Toxic shock syndrome
Encyclopedia
Toxic shock syndrome is a potentially fatal illness caused by a bacterial toxin
. Different bacteria
l 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).
, 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 onslaught 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.
In either case, diagnosis is based strictly upon CDC
criteria modified in 1981 after the initial surge in tampon
-associated infections.:
toxin that allows the nonspecific binding of MHC II with T cell receptor
s, 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 island
s.
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 cephalosporin
s, penicillin
s or vancomycin
. The addition of clindamycin
or gentamicin
reduces toxin production and mortality.
Following a controversial period of 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, the 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.
By the end of 1980, the number of TSS cases reported to the CDC began to decline, however there is some argument as to whether statistics provided by CDC are reliable due to problems with recognition of TSS symptoms by medical staff and the way in which CDC records TSS cases, many estimate that only around a third of all TSS cases reported to the CDC were included in statistics. The reduced incidence was attributed not only to the removal of Rely from the market, but also to reduced use of all tampon brands.
It is noted that TSS is more common in commercial tampon brands which still use synthetic materials such as rayon, rather than 100% cotton tampon brands, there has also been no case of TSS associated with other internal sanitary products such as menstrual sponges, softcups or menstrual cups.
For more information on Toxic Shock Syndrome - visit http://www.tssis.com/
Exotoxin
An exotoxin is a toxin excreted by a microorganism, like bacteria, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host...
. Different bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l toxins may cause toxic shock syndrome, depending on the situation. The causative
Disease causative agent
The term disease causative agent usually refers to a biological agents pathogen that causes a disease. Technically, the term can also refer to a toxin or toxic chemical that causes illness such as parasites or bacteria....
bacteria include Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
and Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...
. 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 feverFever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, accompanied by low blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
and confusion, which can rapidly progress to stupor, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, 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 onslaught of the infection, the rash desquamates, or peels off, after 10–14 days.
In contrast, TSS caused by the bacterium Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...
, 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.
In either case, diagnosis is based strictly upon CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
criteria modified in 1981 after the initial surge in tampon
Tampon
A tampon is a mass of cotton or rayon or a mixture of the two inserted into a body cavity or wound to absorb bodilyfluid. The most common type in daily use is designed to be inserted into the vagina during menstruation to absorb the flow of menstrual fluid...
-associated infections.:
- Body temperature > 38.9 °C (102.02 °F)
- Systolic blood pressureBlood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
< 90 mmHg - Diffuse rashRashA rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, intense erythrodermaErythrodermaErythroderma is an inflammatory skin disease with erythema and scaling that affects nearly the entire cutaneous surface....
, blanchingBlanch (medical)When skin is blanched, it takes on a whitish appearance as blood flow to the region is prevented. This occurs during and is the basis of the physiologic test known as diascopy....
with subsequent desquamationDesquamationDesquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably...
, especially of the palms and soles - Involvement of three or more organ systems:
- Gastrointestinal (vomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
) - Mucous membraneMucous membraneThe mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
hyperemia (vaginal, oral, conjunctival) - Renal failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
(serum creatinine > 2 times normal) - HepaticLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
inflammation (AST, ALT > 2 times normal) - ThrombocytopeniaThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
(platelet count < 100,000 / mm³) - CNSCentral nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
involvement (confusion without any focal neurological findings)
- Gastrointestinal (vomiting
Pathophysiology
In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigenSuperantigen
Superantigens are a class of antigens which cause non-specific activation of T-cells resulting in oligoclonal T cell activation and massive cytokine release...
toxin that allows the nonspecific binding of MHC II with T cell receptor
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
s, 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
Cytokine storm
A cytokine storm, or hypercytokinemia is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.-Symptoms:...
, followed by a multisystem disease. The toxin in S. aureus infections is TSS Toxin-1, or TSST
Toxic shock syndrome toxin
Toxic Shock Syndrome Toxin is a superantigen with a size of 22KDa produced by somewhere between 5% and 25% of Staphylococcus aureus isolates. It causes toxic shock syndrome by stimulating the release of large amounts of interleukin-1, interleukin-2 and tumour necrosis factor...
-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 island
Pathogenicity island
Pathogenicity islands are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. They are incorporated in the genome of pathogenic organisms but are usually absent from those non-pathogenic organisms of the same or closely related species...
s.
Treatment
The severity of this disease frequently warrants hospitalization. Admission to the intensive care unitIntensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...
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
Tampon
A tampon is a mass of cotton or rayon or a mixture of the two inserted into a body cavity or wound to absorb bodilyfluid. The most common type in daily use is designed to be inserted into the vagina during menstruation to absorb the flow of menstrual fluid...
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 cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
s, penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
s or vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
. The addition of clindamycin
Clindamycin
Clindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
or gentamicin
Gentamicin
Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...
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. 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 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.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. 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
Rochester, New York
Rochester is a city in Monroe County, New York, south of Lake Ontario in the United States. Known as The World's Image Centre, it was also once known as The Flour City, and more recently as The Flower City...
and Fort Wayne, Indiana
Fort Wayne, Indiana
Fort Wayne is a city in the US state of Indiana and the county seat of Allen County. The population was 253,691 at the 2010 Census making it the 74th largest city in the United States and the second largest in Indiana...
, in August 1978, Procter and Gamble introduced superabsorbent Rely
Rely (brand)
Rely was a brand of superabsorbent tampons made by Procter & Gamble starting in 1975. It was recalled from the market in September 1980 because it was linked to toxic shock syndrome....
tampons to the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
market in response to women's demands for tampons that could contain an entire menstrual flow without leaking or replacement. Rely used carboxymethylcellulose
Carboxymethyl cellulose
Carboxymethyl cellulose or cellulose gum is a cellulose derivative with carboxymethyl groups bound to some of the hydroxyl groups of the glucopyranose monomers that make up the cellulose backbone...
(CMC) and compressed beads of polyester
Polyester
Polyester is a category of polymers which contain the ester functional group in their main chain. Although there are many polyesters, the term "polyester" as a specific material most commonly refers to polyethylene terephthalate...
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
Wisconsin
Wisconsin is a U.S. state located in the north-central United States and is part of the Midwest. It is bordered by Minnesota to the west, Iowa to the southwest, Illinois to the south, Lake Michigan to the east, Michigan to the northeast, and Lake Superior to the north. Wisconsin's capital is...
and Minnesota
Minnesota
Minnesota is a U.S. state located in the Midwestern United States. The twelfth largest state of the U.S., it is the twenty-first most populous, with 5.3 million residents. Minnesota was carved out of the eastern half of the Minnesota Territory and admitted to the Union as the thirty-second state...
reported the appearance of TSS, mostly in those menstruating, to the CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
. 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, the 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.
By the end of 1980, the number of TSS cases reported to the CDC began to decline, however there is some argument as to whether statistics provided by CDC are reliable due to problems with recognition of TSS symptoms by medical staff and the way in which CDC records TSS cases, many estimate that only around a third of all TSS cases reported to the CDC were included in statistics. The reduced incidence was attributed not only to the removal of Rely from the market, but also to reduced use of all tampon brands.
It is noted that TSS is more common in commercial tampon brands which still use synthetic materials such as rayon, rather than 100% cotton tampon brands, there has also been no case of TSS associated with other internal sanitary products such as menstrual sponges, softcups or menstrual cups.
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/