Materiały źródłowe

• #1 Toxic Shock Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/169177-overview

  Toxic shock syndrome (TSS) is a rare acute life-threatening illness, caused by a toxin-mediated infectious process linked to toxin-producing strains of Staphylococcus aureus or group A Streptococcus (GAS), also called Streptococcus pyogenes. TSS is characterized by high fever, rash, desquamation of palms and soles, hypotension, refractory shock, multiorgan failure, and death. The clinical syndrome can also include severe myalgia, vomiting, diarrhea, headache, and nonfocal neurologic abnormalities […] TSS is linked mostly to toxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes (group A streptococcus). These toxins act as superantigens in inducing nonclassic activation of T cells by antigen-presenting cells (APCs), leading to nonspecific, polyclonal lymphocyte activation of 5-30% of the total population of T cells, which results in massive release of proinflammatory cytokines.

• #2 Toxic Shock Syndrome: A Literature Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10812596/

  Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. The pathophysiology, epidemiology, clinical presentation, microbiological features, management and outcome of TSS are described in this review. Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin1 (TSST-1) and enterotoxins for Staphylococcus aureus and Streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for Streptococcus pyogenes. […] The occurrence of TSS is linked to the bacterial secretion of superantigenic exotoxins, which are bacterial virulence factors genetically encoded and secreted. Superantigenic exotoxins are able to induce unconventional activation of T cells by antigen-presenting cells (APCs).

• #3 Toxic Shock Syndrome (TSS) – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/gram-positive-cocci/toxic-shock-syndrome-tss

  S. pyogenes TSS is defined as any group A beta-hemolytic streptococci (GABHS) infection associated with shock and organ failure. […] TSS may progress within 48 hours to syncope, tissue necrosis, shock, disseminated coagulation, multisystem organ failure, and death. […] Antibiotics given during the acute illness may eradicate pathogen foci and prevent recurrences. […] Passive immunization to TSS toxins with IV immune globulin (2 g/kg, followed by 0.4 g/kg daily for up to 5 days) has been helpful in severe cases of both types of TSS and lasts for weeks, but the disease may not induce active immunity, so recurrences are possible.

• #4 Women’s Health and Education Center (WHEC) – Toxic Shock Syndrome

  http://www.womenshealthsection.com/content/print.php3?title=gyn015&cat=3&lng=english

  Toxic shock syndrome (TSS) was first described in children in 1978 but was quickly identified as an illness occurring primarily in menstruating women 12-24 years of age. […] The cause of toxic shock syndrome is preformed toxins produced by Staphylococcus aureus, so that colonization or infection by this microorganism must occur. TSS-toxin-1 is a protein with a molecular weight of approximately 24,000 daltons and has been proposed as the toxin responsible for TSS. Its production has been demonstrated in 90-100% of S. aureus strains recovered from women with menstrual TSS. […] The pathogenic mechanism for the association of tampons with TSS has not been adequately understood. How toxins gain access to the circulatory system is unknown. […] Regardless of the composition of the tampon, absorbency increased the odds ratio of TSS. The chemical composition of the tampons also influences the odds ratio. […] The longer a tampon is left in place, the greater the risk for development of this syndrome. […] The use of low-absorbency tampon appears to reduce the risk of TSS in tampon use. […] The incidence of non-menstrual disease has shown only a slight increase in the past 10 years.

• #5 Staphylococcal toxic shock syndrome – UpToDate

  https://www.uptodate.com/contents/staphylococcal-toxic-shock-syndrome

  Staphylococcal toxic shock syndrome (TSS) is a clinical illness characterized by rapid onset of fever, rash, hypotension, and multiorgan system involvement. TSS due to Staphylococcus aureus was initially described in 1978; the disease came to public attention in 1980 with the occurrence of a series of menstrual-associated cases. […] The epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of staphylococcal TSS will be reviewed here. […] TSS associated with S. aureus was first described in a series of pediatric cases in 1978. The incidence rose sharply in 1980; more than 800 cases of menses-related TSS occurred, largely among young women. Clinical illness arose during menstruation and was associated with use of highly absorbent tampons. […] The observed increase in the number of cases may reflect increased recognition due to active laboratory testing for toxin-producing strains, rather than an overall increase in incidence.

• #6 Toxic shock syndrome

  https://dermnetnz.org/topics/toxic-shock-syndrome-and-toxic-shock-like-syndrome

  Toxic shock syndrome is an uncommon but severe acute illness due to exotoxins produced by specific strains of Staphylococcus aureus or Streptococcus pyogenes. […] Toxic shock syndrome is caused by the release of exotoxins from toxigenic strains of the bacteria Staph aureus and Strep pyogenes in a person that lacks anti-toxin antibodies. These exotoxins act as superantigens. […] Both menstrual and non-menstrual forms of toxic shock syndrome are caused by these toxins, which release massive amounts of cytokines that produce fever, rash, low blood pressure, tissue injury, and shock. […] Toxic shock syndrome starts from a localised staphylococcal infection which produces the causative exotoxins. […] Non-menstrual toxic shock syndrome is now the more common form and may occur as a complication of other localised or systemic infections such as pneumonia, osteomyelitis, sinusitis, and skin wounds (surgical, traumatic, or burns).

• #7 Toxic Shock Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459345/

  TSS is a toxin-mediated disease that is caused by toxin-producing streptococci or S. aureus. These superantigens bypass the normal pathway for activation of T cells resulting in over-activation of cytokines and inflammatory cells. This then leads to the presenting signs and symptoms of fever, rash, hypotension, and end-organ failure due to capillary leak. Strep pyogenes (GAS) has other toxins that play a role in necrotizing fasciitis and streptococcal toxic shock syndrome. […] TSS is most commonly caused by a toxigenic strain of Staphylococcus aureus or Group A Strep (Streptococcus pyogenes). Other strains of streptococci also produce superantigens, which can lead to TSS. The disease occurs most often in the setting of menstruation despite the discontinuation of high absorbency tampons. However, TSS can also present in non-menstrual settings such as in soft tissue infections, post-surgical infections, burns, retained foreign bodies such as nasal packing, and dialysis catheters. Staphylococcal TSS is typically the result of a localized infection such as an abscess, whereas streptococcal TSS may result from bacteremia, necrotizing fasciitis, or cellulitis.

• #8 Toxic Shock Syndrome (TSS) – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/gram-positive-cocci/toxic-shock-syndrome-tss

  Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. […] Toxic shock syndrome (TSS) is caused by exotoxin-producing cocci. Strains of phage-group 1 Staphylococcus aureus elaborate the TSS toxin-1 (TSST-1) or related exotoxins; certain strains of Streptococcus pyogenes produce at least 2 exotoxins. […] Mechanical or chemical factors related to tampon use probably enhance production of the exotoxin or facilitate its entry into the bloodstream through a mucosal break or via the uterus. […] Staphylococcal TSS has also been reported in both men and women with any type of S. aureus infection. […] Streptococcal TSS is similar to that caused by Staphylococcus aureus, but mortality is higher (20 to 60%) despite aggressive therapy. […] In contrast to staphylococcal TSS, streptococcal TSS is more likely to cause acute respiratory distress syndrome (ARDS) and less likely to cause a typical cutaneous reaction.

• #9 Toxic Shock Syndrome (TSS) – EMCrit Project

  https://emcrit.org/ibcc/tss/

  Some Streptococcus and Staphylococcus species secrete superantigens that causes widespread activation of T-lymphocytes. This triggers a cascade of inflammatory cytokines, leading to multiorgan failure. […] Most people acquire antibodies that neutralize these toxins. A minority of people lack these antibodies, rendering them vulnerable to toxic shock syndrome. […] Streptococcal toxic shock is much more common, potentially affecting patients of all ages. This occurs in the context of an invasive streptococcal infection. The most common source is a soft-tissue infection (e.g., cellulitis, myositis, or necrotizing fasciitis), but any invasive streptococcal infection can cause toxic shock. […] Toxic shock may be more common than generally recognized, affecting ~20% of patients with invasive group A streptococcal infection.

• #10 Toxic Shock Syndrome (TSS) – EMCrit Project

  https://emcrit.org/ibcc/tss/

  Toxic shock syndrome is most closely associated with group A Streptococcus (Streptococcus pyogenes) and Streptococcus dysgalactiae subspecies equisimilis (SDSE). […] Staphylococcal toxic shock is less common, affecting mostly younger patients. It often occurs due to mucosal colonization, without invasive infection. This may result from methicillin-sensitive Staphylococcus aureus (MSSA) or methicillin-resistant Staphylococcus aureus (MRSA).

