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SyphilisAka: Treponema pallidum, Tabes dorsalis, Primary Syphilis, Secondary Syphilis, Tertiary Syphilis, Latent Syphilis, Neurosyphilis, Syphilitic paresis, Dementia paralytica

Epidemiology
1. Resurgence of Syphilis with HIV in 1980s
Etiology
1. Caused by Spirochete Treponema pallidum
Risk factors: Cohorts with highest Prevalence in U.S.
1. Homosexual men
2. Males
3. Southern and urban centers
4. African americans
Stages: Primary Syphilis
1. Findings
  1. Regional Lymphadenopathy
  2. Chancre
    1. Painless Papule ulcerates
    2. Indurated lesion with smooth base and firm border
2. Timing
  1. Chancre at 10 to 90 days after exposure
  2. Chancre heals within 3 to 6 weeks
3. Diagnostic Test Sensitivity in Primary Syphilis
  1. Dark-field Exam of chancre: 80%
  2. Non-Treponemal tests (e.g. RPR): 78-86%
  3. Treponemal tests (e.g. FTA-ABS): 76-84%
Stages: Secondary Syphilis
1. Timing
  1. Begins 2 to 8 weeks following onset of chancre
2. Nonspecific symptoms
  1. Malaise
  2. Fatigue
  3. Headache
  4. Fever
  5. Sore Throat
3. Signs
  1. Generalized Lymphadenopathy
  2. Papulosquamous Dermatosis
    1. Characteristics
      1. Pale, red discrete round lesions
      2. Scaling over surface
    2. Size: "Nickels and Dimes"
      1. Papules <1cm (Dimes): Usually 5-10 mm
      2. Plaques >1cm (Nickels)
    3. Distribution: Symmetric palms, soles and trunk
  3. Condyloma lata
    1. Papules coalesce
    2. Become large, flat highly contagious lesions
      1. Involves moist areas
      2. Involves genitalia
  4. Highly infectious lesions can occur on mucus membrane
4. Systemic manifestations
  1. Hepatitis
  2. Periostitis
  3. Nephropathy
  4. Uveitis or Iritis
5. Diagnostic Test Sensitivity in Secondary Syphilis
  1. Dark-field Exam of chancre: 80%
  2. Non-Treponemal tests (e.g. RPR): 100%
  3. Treponemal tests (e.g. FTA-ABS): 100%
Stages: Latent Syphilis
1. No clinical signs of syphilis (CSF Normal)
2. Early Latency (First year after infection)
3. Late Latency (Latent infection >1 year)
  1. Only infectious in pregnancy and transfusion
4. Diagnostic Test Sensitivity in Latent Syphilis
  1. Non-Treponemal tests (e.g. RPR): 95-100%
  2. Treponemal tests (e.g. FTA-ABS): 97-100%
Stages: Tertiary Syphilis
1. Late benign syphilis (Gumma)
  1. May form 1 to 10 years after initial infection
  2. Destructive Granulomatous lesions affect any area
  3. Responds rapidly to treatment
2. Cardiovascular syphilis
  1. Begins 5 to 10 years after initial infection
  2. Clinically seen 20-30 years after infection
  3. Obliterative endarteritis of vasa vasorum
  4. Ascending aorta develops
    1. Aortic Insufficiency
    2. Aortic aneurysm
3. Neurosyphilis (Occurs in 10% of untreated syphilis)
  1. Symptoms
    1. Slow mental deterioration
    2. Headaches
    3. Personality change
  2. Signs
    1. Tremor of lips, Tongue or hands
    2. Argyll Robertson Pupil
    3. Seizures
    4. Ataxia
    5. Aphasia
    6. Hyperreflexia
    7. Cognitive changes
  3. Types
    1. Asymptomatic (Cerebrospinal Fluid positive VDRL)
    2. Meningovascular
      1. Begins 5 to 10 years after initial infection
      2. Acute or subacute Aseptic Meningitis
    3. Tabes dorsalis
      1. Onset 20 to 30 years after initial infection
      2. Progressive degeneration of spinal cord
        
        Posterior roots
        
        Posterior Columns
      3. Charcot's Joints
      4. Argyll-Robertson pupil (Prostitute pupil)
        
