BASICS
DESCRIPTION
- An acute toxin-mediated illness associated with Staphylococcus aureus infection
- Toxic shock syndrome (TSS) is characterized by sudden onset of high fever and rash with subsequent hypotension, desquamation, and involvement of ≥3 organ systems (1):
- Menstrual (less common): associated with menstruation and tampon use
- Nonmenstrual (more common): associated with postoperative wounds and barrier contraception
- Can occur in children and adults
- System(s) affected: multiple
EPIDEMIOLOGY
- Predominant age: 15 to 35 years; can occur at any age
- Predominant sex: female > male
- Nonmenstrual cases increasingly associated with methicillin-resistant Staphylococcus aureus (MRSA) infections and carry a higher mortality rate (1).
- Newborn: neonatal TSS-like exanthematous disease syndrome
Incidence
66 to 82 cases per year reported to the CDC from 2008 to 2012 (2) ‚
ETIOLOGY AND PATHOPHYSIOLOGY
- S. aureus exotoxins, especially TSS toxin-1 (TSST-1) (in >90% of menstrual cases)
- Staphylococcal enterotoxins A to E and G to I
- Enterotoxins B and C cause 50% of nonmenstrual TSS.
- Production and release of staphylococcal superantigens that bind to APC MHC class II and V- Ž ² region of T-cell receptor (3)
- T cells are activated, releasing cytokines (interleukin [IL]-1, IL-2, Ž ³-interferon, tumor necrosis factor [TNF]-α, TNF- Ž ², IL-6) that cause capillary leak, hypotension, and shock (3).
- IgG1 and IgG4 isotype antibodies are protective (4).
Genetics
- Patient 's individual genetic composition influences inflammatory response to toxins (5).
- Genetic polymorphisms leading to different human leukocyte antigen haplotypes also influence the susceptibility to the toxic effects of superantigens (6).
RISK FACTORS
- High
- Absence of antibody to TSST-1
- Infection with S. aureus variants producing TSST-1
- Only a small proportion of S. aureus isolates carry the TSST-1 gene.
- Moderate
- Use of regular absorbency tampons during menstruation
- Use of contraceptive sponge
- Low
- Surgical wound infections
- Cellulitis
- Early postpartum state, especially after cesarean section or episiotomy
- Pediatric considerations
- TSS may occur as a complication of chickenpox or burns. TSS is the most common cause of unexpected mortality after small burns in children. Prophylactic antibiotic use is not indicated in this situation (7).
GENERAL PREVENTION
- Appropriate use of feminine hygiene products
- Avoid prolonged use of superabsorbent tampons.
- Change tampons frequently.
- Early attention to infected wounds
COMMONLY ASSOCIATED CONDITIONS
Staphylococcal infections ‚
DIAGNOSIS
HISTORY
- Requires high index of suspicion and active search for source of infection
- Improper use of feminine hygiene products
- History of recent wound infection
- Prodrome of 1 to 3 days that often includes malaise, myalgias, fever, chills, vomiting, and/or diarrhea
- Acute-onset fever and chills
- Light-headedness or syncope
- Alteration in mentation or level of consciousness
- Myalgias
- Diffuse macular rash
PHYSICAL EXAM
- Temperature >38.9 ‚ °C (>102 ‚ °F)
- Hypotension
- BP <5th percentile for age in children
- Tachycardia
- Tachypnea
- Diffuse blanching erythroderma, initially appearing on trunk, spreading to arms and legs, including palms and soles
- Skin desquamation of palms and soles 1 to 2 weeks after rash onset
- Signs of multiorgan involvement, including:
- Cardiac (arrhythmias, pericarditis, cardiomyopathy)
- Pulmonary (acute respiratory distress syndrome [ARDS])
- Renal (oliguria)
- Hematologic " ”signs of disseminated intravascular coagulation (DIC)
- CNS involvement (headache, confusion, agitation, photophobia, meningismus, seizure, loss of consciousness)
- Mucosal inflammation (conjunctivitis, strawberry tongue, pharyngitis, vaginitis)
DIFFERENTIAL DIAGNOSIS
- Streptococcal scarlet fever
- Kawasaki disease
- Measles
- Streptococcal TSS
- More often associated with severe pain and tenderness at a site of local trauma and infection
- Staphylococcal scalded skin syndrome
- Necrotizing fasciitis
- Meningococcemia/sepsis (petechial/purpuric rash)
- Gram-negative sepsis (more likely in hospitalized patients)
- Rocky Mountain spotted fever (petechial rash beginning distally; often presents with severe headache)
- Leptospirosis
- Drug reactions (i.e., Stevens-Johnson syndrome)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Neutrophilic leukocytosis
- Thrombocytopenia; increased prothrombin time and activated partial thromboplastin time
- BUN and creatinine may be increased.
