Transcript Toxic Shock Syndrome

Toxic Shock Syndrome
Jared Helms D.O.
7 March 2007
What Comes To Mind?
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Tampon use
Minor trauma
Injuries resulting in hematoma, bruising, or
muscle strain
Surgical procedures (eg, suction lipectomy,
hysterectomy, vaginal delivery ,
bunionectomy, bone pinning, breast
reconstruction, cesarean section)
Viral infections (eg, varicella, influenza)
Use of nonsteroidal antiinflammatory drugs
What Comes To Mind?
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Cause
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Staphylococcus aureus (appx 0.8 per
100,000)
Group A streptococcus (appx 3.5 per
100,000)
Staphylococcal toxic shock
syndrome
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Term toxic shock syndrome was
coined in 1978
Public attention in 1980 based
upon a series of menstrualassociated cases
CDC proposed a revised clinical
case definition in 1981
Case definition of toxic shock
syndrome from the CDC
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Fever
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Hypotension SBP< 90 mmHg; Orthostatic
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Rash Diffuse macular erythroderma
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Desquamation 1 to 2 weeks after onset of
T >38.9°C (102.0°F)
syncope or dizziness
illness, particularly involving palms and soles
Case definition of toxic shock
syndrome from the CDC
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Multisystem involvement
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(3 or more of the following organ systems)
GI: Vomiting or diarrhea at onset of illness
Muscular: Severe myalgia or CPK elevation >2 times the normal
upper limit
Mucous membranes: Vaginal, oropharyngeal, or conjunctival
hyperemia
Renal: BUN or serum creatinine >2 times the normal upper limit, or
pyuria (>5 WBC/hpf)
Hepatic: Bilirubin or transaminases >2 times the normal upper limit
Hematologic: Platelets <100,000/ L
Central nervous system: Disorientation or alterations in
consciousness without focal neurologic signs in the absence of
fever and hypotension
Menstrual
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Between 1979 and 1996, 5,296
TSS cases were reported
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59 percent from 1987 to 1996
number of cases of menstrual TSS to
1 out of 100,000 women since 1986
case-fatality rate was 1.8 percent in
1987 to 1996
Nonmenstrual
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Approximately one-half of
reported TSS cases are
nonmenstrual
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surgical and postpartum wound
infections, mastitis, septorhinoplasty,
sinusitis, osteomyelitis, arthritis, burns,
cutaneous and subcutaneous lesions
(especially of the extremities, perianal
area, and axillae), and respiratory
infections following influenza
The proportion of cases following surgical
procedures increased from 14 percent in
1979 through 1986 to 27 percent in
1987 through 1996
Menstrual versus
nonmenstrual cases
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Clinical presentations of menstrual
and nonmenstrual TSS are similar
Nonmenstrual TSS was associated
with earlier onset of rash and fever
Surgical wound sites and
cutaneous infections are frequently
benign-appearing without obvious
purulence
PATHOGENESIS
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Toxic shock syndrome toxin-1 —
initial exotoxin isolated from S. aureus
isolates implicated in TSS in 1981
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Enterotoxins A, C, D, E, and H
PATHOGENESIS
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S. aureus
exotoxins cause
disease because
they are
superantigens
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Activate large numbers of T cells
Activated T cells then release
interleukin (IL)-1, IL-2, tumor
necrosis factor (TNF)-alpha and
TNF-beta, and interferon (IFN)gamma
Laboratory findings
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Leukocytosis may not be present
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total number of mature and immature
neutrophils usually exceeds 90 percent
immature neutrophils accounting for 25 to
50 percent of the total number of
neutrophils
Thrombocytopenia and anemia
DIAGNOSIS
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Based upon clinical presentation
Isolation of S. aureus is not
required for the diagnosis of
staphylococcal TSS
Cultures from mucosal and wound
sites should be obtained
DIFFERENTIAL
DIAGNOSIS
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Streptococcal TSS
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Rocky Mountain spotted fever
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associated with severe pain and tenderness
signifying infection at a site of local trauma
the rash associated with RMSF typically is
petechial, involves the extremities first
Meningococcemia
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meningitis is frequently seen in conjunction
with meningococcemia and is rare in TSS
MANAGEMENT
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Mainstay of treatment for TSS is
supportive
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may require extensive fluid
replacement (10 to 20 liters per day)
to maintain perfusion
vasopressors may also be required
Episodes of menstrual TSS can
resolve with supportive care only
MANAGEMENT
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Examination for the presence of foreign
material in the vaginal canal
Drainage of any identified infectious
focus
Surgical wounds may not appear to be
infected because of the decreased
inflammatory response but should
nevertheless be explored and debrided
if the patient fulfills the clinical criteria
for TSS.
MANAGEMENT
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It is not clear whether antibiotics
alter the course of acute TSS,
however antistaphylococcal
antibiotic therapy is needed to
eradicate organisms
Antibiotic therapy
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All patients with suspected TSS receive empiric
treatment with clindamycin (adults: 600 mg
IV every eight hours; children: 25 to 40 mg/kg
per day in three divided doses) plus
vancomycin (adults: 30 mg/kg per day IV in
two divided doses; children: 40 mg/kg per day
IV in four divided doses)
Typically treat with a 10 to 14 day course
PROGNOSIS
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Death associated with TSS usually
occurs within the first few days of
hospitalization but may occur as late
as 15 days after admission
Questions about
Staphylococcal toxic shock
syndrome?
