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| {{Syphilis}} | | {{Syphilis}} |
| {{CMG}}; {{AOEIC}} {{LG}} | | {{CMG}}; {{AOEIC}} {{LG}} |
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| ==Treatment==
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| *CNS involvement can occur during any stage of syphilis. However, [[Syphilis laboratory tests#CSF analysis|CSF laboratory abnormalities]] are common in persons with [[Syphilis pathophysiology#Primary syphilis|early syphilis]], even in the absence of clinical neurological findings. No evidence exists to support variation from recommended treatment for early syphilis for patients found to have such abnormalities.
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| *If clinical evidence of neurologic involvement is observed (e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of [[meningitis]]), a [[Syphilis laboratory tests#CSF analysis|CSF examination]] should be performed.
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| *[[uveitis|Syphilitic uveitis]] or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis. Patients who have neurosyphilis or syphilitic eye disease (e.g., [[uveitis]], [[neuroretinitis]], and [[optic neuritis]]) should be treated with the recommended regimen for neurosyphilis; those with eye disease should be managed in collaboration with an ophthalmologist. A [[Syphilis laboratory tests#CSF analysis|CSF examination]] should be performed for all patients with syphilitic eye disease to identify those with abnormalities; patients found to have abnormal CSF test results should be provided follow-up CSF examinations to assess treatment response.
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| *For patients diagnosed with neurosyphilis including ocular or auditory syphilis with or without [[Syphilis laboratory tests#CSF analysis|positive CSF results]], [[Penicillin#Benzylpenicillin (penicillin G)|aqueous crystalline penicillin G]] is the treatment of choice.
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| :*The recommended regimen is intravenous treatment every 4 hours or continuously for 10-14 days
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| :*If intravenous administration is not possible, then [[Pencillin#Procaine benzylpenicillin|procaine penicillin]] is an alternative (administered daily with [[probenecid]] for two weeks).
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| :*Procaine injections are painful, however, and patient compliance may be difficult to ensure.
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| :*To approximate the 21-day course of therapy for [[Syphilis pathophysiology#Latent syphilis|late latent disease]] and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin G]] after the completion of a 14-day course of aqueous crystalline or aqueous [[Pencillin#Procaine benzylpenicillin|procaine penicillin G]]] for neurosyphilis.
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| *No oral antibiotic alternatives are recommended for the treatment of neurosyphilis. The only alternative that has been studied and shown to be effective is intramuscular [[ceftriaxone]] daily for 14 days.
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| ===CDC Recommendations: Pharmacotherapy [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm]===
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| {{cquote|
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| ====Recommended Regimen====
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| '''1.''' [[Penicillin#Benzylpenicillin (penicillin G)|Aqueous crystalline penicillin G]] 18-24 million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion, for 10-14 days.
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| ====Alternative Regimen====
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| '''1.''' [[Pencillin#Procaine benzylpenicillin|Procaine penicillin]] 2.4 million units IM once daily, '''''plus''''' [[probenecid]] 500 mg orally four times a day, both for 10-14 days.}}
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| *If compliance with therapy can be ensured, the following alternative regimen might be considered.
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| *The durations of the recommended and alternative regimens for neurosyphilis are shorter than the duration of the regimen used for late syphilis in the absence of neurosyphilis. Therefore, [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin]], 2.4 million units IM once per week for up to 3 weeks, can be considered after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy.
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| ===Other Management Considerations===
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| *Other considerations in the management of patients who have neurosyphilis are as follows:
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| :*All persons who have syphilis should be tested for HIV.
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| :*Although systemic steroids are used frequently as adjunctive therapy for otologic syphilis, such drugs have not been proven to be beneficial.
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| ===Special Considerations===
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| =====Penicillin Allergy=====
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| *Limited data suggest that [[ceftriaxone]] 2 g daily either IM or IV for 10-14 days can be used as an alternative treatment for patients with neurosyphilis.<ref name="pmid3764632">Hook EW, Baker-Zander SA, Moskovitz BL, Lukehart SA, Handsfield HH (1986) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3764632 Ceftriaxone therapy for asymptomatic neurosyphilis. Case report and Western blot analysis of serum and cerebrospinal fluid IgG response to therapy.] ''Sex Transm Dis'' 13 (3 Suppl):185-8. PMID: [http://pubmed.gov/3764632 3764632]</ref><ref name="pmid14573840">Shann S, Wilson J (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14573840 Treatment of neurosyphilis with ceftriaxone.] ''Sex Transm Infect'' 79 (5):415-6. PMID: [http://pubmed.gov/14573840 14573840]</ref>
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| *However, the possibility of cross-reactivity between [[ceftriaxone]] and [[penicillin]] exists.
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| *Other regimens have not been adequately evaluated for treatment of neurosyphilis. Therefore, if concern exists regarding the safety of [[ceftriaxone]] for a patient with neurosyphilis, [[Syphilis medical therapy#Pencillin allergy: Penicillin skin test|skin testing]] should be performed (if available) to confirm [[Syphilis medical therapy#Pencillin allergy|penicillin allergy]] and, if necessary, [[desensitize]] the patient.
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| =====Pregnancy=====
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| Pregnant patients who are [[Syphilis medical therapy#Pencillin allergy|allergic to penicillin]] should be [[desensitized]] and treated with [[penicillin]].
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| ===Follow-up===
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| *If [[Lumbar puncture#Diagnostics|CSF pleocytosis]] was present initially, a [[Syphilis laboratory tests#CSF analysis|CSF examination]] should be repeated every 6 months until the cell count is normal.
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| *Follow-up CSF examinations also can be used to evaluate changes in the [[Syphilis laboratory tests#CSF analysis|CSF-VDRL or CSF protein]] after therapy; however, changes in these two parameters occur more slowly than cell counts, and persistent abnormalities might be less important.<ref name="pmid15034833">Marra CM, Maxwell CL, Tantalo L, Eaton M, Rompalo AM, Raines C et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15034833 Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter?] ''Clin Infect Dis'' 38 (7):1001-6. [http://dx.doi.org/10.1086/382532 DOI:10.1086/382532] PMID: [http://pubmed.gov/15034833 15034833]</ref><ref name="pmid18715154">Marra CM, Maxwell CL, Tantalo LC, Sahi SK, Lukehart SA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18715154 Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis.] ''Clin Infect Dis'' 47 (7):893-9. [http://dx.doi.org/10.1086/591534 DOI:10.1086/591534] PMID: [http://pubmed.gov/18715154 18715154]</ref>
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| *The leukocyte count is a sensitive measure of the effectiveness of therapy. If the cell count has not decreased after 6 months or if the CSF cell count or protein is not normal after 2 years, '''''retreatment''''' should be considered.
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| *Limited data suggest that in immunocompetent persons and [[HIV|HIV-infected persons]] on highly active [[AIDS medical therapy#Anti Retroviral Therapy (ART)|antiretroviral therapy]], normalization of the [[Rapid plasma reagent|serum RPR titer]] predicts normalization of CSF parameters.<ref name="pmid18715154">Marra CM, Maxwell CL, Tantalo LC, Sahi SK, Lukehart SA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18715154 Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis.] ''Clin Infect Dis'' 47 (7):893-9. [http://dx.doi.org/10.1086/591534 DOI:10.1086/591534] PMID: [http://pubmed.gov/18715154 18715154]</ref>
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| ==Neurosyphilis Among HIV-Infected Persons== | | ==Neurosyphilis Among HIV-Infected Persons== |