- Liver function tests, including total bilirubin, aspartate aminotransferase, and/or alanine aminotransferase, may be increased.
- Creatine phosphokinase may be increased.
- Sterile pyuria (urinary sediment containing WBCs in absence of UTI)
- Culture and Gram stains of possible sites of infection (vaginal and/or wound swabs); vaginal swab is positive in >90% of menstrual-related cases.
- Blood culture positive for S. aureus in <5% of cases
- Throat and CSF cultures usually are negative.
- Serologies for Rocky Mountain spotted fever, leptospirosis, and measles if clinically suspected
Diagnostic Procedures/Other
Acute and convalescent anti " “TSST-1 antibodies ‚
Test Interpretation
- On biopsy, subepidermal cleavage plane with minimal tissue inflammatory reaction
- Lymphocyte depletion in lymph nodes
TREATMENT
Inpatient; typically requires admission to intensive care unit for close monitoring ‚
GENERAL MEASURES
- Fluid resuscitation
- Remove tampon or other vaginal foreign bodies.
- Remove nasal packing if suspected source.
- Local wound care; debridement of infected wound or drainage of focal collection
- Manage renal or cardiac insufficiency.
- Mechanical ventilation if necessary
MEDICATION
First Line
- Treatment of shock or hypotension
- Aggressive fluid replacement with isotonic crystalloids or colloids
- Oxygen support; administer packed RBCs if the hematocrit is <30%.
- Pressors, generally norepinephrine (adults) or dopamine (pediatrics)
- The role of corticosteroids and sepsis has still yet to be clearly understood. There may be some role in children with proven absolute adrenal insuffiency (8)[C].
- Antibiotics to eradicate S. aureus and inhibit toxin production; give within 1 hour of diagnosis if possible (obtain blood cultures prior to start of antibiotics) (9):
- For suspected methicillin-susceptible S. aureus (MSSA), combination of clindamycin (more efficacious than Ž ²-lactams in suppressing in vitro production of TSST-1 and other exotoxins) 900 mg IV q8h (adults); 25 mg/kg/day IV divided q8h (children) plus oxacillin or nafcillin 2 g IV q4h (adults); 100 to 150 mg/kg/day IV q4h (children) (10),(11)[B]
- For suspected MRSA, combination of clindamycin 900 mg IV q8h (adults); 25 mg/kg/day divided q8h (children) plus vancomycin 15 to 20 mg/kg/dose (max 2 g/dose) IV q8 " “12h (adults); 40 mg/kg/day in 4 divided doses (children) (10),(11)[B]
- For patients showing resistance to clindamycin, consider linezolid 600 mg PP or IV q12h (adults) or 10 mg/kg q12h (pediatrics) can be considered as second-line (10)[B].
- Antimicrobial therapy should be continued for at least 10 to 14 days.
- Second Line: poly-clonal IVIG may improve survival in sepsis (12)[A]
- Decreases the production of TNF-a, IL-1, and IL-6 and neutralizes the toxin (13)
- Hyperbaric oxygen has been used; a meta-analysis has yet to prove benefit in surgical and traumatic wounds (14)[A].
INPATIENT CONSIDERATIONS
IV Fluids
Aggressive crystalloid resuscitation with up to 10 to 20 L/day occasionally necessary ‚
Nursing
- Monitor vital signs closely.
- Foley catheter to monitor urine output
Discharge Criteria
- Hemodynamic stability
- Improvement in symptoms
- Tolerating oral diet
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Women can reduce the risk of recurrent TSS by avoiding continuous tampon use during menstruation.
