Toxic shock syndrome

Toxic shock syndrome (TSS) is a rare but potentially fatal disease caused by a bacterial toxin. Different bacterial toxins may cause toxic shock syndrome, depending on the situation. The causative agents are the Gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes. Streptococcal TSS is sometimes referred to as Toxic Shock Like Syndrome (TSLS).

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Routes of infection

This infection can occur via the skin (e.g. cuts, surgery, burns), vagina (via tampon), or pharynx. However, most of the large number of individuals who are exposed to or colonized with toxin-producing strains of S. aureus or S. pyogenes do not develop toxic shock syndrome. One reason is that a large fraction of the population has protective antibodies against the toxins that cause TSS.^[1] It is not clear why the antibodies are present in people who have never had the disease, but likely that given these bacterium's cosmopolitan nature and makeup of normal flora, minor cuts and such allow a natural immunisation on a small scale.

The number of reported staphylococcal toxic shock syndrome cases has decreased significantly in recent years. Approximately half the cases of staphylococcal TSS reported today are associated with tampon use during menstruation, usually in young women, though TSS also occurs in children, men, and non-menstruating women. In the US in 1997, only five confirmed menstrual-related TSS cases were reported, compared with 814 cases in 1980, according to data from the Centers for Disease Control and Prevention (CDC).^[2] It has been estimated that each year 1 to 17 of every 100,000 menstruating females will get TSS.^[3]

Although scientists have recognized an association between TSS and tampon use, no firm causal link has been established. Research conducted by the CDC suggested that use of some high absorbency tampons increased the risk of TSS in menstruating women. A few specific tampon designs and high absorbency tampon materials were also found to have some association with increased risk of TSS. These products and materials are no longer used in tampons sold in the U.S. (The materials include polyester, carboxymethylcellulose and polyacrylate).^[4] Tampons made with rayon do not appear to have a higher risk of TSS than cotton tampons of similar absorbency.^[5]

Toxin production by S. aureus requires a protein-rich environment, which is provided by the flow of menstrual blood, a neutral vaginal pH, which occurs during menstruation, and elevated oxygen levels, which is provided by the tampon that is inserted into the normally anaerobic vaginal environment.^[6] Although ulcerations have been reported in women using super absorbent tampons, the link to menstrual TSS, if any, is unclear. The toxin implicated in menstrual TSS is capable of entering the bloodstream by crossing the vaginal wall in the absence of ulcerations.^[7] Women may avoid problems by choosing a tampon with the minimum absorbency needed to control menstrual flow and using tampons only during active menstruation. Alternately, a woman may choose to use a different kind of menstrual product that may eliminate or reduce the risk of TSS, such as sanitary napkins or a menstrual cup.

History

Initial description of toxic shock syndrome

The term toxic shock syndrome was first used in 1978 by a Denver pediatrician, Dr. J.K. Todd, to describe the staphylococcal illness in three boys and four girls aged 8-17 years.^[8] Even though S. aureus was isolated from mucosal sites from 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. Most notably, 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.^[9]

Rely tampons

Following a controversial period of test marketing in Rochester, New York and Fort Wayne, Indiana,^[10] in August of 1978 Procter and Gamble introduced superabsorbent Rely tampons to the United States market^[11] in response to women's demands for tampons that could contain an entire menstrual flow without leaking or replacement.^[4] 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.

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 of menstrual TSS before Rely was introduced.^[17] It was shown later that higher absorbency of tampons was associated with an increased the 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 from the diminished 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 the March 1980 to March 1981, 40 of whom died.

Symptoms and diagnosis

Symptoms of toxic shock syndrome vary depending on the underlying cause. In either case, diagnosis is based strictly upon CDC criteria modified in 1981 after the initial surge in tampon-associated infections.^[19] TSS resultant of 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, TSLS is caused by the bacteria Streptococcus pyogenes, and it 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.

Diagnosis of TSS and TSLS are strictly based on CDC criteria:

1. Body temperature > 38.9 °C (102.02 °F)
2. Systolic blood pressure < 90 mmHg
3. Diffuse rash, intense erythroderma, blanching ("boiled lobster") with subsequent desquamation, especially of the palms and soles
4. Involvement of three or more organ systems:
   • GI (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)

Pathogenesis

In both TSS (caused by S. aureus) and TSLS (caused by S. 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.

Therapy

Women wearing a tampon at the onset of symptoms should remove it immediately. The severity of this disease warrants hospitalization. Treatment consists of aggressive IV fluid administration and antistaphylococcal antibiotics, such as cephalosporins, penicillinase-resistant semisynthetic penicillins or vancomycin.

Streptococcal toxic shock-like syndrome can result from infection of the skin. Antibiotic treatment consists of penicillin and clindamycin.

With proper treatment, patients usually recover in two to three weeks. The condition, however, can be fatal within hours. Sometimes patients are admitted to the intensive care unit for supportive care in case of multiple organ failure.

See also

• Necrotizing fasciitis
• Septic shock

References