• #11 Toxic shock syndrome | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/toxic-shock-syndrome?lang=us

  Toxic shock syndrome (TSS) is a severe bacterial-toxin mediated condition, characterized by an initial soft tissue infection, which rapidly progresses to systemic disease and circulatory collapse. It is due to a Gram positive infection, most frequently Staphylococcus aureus or Streptococcus pyogenes. […] All cases of toxic shock syndrome are produced by Gram positive bacteria; the most commonly implicated being Staphylococcus aureus or Streptococcus pyogenes (group A streptococci). However similar presentations have been seen in those with group B (S. agalactiae), C (S. equis), and G (S. dysgalactiae) streptococcal infections. Rarely Clostridium species-related toxic shock syndrome has been reported (e.g. C. perfringens, C. sordellii). […] Toxic shock syndrome occurs primarily due to the release of superantigens: staphylococci: toxic shock syndrome toxin-1 (TSST-1), enterotoxins B and C […] streptococci: pyrogenic exotoxins A or B. Superantigens sidestep the normal immune system mechanisms of antigen presenting and hyperstimulate clonal T cells by cross-linking major histocompatibility complex (MHC) class II molecules on antigen-presenting cells to T-cell receptors (TCR). Consequently a massive release of cytokines, including gamma interferon, interleukins and tumor necrosis factors, creating a so-called cytokine storm.

• #12 Toxic Shock Syndrome: Keys in Diagnosis and Management – emDocs

  https://www.emdocs.net/toxic-shock-syndrome-keys-in-diagnosis-and-management/

  Toxic shock syndrome (TSS) is an acute, toxin-mediated sickness with fever, hypotension, multi-organ dysfunction, and a diffuse rash with desquamation. TSS is treatable if diagnosed, but if missed, it can be rapidly lethal. The usual organisms include Staphylococcus aureus and Streptococcus pyogenes, though others include Streptococcus agalactiae, Streptococcus viridans, Group C Streptococcus, Group G Streptococcus, and Clostridium soredellii are also involved. Staphylococcal TSS was first described in 1978 in kids due to S. aureus, followed by the 1980s with an epidemic in association with tampons. Following changes in tampon manufacturing and use, a decline in menstrual-related staphylococcal TSS occurred, though non-menstrual staphylococcal TSS has increased. Other causes of staphylococcal TSS include post-surgical, post-partum, post-abortion, intrauterine device placement, burns, soft tissue injuries, and focal infections (pneumonia). Streptococcal TSS is more common after viral infections, pharyngitis, and local soft tissue trauma. Streptococcal TSS is more common with deeper sites of infection and has greater morbidity and mortality than staphylococcal TSS. Mortality rates in adults ranges from 30-80%, while pediatric patients demonstrate lower rates (3-10%).

• #13 Toxic Shock Syndrome: A Literature Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10812596/

  Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. The pathophysiology, epidemiology, clinical presentation, microbiological features, management and outcome of TSS are described in this review. Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin1 (TSST-1) and enterotoxins for Staphylococcus aureus and Streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for Streptococcus pyogenes. […] The occurrence of TSS is linked to the bacterial secretion of superantigenic exotoxins, which are bacterial virulence factors genetically encoded and secreted. Superantigenic exotoxins are able to induce unconventional activation of T cells by antigen-presenting cells (APCs).

• #14 Toxic Shock Syndrome: A Literature Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10812596/

  In the TSS, the superantigen binds the TCR and MHC II outside the Ag presentation site with high affinity. This results in nonspecific, polyclonal lymphocyte activation of 5 to 30% of the total population of T cells. This simultaneous polyclonal activation results in a significant activation of NF kappa B, which plays a major role in the generation and expansion of the inflammatory response. This results in a massive release of proinflammatory cytokines, with clinical signs, such as capillary leakage, arterial hypotension, organ failure, and coagulation activation, usually being reported in this setting. […] Physiopathological specificities of staphylococcal and streptococcal TSS are detailed in the corresponding subparts. […] The described staphylococcal superantigenic exotoxins include TSST-1 and enterotoxins (of which approximately thirty have been described to date). TSST-1 is a 194 amino acid protein encoded by the gene tst and is responsible for 89 to 95% of m-TSSs and 50% of nm-TSSs, the other half being related to the secretion of staphylococcal enterotoxins A, B, and C.

• #15 Toxic Shock Syndrome: A Literature Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10812596/

  Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. The pathophysiology, epidemiology, clinical presentation, microbiological features, management and outcome of TSS are described in this review. Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin1 (TSST-1) and enterotoxins for Staphylococcus aureus and Streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for Streptococcus pyogenes. […] The occurrence of TSS is linked to the bacterial secretion of superantigenic exotoxins, which are bacterial virulence factors genetically encoded and secreted. Superantigenic exotoxins are able to induce unconventional activation of T cells by antigen-presenting cells (APCs).

• #16 Toxic Shock Syndrome: A Literature Review

  https://www.mdpi.com/2079-6382/13/1/96

  Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. […] Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin—1 (TSST-1) and enterotoxins for Staphylococcus aureus and Streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for Streptococcus pyogenes. […] The occurrence of TSS is linked to the bacterial secretion of superantigenic exotoxins, which are bacterial virulence factors genetically encoded and secreted. Superantigenic exotoxins are able to induce unconventional activation of T cells by antigen-presenting cells (APCs).

• #17 Toxic Shock Syndrome: A Literature Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10812596/

  In the TSS, the superantigen binds the TCR and MHC II outside the Ag presentation site with high affinity. This results in nonspecific, polyclonal lymphocyte activation of 5 to 30% of the total population of T cells. This simultaneous polyclonal activation results in a significant activation of NF kappa B, which plays a major role in the generation and expansion of the inflammatory response. This results in a massive release of proinflammatory cytokines, with clinical signs, such as capillary leakage, arterial hypotension, organ failure, and coagulation activation, usually being reported in this setting. […] Physiopathological specificities of staphylococcal and streptococcal TSS are detailed in the corresponding subparts. […] The described staphylococcal superantigenic exotoxins include TSST-1 and enterotoxins (of which approximately thirty have been described to date). TSST-1 is a 194 amino acid protein encoded by the gene tst and is responsible for 89 to 95% of m-TSSs and 50% of nm-TSSs, the other half being related to the secretion of staphylococcal enterotoxins A, B, and C.

• #18 Toxic Shock Syndrome: A Literature Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10812596/

  The disease occurs after penetration of the exotoxin-producing S. pyogenes through a skin or mucous barrier alteration. S.pyogenes then spreads to deep tissues. The main superantigenic exotoxins described in S. pyogenes are streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA). The majority of streptococcal isolates causing TSS are the emm1 (41.1% of the cases), emm3 (8.4% of the cases), emm28 (8.9% of the cases), and emm89 (9.8% of the cases) genotypes. Streptococcal TSS occurs more frequently with GAS strains harboring SpeA or Spec genes than those harboring Ssa genes. SpeB participates in the rapid dissemination of S. pyogenes in the skin and soft tissues in combination with other streptococcal virulence factors, such as soluble M protein, which participate in the local and systemic excessive activation of T lymphocytes, APCs and neutrophils.

• #19 Toxic shock syndrome toxin-1 – Wikipedia

  https://en.wikipedia.org/wiki/Toxic_shock_syndrome_toxin-1

  Toxic shock syndrome toxin-1 (TSST-1) is a superantigen with a size of 22 kDa produced by 5 to 25% of Staphylococcus aureus isolates. It causes toxic shock syndrome (TSS) by stimulating the release of large amounts of interleukin-1, interleukin-2 and tumor necrosis factor. […] TSST-1 is a bacterial exotoxin found in patients who have developed toxic shock syndrome (TSS), which can be found in menstruating women or any man or child for that matter. […] TSST-1 is the cause of half of non-menstrual TSS cases, and the sole cause for menstrual TSS cases. […] A superantigen such as TSST-1 stimulates human T cells that express VB 2, which may represent 5-30% of all host T cells. PTSAgs induce the VB-specific expansion of both CD4 and CD8- subsets of T-lymphocytes. […] TSST-1 binds primarily to the alpha-chain of class II MHC exclusively through a low-affinity (or generic) binding site on the SAG N-terminal domain. […] MHC-binding by TSST-1 is partially peptide-dependent. […] Initial studies of mutants revealed that residues on the back side of the central alpha helix were required for super antigenic activity.