        Accommodates but does not react
    4. Syphilitic paresis (Dementia paralytica)
      1. Chronic meningoencephalitis
      2. Evolves into Psychosis
4. Diagnostic Test Sensitivity in Tertiary Syphilis
  1. CSF evaluation required (see below)
  2. Non-Treponemal tests (e.g. RPR): 71-73%
  3. Treponemal tests (e.g. FTA-ABS): 94-96%
Differential Diagnosis: Syphilis chancre or condyloma
Diagnosis
1. Dark-field Microscopy
  1. Most specific if chancre or condyloma is present
  2. Accuracy varies with experience of technician
2. Syphilis Serology
  1. Screening
    1. VDRL (Venereal Disease Research Lab Test)
    2. RPR (Rapid Plasma Reagin test)
  2. Negative test with lesions present
    1. Repeat screening in 3 weeks
  3. Confirmation of positive Screening Test
    1. Fluorescent Treponemal Antibody (FTA-ABS)
3. Neurosyphilis CSF Evaluation
  1. Screening
    1. CSF VDRL (high Specificity)
    2. CSF white cell count >10/mm3
    3. CSF Protein >50 mg/dl
  2. Retesting if CSF VDRL negative
    1. Treponemal specific CSF tests (e.g. TPHA)
      1. High false positive rate
      2. Consider TPHA index (compares CSF to serum titer)
    2. Spirochete DNA PCR from CSF sample
      1. Higher Specificity than TPHA
      2. Not yet widely available
Management
1. Incubation stage (post-exposure prophylaxis)
  1. Ceftriaxone 250 mg IM and
  2. Doxycycline 100 mg for 14 days
  3. Azithromycin (Zithromax) 1 gram PO x1 dose
2. Primary, secondary, early latent (under one year)
  1. Benzathine Penicillin G
    1. Adult: 2.4 MU IM for 1 dose
    2. Child: 50,000 units/kg IM for 1 dose (max: 2.4 MU)
  2. Aqueous Procaine Penicillin G 0.6 MU IM qd for 8 days
  3. Jarisch-Herxheimer Reaction may occur
  4. If Penicillin allergic
    1. Ceftriaxone 1 gram IM or IV for 10 days
    2. Tetracycline 500 mg PO qid for 14 days
    3. Doxycycline 100 mg PO bid for 14 days
3. Late latent, Cardiovascular (duration over 1 year)
  1. Benzathine Penicillin G 2.4 MU IM qWeek for 3 weeks
  2. If Penicillin allergic
    1. Tetracycline 500 mg PO qid for 4 weeks
    2. Doxycycline 100 mg PO bid for 4 weeks
4. Neurosyphilis
  1. Aqueous crystalline Penicillin G
    1. Dose: 3-4 MU IV q4 hours for 10-14 days
    2. Alternative: 0.75 to 1 MU/hour continuous IV
  2. Procaine Penicillin (only in compliant patients)
    1. Dose 2.4 MU IM qd for 14 days
    2. Use with Probenecid 500 mg qid for 14 days
  3. Penicillin Allergy
    1. Desensitize and treat with Penicillin
    2. Ceftriaxone 2 g IM/IV qd for 14 days
5. Pregnancy
  1. Treat with Penicillin as above
  2. Desensitize and treat with Penicillin if allergic
Follow-up: 6 months after treatment (Stage 1-2)
1. Repeat quantitative nontreponemal test titers
2. Repeat clinical evaluation
References

Syphilitic chancre (C0007939)
Definition (MSH)	The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection.
Concepts	Sign or Symptom (T184)
MSH	D002601
English	Chancre, Chancres, Primary syphilis, Primary syphilis - chancre, Syphilis Primary, Syphilitic chancre
Spanish	chancro sifilitico, sifilis primaria
Parent Concepts	Syphilis (C0039128), Acquired syphilis (C0343674), Duplicate concept (C1274013)
Sources	COSTAR, DXP, MSH, MTH, NDFRT, QMR, SCTSPA, SNOMEDCT Derived from the NIH UMLS (Unified Medical Language System)

