Introduction
Background
Toxic shock syndrome (TSS) is an acute febrile illness characterized by a generalized erythematous eruption accompanied by systemic involvement. It is due to toxin-producing strains of Staphylococcus aureus, both methicillin-sensitive S aureus (MSSA) and methicillin-resistant S aureus (MRSA). Originally described in 1978 and soon thereafter associated with tampon use,1 TSS is now recognized to occur in both menstrual and nonmenstrual forms. In the late 1980s, a disease similar in appearance to TSS, but caused by invasive streptococci, was recognized. Also known as toxic strep or streptococcal toxic shocklike syndrome, streptococcal TSS (STSS) was found to share many clinical features with TSS.
The Medscape CME course Invasive Group A Streptococcal Disease in Nursing Homes, Minnesota, 1995-2006 and the Emerging and Reemerging Infectious Diseases Resource Center. Additionally, several other eMedicine Specialty sections have articles on TSS, including Toxic Shock Syndrome from Critical Care.
Pathophysiology
Massive cytokine release as a result of toxin/superantigen activity is postulated to be the mediator of the clinical signs of TSS.2 Both menstrual and nonmenstrual forms of TSS have been linked to toxin-producing strains of S aureus. More than 90% of menstrual TSS is mediated by TSS toxin-1 (TSST-1) production, which is associated with massive release of tumor necrosis factor-alpha (TNF-a) and interleukin (IL) – 1. These cytokines have been demonstrated to produce fever, rash, hypotension, tissue injury, and shock.
The absence of an antibody to TSST-1 has been shown to be a major risk factor for acquisition of TSS; failure to generate anti-TSST-1 antibody after an episode of TSS predisposes patients to recurrent episodes. Isolates of S aureus from nonmenstrual TSS produce TSST-1 in approximately 50% of cases, whereas the remainder produces staphylococcal enterotoxin B (SEB) and staphylococcal enterotoxin C (SEC). Staphylococcal enterotoxins have been shown to be potent mediators of cytokine production and release in a similar fashion to TSST-1, thereby producing clinically similar diseases.
In most cases of STSS, toxin-producing group A streptococci have been isolated, with streptococcal pyrogenic exotoxin-A (SPE-A) production being most closely linked with invasive disease. However, group A streptococci producing streptococcal pyrogenic exotoxin-B (SPE-B), streptococcal pyrogenic exotoxin-C (SPE-C), streptococcal superantigen and mitogenic factor, as well as non–group-A streptococci, have been found to be causative in individual cases of STSS.
In a similar manner to classic TSS, it is postulated that massive cytokine release (primarily TNF-a, IL-1beta, and IL-6), as a result of toxin/superantigen activity, mediates the clinical signs of STSS. In addition, streptolysin O, produced by 100% of streptococcal strains associated with STSS, has also been shown to cause TNF-a, and IL-1beta production and has been demonstrated to act synergistically with SPE-A. An absence of protective immunity is postulated as a potential risk factor in this population as well.
Frequency
United States
Both TSS and STSS are relatively rare; the incidence of nonmenstrual TSS exceeds that of menstrual TSS.
Mortality/Morbidity
- TSS: The mortality rate is approximately 5-15%, and recurrences have been reported in as many as 30-40% of cases.
- STSS: Mortality rates are more than 5 times higher than in TSS.
Sex
Young adult women are affected more often than men.
Age
The majority of cases of TSS and STSS have occurred in young, otherwise healthy persons aged 20-50 years, despite the fact that very young, elderly, diabetic, or immunocompromised persons are more susceptible to the acquisition of invasive staphylococcal and streptococcal infections.
Clinical
History
Clinically, menstrual TSS, nonmenstrual TSS, and STSS have similar features. Fever, rash, hypotension, and multiple organ involvement are the hallmarks of TSS. Desquamation of the palms and soles, as seen in many bacterial toxin-mediated disorders, usually follows the onset of the illness by 1-2 weeks.
Physical
- Skin and mucous membrane lesions
- The eruption of TSS is defined as diffuse macular erythroderma; however, a scarlatiniform eruption, often with flexural accentuation, frequently is present.
- Erythema and edema of palms and soles
- Hyperemia of conjunctiva and mucous membranes
- Strawberry tongue
- Delayed desquamation of palms and soles
- Multisystem organ involvement
- Fever greater than 38.9°C (102°F)
- Cardiovascular - Hypotension, cardiomyopathy
- Gastrointestinal - Nausea, vomiting, diarrhea (usually secretory)
- Muscular - Rhabdomyolysis, severe myalgias, muscle tenderness, muscle weakness
- Renal - Azotemia, acute renal failure
- Neurologic - Toxic encephalopathy probably related to cerebral edema
- Pulmonary - Adult respiratory distress syndrome
- Hepatic - Elevated serum aspartate aminotransferase and serum bilirubin levels, centrilobular hepatic necrosis
- Hematologic - Thrombocytopenia, leukocytosis, disseminated intravascular coagulation
- Metabolic - Hypophosphatemia, hypocalcemia, electrolyte imbalances (especially metabolic acidosis)
Causes
- TSS may occur as a complication of S aureus cellulitis. Most frequently, however, infection with the causative strains of staphylococci develop in patients with certain predisposing factors, such as the following:
- Influenza
- Sinusitis
- Tracheitis
- Intravenous drug use
- HIV infection
- Burn wounds
- Allergic contact dermatitis
- Gynecologic infection
- Postpartum period
- Postoperative infection: Importantly, in nonmenstrual TSS caused by a postoperative infection, the classic signs of localized infection, such as erythema, tenderness, and purulence, may be absent from the site of infection, thereby making clinical diagnosis challenging.