- Wound care/hygiene
DIET
As tolerated ‚
PROGNOSIS
- Mortality: 4 " “22%; higher in older patients, nonmenstrual TSS, and if diagnosis is delayed (8)[A]
- Rare recurrence in both menstrual and nonmenstrual cases
COMPLICATIONS
- Common (>20%)
- Acute renal failure
- ARDS
- Menorrhagia
- Alopecia
- Nail loss
- Rare (<20%)
- DIC
- Encephalopathy/memory impairment
- Cardiomyopathy
- Protracted malaise
REFERENCES
11 Walden ‚ A, Harriet ‚ H, Alyaqoobi ‚ M. Methicillin-resistant Staphylococcus aureus toxic shock syndrome. J Infect. 2008;56(2):161 " “162.22 Centers for Disease Control and Prevention. Notifiable diseases and mortality tables. MMWR Morb Mortal Wkly Rep. 2013;62(22):ND-297 " “ND-310.33 Descloux ‚ E, Perpoint ‚ T, Ferry ‚ T, et al. One in five mortality in non-menstrual toxic shock syndrome versus no mortality in menstrual cases in a balanced French series of 55 cases. Eur J Clin Microbiol Infect Dis. 2008;27(1):37 " “43.44 Andrews ‚ JI, Shamshirsaz ‚ AA, Diekema ‚ DJ. Nonmenstrual toxic shock syndrome due to methicillin-resistant Staphylococcus aureus. Obstet Gynecol. 2008;112(4):933 " “938.55 Kimber ‚ I, Nookala ‚ S, Davis ‚ CC, et al. Toxic shock syndrome: characterization of human immune responses to TSST-1 and evidence for sensitivity thresholds. Toxicol Sci. 2013;134(1):49 " “63.66 Kansal ‚ R, Davis ‚ C, Hansmann ‚ M, et al. Structural and functional properties of antibodies to the superantigen TSST-1 and their relationship to menstrual toxic shock syndrome. J Clin Immunol. 2007;27(3):327 " “338.77 Mulgrew ‚ S, Khoo ‚ A, Cartwright ‚ R, et al. Morbidity in pediatric burns, toxic shock syndrome, and antibiotic prophylaxis: a retrospective comparative study. Ann Plast Surg. 2014;72(1):34 " “37.88 Dellinger ‚ RP, Levy ‚ MM, Rhodes ‚ A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580 " “637.99 Silversides ‚ JA, Lappin ‚ E, Ferguson ‚ AJ. Staphylococcal toxic shock syndrome: mechanisms and management. Curr Infect Dis Rep. 2010;12(5):392 " “400.1010 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(5):729 " “730.1111 Stevens ‚ DL, Ma ‚ Y, Salmi ‚ DB, et al. Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. J Infect Dis. 2007;195(2):202 " “211.1212 Alejandria ‚ MM, Lansang ‚ MA, Dans ‚ LF, et al. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev. 2013;(9):CD001090.1313 Low ‚ DE. Toxic shock syndrome: major advances in pathogenesis, but not treatment. Crit Care Clin. 2013;29(3):651 " “675.1414 Eskes ‚ A, Vermeulen ‚ H, Lucas ‚ C, et al. Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. Cochrane Database Syst Rev. 2013;(12):CD008059.
SEE ALSO
Measles (Rubeola); Pancreatitis; Rocky Mountain Spotted Fever; Scarlet Fever ‚
CODES
ICD10
- A48.3 Toxic shock syndrome
- B95.62 Methicillin resis staph infct causing diseases classd elswhr
ICD9
- 040.82 Toxic shock syndrome
- 041.12 Methicillin resistant Staphylococcus aureus in conditions classified elsewhere and of unspecified site
SNOMED
- Toxic shock syndrome (disorder)
- methicillin resistant Staphylococcus aureus infection (disorder)
CLINICAL PEARLS
- TSS is a rare, acute, toxin-mediated illness most commonly associated with S. aureus.
- In women, TSS is traditionally associated with the continuous use of superabsorbent tampons during menstruation.
- Rapid recognition and treatment is important.
- Patients often require ICU care, aggressive volume resuscitation, and IV antibiotics.