Toxic Shock Syndrome and Streptococcal Toxic Shock Syndrome

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Toxic Shock Syndrome and Streptococcal Toxic
Shock Syndrome

• Dr. Batizy, D.O.
• January 26, 2006

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Toxic Shock Syndrome

• Severe life threatening syndrome characterized
  by
• High fevers
• Severe hypotension
• Diffuse erythroderma
• Mucous membrane hyperemia
• Pharyngitis
• Diarrhea

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Toxic Shock Syndrome

• May progress rapidly
• Multisystem disfunction
• Severe electrolyte disturbances
• Renal failure
• Shock

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Toxic Shock Syndrome

• Discovered in 1978 in apparently healthy children
  Staph aureus isolated
• TSS epidemic 1981 associated with increased
  tampon use
• Incidence has dropped significantly,
• Currently most cases are unrelated to menses
• Case Definition of Toxic Shock Syndrome, table
  142-1

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Case Definition of Toxic Shock Syndrome, Table
142-1

• Fever temp gt102.0 F (gt38.9 C)
• Rash diffuse macular erythroderma
• Hypotension
• Multisystem envolvement (three or more)
• GI vomiting or diarrhea at onset of illness
• Muscular sever myalgia or creatine phosphokinase
  level at least twice the upper limit of normal
• Mucous membrane vaginal, oropharyngeal, or
  conjunctival hyperemia

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• Renal blood urea nitrogen or creatinine at least
  twice the upper limit of normal for laboratory or
  urinary sediment with pyuria (greater than or
  equal to 5 leukocytes per highpower field) in the
  absence of urinary tract infection
• Hepatic total bilirubin, alanine
  aminotransferase enzyme, or asparate
  aminotransferase enzyme levels at least twice the
  upper limit of normal for laboratory
• Hematologic platelets less than 100,000/ml

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• CNS disorientation or alterations in
  consciousness without focal neurologic signs when
  fever and hypotension are absent
• Lab criteria negative results on the following
  tests, if obtained
• Blood, throat, or cerebrospinal fliud cultures
  (blood culture may be positive for Staphlococcus
  aureus
• Rise in titer to Rocky Mountain Spotted fever,
  leptospirosis, or measles

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Case Definition of TSS

• Case classification
• Probable five of six clinical findings are
  present
• Confirmed all six clinical findings are present,
  including desquamation, unless patient dies
  before desquamation occurs

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Epidemiology

• TSS initially a disease of young healthy
  menstruating women, comprised fifty percent of
  cases reported in 1986-87
• Tampon use increased risk up to 33
• In 2000, 135 reported cases, 3 were in men, and 2
  fatalities were from menstrual-related TSS
  (MRTSS)
• FDA - Tampons now made of cotton and rayon,
  should be changed every 4-8 hrs

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Epidemiology

• Non-menstrual related cases of Toxic Shock
  Syndrome (NMTSS)
• Increasing since 1980
• 41 NMTSS
• Men comprise one-tenth of population
• Mortality rate 3.3 x that of MRTSS in women
• S. aureus isolated from 98 of women with TSS
• Women with MRTSS most likely colonized with Staph
  aureus before the onset of menstruation

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Epidemiology

• TSS associated with influenza or influenza-like
  illnesses mortality rate (43)
• Nasal packing (nasal tampons) also associated
  with TSS

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Pathophysiology

• Most TSS associated with S. aureus
• TSST-1 toxic shock syndrome toxin, exotoxin
• Induce fever via the hypothalamus or via IL-1 and
  TNF
• T-lymphocyte superantigenation and
  overstimulation
• Induce interferon production
• Enhance delayed hypersensitivity
• Supress neutrophil migration and IG secretion
• Enhance host suseptibility to exotoxins

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Pathophysiology

• Enterotoxins B and C
• Similar chemical structure to TSST-1
• Seen primarily in NMTSS
• Elicit similar clinical manifestations as TSST-1

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Pathophysiology

• Vaginal conditions favorable to TSST-1
• Temp 39-40 C
• Neutral pH
• PO2 gt 5
• Supplemental CO2
• Menstruation neutralizes vaginal pH
• Tampon use may increase O2 and CO2
• Synthetic fibers in tampon composition
• Synergistic relationship between S. aureus and E.
  coli