• #20 1141 PATHOGENESIS OF TOXIC SHOCK SYNDROME (TSS) | Pediatric Research

  https://www.nature.com/articles/pr19851249

  Toxic Shock Syndrome Toxin I (TSST-I), a reliable marker for TSS staph, has not yet been proven to be the sole responsible toxin. […] TSST-I is produced in chamber by 4 hr, reaching peak of 7.4 g/ml (120 g total) at 47 hrs. […] To determine if TSST-I alone is responsible for changes seen in the infection model, we injected purified TSST-I into chamber and produced a syndrome indistinguishable from live infection and clinical TSS. […] Hypotension, renal impairment, hypocalcemia and death occurs by 25 hrs at dose of 300 g and a chronic, ultimately fatal illness lasting 8 days with profound renal failure, hypocalcemia and multiorgan dysfunction occurs at a 150 g TSST-I depot. […] TSST-I is therefore the toxin responsible for the major physiologic changes of TSS and does not require host-derived endotoxin for its action. […] Anti-toxin therapy has promise in therapy of established human TSS.

• #21 Toxic Shock Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/169177-overview

  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 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. […] Toxins produced by strains of S aureus and GAS act as superantigens. These superantigens interact and 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. Massive production of cytokines leads to refractory shock and tissue injury.

• #22 Toxic shock syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Toxic_shock_syndrome

  „Toxic shock syndrome” (TSS) is a condition caused by bacterial toxins. […] TSS is typically caused by bacteria of the Streptococcus pyogenes or Staphylococcus aureus type, though others may also be involved. […] The underlying mechanism involves the production of superantigens during an invasive streptococcus infection or a localized staphylococcus infection. […] In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigen toxin. […] 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. […] 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.

• #23 Streptococcal toxic shock syndrome in the intensive care unit | Annals of Intensive Care | Full Text

  https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-018-0438-y

  The main characteristic of superantigens is their ability to bind to major histocompatibility (MHC) class II molecules outside of the antigen groove, and the V region of the T cell receptor, cross-linking those two receptors. […] Aside from superantigens, S. pyogenes produces and secretes a wide variety of exotoxins and enzymes such as streptolysins, streptokinase, hyaluronidase, and DNAse such as streptodornase and chemokine proteases and toxic molecules that play undoubtedly an important pathogenic role in necrotizing fasciitis and STSS.

• #24 Toxic Shock Syndrome: A Literature Review

  https://www.mdpi.com/2079-6382/13/1/96

  In the TSS, the superantigen binds the TCR and MHC II outside the Ag presentation site with high affinity. This results in nonspecific, polyclonal lymphocyte activation of 5 to 30% of the total population of T cells. […] This simultaneous polyclonal activation results in a significant activation of NF kappa B, which plays a major role in the generation and expansion of the inflammatory response. […] This results in a massive release of proinflammatory cytokines, with clinical signs, such as capillary leakage, arterial hypotension, organ failure, and coagulation activation, usually being reported in this setting. […] Physiopathological specificities of staphylococcal and streptococcal TSS are detailed in the corresponding subparts.

• #25 Toxic Shock Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/169177-overview

  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 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. […] Toxins produced by strains of S aureus and GAS act as superantigens. These superantigens interact and 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. Massive production of cytokines leads to refractory shock and tissue injury.

• #26 Toxic Shock Syndrome: A Literature Review

  https://www.mdpi.com/2079-6382/13/1/96

  In the TSS, the superantigen binds the TCR and MHC II outside the Ag presentation site with high affinity. This results in nonspecific, polyclonal lymphocyte activation of 5 to 30% of the total population of T cells. […] This simultaneous polyclonal activation results in a significant activation of NF kappa B, which plays a major role in the generation and expansion of the inflammatory response. […] This results in a massive release of proinflammatory cytokines, with clinical signs, such as capillary leakage, arterial hypotension, organ failure, and coagulation activation, usually being reported in this setting. […] Physiopathological specificities of staphylococcal and streptococcal TSS are detailed in the corresponding subparts.

• #27

  https://www.bio.davidson.edu/movies/Immunology/Students/spring2000/gramer/restricted/tss.html

  Toxic Shock Syndrome (TSS) is an acute, multisystem disease that is caused by an infection with a strain of Staphylococcus aureus bacterium that secretes an exotoxin known as toxic shock syndrome toxin-1 (TSST-1). […] TSST-1 belongs to a family of proteins known as pyrogenic toxin superantigens (PTSAs). […] Superantigens like TSST-1 are capable of cross-linking major histocompatibility class II (MHCII) molecules and T-cell receptors (TCRs), leading to the activation of a substantial number of T cells. […] This activation often leads to the release of several cytokines, which we will see play an important role in the pathogenesis of TSS. […] TSST-1 does not exert direct toxic effects on the vast majority of tissues, but rather, induction of TSS by TSST-1 may result from massive and unregulated stimulation of the immune system.

• #28 Toxic shock syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Toxic_shock_syndrome

  „Toxic shock syndrome” (TSS) is a condition caused by bacterial toxins. […] TSS is typically caused by bacteria of the Streptococcus pyogenes or Staphylococcus aureus type, though others may also be involved. […] The underlying mechanism involves the production of superantigens during an invasive streptococcus infection or a localized staphylococcus infection. […] In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigen toxin. […] 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. […] 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.

• #29 Toxic shock syndrome with a cytokine storm caused by Staphylococcus simulans: a case report | BMC Infectious Diseases | Full Text

  https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05731-y

  Exotoxins secreted from Staphylococcus aureus or Streptococcus pyogenes act as superantigens that induce systemic release of inflammatory cytokines and are a common cause of toxic shock syndrome (TSS). […] However, little is known about TSS caused by coagulase-negative staphylococci (CoNS) and the underlying mechanisms. […] A likely mechanism is uncontrolled cytokine release (i.e., cytokine storm) induced by non-specific immune reactions against CoNS proliferation. […] The underlying mechanism not only involves superantigens but also interactions among bacterial cell wall components and monocytes, leading to the release of cytokine mediators. […] Known exotoxins causing TSS were undetectable in the current case using the reversed passive latex agglutination method. […] It remains to be determined how TSS is induced by CoNS infection.

• #30

  https://www.bio.davidson.edu/movies/Immunology/Students/spring2000/gramer/restricted/tss.html

  The first mechanism accounts for the activation of T lymphocytes by TSST-1 and involves the engagement of the V component of the T-cell receptor by toxin/Ia complexes resulting in T cell activation and proliferation. […] The second mechanism involves the transduction via Ia molecules of signals that result in the activation of Ia+ immune cells including B lymphocytes, monocytes, activated natural killer (NK) cells and activated T lymphocytes. […] Upon activation by TSST-1, a T lymphocyte is induced to begin producing elevated levels of the cytokines interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), and interferon-gamma (IFN-g). […] TSST-1 is a potent inducer of interleukin-1 (IL-1) production by monocytes/macrophage. […] Thus, following the engagement of MHCII molecules by a superantigen such as TSST-1, a cascade of cytoplasmic and nuclear activation events occur, for TSST-1 transduces activation signals via Ia molecules that result in the induction of monokine gene transcription.

• #31 Streptococcal Toxic-Shock Syndrome: Spectrum of Disease, Pathogenesis, and New Concepts in Treatment – Volume 1, Number 3—July 1995 – Emerging Infectious Diseases journal – CDC

  https://wwwnc.cdc.gov/eid/article/1/3/95-0301_article

  Since the 1980s there has been a marked increase in the recognition and reporting of highly invasive group A streptococcal infections with or without necrotizing fasciitis associated with shock and organ failure. Such dramatic cases have been defined as streptococcal toxic-shock syndrome. […] Current concepts in the pathogenesis of invasive streptococcal infection are also presented, with emphasis on the interaction between group A Streptococcus virulence factors and host defense mechanisms. […] Pyrogenic exotoxins cause fever in humans and animals and also help induce shock by lowering the threshold to exogenous endotoxin. […] Streptococcal pyrogenic exotoxins A and B induce human mononuclear cells to synthesize not only tumor necrosis factor-a (TNFa) but also interleukin-1 (IL-1) and interleukin-6 (IL-6), suggesting that TNF could mediate the fever, shock, and tissue injury observed in patients with streptococcal TSS.

