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Ther Investigation and Treatment for Neurosyphilis

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Ther Investigation and Treatment for Neurosyphilis auditory or ophthalmic abnormalities) warrant fur - cillin (Bicillin C-R) instead of the standard benza - ther investigation and treatment for neurosyphilis. thine penicillin product (Bicillin L-A) widely used Laboratory testing is helpful in supporting the diag - in the United States. Practitioners, pharmacists, and nosis of neurosyphilis; however, no single test can purchasing agents should be aware of the similar be used to diagnose neurosyphilis in all instances. names of these two products to avoid using the inap - Cerebrospinal fluid (CSF) laboratory abnormalities propriate combination therapy agent for treating are common in persons with early syphilis. The syphilis (206) . VDRL in cerebrospinal fluid (CSF-VDRL), which is highly specific but insensitive, is the standard The effectiveness of penicillin for the treatment of serologic test for CSF. When reactive in the absence syphilis was well established through clinical expe - of substantial contamination of CSF with blood, it is rience even before the value of randomized con - considered diagnostic of neurosyphilis; however in trolled clinical trials was recognized. Therefore, early syphilis, it can be of unknown prognostic sig - nearly all the recommendations for the treatment of nificance (203). Most other tests are both insensitive syphilis are based not only on clinical trials and and nonspecific and must be interpreted in relation observational studies, but approximately 50 years of to other test results and the clinical assessment. clinical experience. Therefore, the laboratory diagnosis of neurosyphilis usually depends on various combinations of reac - Parenteral penicillin G is the only therapy with doc - tive serologic test results, CSF cell count or protein, umented efficacy for syphilis during pregnancy. and a reactive CSF-VDRL with or without clinical Pregnant women with syphilis in any stage who manifestations. Among persons with HIV infection, report penicillin allergy should be desensitized and the CSF leukocyte count usually is elevated (>5 treated with penicillin (see Management of Patients 3 white blood cell count [WBC]/mm ); using a higher Who Have a History of Penicillin Allergy). 3 cutoff (>20 WBC/ mm ) might improve the speci - ficity of neurosyphilis diagnosis (204) . The CSF- The Jarisch-Herxheimer reaction is an acute febrile VDRL might be nonreactive even when neu - reaction frequently accompanied by headache, rosyphilis is present; therefore, additional evalua - myalgia, fever, and other symptoms that usually tion using FTA-ABS testing on CSF can be consid - occur within the first 24 hours after the initiation of ered. The CSF FTA-ABS test is less specific for any therapy for syphilis. Patients should be neurosyphilis than the CSF-VDRL but is highly informed about this possible adverse reaction. The sensitive; neurosyphilis is highly unlikely with a Jarisch-Herxheimer reaction occurs most frequently negative CSF FTA-ABS test (205) . among patients who have early syphilis, presum - Treatment ably because bacterial burdens are higher during these stages. Antipyretics can be used to manage symptoms, but they have not been proven to prevent Penicillin G, administered parenterally, is the pre - this reaction. The Jarisch-Herxheimer reaction ferred drug for treating all stages of syphilis. The might induce early labor or cause fetal distress in preparation used (i.e., benzathine, aqueous pro - pregnant women, but this should not prevent or caine, or aqueous crystalline), the dosage, and the delay therapy (see Syphilis During Pregnancy). length of treatment depend on the stage and clinical Management of Sex Partners manifestations of the disease. Selection of the appropriate penicillin preparation is important, because T. pallidum can reside in sequestered sites Sexual transmission of T. pallidum is thought to (e.g., the CNS and aqueous humor) that are poorly occur only when mucocutaneous syphilitic lesions accessed by some forms of penicillin. Combinations are present. Although such manifestations are of benzathine penicillin, procaine penicillin, and uncommon after the first year of infection, persons oral penicillin preparations are not considered exposed sexually to a patient who has syphilis in appropriate for the treatment of syphilis. Reports any stage should be evaluated clinically and sero - have indicated that practitioners have inadvertently logically and treated with a recommended regimen, prescribed combination benzathine-procaine peni - according to the following recommendations: CHAPTER 23A: SEXUALLY TRANSMITTED DISEASES 737 • Persons who were exposed within the 90 days pre - ceding the diagnosis of primary, secondary, or early latent syphilis