Sick, Shocked and Sunburned?

aka Microbial Mystery 004

A 15 year-old female presents with fever (T39.0), vomiting and diarrhoea, widespread muscle aches and a confluent erythematous macular rash resembling sunburn all over her body. She is persistently hypotensive (BP 85/35 mmHg) despite 2L of crystalloid fluid resuscitation.

Her laboratory results are:

  • Full Blood Picture
    • Hb 130 (120-155 g/L)
    • WBC 18.3 (4.5-13.0 x 10E9/L)
    • Plt 250 (150-400 x 10E9/L)
  • Urea and Electrolytes
    • Na 138 (134-146 mM)
    • K 3.8 (3.4-5.0 mM)
    • urea 5.0 (3-8.9 mM)
    • Cr 160 (<75 microM)
  • Other Investigations
    • CK 425 (30-170 IU/L)
    • Alb 28 (35-50 g/L)
    • LFTs unremarkable
    • CRP 73 (<10 mg/L)
    • Blood cultures, throat swabs, and urine MCS were sent and the results are pending.

She completed menstruating the day before, and was otherwise previously well.


Q1. What is the likely diagnosis?

Answer and interpretation

Staphylococcal toxic shock syndrome

Q2. What are the important differential diagnoses to consider?

Answer and interpretation
  • Streptococcal toxic shock syndrome
  • Stevens-Johnson Syndrome
  • Septic shock
  • Meningococcemia
  • Unusual/ tropical infections (depending on geographic location and travel history):
    • Leptospirosis
    • Rickettsial disease (RMSF in the US, Queensland Tick Typhus in Australia)
    • Typhoid fever
    • Arboviruses (e.g. dengue)

Q3. Why is the menstrual history important?

Answer and interpretation

Staphylococcal toxic shock syndrome exploded into the consciousness of doctors in 1980 when there were over 800 documented cases of menses-related TSS, predominantly affecting young Caucasian women.

This was associated with the use of highly-absorbent tampons (about 90% of cases).

Cases of menses-related TSS have dropped from about 9 per 100,000 to about 1 per 100,000 annual incidence in the US since the withdrawal of highly absorbent tampons and polyacrylate rayon-containing products.

However, tampon use remain a risk factor — particularly if:

  • highly absorbent tampons are used
  • tampons are used continuously for most days of the cycle
  • a single tampon is left in situ for a longer time

Q4. What causes the syndrome?

Answer and interpretation

Toxic-shock syndrome toxin-1 (TSST-1) and various enterotoxins produced by S. aureus.

TSST-1 is associated with over 90% of menses-related toxic shock syndrome and about half of non-menses-related toxic shock syndrome. Some of the non-TSST-1 toxins may be more potent.

These toxins act as superantigens, activating large numbers of T cells leading to the massive release of cytokines (e.g. interleukin (IL)-1, IL2, Tumor Necrosis Factor (TNF)-alpha, TNF-beta and interferon-gamma).

  • This occurs because superantigens act directly on the invariant regions of MHCII molecules and do not need to be processed by antigen presenting cells first. Antibodies to these toxins are probably protective. About 80% of people develop antibodies to TST-1 by their teenage ages, and over 90% by their thirties.

Both methicilin-sensitive (MSSA) and resistant (MRSA) strains of S. aureus can cause TSS. Some studies suggest that community-acquired MRSA is more likely to produce TSS.

Q5. What are the criteria for diagnosis of this condition?

Answer and interpretation

The CDC’s revised case definition for a confirmed case of staphylococcal toxic shock syndrome is all 6 of these criteria:

  • 1. Fever — Temperature ≥ 38.9°C (102°F)
  • 2. Rash — Diffuse macular erythroderma
  • 3. Desquamation 1–2 weeks after onset of illness, particularly of palms and soles
  • 4. Hypotension — Systolic blood pressure ≤90 mm Hg for adults or below fifth percentile by age for children less than 16 years of age, orthostatic drop in diastolic blood pressure ≥15 mm Hg from lying to sitting, orthostatic syncope, or orthostatic dizziness
  • 5. Multisystem involvement (3 or more systems involved)
    • Gastrointestinal: Vomiting or diarrhea at onset of illness
    • Muscular: Severe myalgia or creatine phosphokinase level at least twice the upper limit of normal
    • Mucous membrane: Vaginal, oropharyngeal, or conjunctival hyperemia
    • Renal: BUN or creatinine at least twice the upper limit of normal or urinary sediment with pyuria (≥5 leukocytes/hpf) in the absence of urinary tract infection
    • Hepatic: Total bilirubin, AST, and ALT at least twice the upper limit of normal
    • Hematologic: Platelets ≤ 100,000/mm3
    • CNS: Disorientation or alterations in consciousness without focal neurologic signs when fever and hypotension are absent
  • 6. Negative results on the following tests, if obtained:
    • Blood, throat, or CSF cultures (blood culture may be positive for Staphylococcus aureus)
    • Rise in titer to Rocky Mountain spotted fever, leptospirosis, or rubeola

Based on the available information the patient in this case appears to meet these criteria — although it is too early for desquamation. She has fever, eyrthroderma, hypotension and evidence of multisystem involvement — GI, renal and muscular features.

80-90% of cases have S. aureus isolated from mucosal or wound swabs, but this is not essential. Less than 5% have postive blood cultures.

The CDC criteria should not be used to exclude the diagnosis in a case highly suspicious for TSS, even when all of the necessary criteria are not met. If one of the criteria is missing (i.e. 5 of the 6 criteria are met), the diagnosis is a probable case.

Q6. What is the treatment?

Answer and interpretation

Supportive care

  • IV fluids and vasopressor support to maintain systemic perfusion.

Surgical treatment

  • removal of foreign material if present in the vagina
  • incision and drainage of any infected foci


  • may not alter the course of the acute illness but aims to eradicate the causative organism and prevent relapses.
  • e.g. clindamycin + flucloxacillin/ vancomycin for 10-14d
    (Clindamycin may be more effective than flucloxacillin or vancomycin at decreasing toxin production as it is a protein synthesis inhbitor rather than a cell wall targeting agent.)

Other treatments

  • Some clinicians advocate the use of IV immunogloubulin (e.g. 400 mg/kg stat over several hours). It should be considered in cases of refractory TSS.
  • Corticosteroids are not recommended due to a lack of evidence.

Q7. What is the prognosis?

Answer and interpretation

Mortality rate is now <3% for menses-related TSS, and about 6% in non-menses-related TSS.

Some patients are predisposed to relapse of TSS. This may be due to failure of an antibody response from interferon-gamma suppression of polyclonal immunoglobulin production.

  • Lappin E, Ferguson AJ. Gram-positive toxic shock syndromes. Lancet Infect Dis. 2009 May;9(5):281-90. Review. PubMed PMID: 19393958.

Microbial Mystery LITFL FB 700 2


Microbial Mystery

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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