Staphylococcal toxic shock syndrome: EM-focused highlights

Authors: Cameron J. Gettel, MD (EM Resident Physician, Alpert Medical School of Brown University) and Jessica L. Smith, MD (EM Attending Physician/Residency Program Director, Alpert Medical School of Brown University) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Case

A 14 year-old female presents with fever, vomiting, diarrhea, muscle aches, and a diffuse, painless erythroderma all over her body. She is hypotensive despite IV fluid resuscitation. Further history suggests that her menstrual cycle ended yesterday.

Introduction

Staphylococcus aureus colonizes the skin and mucous membranes of 30-50% of healthy adults and children¹ and produces many exotoxins and enzymes that lead to inflammation. Toxic shock syndrome (TSS), caused by toxic shock syndrome toxin-1 (TSST-1),² first came to attention in 1980 with menstrual-associated cases,^3,4 and the disease is associated with a severe, life-threatening syndrome causing electrolyte disturbances, renal failure, and shock.⁵ Half of all cases are related to menstruation, with the remainder of cases observed in surgical/postpartum wound infections, mastitis, septorhinoplasty, osteomyelitis, burns, nasal packing, or complications from intrauterine devices.^6,7 Cases of methicillin-resistant S. aureus (MRSA) have emerged as infection rates rise, but the majority of reported TSS cases are due to methicillin-sensitive S. aureus (MSSA). This post will focus primarily on staphylococcal toxic shock.

Presentation/Diagnosis

Signs and symptoms of TSS develop rapidly, described below in the clinical criteria. Definitive diagnosis requires all criteria, and a probable diagnosis is suggested if one of the confirming criteria is absent.⁸ The criteria below were developed for surveillance and do not exclude TSS cases if the presentation is highly suspicious. Notably, the isolation of S. aureus is not required for confirmation of staphylococcal TSS, but it is recovered from the wound/mucosa in 80-90% of those with TSS, and blood cultures are positive in only 5% of cases.^9,10 For strep TSS, over 60% will have positive blood cultures.

Clinical criteria for staph TSS have been established by the United States Center for Disease Control and Prevention (CDC) and require:¹¹

• Fever, temperature 39°C (102.0°F)
• Hypotension, systolic blood pressure < 90 mmHg for adults and less than 95^th percentile by age for children <16 years of age
• Rash with diffuse macular erythroderma
• Desquamation, 1-2 weeks after onset of illness, particularly of the palms/soles
• Multisystem involvement (3 or more systems):
  • Gastrointestinal – Vomiting or diarrhea at disease onset of illness
  • Muscular – Myalgias or creatine phosphokinase > 2 times the upper limit of normal
  • Mucous membranes – Vaginal, oropharyngeal, or conjunctival hyperemia
  • Renal – Blood urea nitrogen or serum creatinine > 2 times the upper limit of normal or pyuria (>5 white blood cell count/high power field) in the absence of a urinary tract infection
  • Hepatic – Bilirubin or transaminases > 2 times the upper limit of normal
  • Hematologic – Platelets < 100,000/microL
  • Central nervous system – Disorientation or alteration in consciousness without focal neurologic signs in the absence of fever and hypotension
• Negative testing, if obtained of CSF and serologic testing for Rocky Mountain spotted fever, leptospirosis, measles

Persistent hypotension is caused by a decrease in systemic vascular resistance and fluid leakage from the intravascular space to the interstitial space,¹² with massive cytokine release and nonpitting edema. The erythroderma of TSS often resembles a ‘painless sunburn’ that includes the palms and soles. Desquamation is a late manifestation, occurring 1-3 weeks after disease onset, and therefore is not required in the acute diagnostic approach to possible TSS. GI symptoms including diffuse vomiting and diarrhea may be present.  Staphylococcal TSS differs from streptococcal TSS in that the latter often causes severe pain and tenderness at a site of trauma, and it often requires immediate debridement.