• #32 On the Pathogenesis of Toxic Shock Syndrome

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2122035318

  Understanding of the pathogenesis of toxic shock syndrome (TSS) has come from the juxtaposition of epidemiologic, clinical, immunologic, and physiologic studies. […] A hypothesis has been developed for the pathogenesis of menstrually related TSS. […] Certain tampon fibers that are highly absorbent for water are also ion exchangers for magnesium ions. […] The latter ions uniquely affect the production of TSS toxin 1 (TSST-1) by appropriate strains of Staphylococcus aureus, with a marked increase in the amount of toxin when magnesium concentrations are limiting and suppression of toxin production when magnesium is in excess. […] Many epidemiologic features of TSS could be explained by this hypothesis. […] TSST-1 stimulates production of interleukin 1 and of tumor necrosis factor and is highly toxic when absorbed slowly. […] Like TSST-1, staphylococcal enterotoxins are lethal to rabbits when given by slow injection, and some enterotoxins may be more lethal than TSST-1.

• #33 Toxic shock syndrome | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/toxic-shock-syndrome?embed_domain=hackmd.io%2F%40yIPUAFeCSL2JsU8smR5nJQ%2Fbnjhjgjghjghjghfavicon.icoradiopaedia-icon-144.pngradiopaedia-icon-144.png&lang=gb

  Toxic shock syndrome (TSS) is a severe bacterial-toxin mediated condition, characterised by an initial soft tissue infection, which rapidly progresses to systemic disease and circulatory collapse. It is due to a Gram positive infection, most frequently Staphylococcus aureus or Streptococcus pyogenes. […] Toxic shock syndrome occurs primarily due to the release of superantigens: staphylococci: toxic shock syndrome toxin-1 (TSST-1), enterotoxins B and C […] streptococci: pyrogenic exotoxins A or B. Superantigens sidestep the normal immune system mechanisms of antigen presenting and hyperstimulate clonal T cells by cross-linking major histocompatibility complex (MHC) class II molecules on antigen-presenting cells to T-cell receptors (TCR). Consequently a massive release of cytokines, including gamma interferon, interleukins and tumour necrosis factors, creating a so-called cytokine storm.

• #34 Toxic shock syndrome | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/toxic-shock-syndrome?lang=us

  Toxic shock syndrome (TSS) is a severe bacterial-toxin mediated condition, characterized by an initial soft tissue infection, which rapidly progresses to systemic disease and circulatory collapse. It is due to a Gram positive infection, most frequently Staphylococcus aureus or Streptococcus pyogenes. […] All cases of toxic shock syndrome are produced by Gram positive bacteria; the most commonly implicated being Staphylococcus aureus or Streptococcus pyogenes (group A streptococci). However similar presentations have been seen in those with group B (S. agalactiae), C (S. equis), and G (S. dysgalactiae) streptococcal infections. Rarely Clostridium species-related toxic shock syndrome has been reported (e.g. C. perfringens, C. sordellii). […] Toxic shock syndrome occurs primarily due to the release of superantigens: staphylococci: toxic shock syndrome toxin-1 (TSST-1), enterotoxins B and C […] streptococci: pyrogenic exotoxins A or B. Superantigens sidestep the normal immune system mechanisms of antigen presenting and hyperstimulate clonal T cells by cross-linking major histocompatibility complex (MHC) class II molecules on antigen-presenting cells to T-cell receptors (TCR). Consequently a massive release of cytokines, including gamma interferon, interleukins and tumor necrosis factors, creating a so-called cytokine storm.

• #35 Pathogenesis – Primary Care Notebook

  https://primarycarenotebook.com/pages/infectious-disease/toxic-shock-syndrome/pathogenesis

  Toxic shock syndrome is thought to be due to Staphylococcal exotoxin, toxic shock syndrome toxin 1, TSST 1, which is thought to trigger a number of processes. […] Monocytes are stimulated to produce cytokines such as tumour necrosis factor and interleukin-1. The complement system is directly activated and this in turn activates neutrophils which adhere to each other and vascular endothelium. Factor XII is also stimulated, resulting in the promotion of coagulation and the release of hypotensive agents such as bradykinin. […] These events cumulatively result in tissue damage, capillary leakage, fever, metabolic changes, vasodilation and in some cases disseminated intravascular coagulation.

• #36 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Toxic-Shock-Syndrome-Pathogenesis.aspx

  The exotoxins stimulate a response from the T-cells in the body and affect their ability to bind to receptors and class II major histocompatibility complex of antigen presenting cells. As a result, the T-cells proliferate extensively in the body, leading to symptoms of shock and tissue destruction. […] Additionally, polyclonal immunoglobulin production is inhibited by the production of interferon-gamma. This reduces the patients ability to develop antibodies for the toxins and explains why some patients experience a relapse of toxic shock syndrome.

• #37 Toxic shock syndrome – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/329

  Toxic shock syndrome (TSS) is an exotoxin-mediated illness caused by bacterial infection, most commonly group A streptococcus or Staphylococcus aureus. […] Presenting signs and symptoms can be nonspecific, but the course of the disease is precipitous and toxicity occurs early, resulting in serious life-threatening disease and multiorgan system failure. […] Early diagnosis and treatment is essential. […] Staphylococcal TSS can be split into 2 groups: menstrual TSS, which occurs in women during menstruation with extended use of a single tampon or, historically, with highly absorbable tampons; and nonmenstrual TSS, which can result from a variety of staphylococcal postpartum vaginal and cesarean wound infections. […] Although the presenting signs and symptoms can be nonspecific (e.g., fever, chills, myalgias, headache), the course of the disease is precipitous, and shock and multiorgan system failure occur early in the course of the disease.

• #38 Pathogenesis of menstrual Toxic Shock Syndrome — Centre International de Recherche en Infectiologie

  https://ciri.ens-lyon.fr/teams/stapath/projets/menstrual_toxic_shock_syndrome

  TSS is a rare life-threatening infectious disease associated with use of intra-vaginal protection. The colonizing S. aureus strain uses catamenial products absorbed in the tampon as a growth medium for its proliferation. When S. aureus reaches a certain concentration, S. aureus produces TSST-1, which gains access from the vagina to the bloodstream and induce the systemic illness in non-immunized women against TSST-1. Although, 70% of women in Western world use tampons and 4% of women has vaginal colonization by S. aureus producing TSST-1 and 10% are no immunized against TSST-1, the estimated rate of mTSS is only 1/100,000 per year. Thus, only a very small proportion of women at risk develops mTSS, questioning factors that may trigger and/or protect against mTSS. The objectives of our projects will be to identify the mechanisms by which environmental and host factors influence S. aureus TSST-1+ pathogenicity in mTSS by (i) quantification of S. aureus toxins/enzymes and corresponding antibodies in menstrual fluids from healthy women to that of patients with mTSS by mass spectrometry, RNAseq and Luminex analysis; (ii) Characterization of TSST-1 trans-vaginal epithelial passage by using human cellular, artificial tissue models and vaginal explants; (iii) determine at risk-practice for the women by large cases controls study.

• #39 On the Pathogenesis of Toxic Shock Syndrome

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2122035318

  Understanding of the pathogenesis of toxic shock syndrome (TSS) has come from the juxtaposition of epidemiologic, clinical, immunologic, and physiologic studies. […] A hypothesis has been developed for the pathogenesis of menstrually related TSS. […] Certain tampon fibers that are highly absorbent for water are also ion exchangers for magnesium ions. […] The latter ions uniquely affect the production of TSS toxin 1 (TSST-1) by appropriate strains of Staphylococcus aureus, with a marked increase in the amount of toxin when magnesium concentrations are limiting and suppression of toxin production when magnesium is in excess. […] Many epidemiologic features of TSS could be explained by this hypothesis. […] TSST-1 stimulates production of interleukin 1 and of tumor necrosis factor and is highly toxic when absorbed slowly. […] Like TSST-1, staphylococcal enterotoxins are lethal to rabbits when given by slow injection, and some enterotoxins may be more lethal than TSST-1.

