Manoj Pariyadath
TOXIC SHOCK SYNDROME
EPIDEMIOLOGY
Toxic shock syndrome (TSS) is a severe, toxin-mediated, life-threatening syndrome that initially was associated with the use of tampons by menstruating women, although most cases are no longer related to these factors.
Risk factors for TSS include current menstruation, cutaneous lesions including burns, recent surgical procedures, postpartum/postabortion status, use of vaginally inserted devices such as sponges or diaphragms, and nasal packing. Other less common associations include sinusitis, pharyngitis, intrauterine device use, and body art such as tattoos or piercings.
Risk factors in children <2 years of age include non-surgical skin and soft tissue lesions and infections.
One-tenth of the TSS cases are seen in men, with a mortality rate 3.3 times that of menstruating women.
PATHOPHYSIOLOGY
The majority of TSS cases have been directly associated with colonization or infection with Staphylococcus aureus. Production of toxic shock syndrome toxin-1 (TSST-1) is responsible for the clinical manifestation of most cases of menstruation-related TSS via direct toxic effects or through release of secondary mediators. Biochemically similar toxins have been identified in non-menstruation-related TSS.
TSS-1 production is enhanced by certain vaginal conditions including temperature of 39°C to 40°C, neutral pH, partial pressure of oxygen >5%, and supplemental carbon dioxide. These conditions can be met during menses and with the introduction of tampons or intravaginal devices.
Marked vasodilatation, movement of serum proteins and fluids from the intravascular to the extravascular space, depressed cardiac function, and total body water deficits result in hypotension. Subsequent multisystem organ failure may reflect either a direct effect of the toxin on tissues or the rapid onset of hypotension and decreased perfusion.
CLINICAL FEATURES
TSS is characterized by high fever, profound hypotension, diffuse erythrodermatous rash, mucous membrane hyperemia, diffuse myalgias, headache, sore throat, vomiting, diarrhea, and constitutional symptoms that rapidly progress to multisystem dysfunction.
Patients are ill appearing. Other features include tender painful genitalia with vaginal hyperemia, nonpitting edema, rhabdomyolysis, and non-focal neurologic abnormalities without signs of meningeal irritation.
Women with menstruation-related TSS typically present between the third and fifth day of menses. Postoperative patients develop symptoms in 2 days.
The rash associated with TSS is a diffuse, blanch-able erythroderma, often described as a “painless sunburn.” Generalized desquamation with notable peeling over the palms and soles occurs on day 6 to 10 of illness.
DIAGNOSIS AND DIFFERENTIAL
Diagnostic criteria are listed in Table 90-1.
TSS should be considered in any acute febrile illness associated with erythroderma, hypotension, and multiorgan involvement and should be considered before all diagnostic criteria are met.
Lab values involved in the diagnostic criteria of TSS and that should be included in the workup are complete blood cell count, serum creatinine and blood urea nitrogen (BUN), urine analysis, liver function tests, and blood cultures. Throat cultures, cerebrospinal fluid cultures, and titers for disease processes such as Rocky Mountain spotted fever should be obtained if indicated.
Other syndromes to consider in the differential diagnosis of TSS include streptococcal TSS, Kawasaki’s disease, staphylococcal scalded skin syndrome, Rocky Mountain spotted fever, and septic shock.
TABLE 90-1 Diagnostic Criteria for Toxic Shock Syndrome
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The treatment of TSS consists of airway management, aggressive management of circulatory shock, continuous monitoring of vital signs and urinary output, use of antistaphylococcal antimicrobial agents with β-lactamase stability, and the search for a focus of infection.
Crystalloid IV fluids should be used initially for hypotension and fluid resuscitation. A central venous pressure (CVP) or Swan-Ganz catheter may be necessary for patient monitoring if there is an inadequate response to initial fluid resuscitation. Large volumes of fluid (up to 20 L) may be required over the first 24 hours.
Patients with evidence of bleeding and abnormal coagulation profiles or thrombocytopenia may require blood products.
Culture all potentially infected sites, including blood, prior to initiating antibiotic therapy.
Tampons or nasal packing should be removed, if present.
A dopamine or norepinephrine infusion may be necessary to augment fluid resuscitation for refractory hypotension.
