosyphilis developing in HIV-infected patients, often following treatment with approved antibiotic regimens, including standard doses and schedules of penicillin, prompted the need to revisit the issue of LP for these co-infected patients. Obviously, patients with neurologic symptoms and syphilis need to undergo LP, but controversy exists regarding the need for LP in patients without neurologic symptoms.
While this study has many limitations, including small sample size of patients actually undergoing LP and the retrospective application of stratification criteria, the data are useful. Using the criteria of CD4 ≥ 350/uL, RPR titer ≥: 1:32, or serologic nonresponse to treatment results in the need to perform LP in 70%-90% of HIV/syphilis co-infected patients but avoids missing significant numbers of patients with ANS. Unfortunately, no "gold standard" exists for the diagnosis of asymptomatic neurosyphilis. It should be kept in mind that while reactive CSF VDRL is specific for the diagnosis of neurosyphilis, this test lacks sensitivity and has been suggested to be negative in 50% of patients with neurosyphilis. While CSF pleocytosis is sensitive for the diagnosis of neurosyphilis, this lymphocytic pleocytosis lacks specificity since this finding is commonly present in HIV-infected patients without syphilis, particularly in patients not receiving antiretroviral therapy.
We have been following these guidelines in our HIV clinic for several years and perform LPs in our clinic routinely. In individuals found to have evidence of ANS, we generally admit these patients to our hospital and administer 10-14 days of intravenous penicillin G.