• #40 Pathogenesis of menstrual Toxic Shock Syndrome — Centre International de Recherche en Infectiologie

  https://ciri.ens-lyon.fr/teams/stapath/projets/menstrual_toxic_shock_syndrome

  TSS is a rare life-threatening infectious disease associated with use of intra-vaginal protection. The colonizing S. aureus strain uses catamenial products absorbed in the tampon as a growth medium for its proliferation. When S. aureus reaches a certain concentration, S. aureus produces TSST-1, which gains access from the vagina to the bloodstream and induce the systemic illness in non-immunized women against TSST-1. Although, 70% of women in Western world use tampons and 4% of women has vaginal colonization by S. aureus producing TSST-1 and 10% are no immunized against TSST-1, the estimated rate of mTSS is only 1/100,000 per year. Thus, only a very small proportion of women at risk develops mTSS, questioning factors that may trigger and/or protect against mTSS. The objectives of our projects will be to identify the mechanisms by which environmental and host factors influence S. aureus TSST-1+ pathogenicity in mTSS by (i) quantification of S. aureus toxins/enzymes and corresponding antibodies in menstrual fluids from healthy women to that of patients with mTSS by mass spectrometry, RNAseq and Luminex analysis; (ii) Characterization of TSST-1 trans-vaginal epithelial passage by using human cellular, artificial tissue models and vaginal explants; (iii) determine at risk-practice for the women by large cases controls study.

• #41 Toxic shock syndrome – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/329

  Toxic shock syndrome (TSS) is an exotoxin-mediated illness caused by bacterial infection, most commonly group A streptococcus or Staphylococcus aureus. […] Presenting signs and symptoms can be nonspecific, but the course of the disease is precipitous and toxicity occurs early, resulting in serious life-threatening disease and multiorgan system failure. […] Early diagnosis and treatment is essential. […] Staphylococcal TSS can be split into 2 groups: menstrual TSS, which occurs in women during menstruation with extended use of a single tampon or, historically, with highly absorbable tampons; and nonmenstrual TSS, which can result from a variety of staphylococcal postpartum vaginal and cesarean wound infections. […] Although the presenting signs and symptoms can be nonspecific (e.g., fever, chills, myalgias, headache), the course of the disease is precipitous, and shock and multiorgan system failure occur early in the course of the disease.

• #42 Toxic shock syndrome – Infectious Disease Advisor

  https://www.infectiousdiseaseadvisor.com/home/decision-support-in-medicine/infectious-diseases/toxic-shock-syndrome/

  Staph TSS is most commonly associated with tampon use during menstruation. Thus, the source of infection is the vaginal vault. Less commonly staph TSS may occur postoperatively, particularly in patients with packing of the wound. The classic example is rhinoplasty with nasal packing. […] Strep TSS is largely the result of streptococcal pyrogenic exotoxin A (SpeA). Interestingly this toxin and the two S. aureus toxins mentioned above are superantigens that interact concomittantly with V regions of the T-cell receptor and the major histocompatibility complex class II receptor on macrophages with the resultant production of tumor necrosis factor (TNF)-, interleukin (IL)-1 , and IL-6 from macrophages and IL-2, -interferon and TNF- from T-lymphocytes. This cytokine storm is thought to drive the rapid onset of hypotension, fever, tachycardia, and multiorgan failure so characteristic of the toxic shock syndromes.

• #43 Toxic Shock Syndrome (TSS) – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/gram-positive-cocci/toxic-shock-syndrome-tss

  Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. […] Toxic shock syndrome (TSS) is caused by exotoxin-producing cocci. Strains of phage-group 1 Staphylococcus aureus elaborate the TSS toxin-1 (TSST-1) or related exotoxins; certain strains of Streptococcus pyogenes produce at least 2 exotoxins. […] Mechanical or chemical factors related to tampon use probably enhance production of the exotoxin or facilitate its entry into the bloodstream through a mucosal break or via the uterus. […] Staphylococcal TSS has also been reported in both men and women with any type of S. aureus infection. […] Streptococcal TSS is similar to that caused by Staphylococcus aureus, but mortality is higher (20 to 60%) despite aggressive therapy. […] In contrast to staphylococcal TSS, streptococcal TSS is more likely to cause acute respiratory distress syndrome (ARDS) and less likely to cause a typical cutaneous reaction.

• #44 Toxic Shock Syndrome: A Literature Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10812596/

  The disease occurs after penetration of the exotoxin-producing S. pyogenes through a skin or mucous barrier alteration. S.pyogenes then spreads to deep tissues. The main superantigenic exotoxins described in S. pyogenes are streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA). The majority of streptococcal isolates causing TSS are the emm1 (41.1% of the cases), emm3 (8.4% of the cases), emm28 (8.9% of the cases), and emm89 (9.8% of the cases) genotypes. Streptococcal TSS occurs more frequently with GAS strains harboring SpeA or Spec genes than those harboring Ssa genes. SpeB participates in the rapid dissemination of S. pyogenes in the skin and soft tissues in combination with other streptococcal virulence factors, such as soluble M protein, which participate in the local and systemic excessive activation of T lymphocytes, APCs and neutrophils.

• #45 Streptococcal Toxic-Shock Syndrome: Spectrum of Disease, Pathogenesis, and New Concepts in Treatment – Volume 1, Number 3—July 1995 – Emerging Infectious Diseases journal – CDC

  https://wwwnc.cdc.gov/eid/article/1/3/95-0301_article

  M protein contributes to invasiveness through its ability to impede phagocytosis of streptococci by human polymorphonuclear leukocytes. […] The mere presence of virulence factors, such as M protein or pyrogenic exotoxins, may be less important in streptococcal TSS than the dynamics of their production in vivo. […] The interaction between these microbial virulence factors and an immune or nonimmune host determines the epidemiology, clinical syndrome, and outcome.

• #46 Toxic Shock Syndrome: A Literature Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10812596/

  The disease occurs after penetration of the exotoxin-producing S. pyogenes through a skin or mucous barrier alteration. S.pyogenes then spreads to deep tissues. The main superantigenic exotoxins described in S. pyogenes are streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA). The majority of streptococcal isolates causing TSS are the emm1 (41.1% of the cases), emm3 (8.4% of the cases), emm28 (8.9% of the cases), and emm89 (9.8% of the cases) genotypes. Streptococcal TSS occurs more frequently with GAS strains harboring SpeA or Spec genes than those harboring Ssa genes. SpeB participates in the rapid dissemination of S. pyogenes in the skin and soft tissues in combination with other streptococcal virulence factors, such as soluble M protein, which participate in the local and systemic excessive activation of T lymphocytes, APCs and neutrophils.

• #47 Toxic Shock Syndrome (TSS) – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/gram-positive-cocci/toxic-shock-syndrome-tss

  Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. […] Toxic shock syndrome (TSS) is caused by exotoxin-producing cocci. Strains of phage-group 1 Staphylococcus aureus elaborate the TSS toxin-1 (TSST-1) or related exotoxins; certain strains of Streptococcus pyogenes produce at least 2 exotoxins. […] Mechanical or chemical factors related to tampon use probably enhance production of the exotoxin or facilitate its entry into the bloodstream through a mucosal break or via the uterus. […] Staphylococcal TSS has also been reported in both men and women with any type of S. aureus infection. […] Streptococcal TSS is similar to that caused by Staphylococcus aureus, but mortality is higher (20 to 60%) despite aggressive therapy. […] In contrast to staphylococcal TSS, streptococcal TSS is more likely to cause acute respiratory distress syndrome (ARDS) and less likely to cause a typical cutaneous reaction.

• #48 Toxic Shock Syndrome (TSS) – EMCrit Project

  https://emcrit.org/ibcc/tss/

  Some Streptococcus and Staphylococcus species secrete superantigens that causes widespread activation of T-lymphocytes. This triggers a cascade of inflammatory cytokines, leading to multiorgan failure. […] Most people acquire antibodies that neutralize these toxins. A minority of people lack these antibodies, rendering them vulnerable to toxic shock syndrome. […] Streptococcal toxic shock is much more common, potentially affecting patients of all ages. This occurs in the context of an invasive streptococcal infection. The most common source is a soft-tissue infection (e.g., cellulitis, myositis, or necrotizing fasciitis), but any invasive streptococcal infection can cause toxic shock. […] Toxic shock may be more common than generally recognized, affecting ~20% of patients with invasive group A streptococcal infection.

