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Toxic Shock Syndrome

  • Author: Ramesh Venkataraman, MBBS; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
 
Updated: Apr 16, 2015
 

Background

Toxic shock syndrome (TSS) is a toxin-mediated acute life-threatening illness, usually precipitated by infection with either Staphylococcus aureus or group A Streptococcus (GAS), also called Streptococcus pyogenes. It is characterized by high fever, rash, hypotension, multiorgan failure (involving at least 3 or more organ systems), and desquamation, typically of the palms and soles, 1-2 weeks after the onset of acute illness. The clinical syndrome can also include severe myalgia, vomiting, diarrhea, headache, and nonfocal neurologic abnormalities.

See the image below.

A 46-year-old man presented with nonnecrotizing ce A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The patient had diffuse erythroderma, a characteristic feature of the syndrome. The patient improved with antibiotics and intravenous gammaglobulin therapy. Several days later, a characteristic desquamation of the skin occurred over palms and soles. Courtesy of Rob Green, MD.

TSS was first described in children in 1978.[1] Subsequent reports identified an association with tampon use by menstruating women.[2, 3, 4] Menstrual TSS is more likely in women using highly absorbent tampons, using tampons for more days of their cycle, and keeping a single tampon in place for a longer period of time. Over the past two decades, the number of cases of menstrual TSS (1 case per 100,000) has steadily declined; this is thought to be due to the withdrawal of highly absorbent tampons from the market.

Notably, 50% of cases of TSS are not associated with menstruation. Nonmenstrual cases of TSS usually complicate the use of barrier contraceptives, surgical and postpartum wound infections, burns, cutaneous lesions, osteomyelitis, and arthritis. Although most cases of TSS occur in women, about 25% of nonmenstrual cases occur in men.

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. Diabetes, alcoholism, varicella infections, and surgical procedures all increase the risk of severe GAS infections and hence may potentially increase the risk of GAS TSS. 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] See the image below.

Description of M proteins and streptococcal toxins Description of M proteins and streptococcal toxins.
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Pathophysiology

Bacteriology

Toxic shock syndrome (TSS) is caused from intoxication by one of several related Staphylococcus aureus exotoxins. The most commonly implicated toxins include TSS toxin type-1 (TSST-1) and Staphylococcal enterotoxin B.

Almost all cases of menstrual TSS and half of all the nonmenstrual cases are caused by TSST-1. Staphylococcal enterotoxin B is the second leading cause of TSS. Other exotoxins such as enterotoxins A, C, D, E, and H contribute to a small number of cases. Seventy to 80% of individuals develop antibody to TSST-1 by adolescence, and 90-95% have such antibody by adulthood. Apart from host immunity status, host-pathogen interaction, local factors (pH, glucose level, magnesium level), and age all have a direct impact on the clinical expression of this toxin-mediated illness.

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. In some studies, strains producing exotoxins B and C have been implicated in this syndrome, to a lesser extent.

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. Superantigens are molecules that interact with the T-cell receptor in a domain outside of the antigen recognition site and hence are able to activate large numbers of T cells resulting in massive cytokine production. Normally, an antigen has to be taken up, processed by an antigen-presenting cell and expressed at the cell-surface along with class II major histocompatibility complex (MHC). By contrast, superantigens do not require processing by antigen-presenting cells but instead interact directly with the class II MHC molecule. The superantigen-MHC complex then interacts with the T-cell receptor and stimulates large numbers of T cells to cause an exaggerated, dysregulated cytokine response.

In the case of TSS, the implicated 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 simultaneously bind to the beta chain variable region (V-beta) elements on T-cell receptors and 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 5-30% of the entire T-cell population. The net effect is massive production of cytokines that are capable of mediating shock and tissue injury. As part of this T cell response, interferon–gamma is also produced, which subsequently inhibits polyclonal immunoglobulin production. This failure to develop antibodies may explain why some patients are predisposed to relapse after a first episode of TSS.

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Epidemiology

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.

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Contributor Information and Disclosures
Author

Ramesh Venkataraman, MBBS Consultant, Critical Care Medicine, Apollo Hospitals, India

Ramesh Venkataraman, MBBS is a member of the following medical societies: American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, Society of Critical Care Medicine, Indian Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, World Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM is a member of the following medical societies: American College of Chest Physicians, Association of University Anesthetists, European Society of Intensive Care Medicine, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Shock Society, Society of Critical Care Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Masimo<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED for board membership; Received honoraria from Edwards Lifesciences for consulting; Received honoraria from Masimo, Inc for board membership.

Additional Contributors

Cory Franklin, MD Professor, Department of Medicine, Chicago Medical School at Rosalind Franklin University of Medicine and Science; Director, Division of Critical Care Medicine, Cook County Hospital

Cory Franklin, MD is a member of the following medical societies: New York Academy of Sciences, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthors Godfrey Harding, MD, FRCP(C), and Ken Dolynchuk, MD, PhD, FRCSC, to the development and writing of this article.

References
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Description of M proteins and streptococcal toxins.
Group A streptococci cause beta hemolysis on blood agar.
Group A streptococci on Gram stain of blood isolated from a patient who developed toxic shock syndrome. Courtesy of T. Matthews.
This schematic shows interaction among T-cell receptor, superantigen, and class II major histocompatability complex. The binding of superantigen to class II molecules and T-cell receptors is not limited by antigen specificity and lies outside the normal antigen binding sites.
Progression of soft tissue swelling to vesicle or bullous formation is an ominous sign and suggests streptococcal shock syndrome. Courtesy of S. Manocha.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The leg was incised to exclude underlying necrotizing infection. Courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. This patient also had streptococcal pharyngitis. Courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The patient had diffuse erythroderma, a characteristic feature of the syndrome. Courtesy of Rob Green, MD.
A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The patient had diffuse erythroderma, a characteristic feature of the syndrome. The patient improved with antibiotics and intravenous gammaglobulin therapy. Several days later, a characteristic desquamation of the skin occurred over palms and soles. Courtesy of Rob Green, MD.
A 58-year-old patient presented in septic shock. On physical examination, progressive swelling of the right groin was observed. On exploration, necrotizing cellulitis, but not fasciitis, was present. The cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). The CT scanning helped evaluate the extent of infection and exclude other pathologies, such as psoas abscess, osteomyelitis, and inguinal hernia.
A 58-year-old patient presented in septic shock. On physical examination, progressive swelling of the right groin was observed. On exploration, necrotizing cellulitis, but not fasciitis, was present. The cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). The CT scanning helped evaluate the extent of infection and exclude other pathologies, such as psoas abscess, osteomyelitis, and inguinal hernia.
A 58-year-old patient presented in septic shock. On physical examination, progressive swelling of the right groin was observed. On exploration, necrotizing cellulitis, but not fasciitis, was present. The cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). The CT scanning helped evaluate the extent of infection and exclude other pathologies, such as psoas abscess, osteomyelitis, and inguinal hernia.
Necrotizing cellulitis of toxic shock syndrome.
Soft tissue infection secondary to group A streptococci, leading to toxic shock syndrome.
Extensive debridement of necrotizing fasciitis of the hand.
The hand is healing following aggressive surgical debridement of necrotizing fasciitis of the hand (see Image 15).
Necrosis of the little toe of the right foot and cellulitis of the foot secondary to group A streptococci.
 
 
 
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