in a sex partner might be infected even if seronegative; therefore, such per - sons should be treated presumptively. Available data demonstrate that additional doses of • Persons who were exposed >90 days before the benzathine penicillin G, amoxicillin, or other antibi - diagnosis of primary, secondary, or early latent otics in early syphilis (primary, secondary, and early syphilis in a sex partner should be treated pre - latent) do not enhance efficacy, regardless of HIV sumptively if serologic test results are not avail - status. able immediately and the opportunity for follow- Recommended Regimen for Infants and up is uncertain. Children • For purposes of partner notification and presump - tive treatment of exposed sex partners, patients Infants and children aged ≥1 month diagnosed with with syphilis of unknown duration who have high syphilis should have a CSF examination to detect nontreponemal serologic test titers (i.e., >1:32) asymptomatic neurosyphilis, and birth and maternal can be assumed to have early syphilis. For the pur - medical records should be reviewed to assess pose of determining a treatment regimen, however, whether such children have congenital or acquired serologic titers should not be used to differentiate syphilis (see Congenital Syphilis). Children with early from late latent syphilis (see Latent Syphilis, acquired primary or secondary syphilis should be Treatment). evaluated (e.g., through consultation with child-pro - tection services) (see Sexual Assault or Abuse of • Long-term sex partners of patients who have latent Children) and treated by using the following pedi - syphilis should be evaluated clinically and sero - atric regimen. logically for syphilis and treated on the basis of the evaluation findings. Sexual partners of infected patients should be con - Other Management Considerations sidered at risk and provided treatment if they have had sexual contact with the patient within 3 months plus the duration of symptoms for patients diag - All persons who have syphilis should be tested for nosed with primary syphilis, 6 months plus duration HIV infection. In geographic areas in which the of symptoms for those with secondary syphilis, and prevalence of HIV is high, persons who have pri - 1 year for patients with early latent syphilis. mary syphilis should be retested for HIV after 3 Primary and Secondary Syphilis months if the first HIV test result was negative. Treatment Patients who have syphilis and symptoms or signs suggesting neurologic disease (e.g., meningitis and hearing loss) or ophthalmic disease (e.g., uveitis, iri - Parenteral penicillin G has been used effectively for tis, neuroretinitis, and optic neuritis) should have an more than 50 years to achieve clinical resolution evaluation that includes CSF analysis, ocular slit- (i.e., the healing of lesions and prevention of sexual lamp ophthalmologic examination, and otologic transmission) and to prevent late sequelae. How - examination. Treatment should be guided by the ever, no comparative trials have been adequately results of this evaluation. conducted to guide the selection of an optimal peni - cillin regimen (i.e., the dose, duration, and prepara - Invasion of CSF by T. pallidum accompanied by tion). Substantially fewer data are available for non - CSF laboratory abnormalities is common among penicillin regimens. adults who have primary or secondary syphilis (203) . Therefore, in the absence of clinical neuro - 738 EDUCATIONAL REVIEW MANUAL IN URO LOGY logic findings, no evidence exists to support varia - unrecognized CNS infection, CSF examination can tion from the recommended treatment regimen for be considered in such situations. early syphilis. Symptomatic neurosyphilis develops in only a limited number of persons after treatment For retreatment, weekly injections of benzathine with the penicillin regimens recommended for pri - penicillin G 2.4 million units IM for 3 weeks is rec - mary and secondary syphilis. Therefore, unless clin - ommended, unless CSF examination indicates that ical signs or symptoms of neurologic or ophthalmic neurosyphilis is present (see Neurosyphilis). In rare involvement are present or treatment failure is doc - instances, serologic titers do not decline despite a umented, routine CSF analysis is not recommended negative CSF examination and a repeated course of for persons who have primary or secondary syphilis. therapy. In these circumstances, the need for addi - Follow-Up tional therapy or repeated CSF examinations is unclear, but is not generally recommended. Management of Sex Partners Treatment failure can occur with any regimen. However, assessing response to treatment fre - quently is difficult, and definitive criteria for cure or See General Principles, Management of Sex Part - failure have not been established. In addition, non - ners. treponemal test titers
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