A year old male with skin rash

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					A 46 year old male with a rash

     Primary Care Conference
         June 28th, 2006
     Bev Grooms Thom, PA-C
  Case Presentation: 46 y/o male
           with a rash
• 46 y/o single international executive presented for
  evaluation of a 1 month hx of a non pruritic, non
  tender trunkal and upper extremity rash.
  “Occasionally scaly”
• Pt had been in South America x 10 days; rash
  began soon after return.
• Tanned several times before trip
• Had Yellow Fever vaccine prior to trip
• Travels to Asia > 2x per year
• New med: Lipitor x 2 months prior to onset rash
  Case Presentation: 46 y/o male
           with a rash
• Unusual “herald patch”
• Pt admitted to non healing penile lesion x 6
• Penile lesion described as “whitish”, non
• Denies fever, chills, sore throat, weight loss,
  fatigue, alopecia and lymphadenopathy

  Case Presentation: 46 y/o male
           with a rash
• Homosexual male
• Condom use:
  – “Always” with anal insertive or receptive intercourse
  – “Most of the time” with insertive or receptive oral sex
• Number of partners:
  – 15 in past year
  – 2 in last 6 months

  Case Presentation: 46 y/o male
         with a rash: PE
• VS … normal
• ENT: No oral lesions
• Skin: Maculopapular faint erythematous
  rash, irregular shaped and sized (0.5-1.5
  cm) over chest, back, arms and abdomen.
  Palms and plantar aspect feet not involved.

Trunkal rash

 Case Presentation: 46 y/o male
        with a rash: PE
• Genitalia: Single 1.5 cm oval shaped
  ulcerated lesion on penile shaft with
  smooth, whitish border. Non tender.
• Scattered maculopapular erythematous
  lesions elsewhere on penile shaft. No
  urethral discharge
• Testicular exam: Normal

Penile ulcer

  Case Presentation: 46 y/o male
     with a rash: Differential
• Non pruritic trunkal/extremity rash
  secondary to ???
  –   pityriasis rosea
  –   photosensitivity reaction
  –   medication reaction
  –   syphilis

 Case Presentation: 46 y/o male
    with a rash: Diagnostics

• CBC with diff (normal)
• HIV .. Non reactive
• RPR … reactive at 1:32 dilution, confirmed
  on TPPA
• Pt informed, directed to inform partners.

  Case Presentation: 46 y/o male
    with a rash: Management
• Returned to clinic six days after initial visit
• Rash spread to lower extremities and buttock, no
  palmar/plantar involvement.
• At time of rx, pt c/o sore throat. No other c/o.
   – Strep and GC culture negative
• Rx … 2.4 million units IM Benzathine Penicillin

 Case Presentation: 46 y/o male
    with a rash: Follow up
• RTC 2 1/2 months post treatment … ST
  cleared immediately, rash resolved 2 weeks
  post treatment.
• Patient’s partner recently became HIV
  positive but is RPR negative.
• Patient’s repeat 3 month HIV negative
• Follow up RPR within 6 months

Case Presentation: 46 y/o male
with a rash: Learning Objectives
• Awareness of the differential diagnosis of a
  diffuse maculopapular rash
• Have knowledge of the signs, symptoms and
  stages of syphilis
• Understand the ramifications of co-infection of
  syphilis and HIV
• Attain knowledge of the diagnosis and treatment
  of syphilis
• Raise consciousness regarding syphilis as a re-
  emerging entity
          Syphilis: Definition
• A chronic infection caused by the bacterium
  treponema pallidum (Tp)
• Non Tp treponemes may exist elsewhere
• The manifestations of disease are quite varied,
  occurring in any one individual in different stages
  over time
• Primarily sexually transmitted
• Recognized for centuries, origin unknown