• #49 Pathogenesis of menstrual Toxic Shock Syndrome — Centre International de Recherche en Infectiologie

  https://ciri.ens-lyon.fr/teams/stapath/projets/menstrual_toxic_shock_syndrome

  TSS is a rare life-threatening infectious disease associated with use of intra-vaginal protection. The colonizing S. aureus strain uses catamenial products absorbed in the tampon as a growth medium for its proliferation. When S. aureus reaches a certain concentration, S. aureus produces TSST-1, which gains access from the vagina to the bloodstream and induce the systemic illness in non-immunized women against TSST-1. Although, 70% of women in Western world use tampons and 4% of women has vaginal colonization by S. aureus producing TSST-1 and 10% are no immunized against TSST-1, the estimated rate of mTSS is only 1/100,000 per year. Thus, only a very small proportion of women at risk develops mTSS, questioning factors that may trigger and/or protect against mTSS. The objectives of our projects will be to identify the mechanisms by which environmental and host factors influence S. aureus TSST-1+ pathogenicity in mTSS by (i) quantification of S. aureus toxins/enzymes and corresponding antibodies in menstrual fluids from healthy women to that of patients with mTSS by mass spectrometry, RNAseq and Luminex analysis; (ii) Characterization of TSST-1 trans-vaginal epithelial passage by using human cellular, artificial tissue models and vaginal explants; (iii) determine at risk-practice for the women by large cases controls study.

• #50 Toxic Shock Syndrome: Keys in Diagnosis and Management – emDocs

  https://www.emdocs.net/toxic-shock-syndrome-keys-in-diagnosis-and-management/

  Where should we place the blame for TSS? It’s those horrible superantigens resulting in a massive host response. These superantigens are proteins that directly activate T-cells and bypass steps of the normal antigen-mediated immune response sequence, associated with disease morbidity and mortality. This results in a massive, uncontrolled T-cell activation and a large release of cytokines, resulting in more B and T cell activity. Antibodies against these superantigens reduce the risk of TSS. These antibodies against toxic shock syndrome toxin 1 (TSST-1) are present in over 90% of adults (but less in children), and they may be the result of mucosal colonization with TSST-1 producing S. aureus.

• #51 Volume 1, Chapter 43. Toxic Shock Syndrome

  https://mobile.glowm.com/resources/glowm/cd/pages/v1/v1c043.html

  The accepted cause of TSS is TSST-1. This toxin has had several names, including staphylococcal enterotoxin F and pyrogenic exotoxin C. TSST-1 is produced by at least 90% of S. aureus strains recovered from menses-associated cases but only 40% to 80% of non-menses-associated strains. These observations, combined with the results of animal models, suggest that there may be other TSS toxins or that aspects of microbe-toxin-host interactions, including host genomic susceptibilities, may play yet to be discovered roles in producing TSS. Staphylococcal enterotoxins B (SEB), C, E, and possibly others share biologic properties with TSST-1 and are structurally similar to streptococcal exotoxin A (i.e. erythrogenic or scarlet fever toxin). Schlievert was the first to observe that up to 78% of non-menses-associated strains of Staphylococcus produced TSST-1, SEB, or both and to suggest that SEB or other exotoxins are important in the pathogenesis of TSS or TSS-like disease. Crass and Bergdoll demonstrated that coagulase-negative staphylococci (from S. saprophyticus and S. epidermidis) can produce TSST-1 and other implicated enterotoxins.

• #52 Pathogenesis of menstrual Toxic Shock Syndrome — Centre International de Recherche en Infectiologie

  https://ciri.ens-lyon.fr/teams/stapath/projets/menstrual_toxic_shock_syndrome

  TSS is a rare life-threatening infectious disease associated with use of intra-vaginal protection. The colonizing S. aureus strain uses catamenial products absorbed in the tampon as a growth medium for its proliferation. When S. aureus reaches a certain concentration, S. aureus produces TSST-1, which gains access from the vagina to the bloodstream and induce the systemic illness in non-immunized women against TSST-1. Although, 70% of women in Western world use tampons and 4% of women has vaginal colonization by S. aureus producing TSST-1 and 10% are no immunized against TSST-1, the estimated rate of mTSS is only 1/100,000 per year. Thus, only a very small proportion of women at risk develops mTSS, questioning factors that may trigger and/or protect against mTSS. The objectives of our projects will be to identify the mechanisms by which environmental and host factors influence S. aureus TSST-1+ pathogenicity in mTSS by (i) quantification of S. aureus toxins/enzymes and corresponding antibodies in menstrual fluids from healthy women to that of patients with mTSS by mass spectrometry, RNAseq and Luminex analysis; (ii) Characterization of TSST-1 trans-vaginal epithelial passage by using human cellular, artificial tissue models and vaginal explants; (iii) determine at risk-practice for the women by large cases controls study.

• #53 Women’s Health and Education Center (WHEC) – Toxic Shock Syndrome

  http://www.womenshealthsection.com/content/print.php3?title=gyn015&cat=3&lng=english

  Toxic shock syndrome (TSS) was first described in children in 1978 but was quickly identified as an illness occurring primarily in menstruating women 12-24 years of age. […] The cause of toxic shock syndrome is preformed toxins produced by Staphylococcus aureus, so that colonization or infection by this microorganism must occur. TSS-toxin-1 is a protein with a molecular weight of approximately 24,000 daltons and has been proposed as the toxin responsible for TSS. Its production has been demonstrated in 90-100% of S. aureus strains recovered from women with menstrual TSS. […] The pathogenic mechanism for the association of tampons with TSS has not been adequately understood. How toxins gain access to the circulatory system is unknown. […] Regardless of the composition of the tampon, absorbency increased the odds ratio of TSS. The chemical composition of the tampons also influences the odds ratio. […] The longer a tampon is left in place, the greater the risk for development of this syndrome. […] The use of low-absorbency tampon appears to reduce the risk of TSS in tampon use. […] The incidence of non-menstrual disease has shown only a slight increase in the past 10 years.

• #54 On the Pathogenesis of Toxic Shock Syndrome

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2122035318

  Understanding of the pathogenesis of toxic shock syndrome (TSS) has come from the juxtaposition of epidemiologic, clinical, immunologic, and physiologic studies. […] A hypothesis has been developed for the pathogenesis of menstrually related TSS. […] Certain tampon fibers that are highly absorbent for water are also ion exchangers for magnesium ions. […] The latter ions uniquely affect the production of TSS toxin 1 (TSST-1) by appropriate strains of Staphylococcus aureus, with a marked increase in the amount of toxin when magnesium concentrations are limiting and suppression of toxin production when magnesium is in excess. […] Many epidemiologic features of TSS could be explained by this hypothesis. […] TSST-1 stimulates production of interleukin 1 and of tumor necrosis factor and is highly toxic when absorbed slowly. […] Like TSST-1, staphylococcal enterotoxins are lethal to rabbits when given by slow injection, and some enterotoxins may be more lethal than TSST-1.

• #55 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Toxic-Shock-Syndrome.aspx

  Toxic shock syndrome occurs as a result of an infection with bacteria such as Staphylococcus aureus and Streptococcus pyogenes. These bacteria produce a toxin that leads to the symptoms associated with the condition. […] Although it has not been established as a definitive cause, the use of tampons by menstruating women has been suggested as a possible cause, as this group of people are most commonly affected by the syndrome. […] In addition, when greater awareness of appropriate tampons use became widespread, the incidence of women with the syndrome decreased significantly.

• #56 Toxic Shock Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459345/

  TSS is a toxin-mediated disease that is caused by toxin-producing streptococci or S. aureus. These superantigens bypass the normal pathway for activation of T cells resulting in over-activation of cytokines and inflammatory cells. This then leads to the presenting signs and symptoms of fever, rash, hypotension, and end-organ failure due to capillary leak. Strep pyogenes (GAS) has other toxins that play a role in necrotizing fasciitis and streptococcal toxic shock syndrome. […] TSS is most commonly caused by a toxigenic strain of Staphylococcus aureus or Group A Strep (Streptococcus pyogenes). Other strains of streptococci also produce superantigens, which can lead to TSS. The disease occurs most often in the setting of menstruation despite the discontinuation of high absorbency tampons. However, TSS can also present in non-menstrual settings such as in soft tissue infections, post-surgical infections, burns, retained foreign bodies such as nasal packing, and dialysis catheters. Staphylococcal TSS is typically the result of a localized infection such as an abscess, whereas streptococcal TSS may result from bacteremia, necrotizing fasciitis, or cellulitis.

