Morning report: Syphilis

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Morning report Syphilis

• Liz Thomas
• July 18, 2007

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• He who knows syphilis, knows medicine.-
  William Osler

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Overview

• History
• Pathophysiology
• Clinical manifestations
• Diagnosis
• Neurosyphilis
• Ocular syphilis
• Treatment
• Prognosis

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History

• The first description of syphilis occurred during
  and after the 1494 seige of Naples. Charles VIII
  invaded with 30,000 mercenary soldiers who spread
  out over Europe after the army was disbanded.
  They brought with them a mysterious new illness
  known first as the Neopolitan disease, later as
  the French sickness and great pox. During
  the 19th century the term syphilis became
  universally accepted.

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• There are differing theories regarding the origin
  of syphilis.
• Columbian Exchange theory describes syphilis as a
  New World disease brought back by Columbus,
  citing as evidence the timing of the outbreak and
  skeletal evidence of syphilis in the Americas.
• Pre-Columbian theory holds that syphilis was
  present in Europe before the voyage of Columbus,
  using evidence of descriptions of disease
  consistent with syphilis in the Bible and by
  Hippocrates in Classical Greece.
• Another theory asserts that precursors to the
  syphilis bacterium existed in both the New and
  Old Worlds, and that differing environmental
  conditions produced different strains. Native
  Americans thus had some immunity against the more
  virulent European strain.

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Epidemiology

• Worldwide 12 million new syphilis cases/year
• 90 in the developing world
• In the US the rate of primary and secondary
  syphilis infection decreased through the 1990s to
  lowest recorded rate in 2000.
• However, there was a 29 increased annual rate of
  primary and secondary syphilis in 2004 (2.7 per
  100,000) from 2000 (2.1 per 100,000)
• Nearly all of the increase is in men
• MSM account for most of the increase
• One study in Chicago reported transmission via
  oral sex may constitute as much as 13.7 of
  contagion

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Pathophysiology

• Syphilis is caused by the spirochete Treponema
  pallidum.
• It initiates infection after gaining access to
  subcutaneous tissues via abrasions that occur
  during sexual intercourse

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Pathophysiology

• After invading the subcutaneous tissue the
  organism establishes the chancre.
• Some organisms also establish infection in
  regional lymph nodes during early local
  replication.

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Pathophysiology

• Nearly all cases of syphilis are sexually
  acquired (aside from congenital syphilis)
• Transmission rate during primary and secondary
  syphilis is about 30 and requires exposure to
  open lesions either primary chancre or
  mucocutaneous lesions.
• The incubation period varies but ranges from 10
  90 days.

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Clinical manifestations Primary syphilis

• The initial clinical manifestations is the
  primary chancre.
• Usually painless, which distinguishes it from
  other causes of genital ulcers herpes simplex
  (genital herpes) and Hemophilus ducreyi
  (chancroid).
• Most often heals without treatment over a period
  of a few weeks.

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Secondary syphilis

• If untreated, approximately 25 of patients will
  go on to develop systemic symptoms
• Rash
• Fever
• Headache
• Malaise
• Diffuse lymphadenopathy
• Alopecia

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Late vs. Latent syphilis

• Latent syphilis refers to patients without
  symptoms who have positive serologic testing for
  syphilis.
• Early latent refers to duration less than one
  year
• Late latent refers to duration greater than one
  year or of unknown duration
• Late or tertiary syphilis refers to the group of
  clinical manifestations that may occur anywhere
  between 1 and 30 years after infection when the
  infection is not treated.

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Tertiary syphilis

• Patients may not have experienced symptomatic
  primary or secondary syphilis prior to developing
  tertiary syphilis
• Most common manifestations are central nervous
  system, the cardiovascular system, or the skin
  and subcutaneous tissues (gummas).