       Syphilis: Epidemiology
• Reportable disease, therefore allows a relatively
  accurate # of early cases
• Late 1980s/early 1990s … mini epidemic of early
  syphilis led to rates higher than any time since
  introduction of penicillin
• 2000 … incidence falls to all time low, raising
  hopes for eradication. Targeted groups had been
  women (decline incidence by 35%) and African-
  Americans (similar decline)

       Syphilis: Epidemiology
• Since 2001, early syphilis rates have increased and
  this trend continues
• This increase has occurred mainly among men
  who have sex with men (MSM)
• Relatively high rate of HIV co-infection in
  persons with syphilis
   – 25% co-infection rate in 2002 among 6862 pts with
     primary and secondary syphilis

   Syphilis: Epidemiology: HIV
• Strong association between both diseases
   – Both primarily sexually transmitted
   – Increased HIV transmission in setting of genital ulcer
• Little evidence syphilis more severe in HIV
  disease but interaction between the two may alter
  some of the manifestations of syphilis.
   – More likely to present with secondary syphilis and
     those pts more likely to have persistent chancres
   – More likely to have multiple and persistent chancres

   Syphilis: Epidemiology: HIV
• Pts with untreated syphilis may have higher
  HIV RNA load and lower CD4 counts that
  respond favorably to effective treponemal
• Fulminant presentation, rapid progression
  and treatment failures are rare
  – Some reports state risk of treatment failure may
    depend on degree of immunosuppression
    induced by HIV
Geographic features in the U.S.

         Syphilis: Epidemiology
• In addition to US, syphilis an important problem
  elsewhere in the world.
• In 1999 WHO estimated new cases
   –   North America .. 100,000
   –   Western Europe .. 140,000
   –   Eastern Europe and Central Asia .. 100,000
   –   North Africa and Middle East .. 370,000
   –   Latin America and Caribbean, sub-Saharan Africa,
       south and southeast Asia … 3-4 million each!
            Syphilis: Etiology
• Transmission primarily via sexual contact between
  infected and uninfected partners
• Portal of entry via small abrasions.
• Replication locally with spread to regional lymph
• Early lesions very infectious; chancres, mucous
  patches and condyloma lata
   – Transmission occurs in 1/3 patients exposed to these

         Syphilis: Etiology
• May be transmitted by kissing or touching
  active lesions on the lips, oral cavity,
  breasts or genitals
• In MSM, transmission documented in those
  individuals who only have had oral sex as
  their only risk factor for acquisition

         Syphilis: Etiology

• Other modes include transplacental, non-
  sexual contact with infections lesions,
  laboratory accidents and contaminated
  blood products (rare because donors are
  screened and Tp cannot survive >24-48 hrs
  under current blood bank storage
          Syphilis: Etiology
• Risk factors in MSM and bisexual men:
  – HIV infection
  – Combined use of methamphetamine and
  – Recent sexual partners from the Internet

      Syphilis: Clinical
Manifestations: Early or primary
• After 2-3 week incubation period, a papule
  appears at site of inoculation. May be as long as 3
  months due to inoculation load and previous
  infection with syphilis
• Usually painless, soon ulcerates to produce classic
• Multiple chancres may occur, but not common.
  Increased in HIV infected persons
• 1-2 cm ulcer with raised, indurated margin
• Usually non-exudative base, associated with mild
  to moderate regional bilateral lymphadenopathy 25
      Syphilis: Clinical
Manifestations: Early or primary
• Spontaneous healing of chancres within 2-8
  weeks, potentially longer in immunocompromised
  patients, even in absence of treatment.
• Mechanism of healing not known, but thought
  secondary local immune responses.
• Systemic spread occurs quickly
• Spirochetes disseminate during the primary stage
  of infection

    Syphilis: Differential Diagnosis:
            Early or primary
•   Syphilis
•   Chancroid
•   Genital Herpes
•   Behcet’s disease
•   Drug eruptions

