Question 1

College Answer

Pathogenesis

•    Due to toxin (TSST-1, 2 or 3) released by Staph and enteroxin

•    TSST acts as a superantigen activating T-cells directly with massive elevation of cytokines

•    Classically associated with tampon use but also seen with surgical procedures and wound infection, cellulitis, sinusitis, HIV

•    Very similar and cause seen with other bacteria (toxic shock like syndrome) such asStreptococci

Presentation

•    Initially myalgia, fever

•    Vasodilated shock and multiple organ dysfunction

•    Marked erythema with desquamation 7-14 days later

•    Edema due to capillary leak syndrome

•    Blood cultures usually negative

Management

•    Resuscitation and support including adequate fluids, inotropes/organ support…

•    Search for source which may be covert – drain abscess……remove tampon

•    There may be a role for IVIg to bind toxin

•    Antibiotics may not alter course but infection should be treated

•    Lincomycin/Clindamycin may have a particular role as it inhibits synthesis of bacterial toxins

Discussion

A nice case of this was presented in the NEJM in 2013. PLOS have a good review article which presents observational data regarding the typical clinical manifestations. Donald Low has recently published an excellent overview in Critical Care Clinics. A summary of toxic shock syndromescraped together from these sources is available in the Required Reading section.

Pathogenesis of toxic shock syndrome

Some staphylococci produce a characteristic protein (the Toxic Shock Syndrome Toxin, or TSST-1, 2 and 3).

• TSST activates T-cells directly, acting as a "superantigen"
• Massive inflammatory cytokine release is the result
• Endothelial dysfunction and vasodilatory shock ensues, which is out of proportion to the severity of the initiating infection.

Risk factors for toxic shock syndrome

• Being female
• Use of tampons

In fact, in Low's article, staphylococcal TSS is separated into "mentsrual" and "non-menstrual" categories. Apparently, the tampon introduces oxygen, which is required for TSS-1 production.

• Surgical wound infection
• Mastitis
• Sinusitis
• Osteomyelitis
• Burns
• Compromised immune system (eg. HIV)

Clinical manifestations of toxic shock syndrome

According to the CDC, there are four stereotypical criteria for toxic shock syndrome, all of which must be met:

• High fever (> 38.9°)
• Hypotension and shock
• Rash consistent with diffuse macular erythroderma
• Desquamation, particularly of the palms and soles

There are also non-diagnostic associated features:

• Rapid onset: ~ 2 days
• Staphylococcus may grow in the blood (but blood cultures otherwise negative)
• Multisystem organ involvement

Management

• Vigorous resuscitation a'la Surviving Sepsis guidelines, or perhaps something evidence-based.
• Source control
• β-lactam antibiotics
• Clindamycin as an adjunct (prevents the synthesis of TSST)
• Intravenous immunoglobulin (to bind circulating TSST)
  The dose of IV IG has generally been either 2g/kg as one hit. If the patient has already been "well filled" (i.e. they are in florid pulmonary oedema) one may split the dose into three days, with 1g/kg on the first day and 0.5g/kg on each subsequent day.

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Chan, Bob CY, and Paul Maurice. "Staphylococcal Toxic Shock Syndrome."New England Journal of Medicine 369.9 (2013): 852-852.

 

DeVries, Aaron S., et al. "Staphylococcal toxic shock syndrome 2000–2006: epidemiology, clinical features, and molecular characteristics." PLoS One 6.8 (2011): e22997.

 

Kare, M., and A. Dang. "Staphylococcal toxic shock syndrome." JAPI 56 (2008).

 

KEHRBERG, MARK W., et al. "Risk factors for staphylococcal toxic-shock syndrome." American journal of epidemiology 114.6 (1981): 873-879.

 

Parsonnet, Jeffrey. "Mediators in the pathogenesis of toxic shock syndrome: overview." Reviews of infectious diseases (1989): S263-S269.

 

Low, Donald E. "Toxic Shock Syndrome." Crit Care Clin 29 (2013): 651-675.

 

Brosnahan, Amanda J., and Patrick M. Schlievert. "Gram‐positive bacterial superantigen outside‐in signaling causes toxic shock syndrome." FEBS Journal278.23 (2011): 4649-4667.

 

Kulhankova, Katarina, Jessica King, and Wilmara Salgado-Pabón. "Staphylococcal toxic shock syndrome: superantigen-mediated enhancement of endotoxin shock and adaptive immune suppression." Immunologic research(2014): 1-6.