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Toxic Shock Syndrome, Emergency Medicine

Basics

Description

- Exotoxins act as superantigens causing overwhelming immune response: - Massive cytokine production - Induce fever directly at the hypothalamus or indirectly via interleukin-1 (IL-1) and tumor necrosis factor (TNF) production - Enhance delayed hypersensitivity - Suppress neutrophil migration and immunoglobulin - Enhance host susceptibility to endotoxins

- Massive vasodilation occurs - Serum protein and fluid shifts leading to hypotension

- Approximately one-half of reported TSS cases are nonmenstrual: - Surgical wounds - Postpartum wound infections - Mastitis - Septorhinoplasty - Sinusitis - Osteomyelitis - Arthritis - Burns - Nasal packing (nasal tampons) - Cutaneous and subcutaneous lesions

- CDC case definition: - Fever >38.9 ‚ °C (102 ‚ °F) - Hypotension (systolic BP <90 mm Hg) or shock - Diffuse, blanching nonpruritic macular erythroderma rash - Subsequent desquamation 1 " “2 wk after the onset of illness (particularly involving palms and soles) - Multisystem involvement " ”at least 3 of the following should be present: - GI: Profuse diarrhea or vomiting at onset of illness - Musculoskeletal: Severe myalgias or greater than a 2-fold increase in creatine phosphokinase (CPK) - Mucosal inflammation: Conjunctival, vaginal, or pharyngeal hyperemia - Renal: Increase in BUN or creatinine >2 times normal upper limit or sterile pyuria without evidence of infection - Hepatic: Total bilirubin or transaminases >2 times normal upper limit - Hematologic: Thrombocytopenia <100,000/mm3 - CNS: Disorientation, confusion, or hallucinations

- CDC case definition: - Isolation of GAS from a normally sterile site - Hypotension - Plus 2 or more of the following: - Renal impairment (creatinine >2) - Coagulopathy - Liver involvement (>2 times the upper limit of normal for transaminases or bilirubin) - ARDS - Erythematous macular rash, may desquamate - Soft tissue necrosis

- Leptospirosis: - Transmitted through contact with infected animals - Fever, headache, severe myalgias, and conjunctival suffusion - Truncal rash that only desquamates in children

- RMSF: - Rash is pink and macular, beginning on the wrists, palms, ankles, and soles spreading to the trunk and face - Petechiae appear after 4 days

  • Toxic shock syndrome (TSS) is a severe, acute life-threatening illness
  • Etiologic organisms:Staphylococcus aureus, more common (TSS)Group A streptococcus or GAS, less common (Streptococcal TSS or STSS)
  • S. aureus produce structurally similar toxins:Toxic shock syndrome toxin (TSST-1)Enterotoxin B (SEB)Enterotoxin C (SEC)
  • GAS pyrogenic exotoxins:Exotoxin A (SPEA)Exotoxin B (SPEB)
  • Exotoxins act as superantigens causing overwhelming immune response:Massive cytokine productionInduce fever directly at the hypothalamus or indirectly via interleukin-1 (IL-1) and tumor necrosis factor (TNF) productionEnhance delayed hypersensitivitySuppress neutrophil migration and immunoglobulinEnhance host susceptibility to endotoxins
  • Massive vasodilation occursSerum protein and fluid shifts leading to hypotension

Etiology

  • Initial cases described in young healthy menstruating females due to highly absorbent tamponsChanges made in tampon composition to decrease incidence
  • Approximately one-half of reported TSS cases are nonmenstrual:Surgical woundsPostpartum wound infectionsMastitisSeptorhinoplastySinusitisOsteomyelitisArthritisBurnsNasal packing (nasal tampons)Cutaneous and subcutaneous lesions
  • Nonmenstrual cases predominantly due to SEB and SEC producing S. aureus
  • 30 " “50% of healthy adults and children carry S. aureus in the nasal vestibule, vagina, rectum and/or on the skin
  • GAS infections often begin within 24 " “72 hr at the site of minor trauma, often without a visible in skin
  • Despite increased incidence of Methicillin-resistant S. aureus (MRSA) infections, a recent study reported MRSA only accounting for 7% of cases