        Syphilis: Clinical
     Manifestations: Secondary
• In untreated primary infection, within weeks to
  months, 25-30% patients will develop illness due
  to secondary syphilis
• Fever, malaise, diffuse lymphadenopathy
• Patchy alopecia, HA, ST and weight loss
• Classic hyperpigmented, scaly maculopapular rash
  on trunk, extremities, including palms and soles
• Condylomata lata (raised, grey to white lesions
  involving warm, moist areas) may develop in
  some patients
        Syphilis: Clinical
     Manifestations: Secondary
• The findings of enlarged epitrochlear lymph nodes
  in the absence of upper extremity pathology is
  considered to be highly suspicious for syphilis.
• Skeletal manifestations: Osteitis, arthritis, bursitis
• GI: Hepatitis, hepatomegaly, elevated alk phos,
• GU: Nephropathy (glomerulonephritis and
  nephrotic syndrome)

       Syphilis: Clinical
    Manifestations: Secondary
• Visual: Anterior and posterior uveitis
  – May be asymptomatic or have altered vision …
  – Syphilis may be correctly diagnosed after
    failure to respond to or worsening following
    steroid treatment.

        Syphilis: Clinical
     Manifestations: Secondary:
• Neurologic abnormalities may occur within the
  first few weeks after initial infection or for up to
  25 years without treatment (causing diagnostic
  confusion - different forms may coexist and
• Manifestations may include headache, stiff neck,
  N&V, photophobia, cranial neuropathies
  associated with ocular and otic deficits, facial
  nerve palsies, papilledema and encephalopathy.
        Syphilis: Clinical
     Manifestations: Secondary:
• Most patients do not have the rash of secondary
  syphilis by the time significant neurologic findings
  are present.
• Occasionally neurologic (and other)
  manifestations of secondary syphilis can occur for
  up to 5 years in the untreated patient.
• A common clinical problem is when lumbar
  puncture should be performed in patients with
  early syphilis
       Syphilis: Clinical
    Manifestations: Secondary:
• No evidence that treatment failures more common
  in pts with early syphilis and abnl CSF analysis
  after rx with benzathine PCN
• The primary indications for lumbar puncture are
  symptoms of meningitis or other focal neurologic
• A serum RPR > 1:32 is associated with a > 10
  fold increase risk of neurosyphilis
• Therefore, the decision to do an LP rests on both
  symptoms and RPR titer
       Syphilis: Clinical
    Manifestations: Secondary
• Similar to primary disease, acute
  manifestations of secondary syphilis
  typically resolve spontaneously, even in the
  absence of treatment

          Syphilis: Clinical
         Manifestations: Latent
• Latent syphilis is defined as the period during
  which patients have no symptoms but have
  infection demonstrable by serologic testing
• There are two periods of latent syphilis
   – Early latent … secondary syphilis may recur
     (mucocutaneous relapses … potentially infectious)
   – Late latent … no clinical manifestations, transmission
     no longer probable.

         Syphilis: Clinical
        Manifestations: Latent
• USPHS has modified the definition by
  categorizing early latent syphilis as
  infection of one year’s duration or less
• All other cases referred to as late latent or
  latent syphilis of unknown duration
• In late latent disease, the organisms dividing
  time is probably longer and treatment may
  need to be more prolonged

       Syphilis: Clinical
  Manifestations: Late or tertiary
• Defined as stages of syphilis that occur after early
  (primary or secondary) or latent syphilis
• May arise within a year of initial infection or up to
  30 years later.
   – Occurs in uncertain proportion of infected patients.
     Remains to be seen how many cases of late syphilis
     will occur given the recent resurgence of early syphilis
• Typically involves CNS, cardiovascular, skin or
  subcutaneous tissues
  Syphilis: Diagnosis: Primary
• Complicated by fact that organism can not
  be cultivated in vitro
• Dark field microscopy of lesion exudate
  – Spirochetes manifesting corkscrew morphology
    of treponemes showing white organisms against
    a black background
• Obtain from base of chancre after cleaning
  with saline and applying gentle pressure
Dark Field Microscopy