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Diagnosis

• T. pallidum cannot be grown in culture, so other
  methods must be used to identify organisms
• Dark field microscopy allows direct visualization
  of spirochetes taken directly from lesions
• Direct fluorescent antibody testing can also be
  used it is specific T. pallidum antigens

• More often, serologic tests are used
• Nontreponemal tests (VDRL and RPR) measure
  reactivity of serum from patients with syphilis
  to a cardiolipin-cholesterol-lecithin antigen.
  They measure IgG and IgM antibodies and are
  reported as titers.
• Treponemal tests (FTA-ABS, MHA-TP and TPPA) are
  based upon the detection of antibodies directed
  against treponemal cellular components.

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Neurosyphilis

• Neurosyphilis refers to invasion of the CSF by T.
  pallidum and can occur at any stage of disease
• Early in the disease the most common
  manifestations are asymptomatic meningitis,
  symptomatic meningitis, and meningovascular
  disease.
• Late in disease, the most common forms involve
  the brain and spinal cord parenchyma (general
  paresis of the insane and tabes dorsalis).

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Asymptomatic neurosyphilis

• By definition, no symptoms or signs of CNS
  involvement
• Can occur within weeks of infection
• Characterized by lymphocytic pleocytosis
  typically
  concentration usually
  VDRL, or a combination of these.
• WBC count 5 lymphocytes per microliter or a
  protein concentration 45 mg/dL in patients with
  suspected neurosyphilis (without HIV) is
  diagnostic
• In HIV positive patients with a negative CSF VDRL
  there is no consensus regarding CSF findings, as
  mild pleocytosis and elevated protein are typical
  in HIV infected patients.

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Symptomatic neurosyphilis

• Usually occurs within 1 year of infection
• Symptoms include headache, confusion, nausea and
  vomiting, and stiff neck may have decreased
  visual acuity if there is concomitant uveitis,
  vitritis, retinitis, or optic neuritis.
• Patients can have cranial neuropathies,
  particularly of the optic, facial, or auditory
  nerves.
• Can cause small, medium or large vessel arteritis
  leading to ischemia or infarction
• Syphilitic gummas may present as mass lesions and
  can cause seizures
• Uncommonly affects spinal cord with
  meningomyelitis or hyperplastic pachymeningitis
  with polyradiculopathy
• CSF abnormalities are more severe, with cell
  count between 200-400, protein between 100-200,
  and almost always positive VDRL.

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Meningovascular syphilis

• Syphilis can cause an infectious arteritis that
  may affect any vessel in the subarachnoid space
  and result in thrombosis, ischemia, and
  infarction.
• Can develop at any time from first months to
  several years after infection.
• May present as an ischemic stroke in a young
  person.

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Late neurosyphilis

• General paresis
• Progressive dementing illness initially with
  forgetfulness and personality changes
• Usually occurs 10 to 25 years after infection
• In the first half of the 20th century, it
  accounted for about 10 of admissions to
  psychiatric hospitals.

• Tabes dorsalis
• - Disease of the posterior columns of the spinal
  cord and of the dorsal roots
• - Average interval is 20 years after infection
• Characterized by ataxia and lancinating pains
• Not common in post-antibiotic era.

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Syphilis and HIV

• HIV and syphilis are prevalent in the same risk
  groups men who have sex with men, injection drug
  users, and individuals engaging in sex in
  exchange for drugs or money.
• Both infections have been reported to enhance the
  acquisition and transmission of each other
• Neurosyphilis may be more common in persons
  co-infected with HIV there have been many case
  reports of such patients who have rapidly
  progressed from early syphilis to neurosyphilis.
• For this reason, many experts recommend
  performing LP on all HIV-infected patients with
  syphilis.