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Pathophysiology

• Vasodilation rapid and massive onset
• Hypotension
• Decreased vasomotor tone, blood pooling,
  decreased vascular return
• Nonhydrostatic leakage of fluid into the
  interstitium, contributing to hypotension and
  nonpitting edema of the head and neck
• Depressed cardiac function
• Total body water deficits from vomiting and
  diarrhea and fever

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Pathophysiology

• IL-1
• Hypoalbuminemia, hypoferrinemia, and proteolysis
  manifest as peripheral edema, anemia, and
  rhabdomyolysis seen in TSS
• TNF
• Acidosis, shock, and multisystem organ failure
• Multisystem organ failure
• Direct result from toxin
• Rapid onset of hypotension and decreased
  perfusion
• Small amts of TSST-1 and enterotoxins B and C can
  be detected in pts with TSS up to 1 year

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Clinical Features

• TSS must be considered when
• Unexplained febrile illness with erythroderma,
  hypotension, and diffuse organ pathology
• Pts with NMTSS present 3rd to 5th days of menses
• Postoperative NMTSS approx 2 days

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Clinical Features

• Mild TSS
• Fever
• Chills
• myalgias
• Abdominal pain
• Sore throat
• Nausea
• Vomiting
• Diarrhea
• Self-limiting

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Clinical Features

• Severe
• Acute onset
• Early multiorgan envolvement
• Prodrome
• Headache, malaise, myalgias, nausea, vomiting,
  and diarrhea
• Sudden onset of fevers and chills 1-4 days prior
  to presentation
• Orthostatic lightheadedness, profuse watery
  diarrhea, sore throat, paresthesias, photophobia,
  abdominal pain, and cough

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Clinical Presentation

• PE
• Hypotension
• Pt appears acutely ill
• Change in mental status
• Oliguria
• Nonpitting edema of face and extremities
• Watery diarrhea
• Pharygitis strawberry red tongue
• Tender erythematous external genitalia diffuse
  vaginal hyperemia, strawberry cervix, scant
  purulent cervical discharge, bilat adenexal
  tenderness

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Clinical Features

• Rash diffuse painless blanching erythroderma,
  fades in three days
• Followed by full-thickness desquamation
  particularly of palms and soles of feet
• Severely affected patients may have hair and nail
  loss 2-3 months later

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Clinical Features

• Focal neuro findings are rare
• Varying degrees of altered consciousness
• Toxic encephalopathy - confusion, disorientation,
  agitation, hysteria, somnolence, and seizures
• CT and LP will help deliniate

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Clinical Features

• Lab findings
• Leukocytosis
• lymphocytopenia
• Anemia
• ARF azotemia, myoglobinuria, sterile pyuria, RBC
  casts
• Liver abnormalities
• Metabolic acidosis 2nd to hypotension
• Electrolyte abnormalities
• Arrhythmias
• ARDS

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Differential Diagnosis

• Acute pyelonephritis
• Septic shock
• Acute rheumatic fever
• Scarlet fever strep or staph etiologies
• Leigionares disease
• PID
• HUS

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Differential Diagnosis

• Acute viral syndrome
• Leptospirosis
• SLE
• Rocky Mountain Spotted fever
• Tick typhus
• Gastroenteritis
• Kawasaki disease
• Reye syndrome
• Toxic epidermal necrolysis
• Erythema multiforme

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Treatment

• Aggressive shock management
• Continuous monitoring central
• Aggressive fluid replacement 4-20 L of
  crystalloid and FFP
• Ventilatory management if ARDS develops
• Complete blood work and cultures
• Removal of foreign bodies, i.e. tampon or nasal
  packing
• Antistaphlococcal penicillin or cephalosporin

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Treatment

• Antistaphlococcal penicillin or cephalosporin
• Nafcillin or oxacillin 2g IV every 4hrs
• Cefazolin 2g IV every 6hrs
• Oral anti-staphlococcal ABx for the next 10 -14
  days

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Treatment

• Pt not treated with ß-lactamase-stable abx can
  have recurrence
• MRTSS recurrence occurs in second month after
  the initial disease, recurring on the same day of
  the menstrual cycle
• Initial episode is the most severe

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Streptococcocal Toxic Shock Syndrome

• Group A Strep
• Soft tissue infection, early shock, multisystem
  organ failure, higher mortality than TSS, Flesh
  eating bacteria
• Most serious Strep necrotizing fasciitis and
  myositis
• STSS
• Most commonly affects 20 50 yr olds without
  prior illness