  Syphilis: Diagnosis: Primary
• DFA test on exudate may be done when
  immediate processing of specimen not
• PCR of exudate possible (relatively new)
  – PCR combined probe for syphilis, chancroid
    and HSV available
  – Available at UW as a “send out” test

  Syphilis: Diagnosis: Serologic
• RPR is screening test done at UW core lab
   – If positive, core lab reflexly obtains a TPPA
• Early syphilis
   – Screening tests (non treponemal, e.g RPR) 78-86%
     sensitive in primary syphilis
• Secondary syphilis
   – Likelihood of false negative RPR remote
   – Usually high antibody titers by this time
• Latent syphilis
   – Titers decline. Not uncommon to see 1:1 to 1:16 levels
   – Diagnosis of late or tertiary depends on clinical findings
     and not serologic testing
  Syphilis: Treatment of early or
        secondary disease
• All manifestations of primary and
  secondary syphilis will resolve without
• Therapy must be prolonged since Tp
  divides slowly, averaging one doubling per
  day in vivo
• Long acting penicillin preparations are the
  mainstay of treatment

  Syphilis: Treatment of early or
        secondary disease
• Benzathine penicillin G, 2.4 million units x one
  dose remains treatment of choice per CDC and
• Only long acting penicillin should be used since
  low, continuous levels are necessary to eliminate
• Use of CR Bicillin (= concentrations of procaine
  and benzathine PCN G) results in detectable
  serum levels for only 7 days!!
  Syphilis: Treatment of early or
        secondary disease
• IM only route; IV has been associated with
  cardiopulmonary arrest and death
• No resistance has been reported to date despite several
  decades of use
• Potential complication: Jarisch-Herxheimer reaction
   – Release of pyrogenic endotoxins from rapid kill of
   – Occurs within first few hours of rx of syphilis, usually

  Syphilis: Treatment of early or
        secondary disease
• Penicillin allergic patients
   – Azithromycin, single 2 gram dose shown to be effective
     (98% cure vs. 95% PCN Rx), but increasing reports of
     macrolide resistance
   – Doxycycline, 100mg bid x 14 days or TCN, 500mg qid
     x 14 days
• Settings where penicillin must be used
   – Congenital syphilis
   – Syphilis in pregnancy
      • Rx late in pregnancy carries > risk for congenital syphilis than
        rx in early pregnancy
   – Neurosyphilis                                                     45
    Syphilis: Treatment of latent
• Single dose treatment only appropriate if
   – There is documentation of a non reactive syphilis
     serology in the past year or …
   – If there is documentation of a seropositivity and
     chancre within the past year
• In the absence of above, treatment should be for
  “latent syphilis of unknown duration” … 3 doses
  of 2.4 mu benzathine PCN at weekly intervals
• Rx issues in HIV patients
Treatment issues in HIV patients
• Primary and secondary syphilis: Single
  dose benzathine penicillin G, 2.4 mu IM
  unless patient presents with abnormal
  neurologic signs or symptoms
• Early latent patients can be managed the
  same as primary or secondary syphilis

Treatment issues in HIV patients
• Syphilis of unknown duration or late latent should
  have a CSF exam before treatment
   – Normal CSF .. Rx with benzathine PCN G, 2.4 mu x 3
     consecutive weeks
   – Abnormal CSF, i.e. neurosyphilis … aqueous
     crystalline PCN G, 3-4 million units IV q 4hr or
     continuous infusion total 18-24 million units per day x
     10-14 days.
• PCN allergic patients may receive ceftriaxone or
  be desensitized to PCN

   Syphilis: Treatment followup
• RPR should fall four fold in 6 to 12 months
• Some serologic non-responders may be due
  to reinfection … therefore treatment with a
  second course required
• Be sure all sexual partners are treated
• CDC suggests LP if patients do not see 4
  fold decrease in RPR titers


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