List key features in pathogenesis, clinical presentation and management of staphylococcal toxic shock syndrome.
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.
References
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.