Toxic shock syndrome

Toxic shock syndrome
Classification and external resources
Specialty	Infectious disease
ICD-10	A48.3
ICD-9-CM	040.82
DiseasesDB	13187
MedlinePlus	000653
eMedicine	med/2292 emerg/600 derm/425 ped/2269
Patient UK	Toxic shock syndrome
MeSH	D012772

Toxic shock syndrome (TSS) is a potentially fatal illness caused by a bacterial toxin. Different bacterial toxins may cause toxic shock syndrome, depending on the situation. The causative bacteria include Staphylococcus aureus, where TSS is caused by enterotoxin type B or TSST-1, and Streptococcus pyogenes, where it is caused by streptococcal pyrogenic exotoxins. Streptococcal TSS is sometimes referred to as toxic shock-like syndrome (TSLS) or streptococcal toxic shock syndrome (STSS).

Signs and symptoms

Symptoms of toxic shock syndrome vary depending on the underlying cause. TSS resulting from infection with the bacterium Staphylococcus aureus typically manifests in otherwise healthy individuals with high fever, accompanied by low blood pressure, malaise and confusion, which can rapidly progress to stupor, coma, and multiple organ failure. The characteristic rash, often seen early in the course of illness, resembles a sunburn, and can involve any region of the body, including the lips, mouth, eyes, palms and soles. In patients who survive the initial phase of the infection, the rash desquamates, or peels off, after 10–14 days.

In contrast, TSS caused by the bacterium Streptococcus pyogenes, or TSLS, typically presents in people with pre-existing skin infections with the bacteria. These individuals often experience severe pain at the site of the skin infection, followed by rapid progression of symptoms as described above for TSS. In contrast to TSS caused by Staphylococcus, streptococcal TSS less often involves a sunburn-like rash.

For staphylococcal toxic shock syndrome, the diagnosis is based strictly upon CDC criteria defined in 2011, as follows:

1. Body temperature > 38.9 °C (102.02 °F)
2. Systolic blood pressure < 90 mmHg
3. Diffuse macular erythroderma
4. Desquamation (especially of the palms and soles) 1–2 weeks after onset.
5. Involvement of three or more organ systems:
   • Gastrointestinal (vomiting, diarrhea)
   • Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal for laboratory
   • Mucous membrane hyperemia (vaginal, oral, conjunctival)
   • Kidney failure (serum creatinine > 2 times normal)
   • Liver inflammation (bilirubin, AST, or ALT > 2 times normal)
   • Low platelet count (platelet count < 100,000 / mm³)
   • Central nervous system involvement (confusion without any focal neurological findings)
6. Negative results of:
   • blood, throat, and CSF cultures for other bacteria (besides S. aureus)
   • negative serology for Rickettsia infection, leptospirosis, and measles.

Cases are classified as confirmed or probable based on the following:

• Confirmed: All six of the criteria above are met (unless the patient dies before desquamation can occur)
• Probable: Five of the six criteria above are met.

Pathophysiology

In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigen toxin that allows the nonspecific binding of MHC II with T cell receptors, resulting in polyclonal T cell activation. In typical T cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex (MHC) in a groove formed by the alpha and beta chains of class II MHC, and recognized by an antigen-specific T cell receptor.

By contrast, superantigens do not require processing by antigen-presenting cells but instead interact directly with the invariant region of the class II MHC molecule. In patients with TSS, up to 20% of the body's T cells can be activated at one time. This polyclonal T-cell population causes a cytokine storm, followed by a multisystem disease. The toxin in S. aureus infections is TSS Toxin-1, or TSST-1. The TSST-1 is secreted as a single polypeptide chain.

The gene encoding toxic shock syndrome toxin is carried by a mobile genetic element of S. aureus in the SaPI family of pathogenicity islands.

Treatment

The severity of this disease frequently warrants hospitalization. Admission to the intensive care unit is often necessary for supportive care (for aggressive fluid management, ventilation, renal replacement therapy and inotropic support), particularly in the case of multiple organ failure. The source of infection should be removed or drained if possible: abscesses and collections should be drained. Anyone wearing a tampon at the onset of symptoms should remove it immediately. Outcomes are poorer in patients who do not have the source of infection removed.

