Introduction
Background
Toxic shock syndrome (TSS) is a toxin-mediated multisystem disease precipitated by infection with either Staphylococcus aureus or group A Streptococcus (GAS), also called Streptococcus pyogenes. The clinical syndrome is characterized by a rapid onset of high fever, hypotension, diffuse rash (petechial or maculopapular), severe myalgia, vomiting, diarrhea, headache, and nonfocal neurologic abnormalities. Mortality is high.
TSS was first described in children in 1978.1 Subsequent reports identified an association with tampon use by menstruating women.2,3,4 In the 1980s, Cone initially reported and Stevens subsequently characterized GAS as a pathogen responsible for invasive soft tissue infection ushered by toxic shock–like syndrome.5,6 The streptococcal TSS is identical to staphylococcal TSS (STSS), except that the blood cultures usually are positive for staphylococci in STSS. Toxin-producing strains of S aureus infect or colonize people who have risk factors for the development of the syndrome. Most cases are related to the staphylococcal toxin, now called TSS toxin-1 (TSST-1).
GAS is an aerobic gram-positive organism that forms chains and is an important cause of soft tissue infections. Severe, invasive GAS infections can cause necrotizing fasciitis and spontaneous gangrenous myositis. An increasing number of severe GAS infections associated with shock and organ failure have been reported. These infections are termed streptococcal TSS.7
Description of M proteins and streptococcal toxins.
Pathophysiology
Bacteriology
M protein is an important virulent determinant of GAS; strains lacking M protein are less virulent. M protein is a filamentous protein anchored to the cell membrane, which has antiphagocyte properties. M types 1, 3, 12, and 28 are the most common isolates found in patients with shock and multiorgan failure; furthermore, 3 distinct streptococcal pyrogenic exotoxins (ie, A, B, C) also have been identified. These toxins induce cytotoxicity and pyrogenicity and enhance the lethal effects of endotoxins. Recently, the streptococcal super antigen, a pyrogenic exotoxin, has been isolated from an M-3 strain.
Mechanism of shock and tissue destruction
Colonization or infection with certain strains of S aureus and GAS is followed by the production of 1 or more toxins. These toxins are absorbed systemically and produce the systemic manifestations of TSS in people who lack a protective antitoxin antibody. Possible mediators of the effects of the toxins are cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). Pyrogenic exotoxins induce human mononuclear cells to synthesize TNF-alpha, IL-1-beta, and interleukin 6 (IL-6).
TSS likely relates to the ability of pyrogenic exotoxins of GAS and enterotoxins of S aureus to act as super antigens. These exotoxins and several staphylococcal toxins (eg, TSST-1) can stimulate T-cell responses through their ability to bind to both the class II major histocompatibility complex of antigen-presenting cells and T-cell receptors. These toxins bind the beta chain variable region (V-beta) elements on T-cell receptors and simultaneously bind to the class II major histocompatability antigen-processing cells. This mechanism bypasses the classical antigen-processing procedures and results in excessive T-cell proliferation.
The conventional antigens activate only about 0.01% to 0.1% of the T-cell population, whereas, the superantigens set in motion 5 to 30% of the entire T-cell population. The net effect is massive production of cytokines that are capable of mediating shock and tissue injury. Other exotoxins (eg, streptolysin O, exotoxin B) and cell wall components also are important inducers of TNF-alpha and IL-1 and IL-6. Both TNF-alpha and IL-1-beta play a role in the pathogenesis of TSS.
Frequency
United States
Estimates from population-based studies have documented an incidence of invasive GAS infection of 1.5-5.2 cases per 100,000 people annually.8 Approximately 8-14% of these patients also will develop TSS.9 A history of recent varicella infection markedly increases the risk of infection with GAS to 62.7 cases per 100,000 people per year. Severe soft tissue infections, including necrotizing fasciitis, myositis, or cellulitis, were present in approximately half of the patients.
STSS is much more common, although data on prevalence do not exist. In the United States, from 1979-1996, 5296 cases of STSS were reported. The number of cases of menstrual STSS is estimated at 1 per 100,000. The incidence of nonmenstrual STSS now exceeds menstrual STSS after the hyperabsorbable tampons were removed from the market.
