Download A 46 year old male with a skin rash

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
2
Case Presentation: 46 y/o male
with a rash
• Unusual “herald patch”
• Pt admitted to non healing penile lesion x 6
weeks
• Penile lesion described as “whitish”, non
tender.
• Denies fever, chills, sore throat, weight loss,
fatigue, alopecia and lymphadenopathy
3
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
4
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.
5
Trunkal rash
6
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
7
Penile ulcer
8
Case Presentation: 46 y/o male
with a rash: Differential
• Non pruritic trunkal/extremity rash
secondary to ???
–
–
–
–
pityriasis rosea
photosensitivity reaction
medication reaction
syphilis
9
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.
10
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
G
11
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
12
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 reemerging entity
13
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
14
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 AfricanAmericans (similar decline)
15
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
16
Syphilis: Epidemiology: HIV
associations
• Strong association between both diseases
– Both primarily sexually transmitted
– Increased HIV transmission in setting of genital ulcer
disease
• 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
17
Syphilis: Epidemiology: HIV
associations
• Pts with untreated syphilis may have higher
HIV RNA load and lower CD4 counts that
respond favorably to effective treponemal
therapy.
• 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
18
Geographic features in the U.S.
19
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!
20
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
nodes
• Early lesions very infectious; chancres, mucous
patches and condyloma lata
– Transmission occurs in 1/3 patients exposed to these
lesions
21
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
22
Syphilis: Etiology
• Other modes include transplacental, nonsexual 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
conditions)
23
Syphilis: Etiology
• Risk factors in MSM and bisexual men:
– HIV infection
– Combined use of methamphetamine and
sildenafil
– Recent sexual partners from the Internet
24
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
chancre
• 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
26
Syphilis: Differential Diagnosis:
Early or primary
•
•
•
•
•
Syphilis
Chancroid
Genital Herpes
Behcet’s disease
Drug eruptions
27
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
28
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,
gastritis
• GU: Nephropathy (glomerulonephritis and
nephrotic syndrome)
29
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.
30
Syphilis: Clinical
Manifestations: Secondary:
Neurologic
• 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
overlap).
• Manifestations may include headache, stiff neck,
N&V, photophobia, cranial neuropathies
associated with ocular and otic deficits, facial
nerve palsies, papilledema and encephalopathy.
31
Syphilis: Clinical
Manifestations: Secondary:
Neurologic
• 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
32
Syphilis: Clinical
Manifestations: Secondary:
Neurologic
• 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
findings
• 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
33
Syphilis: Clinical
Manifestations: Secondary
• Similar to primary disease, acute
manifestations of secondary syphilis
typically resolve spontaneously, even in the
absence of treatment
34
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.
35
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
36
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
37
Syphilis: Diagnosis: Primary
syphilis
• 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
38
Dark Field Microscopy
39
Syphilis: Diagnosis: Primary
syphilis
• DFA test on exudate may be done when
immediate processing of specimen not
possible
• PCR of exudate possible (relatively new)
– PCR combined probe for syphilis, chancroid
and HSV available
– Available at UW as a “send out” test
40
Syphilis: Diagnosis: Serologic
testing
• 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
41
and not serologic testing
Syphilis: Treatment of early or
secondary disease
• All manifestations of primary and
secondary syphilis will resolve without
therapy
• Therapy must be prolonged since Tp divides
slowly, averaging one doubling per day in
vivo
• Long acting penicillin preparations are the
mainstay of treatment
42
Syphilis: Treatment of early or
secondary disease
• Benzathine penicillin G, 2.4 million units x one
dose remains treatment of choice per CDC and
WHO
• Only long acting penicillin should be used since
low, continuous levels are necessary to eliminate
treponemes
• Use of CR Bicillin (= concentrations of procaine
and benzathine PCN G) results in detectable
serum levels for only 7 days!!
43
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
treponemes.
– Occurs within first few hours of rx of syphilis, usually
secondary.
44
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
disease
• 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
46
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
47
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
48
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
49