Antibiotic treatment should cover both S. pyogenes and S. aureus. This may include a combination of cephalosporins, penicillins or vancomycin. The addition of clindamycin or gentamicin reduces toxin production and mortality.

Prognosis

With proper treatment, patients usually recover in two to three weeks. The condition can, however, be fatal within hours.

Epidemiology

Staphylococcal toxic shock syndrome is rare and the number of reported cases has declined significantly since the 1980s. Patrick Schlievert, who published a study on it in 2004, determined incidence at 3 to 4 out of 100,000 tampon users per year; the information supplied by manufacturers of sanitary products such as Tampax and Stayfree puts it at 1 to 17 of every 100,000 menstruating people per year.

There was a rise in reported cases in the early 2000s: eight deaths from the syndrome in California in 2002 after three successive years of four deaths per year, and Schlievert's study found cases in part of Minnesota more than tripled from 2000 to 2003. Schlievert considers earlier onset of menstruation to be a cause of the rise; others, such as Philip M. Tierno and Bruce A. Hanna, blame new high-absorbency tampons introduced in 1999 and manufacturers discontinuing warnings not to leave tampons in overnight.

History

Initial description

The term "toxic shock syndrome" was first used in 1978 by a Denver pediatrician, James K. Todd, to describe the staphylococcal illness in three boys and four girls aged 8–17 years. Even though S. aureus was isolated from mucosal sites in the patients, bacteria could not be isolated from the blood, cerebrospinal fluid, or urine, raising suspicion that a toxin was involved. The authors of the study noted reports of similar staphylococcal illnesses had appeared occasionally as far back as 1927, but the authors at the time failed to consider the possibility of a connection between toxic shock syndrome and tampon use, as three of the girls who were menstruating when the illness developed were using tampons. Many cases of TSS occurred after tampons were left in the person using them.

Rely tampons

Following controversial test marketing in Rochester, New York and Fort Wayne, Indiana in August 1978, Procter and Gamble introduced superabsorbent Rely tampons to the United States market in response to women's demands for tampons that could contain an entire menstrual flow without leaking or replacement. Rely used carboxymethylcellulose (CMC) and compressed beads of polyester for absorption. This tampon design could absorb nearly 20 times its own weight in fluid. Further, the tampon would "blossom" into a cup shape in the vagina to hold menstrual fluids without leakage.

In January 1980, epidemiologists in Wisconsin and Minnesota reported the appearance of TSS, mostly in those menstruating, to the CDC. S. aureus was successfully cultured from most of the subjects. The Toxic Shock Syndrome Task Force was created and investigated the epidemic as the number of reported cases rose throughout the summer of 1980. In September 1980, CDC reported users of Rely were at increased risk for developing TSS.

On 22 September 1980, Procter and Gamble recalled Rely following release of the CDC report. As part of the voluntary recall, Procter and Gamble entered into a consent agreement with the FDA "providing for a program for notification to consumers and retrieval of the product from the market". However, it was clear to other investigators that Rely was not the only culprit. Other regions of the United States saw increases in menstrual TSS before Rely was introduced.

It was shown later that higher absorbency of tampons was associated with an increased risk for TSS, regardless of the chemical composition or the brand of the tampon. The sole exception was Rely, for which the risk for TSS was still higher when corrected for its absorbency. The ability of carboxymethylcellulose to filter the S. aureus toxin that causes TSS may account for the increased risk associated with Rely.

Notable cases

• Clive Barker, fully recovered, contracted the syndrome after visiting the dentist.
• Lana Coc-Kroft, fully recovered, contracted the syndrome due to Group A streptococcal infection.
• Jim Henson, d. 1990, contracted the syndrome due to Group A streptococcal infection.
• Nan C. Robertson, d. 2009, 1983 winner of the Pulitzer Prize for Feature Writing for her medically detailed account of her struggle with toxic shock syndrome, a cover story for The New York Times Magazine which at that time became the most widely syndicated article in Times history.
• Mike Von Erich, d. 1987, developed the syndrome after shoulder surgery: he made an apparent recovery but suffered brain damage as a result of the condition.

See also

• Necrotizing fasciitis
• Septic shock
• Toxic headache