Diagnosis

Signs and Symptoms

TSS Criteria for Diagnosis

  • CDC case definition:Fever >38.9 ‚ °C (102 ‚ °F)Hypotension (systolic BP <90 mm Hg) or shockDiffuse, blanching nonpruritic macular erythroderma rashSubsequent desquamation 1 " “2 wk after the onset of illness (particularly involving palms and soles)Multisystem involvement " ”at least 3 of the following should be present:GI: Profuse diarrhea or vomiting at onset of illnessMusculoskeletal: Severe myalgias or greater than a 2-fold increase in creatine phosphokinase (CPK)Mucosal inflammation: Conjunctival, vaginal, or pharyngeal hyperemiaRenal: Increase in BUN or creatinine >2 times normal upper limit or sterile pyuria without evidence of infectionHepatic: Total bilirubin or transaminases >2 times normal upper limitHematologic: Thrombocytopenia <100,000/mm3CNS: Disorientation, confusion, or hallucinationsNegative results on the following tests, if obtained: Throat, or CSF cultures, rise in titer to Rocky Mountain spotted fever (RMSF), leptospirosis, or rubeola

Streptococcal TSS (STSS) Criteria for Diagnosis

  • CDC case definition:Isolation of GAS from a normally sterile siteHypotensionPlus 2 or more of the following:Renal impairment (creatinine >2)CoagulopathyLiver involvement (>2 times the upper limit of normal for transaminases or bilirubin)ARDSErythematous macular rash, may desquamateSoft tissue necrosis

Other

  • Tachycardia frequently present
  • Can rapidly progress to multisystem dysfunction (ARDS or DIC)
  • STSS often presents with diffuse or localized pain " ”abrupt in onset and severe
  • Pain precedes physical findings
  • Nearly 80% of patients with STSS have clinical signs of soft tissue infection

Essential Workup

  • Clinical diagnosis using diagnostic criteria in the absence of other attributable illness
  • Thorough history and physical exam

Diagnosis Tests & Interpretation

Lab

  • CBC:Leukocytosis or leukopenia, marked bandemia common
  • Electrolytes, BUN, creatinine, glucose:Elevated BUN and creatinine common
  • Calcium, magnesium:Hypocalcemia/hypomagnesemia often present
  • Urinalysis:Normal or sterile pyuria without evidence of infection
  • CPK:
  • Hepatic function:Elevated total bilirubin, AST, ALT
  • Prothrombin time (PT), partial thromboplastin time (PTT), platelets:Thrombocytopenia <100,000 platelets/mm3
  • Culture the site of injury/infection if possible
  • Blood, urine, throat, and CSF cultures as indicated:The case definition does not require a positive blood culture for S. aureus, but does for Streptococcus organisms.
  • Serology for RMSF, rubeola, and leptospirosis
  • Hepatitis B surface antigen

Imaging

  • Chest x-ray " “ to rule out other sources of systemic illness
  • Consider x-ray or CT scan if localized pain is concerning for abscess or necrotizing infection

Differential Diagnosis

  • Staphylococcal scalded skin syndrome:In children <5 yr of ageInitial macular rash followed by the formation of ill-defined bullae that can be rubbed off revealing a shiny, moist epidermis (positive Nikolsky sign)
  • Scarlet fever:Preceding streptococcal pharyngitisRash begins on the upper chest, neck, and back spreading to the remainder of the trunk, sparing the palms and solesHypotension absent
  • Kawasaki disease:Fever, conjunctival hyperemia, and erythema of the mucous membranesNot associated with renal failure, hypotension, or thrombocytopenia
  • Stevens " “Johnson syndrome:Severe multisystem involvementMucosal involvement of the mouth, conjunctivae, vagina, anus, and urethral meatus
  • Leptospirosis:Transmitted through contact with infected animalsFever, headache, severe myalgias, and conjunctival suffusionTruncal rash that only desquamates in children
  • RMSF:Rash is pink and macular, beginning on the wrists, palms, ankles, and soles spreading to the trunk and facePetechiae appear after 4 days
  • Meningococcemia:Meningismus presentRash is petechial

Treatment

Pre-Hospital

  • ABCs
  • IV access
  • IV fluids for hypotension

Initial Stabilization

  • Again, ABCs
  • Aggressive management of circulatory shock

Ed Treatment/Procedures

Hypotension

  • Aggressive fluid replacementThe 1st 24 hr may require 4 " “20 L of crystalloid and/or fresh frozen plasma (colloid)Caution: Large amounts of IV fluids and pressors used to treat refractory hypotension can result in rapid onset pulmonary edemaPressors (dopamine/norepinephrine) if fluid correction fails to restore normal arterial pressure