Mortality/Morbidity
Mortality rates for streptococcal TSS are 30-70%.10,11 Morbidity also is high; in one series, 13 of 20 patients underwent major surgical procedures, such as fasciotomy, surgical debridement, laparotomy, amputation, or hysterectomy.6,10
The case fatality rates for menstrual-related STSS have declined from 5.5% in 1980 to 1.8% in 1996.
Race
TSS has occurred in all races, although most cases have been reported from North America and Europe.
Sex
STSS most commonly occurs in women, usually those who are using tampons.
Age
Some studies have shown no predilection for any particular age for either the streptococcal TSS or STSS. However, other studies have reported STSS to be more common in older individuals with underlying medical problems. In a Canadian survey, STSS accounted for 6% of cases in individuals younger than 10 years compared with 21% in people older than 60 years.8 Furthermore, menstruation-associated STSS occurred in younger women who were using tampons.
Clinical
History
The possibility of toxic shock should be considered in any individual who presents with sudden onset of fever, rash, hypotension, renal or respiratory failure, and changes in mental status.12
- STSS most commonly occurs in women, usually those who are using tampons, TSS develops within 5 days after the onset of menstruation. The other clinical settings where STSS has been reported include the following:
- Surgical wound infections
- Postpartum infections
- Focal cutaneous and subcutaneous lesions
- Deep abscesses
- Empyema
- Peritonsillar abscess
- Sinusitis
- Osteomyelitis
- Soft tissue infections from GAS include necrotizing fasciitis, myositis, or cellulitis. The most common initial symptom of patients with streptococcal TSS is diffuse or localized pain that is abrupt and severe. Other manifestations include the following:
- Influenzalike syndrome
- Fever
- Confusion
- Signs of soft tissue infection
- Approximately 20% of patients with STSS have an influenzalike syndrome characterized by the following:
- Fever
- Chills
- Myalgia
- Nausea
- Vomiting
- Diarrhea
- The other reported types of infection are pneumonia, unidentified bacteremia, surgical site infection, septic arthritis, thrombophlebitis, meningitis, pelvic infection, and endophthalmitis.
- Common presenting symptoms and frequency of STTS are as follows10 :
- Pain (44-85%)
- Vomiting (25-26%)
- Nausea (20%)
- Diarrhea (14-30%)
- Influenzalike symptoms (14-20%)
- Headache (10%)
- Dyspnea (8%)
- The following risk factors have been reported to be associated with STSS:
- Patients with HIV, diabetes, cancer, ethanol abuse, and other chronic diseases
- Patients with a recent history of varicella infection (chicken pox)
- Patients who used nonsteroidal anti-inflammatory drugs (NSAIDs)
Physical
Fever is the most common presenting sign, although patients in shock may present with hypothermia. Shock is apparent at the time of hospitalization or within 4-8 hours for all patients. Patients become severely hypotensive and do not respond to intravenous fluid administration. Renal dysfunction progresses or persists in all patients, precedes shock in many patients, and is apparent early. Acute respiratory distress syndrome occurs in 55% of patients and requires mechanical ventilation.
A thorough search for possible sites of streptococcal and staphylococcal infection is a must. The surgical wounds should be carefully examined even if no signs of infection are apparent. Vaginal examination and removal of tampon or other foreign body should be de rigueur.
- Confusion is present in 55% of patients, and coma or agitation may occur.
- Nearly 50% of patients are normotensive on presentation but become hypotensive within 4 hours.
- Approximately 80% of patients have clinical signs of soft tissue infection (eg, localized swelling, erythema), which usually progresses to necrotizing fasciitis or myositis.
- Approximately 20% of patients have various clinical presentations, including the following:
- Endophthalmitis
- Myositis
- Perihepatitis
- Peritonitis
- Myocarditis
- Diffuse scarlatinalike erythema occurs in 10% of patients.
