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| '''For patient information on Neurosyphilis, click [[Neurosyphilis (patient information)|here]]'''
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| {{DiseaseDisorder infobox | | | {{DiseaseDisorder infobox | |
| Name = Syphilis | | | Name = Syphilis | |
| Image = Treponema pallidum.jpg | | | Image = Treponema pallidum.jpg | |
| Caption = Image of spiral-shaped organisms responsible for causing syphilis | | | Caption = Image of spiral-shaped organisms responsible for causing syphilis | |
| ICD10 = {{ICD10|A|50||a|50}}-{{ICD10|A|53||a|50}} |
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| ICD9 = {{ICD9|090}}-{{ICD9|097}} |
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| ICDO = |
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| OMIM = |
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| DiseasesDB = |
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| MedlinePlus = 001327 |
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| eMedicineSubj =|
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| eMedicineTopic = |
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| eMedicine_mult =
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| }} | | }} |
| {{Syphilis}} | | {{Neurosyphilis}} |
| {{CMG}}; {{AOEIC}} {{LG}} | | {{CMG}}; {{AE}}{{MMJ}} |
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| ==Treatment== | | ==[[Neurosyphilis overview|Overview]]== |
| *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.
| | ==[[Neurosyphilis pathophysiology|Pathophysiology]]== |
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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.
| | ==[[Neurosyphilis causes|Causes]]== |
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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.
| | ==[[Neurosyphilis differential diagnosis|Differentiating Neurosyphilis from other Diseases]]== |
| :*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.
| | ==[[Neurosyphilis risk factors|Risk Factors]]== |
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| ===CDC Recommendations: Pharmacotherapy [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm]=== | | ==[[Neurosyphilis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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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==== | | ==Diagnosis== |
| '''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.
| | [[Neurosyphilis history and symptoms|History and Symptoms]] | [[Neurosyphilis physical examination|Physical Examination]] | [[Neurosyphilis laboratory findings|Laboratory Findings]] | [[Neurosyphilis MRI|MRI]] | [[Neurosyphilis other imaging findings|Other Imaging Findings]] | [[Neurosyphilis other diagnostic studies|Other Diagnostic Studies]] |
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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.
| | ==Treatment== |
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| ===Other Management Considerations=== | |
| *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.
| | [[Neurosyphilis medical therapy|Medical Therapy]] | [[Neurosyphilis primary prevention|Primary Prevention]] | [[Neurosyphilis secondary prevention|Secondary Prevention]] | [[Neurosyphilis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Neurosyphilis future or investigational therapies|Future or Investigational Therapies]] |
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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>
| | ==Case Studies== |
| | [[Neurosyphilis case study one|Case #1]] |
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| ==Neurosyphilis Among HIV-Infected Persons==
| | ==Related Chapters== |
| ====Treatment====
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| [[HIV]]-infected patients with [[neurosyphilis]] should be treated according to the recommendations for HIV-negative patients with neurosyphilis.
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| ====Special considerations====
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| *HIV-infected, [[Syphilis medical therapy#Pencillin allergy|penicillin-allergic]] patients who have [[neurosyphilis]] should be managed according to the recommendations for penicillin-allergic, HIV-negative patients with neurosyphilis.
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| *Several small observational studies conducted in HIV-infected patients with neurosyphilis suggest that [[ceftriaxone]] 1-2 g IV daily for 10-14 days might be effective as an alternate agent.<ref name="pmid1442850">Dowell ME, Ross PG, Musher DM, Cate TR, Baughn RE (1992) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=1442850 Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.] ''Am J Med'' 93 (5):481-8. PMID: [http://pubmed.gov/1442850 1442850]</ref><ref name="pmid15117503">Smith NH, Musher DM, Huang DB, Rodriguez PS, Dowell ME, Ace W et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15117503 Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin.] ''Int J STD AIDS'' 15 (5):328-32. [http://dx.doi.org/10.1258/095646204323012823 DOI:10.1258/095646204323012823] PMID: [http://pubmed.gov/15117503 15117503]</ref><ref name="pmid18532887">Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18532887 Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients.] ''Clin Infect Dis'' 47 (2):258-65. [http://dx.doi.org/10.1086/589295 DOI:10.1086/589295] PMID: [http://pubmed.gov/18532887 18532887]</ref>
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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 gauge response after therapy.
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| *Limited data suggest that changes in CSF parameters might occur more slowly in HIV-infected patients, especially those with more advanced immunosuppression.<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="pmid18525260">Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18525260 Neurosyphilis in a clinical cohort of HIV-1-infected patients.] ''AIDS'' 22 (10):1145-51. [http://dx.doi.org/10.1097/QAD.0b013e32830184df DOI:10.1097/QAD.0b013e32830184df] PMID: [http://pubmed.gov/18525260 18525260]</ref>
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| *If the cell count has not decreased after 6 months or if the CSF is not normal after 2 years, retreatment should be considered.
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| ==Related chapters== | |
| *[[Syphilis]] | | *[[Syphilis]] |
| *[[Congenital syphilis]] | | *[[Congenital syphilis]] |
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| ==Resources== | | ==External Links== |
| *[http://hivinsite.ucsf.edu/InSite?page=kb-05-01-04 UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV]
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| *[http://colman.net/eadv/index.html "A New Gold Standard For Syphilis?" Poster Presentation for European Academy of Dermatology and Venereology 2004 Spring Symposium]
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| *[http://www.stdhelp.org/about/syphilis.php Syphilis Pictures and Information]
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| *[http://medinfo.ufl.edu/other/histmed/clancy/ Kipkeepers, Pox and Gleet Vendors: A Rapid History of Syphilis]
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| *[http://www.poxhistory.com/ POX: Genius, Madness, and the Mysteries of Syphilis]
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| *[http://www.yourstdhelp.com/syphilis.html Syphilis Informational resource ]
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| *[http://www.pbs.org/wnet/secrets/case_syphilis/index.html Secrets of the Dead (PBS): The Syphilis Enigma]
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| *[http://www.cbc.ca/ideas/Aids Syphilis and AIDS: Lessons from history]
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| *[http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm "Syphilis fact sheet" from the Center for Disease Control] | | *[http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm "Syphilis fact sheet" from the Center for Disease Control] |
| *[http://www.nobel.se/medicine/laureates/1927/wagner-jauregg-lecture.html The treatment of dementia paralytica by malaria inoculation (A Nobel Prize lecture, December 13, 1927)]
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| *[http://www.niaid.nih.gov/factsheets/stdsyph.htm National Institute of Allergy and Infectious Diseases Factsheet]
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| *[http://uk.reuters.com/article/oddlyEnoughNews/idUKN1443055520080115 New study blames Columbus for syphilis spread from Reuters Jan 15, 2008]
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| ==References==
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| {{reflist|2}}
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| {{Diseases of the skin and appendages by morphology}} | | {{Diseases of the skin and appendages by morphology}} |
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| [[Category:Disease]] | | [[Category:Disease]] |
| [[Category:Gynecology]] | | [[Category:Gynecology]] |
| [[Category:Infectious disease]]
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| [[Category:Bacterial diseases]] | | [[Category:Bacterial diseases]] |
| [[Category:Sexually transmitted diseases]] | | [[Category:Sexually transmitted diseases]] |