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Ocular syphilis

• All structures of the eye may be affected
• Uveitis is most common
• Nothing is pathognomonic
• Uveitis
• Anterior uveitis granulomatous or
  nongranulomatous.
• Posterior segment involvement posterior placoid
  chorioretinitis, vitritis, focal retinitis,
  retinal vasculitis, and papillitis,
  periphlebitis, retinal hemorrhages, and serous
  and exudative retinal detachments
• Panuveitis often granulomatous
• Other eye manifestations
• Optic neuritis, neuroretinitis, arterial and
  venous occlusion

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Ocular Syphilis

• Acute syphilitic posterior placoid
  chorioretinitis
• Interstitial keratitis

• Anterior uveitis
• Extensive retinitis with multifocal satellite
  lesions

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Ocular syphilis and HIV

• With untreated HIV coinfection
• Bilateral eye involvement and posterior segment
  may be more common
• Retrospective review of HIV on HAART with ocular
  syphilis in Georgetown HIV clinic
• No correlation with CD4 count
• Mean408 (Range 388-594)
• No cases of CMV retinitis during the same period

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Treatment

• Early syphilis is a reportable disease and should
  be brought to the attention of the department of
  public health
• T. pallidum remains highly sensitive to
  penicillin and no resistance has been reported to
  date despite several decades of use

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Treatment

• Standard therapy for primary, secondary, or early
  latent syphilis is benzathene penicillin G (one
  dose 2.4 million units IM)
• If the patient has had syphilis of greater than 1
  year duration or if duration is unknown,
  treatment should be benzathene penicillin G 2.4
  million units IM x 3 doses, 1 week apart.
• Neurosyphilis and ocular syphilis 18 to 24
  million units per day, administered as 3 to 4
  million units IV every four hours or continuous
  infusion, for 10 to 14 days
• For penicillin allergic patients
• Early syphilis Doxycyline 100mg BID x 14 days,
  or tetracycline 500mg QID x 14 days. Ceftriaxone
  and azithromycin have both been studied but are
  not currently recommended.
• Gummatous syphilis Doxycycline 100mg BID for 28
  days.
• Cardiovascular syphilis Ceftriaxone 1g daily for
  10-14 days (if history of mild PCN allergy)
• Neurosyphilis Patients should undergo
  desensitization and treatment with PCN

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Jarisch-Herxheimer Reaction

• Dramatic but usually mild reaction consisting of
  fever, chills, myalgias, headache, tachycardia,
  increased respiratory rate, increased circulating
  neutrophil count and vasodilation with mild
  hypotension may follow initiation of treatment
• Occurs in nearly 50 with primary, 90 with
  secondary, and 25 with early latent syphilis.
• Defervescence occurs within 12 to 24 hours
• Treatment of the reaction is symptomatic

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Prognosis

• Monitor response to treatment using RPR or VDRL
  titers
• After treatment of first episode primary or
  secondary syphilis the VDRL titer declines,
  becoming negative by 12 months in 40-75 in
  primary and 20-40 in secondary cases.
• Re-treatment should be considered if serologic
  responses are not adequate or if clinical signs
  persist or recur.
• CSF should be examined in patients with suspected
  treatment failure, and if abnormal the patient
  should be treated for neurosyphilis.
• Patients with late latent syphilis may not have a
  dramatic drop in antibody titers but should not
  be retreated unless titers rise or symptoms
  recur.
• Most patients with ocular syphilis will have
  improvement in vision, but not necessarily to
  baseline. Even delayed treatment can improve
  vision. Prolonged disease can ultimately result
  in eye destruction.

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References

• 2007 UpToDate
• Workowski, KA, Berman, SM. Sexually transmitted
  diseases treatment guidelines, 2006. MMWR Recomm
  Rep 2006 551.
• Balba, GP, Kumar, PN, James, AN, et al. Ocular
  syphilis in HIV-positive patients receiving
  highly active antiretroviral therapy. Am J Med
  2006 119448.
• Bordon J, Martinez-Vasquez, C, et al. Eur J Clin
  Microbiol Infect Dis. 1999 Oct18(10)729-32.
• Kasper, Braunwald, et al. Harrisons Principles
  of Internal Medicine. 16th Edition. 2005
  977-988.