- Skin manifestations of streptococcal infection include the following:
- Bullae
- Scarlet fever–like rash
- Petechiae or maculopapular rashes
- Desquamation
- The possibility of STSS should be entertained in any patient who presents with a sudden onset of fever, rash, hypotension, and systemic evidence of toxicity. Five categories of clinical features are needed for the diagnosis, as follows (Centers for Disease Control and Prevention, 1990):
- Fever
- Rash - A diffuse macular erythroderma
- Desquamation - Occurs 1-2 weeks after onset of illness, involving palms and soles
- Hypotension (systolic blood pressure <90 mm Hg, orthostatic drop in diastolic blood pressure <15 mm Hg, orthostatic syncope, and dizziness)
- Evidence of multisystem involvement in 3 or more of the following systems:
- Gastrointestinal - Vomiting or diarrhea at the onset of illness
- Muscular - Severe myalgia or creatine kinase (CK) elevation (>2 times normal upper limit)
- Mucous membrane - Vaginal, oropharyngeal, or conjunctival erythema
- Renal - BUN or serum creatinine greater than 2 times the upper limit of normal
- Hepatic - Bilirubin or transaminases greater than 2 times the upper limit of normal
- Hematological - Platelets less than 100,000
- Central nervous system - Disorientation or alteration in consciousness without focal signs
- Common presenting symptoms and frequency of STTS are as follows6 :
- Tachycardia (80%)
- Fever (70-81%)
- Hypotension (44-65%)
- Confusion (55%)
- Localized erythema (44-65%)
- Localized swelling and erythema (30-75%)
- Scarlatiniform rash (0-4%)
- Case definition of streptococcal TSS (Working group definition, JAMA 1993)
- Isolation of GAS (S pyogenes) from a normally sterile site, eg, blood, cerebrospinal fluid, pleural fluid (definite case), or nonsterile site (probable case) and hypotension (systolic pressure £ 90 mm Hg in adults or less than fifth percentile for children)
- Multiorgan involvement, as evidenced by at least 2 of the following:
- Renal impairment - Creatinine level more than 177 µmol/L for adults or twice upper normal limit for age or more than twice the baseline level for patients with renal disease
- Coagulopathy - Platelet count less than 100 X 106/L or disseminated intravascular coagulation
- Liver involvement - Alanine aminotransferase, aspartate aminotransferase, or total bilirubin level more than twice normal limit for age or more than twice baseline in patients with chronic liver disease
- Pulmonary involvement - Adult respiratory distress syndrome or evidence of diffuse capillary leak syndrome
- Generalized erythematous macular rash
- Soft tissue necrosis (necrotizing infection, necrotizing myositis, or gangrene)
Causes
- Acquisition of infection
- Risk factors for the development of STSS are tampon use, vaginal colonization with toxin-producing S aureus, and lack of serum antibody to the staphylococcal toxin.13 STSS also has occurred following use of nasal tampons for procedures of the ears, nose, and throat.
- The portal of entry for streptococci is unknown in almost one half of the cases. Procedures such as suction lipectomy, hysterectomy, vaginal delivery, and bone pinning have been identified as the portal of entry in many cases. Most commonly, infection begins at a site of minor local trauma, which may be nonpenetrating. Viral infections, such as varicella and influenza, also have provided a portal of entry.
More on Toxic Shock Syndrome |
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| Follow-up: Toxic Shock Syndrome |
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| References |
| Further Reading |
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Further Reading
Clinical guidelines
Female barrier methods.
Faculty of Sexual and Reproductive Healthcare - Professional Association. 2007 Jun. 17 pages. NGC:006305
Practice guidelines for the diagnosis and management of skin and soft-tissue infections.
Infectious Diseases Society of America - Medical Specialty Society. 2005 Nov 15. 34 pages. NGC:004581
Clinical trials
Long Term Follow-up of Patients With Group A Streptococcal Infection Originating From the Genital Tract
Early-Onset Sepsis Surveillance Study
Related eMedicine topics
Staphylococcus Aureus Infection
Streptococcal Infection, Group A
Staphylococcal Infections
Toxic Shock Syndrome (Dermatoloy)
Toxic Shock Syndrome (Emergency Medicine)
Toxic Shock Syndrome (Pediatrics)
Keywords
toxic shock syndrome, TSS, flesh-eating disease, toxic shock, septic shock, Staphylococcus aureus, S aureus, group A Streptococcus, GAS, Streptococcus pyogenes, S pyogenes