Neurosyphilis (C0027927)
Definition (MSH)	Infections of the central nervous system caused by TREPONEMA PALLIDUM which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as BRAIN INFARCTION. The infection may also remain subclinical for several years. Late syndromes include general paresis; TABES DORSALIS; meningeal syphilis; syphilitic OPTIC ATROPHY; and spinal syphilis. General paresis is characterized by progressive DEMENTIA; DYSARTHRIA; TREMOR; MYOCLONUS; SEIZURES; and Argyll-Robertson pupils. (Adams et al., Principles of Neurology, 6th ed, pp722-8)
Concepts	Disease or Syndrome (T047)
ICD9	094, 094.9, 094.9
MSH	D009494
English	Central Nervous System Syphilis, CNS SYPHILIS, Neurosyphilis, SYPHILIS CNS, Syphilis of central nervous system
Spanish	neurosifilis, sifilis del sistema nervioso central, sifilis del SNC
Parent Concepts	Neurosyphilis (C0027927), Syphilis and other venereal diseases (C0178243), Syphilis (C0039128), Central Nervous System Bacterial Infections (C0752180), [X]Late syphilis, unspecified (C0153188), Late quaternary neurosyphilis (C0554635), Duplicate concept (C1274013)
Sources	COSTAR, DXP, ICD9CM, LCH, MSH, MTH, MTHICD9, NDFRT, SCTSPA, SNOMEDCT Derived from the NIH UMLS (Unified Medical Language System)

Syphilis (C0039128)
Definition (MSH)	A contagious venereal disease caused by the spirochete TREPONEMA PALLIDUM.
Definition (CSP)	subacute to chronic infectious venereal disease caused by the spirochete treponema pallidum.
Concepts	Disease or Syndrome (T047)
ICD9	097.9, 097.9
MSH	D013587
English	Great Pox, Infection by Treponema pallidum, Lues, Luetic disease, Syphilis
Spanish	infeccion por Treponema pallidum, lues, sifilis
Parent Concepts	spimychetal disease (C0679363), Sexually Transmitted Diseases (C0036916), Treponemal Infections (C0040843), Other syphilis (C0558995), Sexually Transmitted Diseases, Bacterial (C0036917), Spirochaetales Infections (C0037974), Syphilis (C0039128), Duplicate concept (C1274013)
Sources	AOD, COSTAR, CSP, DXP, ICD9CM, LCH, MEDLINEPLUS, MSH, MTH, MTHICD9, NCI, NDFRT, SCTSPA, SNOMEDCT Derived from the NIH UMLS (Unified Medical Language System)

Syphilis, Latent (C0039133)
Concepts	Disease or Syndrome (T047)
ICD9	097.1
MSH	D013592
English	Latent Syphilis, Latent syphilis unspecified
Spanish	sifilis latente no especificada
Parent Concepts	Other syphilis (C0558995), Syphilis (C0039128), Latent Infection (C0872054)
Sources	DXP, ICD9CM, MSH, NCI, NDFRT, SCTSPA, SNOMEDCT Derived from the NIH UMLS (Unified Medical Language System)

Secondary syphilis (C0149985)
Concepts	Disease or Syndrome (T047)
ICD9	091.9
English	Secondary syphilis, SYPHILIS SECONDARY, Unspecified secondary syphilis
Spanish	sifilis secundaria, sifilis secundaria no especificada
Parent Concepts	Early symptomatic syphilis (C0153139), Secondary syphilis (C0149985), Acquired syphilis (C0343674), Duplicate concept (C1274013)
Sources	COSTAR, DXP, ICD9CM, QMR, SCTSPA, SNOMEDCT Derived from the NIH UMLS (Unified Medical Language System)

General Paralysis (C0205858)
Concepts	Disease or Syndrome (T047)
ICD9	094.1, 094.1
MSH	D009494
English	Dementia paralytica, General Paralyses, General Paralysis, General paralysis of insane, General paralysis of the insane, General Pareses, General paresis, General paresis - neurosyphilis, General Paresis of the Insane, GPI - General paresis of the insane, GPI-general paralysis insane, Paralytic dementia, Paretic neurosyphilis, Progressive general paralysis, Progressive general paresis
Spanish	demencia paralitica, neurosifilis paretica, paresia general, paresia general progresiva
Parent Concepts	Neurosyphilis (C0027927), Tabes Dorsalis (C0039223), Dementia (C0497327), Late quaternary neurosyphilis (C0554635), Bacterial infectious disease of brain (C1264611)
Sources	DXP, ICD9CM, MSH, MTH, MTHICD9, SCTSPA, SNOMEDCT Derived from the NIH UMLS (Unified Medical Language System)

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SyphilisAka: Treponema pallidum, Tabes dorsalis, Primary Syphilis, Secondary Syphilis, Tertiary Syphilis, Latent Syphilis, Neurosyphilis, Syphilitic paresis, Dementia paralytica

Syphilitic chancre (C0007939)

Neurosyphilis (C0027927)

Syphilis (C0039128)

Syphilis, Latent (C0039133)

Secondary syphilis (C0149985)

General Paralysis (C0205858)

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