Initiate antistaphylococcal antimicrobial therapy with β-lactamase stability. Nafcillin or oxacillin in doses of 2 grams IV every 4 hours, or a cephalosporin such as cefazolin given 2 grams every 6 hours, provides adequate coverage. Some authors recommend clin-damycin, 600 to 900 milligrams IV every 8 hours, or linezolid, 600 milligrams IV every 12 hours because of evidence that these antibiotics may decrease toxin production. Vancomycin, 1 gram every 12 hours, should be used if methicillin-resistant strains of staphlococci are suspected. In penicillin-allergic patients, clindamycin, vancomycin, or potentially cephalosporins may be used.
Administration of methylprednisolone and intravenous immunoglobulin (IVIG) may result in clinical improvement. IVIG, 1 to 2 grams/kg, should be considered if there is no clinical improvement after 6 hours of aggressive supportive care.
Patients are typically admitted to the ICU.
Recurrence of TSS can be seen in patients not treated with β-lactamase-stable antibiotics.
STREPTOCOCCAL TOXIC SHOCK SYNDROME
EPIDEMIOLOGY
Streptococcal TSS is defined as any group A strepto-coccal infection associated with invasive soft tissue infection, early onset of shock, and organ failure. Streptococcal toxic shock is very similar to staphy-lococcal TSS; however, streptococcal toxic shock is associated with a soft tissue infection that is culture positive for Streptococcus pyogenes.
Streptococcal toxic shock commonly affects individuals between the ages of 20 and 50 years who may be without predisposing illness.
Risk factors for group A streptococcal infections include extremes of age, diabetes, alcohol or drug abuse, treatment with NSAIDs, and immunodeficiency.
PATHOPHYSIOLOGY
Virulent streptococcal pyogenic exotoxins are produced by 90% of group A streptococcal isolates and are felt to be accountable for the multisystem failure seen with streptococcal toxic shock.
The portals of entry of streptococci include the pharynx, vagina, mucosa, and skin in 50% of streptococcal toxic shock cases, but the source cannot be identified in most cases.
Infection may begin with minor local trauma, although disruption of the skin is not required.
CLINICAL FEATURES
Pain is the most common presenting symptom, and is often out of proportion to physical findings and abrupt in onset.
Disease may be heralded by a prodromal episode of fever, chills, myalgias, and diarrhea.
The development of vesicles and bullae at the site of soft tissue infection, which progresses to violaceous or blue discoloration, is considered an ominous sign of necrotizing fasciitis or myositis.
Adult respiratory distress syndrome develops in 55% of patients, usually following the onset of hypotension.
Patients are usually febrile, hypotensive, and confused, and develop multisystem organ dysfunction.
DIAGNOSIS AND DIFFERENTIAL
Diagnostic criteria are listed in Table 90-2.
When considering streptococcal toxic shock, look for soft tissue infection and culture the site. Laboratory evaluation includes CBC, arterial blood gas (ABG), liver function tests, serum creatinine and BUN, serum electrolytes including magnesium and calcium, coagulation profile, blood cultures, CXR, ECG, and urinalysis (UA).
Consider TSS, invasive infections caused by group A streptococci, serious infections caused by other bacteria including Clostridium perfringens, Kawasaki’s disease, Rocky Mountain spotted fever, and septic shock.
TABLE 90-2 Diagnostic Criteria for Streptococcal Toxic Shock Syndrome
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Treatment is similar to that for TSS, with airway management and aggressive fluid resuscitation with vasopressors as needed.
Begin antistreptococcal antimicrobial therapy with IV penicillin G, 24 million U/d in divided doses; IV clindamycin, 900 milligrams every 8 hours; or IV linezolid, 600 milligrams IV every 12 hours. In penicillin-allergic patients substitute ceftriaxone 2 grams IV q24h (at the discretion of the treating physician) and clindamycin 900 milligrams IV q8h.
Obtain immediate surgical consultation, as most patients with streptococcal toxic shock require debridement, fasciotomy, or amputation.
IVIG may be considered.
All patients suspected of having streptococcal toxic shock require admission to the ICU.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 145, “Toxic Shock Syndrome and Streptococcal Toxic Shock Syndrome,” by Shawna J. Perry and Reneé D. Reid.