Management

Inspection for foreign material in the vaginal canal (tampon, contraceptive sponge, IUD) should be undertaken, with removal and subsequent culture. Source control is essential, as in all cases of sepsis. Given the extensive capillary leak, patients with TSS may require 10 to 20 liters of fluid per day, and supportive care starts in the Emergency Department with vasopressors such as norepinephrine to augment blood pressure.

All patients with suspected staph TSS require empiric antibiotics with:

• Clindamycin 900 mg IV every 8 hours for adults, and 25-40 mg/kg/day divided in 3 doses for children
• Vancomycin 15-20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g/dose, and 40 mg/kg/day divided in 4 doses for children
• Linezolid is another option. Similar to clindamycin, this medication reduces toxin production.

If culture results confirm:

• Patients with MSSA TSS should receive clindamycin, as above, plus oxacillin or nafcillin 2 g IV every 4 hours for adults, and 100-150 mg/kg/day divided in 4 doses for children
• Patients with MRSA TSS, should receive empiric regimen above including clindamycin and vancomycin, or single agent linezolid 600 mg PO/IV every 12 hours for adults, and 10 mg/kg PO/IV every 12 hours for children

TSS should be treated for a duration of 1-2 weeks, and nasal carriage eradication should be attempted with mupirocin. An additional treatment option is intravenous immune globulin. In severe cases nonresponsive to supportive care, IVIG can be considered, dosed as 1 g/kg in a single dose administered on day 1, and repeat doses of 0.5 g/kg on days 2 and 3. Corticosteroids have not been proven to show benefit in TSS cases. Mortality rate is <3% for menses-related cases of TSS, and <6% in non-menses related TSS cases.

Key Points for the ED provider

• TSS is often a late diagnosis, and there have been many unfortunate cases, which were initially given a more benign diagnosis.
• Systemic illness plus blanchable, diffuse rash or ‘pain out of proportion’ should clue the clinician into TSS, either from S. aureus or S. pyogenes.
• Half of the cases are from tampon use, while other common precipitants include nasal packing and surgical wound infections.
• Resuscitation efforts should be initiated by the ED provider, including source control and supportive care with IV fluids, vasopressors, and appropriate antibiotics.

References / Further Reading

¹Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 1997;10:505.

²Spaulding A, Salgado-Pabon W, Kohler P, et al. Staphylococcal and streptococcal superantigen exotoxins. Clin Microbiol Rev 2013:26:422.

³Davis J, Chesney P, Wand P, LaVenture M. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med 1980;303:1429.

⁴Centers for Disease Control (CDC). Update: toxic-shock syndrome – United States. MMWR Morb Mortal Wkly Rep 1983;32:398.

⁵Lappin E, Ferguson A. Gram-positive toxic shock syndromes. Lancet Infect Dis 2009;9(5):281.

⁶Reingold A, Hargrett N, Dan B, et al. Nonmenstrual toxic shock syndrome: a review of 130 cases. Ann Intern Med 1982;96:871.

⁷Weidner V. Toxic shock. In: Tintinalli J, Cline D, Ma O, Cydulka R, Meckler G, Handel D, Thomas S., editors. Tintinalli’s Emergency Medicine. 7th ed. New York: McGraw-Hill; 2012;(cited 2017 Jan 22).

⁸Tofte R, Williams D. Toxic shock syndrome. Evidence of a broad clinical spectrum. JAMA 1981;246:2163.

⁹Davis J, Osterhold M, Helms C, et al. Tri-state toxic-shock syndrome study. J Infect Dis 1982;145:441.

¹⁰Reingold A, Dan BB, Shands K, Broome C. Toxic-shock syndrome not associated with menstruation. A review of 54 cases. Lancet 1982;1:1.

¹¹Case definitions for infectious conditions under public health surveillance. Centers for Disease Control and Prevention. MMWR Recomm Rep 1997;46:1.

¹²Chesney P. Clinical aspects and spectrum of illness of toxic shock syndrome: overview. Rev Infect Dis 1989;11 Suppl 1:S1.