Infection Management

  • Search for and treat the focus of infection
  • Remove the source of infection (e.g., tampon, nasal or wound packing)
  • Early surgical/gynecologic consultation if drainage or debridement of infectious sites necessary
  • AntibioticsRecommended to reduce recurrence, but have not been shown to alter the course of the initial infectionClindamycin and linezolid are potent suppressers of bacterial toxin synthesisClindamycin or linezolid+vancomycin for TSSLinezolid+vancomycin for TSS with extensive infectionIf TSS due to known methicillin-susceptible S. aureus then clindamycin +oxacillin or nafcillinClindamycin + imipenem or meropenem or ticarcillin " “clavulanate or piperacillin " “tazobactam for STSS
  • IV immunoglobulin (IVIG) treatment:May be efficacious in streptococcal toxic shock, but no controlled trials have proven efficacy in staphylococcal TSS.May initiate if no response to fluids, pressors, and antibiotics in patients with pulmonary edema and hypotension

Medication

  • Clindamycin: 600 " “900 mg (peds: 20 " “40 mg/kg/24 h) IV q6 " “8h
  • Dopamine: 2 " “20 Ž ¼g/kg/min IV, titrate to BP
  • Linezolid: 600 mg (peds: 10 mg/kg/12 h) IV q12h
  • Meropenem: 1 g IV q8h
  • Nafcillin: 1.5 g (peds: 100 mg/kg/24 h) IV q4h
  • Norepinephrine: 0.01 " “3 mcg/kg/min IV, titrate to BP
  • Oxacillin: 1 " “2 g (peds: 50 " “100 mg/kg/24 h) IV q4h
  • Piperacillin " “tazobactam: 4.5 g q6h
  • Ticarcillin " “clavulanate: 3.1 g q4h
  • Vancomycin: 30 mg/kg QD IV div. in 2 doses (peds: 40 mg/kg QD IV div. in 4 doses)
  • Staphylococcal TSS: IVIG, 400 mg/kg over several hours
  • Streptococcal TSS: IVIG 1 g/kg on day 1 then 0.5 g/kg on days 2 and 3

Follow-Up

Disposition

Admission Criteria

  • Cases necessitateadmission
  • ICU admission for critically ill or those in shock

Discharge Criteria

None ‚

Issues for Referral

Early surgical/gynecologic consultation if drainage or debridement is needed ‚

Follow-Up

Follow-Up Recommendations

  • Patients who are bacteremic are treated for a minimum of 14 days:Depending on the clinical courseContinue treatment for 14 days from the last positive culture.
  • Screening for S. aureus nasal carriage in patient with S. aureus TSS and eradication of the carrier state with mupirocin

Pearls and Pitfalls

  • Consider the diagnoses of staphylococcal TSS and GAS TSS
  • Ensure adequate supportive care for hypotension in TSS
  • Prompt and aggressive exploration and debridement of suspected deep-seated infection
  • Empiric broad-spectrum antibiotics including clindamycin or linezolid is recommended

Additional Reading

  • DeVries ‚ AS, Lesher ‚ L, Schlievert ‚ PM, et al. Staphylococcal toxic shock syndrome 2000 " “2006: Epidemiology, clinical features, and molecular characteristics. PLoS One. 2011;6(8):e22997.
  • Darenberg ‚ J, Ihendyane ‚ N, Sj ƒ ¶lin ‚ J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: A European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37:333 " “340.
  • Lappin ‚ E, Ferguson ‚ AJ: Gram-positive toxic shock syndromes. Lancet Infect Dis. 2009;281 " “290.
  • O 'Brien ‚ KL, Beall ‚ B, Barrett ‚ NL, et al. Epidemiology of invasive group A streptococcus disease in the United States, 1995 " “1999. Clin Infect Dis. 2002;35:268 " “276.
  • Stevens ‚ DL, Wallace ‚ RJ, Hamilton ‚ SM, et al. 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;42:729 " “730.

See Also (Topic, Algorithm, Electronic Media Element)

  • Streptococcal Infections
  • Kawasaki Disease
  • Meningococcemia
  • Leptospirosis

Codes

ICD9

040.82 Toxic shock syndrome ‚

ICD10

A48.3 Toxic shock syndrome ‚

SNOMED

  • 18504008 Toxic shock syndrome (disorder)
  • 240450004 Staphylococcal toxic shock syndrome (disorder)
  • 240451000 Streptococcal toxic shock syndrome (disorder)