• #57 Toxic Shock Syndrome from Surgical Infections | SpringerLink

  https://link.springer.com/chapter/10.1007/978-1-4471-3454-1_15

  The majority of toxic shock syndrome cases are caused by a specific toxin, toxic shock syndrome toxin 1, produced by some strains of Staphylococcus aureus. […] A number of cases of toxic shock syndrome have resulted from staphylococcal infected incisions in surgery patients following many different types of surgical procedures, including nasal operations. […] In some cases the staphylococcal strain isolated from the infection was identical to one isolated from the surgeon.

• #58 Toxic Shock Syndrome: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/169177-overview

  Toxic shock syndrome (TSS) is a rare acute life-threatening illness, caused by a toxin-mediated infectious process linked to toxin-producing strains of Staphylococcus aureus or group A Streptococcus (GAS), also called Streptococcus pyogenes. TSS is characterized by high fever, rash, desquamation of palms and soles, hypotension, refractory shock, multiorgan failure, and death. The clinical syndrome can also include severe myalgia, vomiting, diarrhea, headache, and nonfocal neurologic abnormalities […] TSS is linked mostly to toxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes (group A streptococcus). These toxins act as superantigens in inducing nonclassic activation of T cells by antigen-presenting cells (APCs), leading to nonspecific, polyclonal lymphocyte activation of 5-30% of the total population of T cells, which results in massive release of proinflammatory cytokines.

• #59 Toxic shock syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Toxic_shock_syndrome_pathophysiology

  The pathophysiology of toxic shock syndrome can be explained based on the etiological agent causing the disease. The general mechanism for all the etiological agents is the same, which involves non-specific activation of T lymphocytes by toxins acting as superantigens leading to release of cytokines. […] Toxic shock syndrome (TSS) is known to be caused by the intoxication by one of the various exotoxins produced by Staphylococcus aureus, namely toxic shock syndrome toxin-1 (TSST-1). It may also be caused by some strains of Streptococcus pyogenes or Group A streptococcal (GAS) infection. […] Various attachment proteins for example, fibronectin-binding proteins and collagen-binding proteins among many others, facilitate attachment to host cells, or interfere with host immune responses through the antiphagocytic action of proteins such as protein A. After attachment to host cells (particularly epithelial cells), the S. aureus produces cytolysins, which aid entry of the Toxic shock syndrome toxin-1 (TSST-1–the major toxin involved in TSS) into the system.

• #60 Toxic shock syndrome pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Toxic_shock_syndrome_pathophysiology

  SAgs cause release of IL-1 beta and IL-6 from antigen presenting cells (APC) and have a direct action on the hypothalamic temperature control center. […] The pyrogenic exotoxin type A gene is associated with group A streptococcal strains isolated from patients with TSLS and may play a causative role in this illness. […] SpeA and SpeB non-specifically activate T cells causing release of pro-inflammatory cytokines like IL-6, IL-8, and MIP-3, which leads to fever, rash, capillary leak, and subsequent hypotension, the major symptoms of toxic shock syndrome. […] TcsL is the most important virulence factor required for producing Toxic shock syndrome (TSS). It is a major pathogenicity factor, which in addition to its in vivo effects, is cytotoxic to cultured cell lines. […] The covalent attachment of the glucose moiety to a conserved threonine within the effector region of the GTPases causes inactivation of Rho-GTPases.

• #61 Toxic shock syndrome | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/toxic-shock-syndrome?lang=us

  The toxic shock syndrome toxin-1 (TSST-1) also has deleterious effects on the vasculature, with marked capillary leakiness, fluid shifts and hypotension. Most cases of menstruation-related toxic shock syndrome are secondary to the release of TSST-1. For non-menstrual-related presentations the toxic shock syndrome toxin is only implicated in half the cases, with enterotoxins responsible for the other 50%.

• #62 Toxic Shock Syndrome: A Literature Review

  https://www.mdpi.com/2079-6382/13/1/96

  In the TSS, the superantigen binds the TCR and MHC II outside the Ag presentation site with high affinity. This results in nonspecific, polyclonal lymphocyte activation of 5 to 30% of the total population of T cells. […] This simultaneous polyclonal activation results in a significant activation of NF kappa B, which plays a major role in the generation and expansion of the inflammatory response. […] This results in a massive release of proinflammatory cytokines, with clinical signs, such as capillary leakage, arterial hypotension, organ failure, and coagulation activation, usually being reported in this setting. […] Physiopathological specificities of staphylococcal and streptococcal TSS are detailed in the corresponding subparts.

• #63 Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2 | PLOS Medicine

  https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0030151

  STSS caused by non-GAS streptococci, including group B streptococci, group C streptococci, and group G streptococci, has not been well documented. […] We describe two recent outbreaks of S. suis 2, a non-GAS, in China and characterize the STSS they caused in human patients. […] The outbreak was immediately recognized as a zoonotic disease, because almost all the patients had been in contact with pigs, and there was a concurrent disease outbreak among the local pig population, with more than 640 pig fatalities. […] In the fatal human cases, the disease started with acute illness, malaise, fever, headache, diarrhea, rapidly developing hyperpyrexia, hypotension, and a decline of pulse pressure. […] All of these symptoms are indicative of possible TSS. […] Ultimately, some cases progressed to multisystem dysfunction, such as acute respiratory distress syndrome (ARDS), liver failure, heart failure, disseminated intravascular coagulation (DIC), and acute renal failure.

• #64 Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2 | PLOS Medicine

  https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0030151

  STSS caused by non-GAS streptococci, including group B streptococci, group C streptococci, and group G streptococci, has not been well documented. […] We describe two recent outbreaks of S. suis 2, a non-GAS, in China and characterize the STSS they caused in human patients. […] The outbreak was immediately recognized as a zoonotic disease, because almost all the patients had been in contact with pigs, and there was a concurrent disease outbreak among the local pig population, with more than 640 pig fatalities. […] In the fatal human cases, the disease started with acute illness, malaise, fever, headache, diarrhea, rapidly developing hyperpyrexia, hypotension, and a decline of pulse pressure. […] All of these symptoms are indicative of possible TSS. […] Ultimately, some cases progressed to multisystem dysfunction, such as acute respiratory distress syndrome (ARDS), liver failure, heart failure, disseminated intravascular coagulation (DIC), and acute renal failure.

• #65 Toxic Shock Syndrome Management: A tale of two patients

  https://emcrit.org/pulmcrit/toxic-shock-syndrome-management-a-tale-of-two-patients/

  Toxic shock syndrome (TSS) is a true resuscitationist’s disease. It is potentially quite lethal, with many series of streptococcal toxic shock syndrome reporting mortality in the range of 30-50%. However, recent observational studies suggest that treatment with modern critical care, toxin-suppressive antibiotics, and IVIG may reduce the mortality to 10% (Linner 2014). […] The primary problem in TSS is often not the presence of bacteria in the tissues, but rather toxin secretion causing massive cytokine release. Therefore, antibiotic therapy focuses on protein-synthesis inhibiting drugs which act immediately to shut off toxin synthesis. […] Clindamycin is the most widely recommended antibiotic for toxin suppression. Clindamycin has activity against 99% of Group A streptococci as well as some activity against staphylococci including some MRSA. Clindamycin acts on the 50s ribosomal subunit to inhibit protein synthesis, thereby stopping toxin synthesis.

• #66 Toxic Shock Syndrome Management: A tale of two patients

  https://emcrit.org/pulmcrit/toxic-shock-syndrome-management-a-tale-of-two-patients/

  Toxic shock syndrome (TSS) is a true resuscitationist’s disease. It is potentially quite lethal, with many series of streptococcal toxic shock syndrome reporting mortality in the range of 30-50%. However, recent observational studies suggest that treatment with modern critical care, toxin-suppressive antibiotics, and IVIG may reduce the mortality to 10% (Linner 2014). […] The primary problem in TSS is often not the presence of bacteria in the tissues, but rather toxin secretion causing massive cytokine release. Therefore, antibiotic therapy focuses on protein-synthesis inhibiting drugs which act immediately to shut off toxin synthesis. […] Clindamycin is the most widely recommended antibiotic for toxin suppression. Clindamycin has activity against 99% of Group A streptococci as well as some activity against staphylococci including some MRSA. Clindamycin acts on the 50s ribosomal subunit to inhibit protein synthesis, thereby stopping toxin synthesis.