- The following are predisposing factors for STSS:
- Wounds: The skin is often the portal of entry in STSS, with soft-tissue infections developing in 80% of patients. The initial presentation of STSS often is localized pain in an extremity, which rapidly progresses over 48-72 hours to manifest both local and systemic signs of STSS. Cutaneous signs may include localized edema and erythema, a bullous and hemorrhagic cellulitis, necrotizing fasciitis or myositis, or gangrene. Soft-tissue involvement of this nature is distinctly uncommon in staphylococcal TSS. STSS may uncommonly occur in the absence of cutaneous involvement; in these cases, differentiation from staphylococcal TSS becomes more difficult.
- Varicella
- Influenza A
- Nonsteroidal anti-inflammatory drug use (controversial association)
More on Toxic Shock Syndrome |
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| Follow-up: Toxic Shock Syndrome |
| References |
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References
Shands KN, Schmid GP, Dan BB, Blum D, Guidotti RJ, Hargrett NT, et al. Toxic-shock syndrome in menstruating women: association with tampon use and Staphylococcus aureus and clinical features in 52 cases. N Engl J Med. Dec 18 1980;303(25):1436-42. [Medline].
Rosen H. Superantigens. Int J Dermatol. Jan 1997;36(1):14-6. [Medline].
Haddadin DW, Samnani IQ, Moorman JP. Drotrecogin alfa (activated) for nonmenstrual toxic shock syndrome associated with methicillin resistant Staphylococcus aureus infection. South Med J. Nov 2006;99(11):1295-6. [Medline].
Darenberg J, Ihendyane N, Sjölin J, Aufwerber E, Haidl S, Follin P, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. Aug 1 2003;37(3):333-40. [Medline].
Davis JP, Chesney PJ, Wand PJ, LaVenture M. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med. Dec 18 1980;303(25):1429-35. [Medline].
Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. Mar 2004;32(3):858-73. [Medline].
Drage LA. Life-threatening rashes: dermatologic signs of four infectious diseases. Mayo Clin Proc. Jan 1999;74(1):68-72. [Medline].
Durand G, Bes M, Meugnier H, Enright MC, Forey F, Liassine N, et al. Detection of new methicillin-resistant Staphylococcus aureus clones containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France. J Clin Microbiol. Mar 2006;44(3):847-53. [Medline].
Hoge CW, Schwartz B, Talkington DF, Breiman RF, MacNeill EM, Englender SJ. The changing epidemiology of invasive group A streptococcal infections and the emergence of streptococcal toxic shock-like syndrome. A retrospective population-based study. JAMA. Jan 20 1993;269(3):384-9. [Medline].
Larkin SM, Williams DN, Osterholm MT, Tofte RW, Posalaky Z. Toxic shock syndrome: clinical, laboratory, and pathologic findings in nine fatal cases. Ann Intern Med. Jun 1982;96(6 Pt 2):858-64. [Medline].
Manders SM. Toxin-mediated streptococcal and staphylococcal disease. J Am Acad Dermatol. Sep 1998;39(3):383-98; quiz 399-400. [Medline].
Nelson C. Early recognition and treatment of staphylococcal and streptococcal toxic shock. J Pediatr Adolesc Gynecol. Aug 2004;17(4):289-92. [Medline].
Reingold AL, Hargrett NT, Shands KN, Dan BB, Schmid GP, Strickland BY. Toxic shock syndrome surveillance in the United States, 1980 to 1981. Ann Intern Med. Jun 1982;96(6 Pt 2):875-80. [Medline].
Stevens DL. The toxic shock syndromes. Infect Dis Clin North Am. Dec 1996;10(4):727-46. [Medline].
Strausbaugh LJ. Toxic shock syndrome. Are you recognizing its changing presentations?. Postgrad Med. Nov 1 1993;94(6):107-8, 111-3, 117-8. [Medline].
Wenisch C, Laferl H, Szell M, Smolle KH, Grisold A, Bertha G, et al. A holistic approach to MRSA eradication in critically ill patients with MRSA pneumonia. Infection. Jun 2006;34(3):148-54. [Medline].
Wolf JE, Rabinowitz LG. Streptococcal toxic shock-like syndrome. Arch Dermatol. Jan 1995;131(1):73-7. [Medline].
Wood TF, Potter MA, Jonasson O. Streptococcal toxic shock-like syndrome. The importance of surgical intervention. Ann Surg. Feb 1993;217(2):109-14. [Medline].
Working Group on Severe Streptococcal Infections. Defining the group A streptococcal toxic shock syndrome. Rationale and consensus definition. The Working Group on Severe Streptococcal Infections. JAMA. Jan 20 1993;269(3):390-1. [Medline].
Further Reading
Keywords
shock, TSS, STSS, toxic strep, streptococcal toxic shock-like syndrome, streptococcal TSS, Staphylococcus aureus, S aureus