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STSS

• Risk factors
• Extremes of age
• Diabetes
• EtOH
• Drug abuse
• NSAIDS
• Immunodeficiency
• Rarely develops from symptomatic pharyngitis

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STSS

• 2000-3000 cases annually with 500 to 1500 cases
  of necrotizing fasciitis
• Mortality rate of 30 80
• 70 of cases progress to necrotizing fasciitis
• Surgical intervention
• Mortality
• Strep fasciitis 60
• Strep Myositis 85-100

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Case Definition of Streptococcocal Toxic Shock
Syndrome

• An illness with
• Hypotension
• Multiorgan involvement with two or more of the
  following
• Renal impairment
• Coagulopathy
• Liver involvement
• ARDS
• Generalized erythematous macular rash that may
  desquamate
• Soft tissue necrosis

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Case Definition of Streptococcal Toxic Shock
Syndrome

• Laboratory Criteria
• Isolation of group A streptococcus
• Case Classification
• Probable clinical case definition in the
  absence of another identified etiology with
  isolation of group A strep from a nonsterile site
• Confirmed clinical case definition with
  isolation of group A streptococcus from an
  otherwise sterile site

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STSS

• Epidemiology
• Incidence 1-5 per 100,000
• STSS associated Necrotizing Fasciitis 13-46
• Pathophysiology
• GAS invasive infections more virulent exotoxins
  than TSS
• SPE Streptococcal pyogenic exotoxins
• SPE A Scarlet fever toxin most potent and
  commonly isolated SPE in STSS cases
• SPE A and B pyrogenicity, superactivation of
  T-cells, synthesis of TNF, IL-1 and IL-6, leading
  to acidosis, shock, organ failure

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STSS

• Patients without immunity to M-type SPE A and B
  producing strains of GAS are most susceptible to
  STSS
• Portal of entry
• Vagina, pharynx, mucosa, and skin, most are
  unidentifiable
• Commonly begins at site of minor skin trauma

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STSS

• Clinical Features
• Pain most common with preceding local tenderness
• May present as
• Peritonitis
• PID
• Pneumonia
• Pericarditis
• Fever
• Severe pain
• Swelling
• Redness
• Compartment syndrome

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STSS

• PE
• Fever
• Shock on admission or within 4-8hrs
• Vesicles and/or bullae at infection site
• ARDS
• Less commonly erythematous rash
• Labs
• Mild increase in WBC
• LFT 2x normal

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STSS

• Labs
• Decreased platelets
• Disseminated intravascular coagulopathy
• Renal dysfunction requiring dyalysis
• Blood cultures - GAS 60
• Tissue cultures 90

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STSS

• Diagnosis
• Differential is the same as for TSS with the
  addition of invasive and noninvasive GAS
  infections, necrotizing fasciitis, myositis,
  serious infections caused by C. perforingens and
  C. septicum, and mixed aneorbic and aerobic
  organisms
• Treatment
• Aggressive shock management with early use of
  vasopressors

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STSS

• IV ABx should be started in the ED once cultures
  have been taken. Inability to obtain Cx should
  not delay administration of IV ABx
• Pen G 24 million U/d divided
• Clindamycin 900mg IV q 8hr
• Erythromycin 1g IV q 6 hr in PCN allergic pts
• Ceftriaxone 2g IV q 24 hr with Clindamycin 900mg
  IV q 8hr
• IVIG 2g/kg q 48 hr in patients without IGA
  deficiency improve 30 day mortality

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STSS

• Surgery
• Prompt consultation in addition to IV ABx
• Exploration
• Debridement
• 70 of cases require debridement, fasciotomy, or
  amputation

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TSS and STSS

• 1.) Toxic Shock Syndrome is only a disease of
  young healthy menstruating women. T/F
• 2.) The rash of TSS is a diffuse, blanching,
  erythroderma, classically described as a
  painless sunburn, that fades within 3-4 days of
  its appearance and is followed by full-thickness
  desquamation of the palms and soles during
  convalescence. T/F

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TSS and STSS

• 3.) STSS is defined as any group A
  streptococcocal (GAS) infection with invasive
  soft tissue infection, early onset of shock, and
  organ failure. T/F
• 4.) STSS associated with GAS invasive infections
  most commonly affects individual between the ages
  of 20 50 with a predisposing illness. T/F
• Answers 1.) F, 2.) T, 3.) T, 4.) F

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TSS and STSS

• Tintinalli et al Emergency Medicine A
  Comprehensive Study Guide. Chap. 142, pg.
  913-918.