emDOCs Podcast – Episode 61: Toxic Shock Syndrome

Today on the emDOCs cast with Brit Long, MD (@long_brit), we cover toxic shock syndrome.


Episode 61: Toxic Shock Syndrome

Background:

  • Toxic shock syndrome is an infection with bacteria that release harmful toxins, which can function as superantigens.
  • Mortality reaches 80% if not treated.
  • Challenging to diagnose in early stages because it presents with nonspecific symptoms, and it mimics many other conditions.

 

Pathophysiology:

  • Certain strains of bacteria produce superantigens, which are proteins that trigger T lymphocytes.
  • These T cells bypass normal immune checkpoints and lead to cytokine release and multiorgan injury.
  • The most common bacteria involved are Streptococcus pyogenes and Staphylococcus aureus.
  • Streptococcal TSS is more common and affects all ages. This usually starts as a local, invasive infection like cellulitis, pharyngitis, pneumonia, or necrotizing fasciitis. Up to 20% of these patients with an invasive infection can experience TSS. Streptococcal TSS may also follow a viral infection.
  • Staphylococcal TSS (due to MSSA or MRSA) is less common and usually affects those < 40 years. Usually occurs due to colonization and not invasive infection. May occur due to menstrual related causes (50% of cases) but is also associated with postsurgical, postpartum, burns, focal infections, soft tissue injuries.

 

Presentation:

  • Combination of two factors: 1) toxin production (rash, multiorgan dysfunction, flu-like symptoms) and 2) significant focus of infection.
  • Classic presentation: skin changes or a rash, hypotension, fever, organ dysfunction. Patients may also have chills, myalgias, weakness, nausea, vomiting, diarrhea.
  • Rash is typically diffuse, red, and macular to begin with and looks like a sunburn. However, this is transient and may be subtle. It may not be apparent on exam. Patients may have mucosal involvement, and desquamation should not be relied on as it does not occur until 1-3 weeks after initial symptoms.
  • Staphylococcal TSS more often presents in toxin mediated symptoms and fewer symptoms from a primary site of infection, as the staphylococcal toxin inhibits neutrophil function.
  • Streptococcal infection can present with toxin mediated symptoms with an occult focus of infection, or it may present with local invasive infection causing severe symptoms. The local infection that causes the streptococcal form is usually apparent on history and exam.
  • If surgical wound present, it may not demonstrate evidence of infection due to toxins suppressing neutrophil function.
  • Patients rapidly decompensate: shock, acute kidney injury, neurologic symptoms due to cerebral edema, cardiopulmonary complications.

 

Evaluation:

  • Laboratory analysis can suggest the disease, but not exclude it.
  • CBC may show leukocytosis, left shift, elevated neutrophil to lymphocyte ratio.
  • One of the first findings is renal injury, which may precede hypotension.
  • CK elevation, electrolyte abnormalities, and liver function test abnormalities common.
  • Thrombocytopenia, anemia, and DIC may occur in later stages.
  • Blood cultures positive in 60% of streptococcal cases but < 5% of staphylococcal cases.

 

CDC Criteria:

  • CDC criteria consist of clinical and laboratory components. Depending on number of criteria, patients may have probable or confirmed TSS.
  • Designed for research and not clinical use. Not validated in clinical setting.
  • Patient may not meet criteria until later in the course of the disease.
  • Criteria do not consider mimics: adrenal insufficiency, meningitis, myocarditis, tick-borne illness, other causes of shock
  • If suspicious based on history and exam, begin treatment for TSS; do not wait for CDC criteria.

 

Red flags:

  • Diffuse rash in a patient with systemic illness.
  • Known or suspected streptococcal or staphylococcal infection plus sepsis/hemodynamic instability.
  • Localized infection that appears minor in comparison to the patient hemodynamics. A small area of cellulitis or pharyngitis usually doesn’t cause septic shock with severe hypotension and tachycardia.
  • Patient with viral, GI, or flu like illness who is hemodynamically unstable with no clear etiology.
  • Patient who is pregnant and presents with septic shock. Pregnancy increases the risk of TSS dramatically (20-fold).

 

Management:

  • Considering the diagnosis is key. Early treatment essential to management and improving patient outcomes.
  • Resuscitate with IV fluid and early vasopressors. Many patients will have endothelial injury and increased risk of edema with extensive IV fluid resuscitation. Use stress dose steroids (hydrocortisone) if hemodynamics refractory to IV fluid and vasopressors.
  • Broad spectrum antibiotics with a beta lactam/carbapenem backbone, MRSA coverage, and toxin inhibition.
    • Clindamycin and linezolid inhibit toxin production.
    • Literature suggests combining clindamycin and linezolid may be more effective  compared to either alone.
  • Source control (remove foreign body, drain abscess, debridement for necrotizing fasciitis).

 

Other treatments:

  • IVIG can neutralize the toxin. Observational studies suggest mortality benefit. RCTs show no statistically significant benefit, but improved SOFA score.
  • Plasmapheresis not proven to improve outcomes

 

Pitfalls:

  1. Failure to consider.
  2. Dismissing patient symptoms.
  3. Relying on the presence of a rash or ‘classic’ findings.
  4. Relying on formal CDC criteria.

 

References:

  1. Gottlieb M, Long B, Koyfman A. The Evaluation and Management of Toxic Shock Syndrome in the Emergency Department: A Review of the Literature. J Emerg Med. 2018 Jun;54(6):807-814.
  2. https://www.cdc.gov/groupastrep/diseases-hcp/Streptococcal-Toxic-Shock-Syndrome.html
  3. https://ndc.services.cdc.gov/case-definitions/toxic-shock-syndrome-2011/
  4. Coyle EA, Cha R, Rybak MJ. Influences of Linezolid, Penicillin, and Clindamycin, Alone and in Combination, on Streptococcal Pyrogenic Exotoxin A Release. Antimicrobial Agents and Chemotherapy. 2003;47(5):1752-1755.
  5. Stevens DL, Wallace RJ, Hamilton SM, Bryant AE. Successful treatment of staphylococcal toxic shock syndrome with linezolid: a case report and in vitro evaluation of the production of toxic shock syndrome toxin type 1 in the presence of antibiotics. Clin Infect Dis. 2006 Mar 1;42(5):729-30.
  6. Zimbelman J, Palmer A, Todd J. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr Infect Dis J. 1999 Dec;18(12):1096-100.
  7. Carapetis JR, Jacoby P, Carville K, et al. Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group a streptococcal infections. Clin Infect Dis. 2014 Aug 1;59(3):358-65.

 

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