Toxic shock syndrome

Toxic shock syndrome (TSS) is a very rare but 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 and Streptococcus pyogenes. 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 bacteria 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 multi-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 onslaught of the infection, the rash desquamates, or peels off, after 10–14 days.

In contrast, TSS caused by the bacteria 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 rash.

In either case, diagnosis is based strictly upon CDC criteria modified in 1981 after the initial surge in tampon-associated infections.^[1]:

1. Body temperature > 38.9 °C (102.02 °F)
2. Systolic blood pressure < 90 mmHg
3. Diffuse rash, intense erythroderma, blanching with subsequent desquamation, especially of the palms and soles
4. Involvement of three or more organ systems:
   • Gastrointestinal (vomiting, diarrhea)
   • Mucous membrane hyperemia (vaginal, oral, conjunctival)
   • Renal failure (serum creatinine > 2x normal)
   • Hepatic inflammation (AST, ALT > 2x normal)
   • Thrombocytopenia (platelet count < 100,000 / mm³)
   • CNS involvement (confusion without any focal neurological findings)

Pathophysiology

TSST-1 structure. The protein is a dimer.

In both TSS (caused by Staph. aureus) and TSLS (caused by Strep. pyogenes), disease progression stems from a superantigen toxin that allows the non-specific 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 Toxic Shock Syndrome Toxin-1, or TSST-1.

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.^[2] The source of infection should be removed or drained if possible: abscesses and collections should be drained. Women 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.^[2]

Antibiotic treatment should cover both S. pyogenes and S. aureus: this may include a combination of cephalosporins, penicillins or vancomycin. The addition of clindamycin^[3] or gentamicin^[4] reduces toxin production and reduces 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-using females 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 females per year.^[5][6] The CDC has stopped tracking TSS. However, 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 that cases in part of Minnesota more than tripled from 2000 to 2003.^[5] 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.^[5]

History

Initial description

The term toxic shock syndrome was first used in 1978 by a Denver pediatrician, Dr. James K. Todd, to describe the staphylococcal illness in three boys and four girls aged 8–17 years.^[7] 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 that 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 woman using them.^[8]

Rely tampons

Package of Rely Tampons

Following a controversial period of test marketing in Rochester, New York and Fort Wayne, Indiana,^[9] in August 1978 Procter and Gamble introduced superabsorbent Rely tampons to the United States market^[10] in response to women's demands for tampons that could contain an entire menstrual flow without leaking or replacement.^[11] Rely used carboxymethylcellulose (CMC) and compressed beads of polyester for absorption. This tampon design could absorb nearly 20 times its own weight in fluid.^[12] Further, the tampon would "blossom" into a cup shape in the vagina in order to hold menstrual fluids without leakage.

In January 1980, epidemiologists in Wisconsin and Minnesota reported the appearance of TSS, mostly in menstruating women, to the CDC.^[13] S. aureus was successfully cultured from most of the women. A CDC task force investigated the epidemic as the number of reported cases rose throughout the summer of 1980, accompanied by widespread publicity. In September 1980, the CDC reported that users of Rely were at increased risk for developing TSS.^[14]

On September 22, 1980, Procter and Gamble recalled Rely^[15] 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."^[16] 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.^[17] 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.^[18] The ability of carboxymethylcellulose to filter the S. aureus toxin that causes TSS may account for the increased risk associated with Rely.^[12]

By the end of 1980, the number of TSS cases reported to the CDC began to decline. The reduced incidence was attributed not only to the removal of Rely from the market, but also to reduced use of all tampon brands. According to the Boston Women's Health Book Collective, 942 women were diagnosed with tampon-related TSS in the USA from March 1980 to March 1981, 40 of whom died.

See also

• Necrotizing fasciitis
• Septic shock
• Toxic headache

References

External links

• Toxic Shock Syndrome and Tampons at the University of Illinois' McKinley Health Center website
• Streptococcal Toxic-Shock Syndrome: Spectrum of Disease, Pathogenesis, and New Concepts in Treatment - a 1995 paper on TSS
• eMedicine Health

For more information on Toxic Shock Syndrome - visit http://www.tssis.com/