• #67 Toxic Shock Syndrome Management: A tale of two patients

  https://emcrit.org/pulmcrit/toxic-shock-syndrome-management-a-tale-of-two-patients/

  TSS may occur due to staph infection including MRSA, or rarely Group A streptococci resistant to clindamycin. Therefore, adding a second antibiotic is advisable. Linezolid may be a logical choice here, because it has excellent coverage for gram positive pathogens and acts similarly to stop toxin synthesis by inhibiting the 50s ribosomal subunit. […] The presence of a retained tampon, sinus packing, or any infected foreign material must be excluded. […] Source control is a cornerstone of sepsis management in general. This is especially critical if the focus of infection is continuing to secrete toxin. […] TSS is unusual in its ability to cause severe septic shock in previously normal young people. Given that patients often have high physiologic reserve, they may initially look deceptively OK, masking the severity of their illness. This often causes delays in instituting sufficiently aggressive management. In addition to aggressive supportive care, specific therapies including IVIG and toxin-suppressive antibiotics may be very important.

• #68 Toxic Shock Syndrome Management: A tale of two patients

  https://emcrit.org/pulmcrit/toxic-shock-syndrome-management-a-tale-of-two-patients/

  TSS may occur due to staph infection including MRSA, or rarely Group A streptococci resistant to clindamycin. Therefore, adding a second antibiotic is advisable. Linezolid may be a logical choice here, because it has excellent coverage for gram positive pathogens and acts similarly to stop toxin synthesis by inhibiting the 50s ribosomal subunit. […] The presence of a retained tampon, sinus packing, or any infected foreign material must be excluded. […] Source control is a cornerstone of sepsis management in general. This is especially critical if the focus of infection is continuing to secrete toxin. […] TSS is unusual in its ability to cause severe septic shock in previously normal young people. Given that patients often have high physiologic reserve, they may initially look deceptively OK, masking the severity of their illness. This often causes delays in instituting sufficiently aggressive management. In addition to aggressive supportive care, specific therapies including IVIG and toxin-suppressive antibiotics may be very important.

• #69 Toxic Shock Syndrome (TSS) – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/gram-positive-cocci/toxic-shock-syndrome-tss

  S. pyogenes TSS is defined as any group A beta-hemolytic streptococci (GABHS) infection associated with shock and organ failure. […] TSS may progress within 48 hours to syncope, tissue necrosis, shock, disseminated coagulation, multisystem organ failure, and death. […] Antibiotics given during the acute illness may eradicate pathogen foci and prevent recurrences. […] Passive immunization to TSS toxins with IV immune globulin (2 g/kg, followed by 0.4 g/kg daily for up to 5 days) has been helpful in severe cases of both types of TSS and lasts for weeks, but the disease may not induce active immunity, so recurrences are possible.

• #70

  https://step2.medbullets.com/evidence/23830657

  Toxic shock syndrome (TSS) is primarily the result of a superantigen-mediated cytokine storm and M protein-mediated neutrophil activation, resulting in the release of mediators leading to respiratory failure, vascular leakage, and shock. […] Mortality for streptococcal TSS still hovers at 50%. […] There is evidence to support a role for intravenous immunoglobulin (IVIG) in the treatment of streptococcal TSS.

• #71 Toxic Shock Syndrome Management: A tale of two patients

  https://emcrit.org/pulmcrit/toxic-shock-syndrome-management-a-tale-of-two-patients/

  Toxic shock syndrome (TSS) is a true resuscitationist’s disease. It is potentially quite lethal, with many series of streptococcal toxic shock syndrome reporting mortality in the range of 30-50%. However, recent observational studies suggest that treatment with modern critical care, toxin-suppressive antibiotics, and IVIG may reduce the mortality to 10% (Linner 2014). […] The primary problem in TSS is often not the presence of bacteria in the tissues, but rather toxin secretion causing massive cytokine release. Therefore, antibiotic therapy focuses on protein-synthesis inhibiting drugs which act immediately to shut off toxin synthesis. […] Clindamycin is the most widely recommended antibiotic for toxin suppression. Clindamycin has activity against 99% of Group A streptococci as well as some activity against staphylococci including some MRSA. Clindamycin acts on the 50s ribosomal subunit to inhibit protein synthesis, thereby stopping toxin synthesis.

• #72 Streptococcal toxic shock syndrome in the intensive care unit | Annals of Intensive Care | Full Text

  https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-018-0438-y

  The streptococcal toxic shock syndrome is a severe complication associated with invasive infections by group A streptococci. […] The exact mechanism of STSS is not entirely understood but has to do with a combination of the effect of streptococcal toxins enterotoxins with superantigen activity other streptococcal enzymes and toxins, and the host response to streptococcal infection, a complex interplay between host immunity and pathogen virulence. […] The pathophysiology of STSS is based on bacterial toxins. Superantigens are proteins that share the ability to trigger excessive and nonspecific T cell activation, therefore generating the massive secretion pro-inflammatory cytokines and other mediators producing capillary leak and arterial hypotension. […] Staphylococci and streptococci are the two most common bacterial genera known to produce superantigens.

• #73 Toxic Shock Syndrome: Symptoms and Treatment | Doctor

  https://patient.info/doctor/toxic-shock-syndrome-pro

  Toxic shock syndrome (TSS) is a multisystem inflammatory response to the presence of bacterial exotoxins. […] The infecting staphylococcal or streptococcal exotoxin acts as a superantigen, setting off a reactive inflammatory cascade, mediated predominantly by tumour necrosis factor alpha and interleukin-1.

• #74

  https://journals.lww.com/shockjournal/abstract/1995/02000/the_pathogenesis_of_experimental_toxic_shock.10.aspx

  Toxic shock syndrome (TSS) is a multisystem disorder characterized by fever, hypotension, and involvement of three other organ systems. The etiologic agent is a toxigenic strain of Staphylococcus aureus which secretes the exotoxin, TSST-1. The toxin is a superantigen which stimulates the immune system to produce interleukin-1 (IL-1), interleukin-2, and tumor necrosis factor (TNF). […] We hypothesized that TSST-1 induces the release of IL-2 which in turn is either directly involved or acts via an additional mediator to produce hypotension. […] We conclude that the cytokine IL-2 is an important host mediator involved in the pathogenesis of TSS.

• #75 Women’s Health and Education Center (WHEC) – Toxic Shock Syndrome

  http://www.womenshealthsection.com/content/print.php3?title=gyn015&cat=3&lng=english

  Toxic shock syndrome (TSS) was first described in children in 1978 but was quickly identified as an illness occurring primarily in menstruating women 12-24 years of age. […] The cause of toxic shock syndrome is preformed toxins produced by Staphylococcus aureus, so that colonization or infection by this microorganism must occur. TSS-toxin-1 is a protein with a molecular weight of approximately 24,000 daltons and has been proposed as the toxin responsible for TSS. Its production has been demonstrated in 90-100% of S. aureus strains recovered from women with menstrual TSS. […] The pathogenic mechanism for the association of tampons with TSS has not been adequately understood. How toxins gain access to the circulatory system is unknown. […] Regardless of the composition of the tampon, absorbency increased the odds ratio of TSS. The chemical composition of the tampons also influences the odds ratio. […] The longer a tampon is left in place, the greater the risk for development of this syndrome. […] The use of low-absorbency tampon appears to reduce the risk of TSS in tampon use. […] The incidence of non-menstrual disease has shown only a slight increase in the past 10 years.

• #76 Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2 | PLOS Medicine

  https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0030151

  Based on the clinical features, we suspected that the patients had bacterial TSS, and we sought to identify the pathogenic bacteria. […] Thus, the animal infection experiments confirmed that these isolates are highly pathogenic strains and supported the conclusion that an invasive strain of S. suis 2 caused the STSS symptoms associated with the human outbreaks. […] We failed to identify so-called superantigens in our isolates, suggesting that the molecular mechanisms by which S. suis 2 causes STSS might be different from those of GAS. […] Our data indicate that highly virulent strains of S. suis 2 caused human STSS in two recent large-scale outbreaks. However, the exact mechanism by which S. suis 2, a non-GAS, causes STSS is yet to be unveiled. […] The molecular mechanisms in the pathogen and the host underlying the outbreaks should be addressed in future studies.

Zobacz więcej