Group A streptococcus TSS
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Defined as any GAS infection associated
with the acute onset of shock and
organ failure
Any infection associated with the
isolation of GAS from a normally sterile
body site
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aerobic gram-positive coccus that causes
pharyngitis and a spectrum of skin and soft tissue
infections such as impetigo, erysipelas, and
localized cellulitis
PATHOGENESIS
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Group A streptococcal TSS is mediated
by toxins that act as superantigens
Cytokines cause capillary leak and
tissue damage, leading to shock and
multiorgan failure
PATHOGENESIS
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Most common portals of entry for
streptococcal infections are the skin,
vagina, or pharynx
Portal of entry cannot be identified in
45% of cases
CLINICAL PRESENTATION
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Most common initial symptom is severe pain
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abrupt in onset
diffuse or localized
typically involves an extremity
may also mimic peritonitis, pelvic inflammatory disease,
pneumonia, acute myocardial infarction, cholecystitis, or
pericarditis
Fever is the most common presenting sign
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hypothermia may be present in patients with shock
Other manifestations
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80 % clinical signs of soft tissue
infection
influenza-like syndrome (20%)
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fever, chills, myalgia, nausea, vomiting, and
diarrhea
50% of patients are normotensive on
presentation or admission, but become
hypotensive within the subsequent four
hours.
Laboratory findings
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Mild leukocytosis
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Serum creatinine is frequently elevated
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percentage of immature neutrophils may reach 40
to 50 percent
precedes the development of hypotension in 40 to
50 percent of cases
Myoglobinuria and hemoglobinuria
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can contribute to the development of acute renal
failure
Laboratory findings
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Increase in the serum creatinine kinase
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suggests the presence of necrotizing fasciitis
or myositis
Positive blood cultures
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approximately 60 % of cases (5% in Staph
TSS)
DIFFERENTIAL DIAGNOSIS
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Staphylococcal toxic shock syndrome
Gram-negative sepsis
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Rocky Mountain spotted fever
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uncommon in healthy patients outside the hospital setting
severe headache and rash are present in most
patients with RMSF; rash is present in only 10%
of patients with GAS TSS
Acute meningococcemia
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rash is petechial and meningitis is common in
meningococcemia but is infrequent in GAS TSS
DIAGNOSIS
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Isolation of GAS from a normally sterile site
Hypotension (systolic blood pressure 90 mm Hg in
adults )
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Plus two or more of the following:
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Renal impairment
Coagulopathy
Liver involvement
Erythematous macular rash, may desquamate
Soft tissue necrosis
Treatment
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Hemodynamic support
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Massive amounts of intravenous fluids (10
to 20 L/day) are often necessary
vasopressors may also be required
Surgical therapy
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Prompt and aggressive exploration and
debridement of suspected deep-seated
infection is mandatory
Treatment
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Antibiotic therapy
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Presumptive therapy should be initiated
pending culture results
Clindamycin suppresses the synthesis of
bacterial toxins and suppresses TNF
The role of IVIG in GAS TSS remains to
be determined by controlled trials.
Recommended Empiric
Therapy
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Clindamycin (900 mg IV every eight
hours)
plus one of the following:
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A carbapenem (meropenum 1g every eight
hours)
A combination drug containing a penicillin plus
beta-lactamase inhibitor (eg, ticaracillinclavulanate 3.1 g every four hours or
piperacillin-tazobactam
4.5 g every six hours)
PROGNOSIS
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Overall mortality rate in GAS TSS varies
from 30 to 70 percent
Signs of poor prognosis*:
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Lower white blood cell count (1000 vs
16000)
Lower platelet counts (120 vs 170)
Higher serum creatinine (3.0 vs 2.0)
Lower systolic blood pressure (99 vs 120)
Review
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Toxic shock syndrome is bad
Fortunately, it is uncommon
Treat hypotension with lots of fluids
Surgical debridement should be considered
early
Clindamycin is the drug of choice
A 29 year old man comes to the ER with
1 day history of increasing pain in the
upper right thigh. Two days ago, he was
cutting rebar with a power saw when he
suddenly developed right thigh pain from a
splinter thrown by the saw. The pain
abated over the next hour, and there was
no lesion when he examined the thigh that
evening. PMH is unremarkable. On physical
exam vitals are 96/68-108-16-101.1. The
right thigh is moderately tender. There is no
erythema or swelling.
CT scan shows a minute metal fragment in the
facial plane beneath the subcutaneous tissue
with edema and stranding in adjacent areas.
The patient is hospitalized and
begun on empiric vancomycin pending culture
results. Three hours after admission, his BP
drops to 60/0. IV fluids and vasopressors are
started with mild improvement in pressure.
Over the next several days the patient
develops signs of renal and hepatic
insufficiency (gradually returns to normal).
Armed with the knowledge of a stellar
noon-time lecture you astutely diagnose:
1.
A.
B.
C.
D.
Cellulitis
Staphylococcal toxic shock syndrome
Streptococcal toxic shock syndrome
Adverse reaction to vancomycin
2. Management of this patient includes:
A.
B.
C.
D.
Continue vancomycin and increase fluids
Switch to clindamycin and nafcillin
Add clindamycin to the vancomycin and get a
surgical evaluation
Have him (or DPOAHC) fill out DNR papers
3. When grilled on rounds about the
incidence of this infection, you confidently
answer:
A.
B.
C.
D.
0.8 cases per 100,000
3.5 cases per 100,000
“It’s actually pretty common”
Million to one shot doc