Epidemiology, clinical manifestations, and diagnosis of streptococcal toxic shock syndrome
- Dennis L Stevens, MD, PhD
Dennis L Stevens, MD, PhD
- Professor of Medicine
- University of Washington School of Medicine
Streptococcal toxic shock syndrome (TSS) is a clinical illness characterized by shock and multiorgan failure. Streptococcal TSS consists of isolation of group A Streptococcus (GAS) from a normally sterile body site, together with hypotension, tachycardia, and evidence of organ failure, such as acute respiratory distress syndrome, coagulopathy, liver failure, or renal failure . It occurs as a result of capillary leak and tissue damage due to release of inflammatory cytokines induced by streptococcal toxins.
Streptococcal TSS occurs most frequently in the setting of invasive infection due to group A Streptococcus (Streptococcus pyogenes). GAS typically causes pharyngitis or skin and soft tissue infection; these are generally responsive to appropriate antibiotic therapy, and patients do not develop streptococcal TSS . Less commonly, GAS causes invasive disease such as necrotizing infection of the skin and fascia, gangrenous myositis, bacteremia, or pneumonia , and these types of infection are complicated by TSS in approximately one-third of cases .
The epidemiology, clinical manifestations, and diagnosis of streptococcal toxic shock syndrome will be reviewed here. The treatment of streptococcal toxic shock syndrome is discussed separately. (See "Treatment of streptococcal toxic shock syndrome".)
Invasive infections associated with group A streptococcal (GAS) toxic shock syndrome (TSS) have been reported with increasing frequency, predominantly from North America and Europe [1,4-13]. There are an estimated 3.5 cases of streptococcal TSS per 100,000 persons, with a case-fatality rate of 30 to 60 percent [3,13-16]. One study noted an increase in the incidence of invasive group A streptococcal disease in Utah between 2002 and 2010, from 3.5 to 9.8 cases per 100,000 . Up to one-third of patients with invasive GAS disease developed TSS in reported case series [15,18]. The rate of TSS among patients with necrotizing fasciitis is approximately 50 percent [3,19].
Risk factors — GAS TSS occurs among all age groups. Most patients are not immunosuppressed; diabetes and alcoholism are risk factors described in some studies [7,20-25]. Among reports of invasive GAS infections associated with bacteremia in the late 1980s, most patients were either <10 or >60 years of age and had underlying diseases, such as cancer, renal failure, leukemia, and severe burns, or were receiving corticosteroids or other immunosuppressive drugs [22-24]. Invasive infection remains highest in patients >50 years of age.
- Defining the group A streptococcal toxic shock syndrome. Rationale and consensus definition. The Working Group on Severe Streptococcal Infections. JAMA 1993; 269:390.
- Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med 1996; 334:240.
- Darenberg J, Luca-Harari B, Jasir A, et al. Molecular and clinical characteristics of invasive group A streptococcal infection in Sweden. Clin Infect Dis 2007; 45:450.
- Stevens DL, Tanner MH, Winship J, et al. Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A. N Engl J Med 1989; 321:1.
- Group A streptococcal infections and a toxic shock-like syndrome. N Engl J Med 1989; 321:1545.
- Martin PR, Høiby EA. Streptococcal serogroup A epidemic in Norway 1987-1988. Scand J Infect Dis 1990; 22:421.
- Wheeler MC, Roe MH, Kaplan EL, et al. Outbreak of group A streptococcus septicemia in children. Clinical, epidemiologic, and microbiological correlates. JAMA 1991; 266:533.
- Bartter T, Dascal A, Carroll K, Curley FJ. 'Toxic strep syndrome'. A manifestation of group A streptococcal infection. Arch Intern Med 1988; 148:1421.
- Hríbalová V. Streptococcus pyogenes and the toxic shock syndrome. Ann Intern Med 1988; 108:772.
- Greenberg RN, Willoughby BG, Kennedy DJ, et al. Hypocalcemia and "toxic" syndrome associated with streptococcal fasciitis. South Med J 1983; 76:916.
- Thomas JC, Carr SJ, Fujioka K, Waterman SH. Community-acquired group A streptococcal deaths in Los Angeles County. J Infect Dis 1989; 160:1086.
- Stevens DL. The toxic shock syndromes. Infect Dis Clin North Am 1996; 10:727.
- Lepoutre A, Doloy A, Bidet P, et al. Epidemiology of invasive Streptococcus pyogenes infections in France in 2007. J Clin Microbiol 2011; 49:4094.
- Nelson GE, Pondo T, Toews KA, et al. Epidemiology of Invasive Group A Streptococcal Infections in the United States, 2005-2012. Clin Infect Dis 2016; 63:478.
- Ekelund K, Skinhøj P, Madsen J, Konradsen HB. Reemergence of emm1 and a changed superantigen profile for group A streptococci causing invasive infections: results from a nationwide study. J Clin Microbiol 2005; 43:1789.
- O'Brien KL, Beall B, Barrett NL, et al. Epidemiology of invasive group a streptococcus disease in the United States, 1995-1999. Clin Infect Dis 2002; 35:268.
- Stockmann C, Ampofo K, Hersh AL, et al. Evolving epidemiologic characteristics of invasive group a streptococcal disease in Utah, 2002-2010. Clin Infect Dis 2012; 55:479.
- Svensson N, Oberg S, Henriques B, et al. Invasive group A streptococcal infections in Sweden in 1994 and 1995: epidemiology and clinical spectrum. Scand J Infect Dis 2000; 32:609.
- Kaul R, McGeer A, Low DE, et al. Population-based surveillance for group A streptococcal necrotizing fasciitis: Clinical features, prognostic indicators, and microbiologic analysis of seventy-seven cases. Ontario Group A Streptococcal Study. Am J Med 1997; 103:18.
- Schwartz B, Facklam RR, Breiman RF. Changing epidemiology of group A streptococcal infection in the USA. Lancet 1990; 336:1167.
- Stegmayr B, Björck S, Holm S, et al. Septic shock induced by group A streptococcal infection: clinical and therapeutic aspects. Scand J Infect Dis 1992; 24:589.
- Francis J, Warren RE. Streptococcus pyogenes bacteraemia in Cambridge--a review of 67 episodes. Q J Med 1988; 68:603.
- Barnham M. Invasive streptococcal infections in the era before the acquired immune deficiency syndrome: a 10 years' compilation of patients with streptococcal bacteraemia in North Yorkshire. J Infect 1989; 18:231.
- Braunstein H. Characteristics of group A streptococcal bacteremia in patients at the San Bernardino County Medical Center. Rev Infect Dis 1991; 13:8.
- Holm SE, Norrby A, Bergholm AM, Norgren M. Aspects of pathogenesis of serious group A streptococcal infections in Sweden, 1988-1989. J Infect Dis 1992; 166:31.
- Hamilton SM, Stevens DL, Bryant AE. Pregnancy-related group a streptococcal infections: temporal relationships between bacterial acquisition, infection onset, clinical findings, and outcome. Clin Infect Dis 2013; 57:870.
- Smit MA, Nyquist AC, Todd JK. Infectious shock and toxic shock syndrome diagnoses in hospitals, Colorado, USA. Emerg Infect Dis 2013; 19:1855.
- Hellström P. Urinary and sexual dysfunction after rectosigmoid surgery. Ann Chir Gynaecol 1988; 77:51.
- Wasserzug O, Valinsky L, Klement E, et al. A cluster of ecthyma outbreaks caused by a single clone of invasive and highly infective Streptococcus pyogenes. Clin Infect Dis 2009; 48:1213.
- Agerson AN, Wilkins EG. Streptococcal toxic shock syndrome after breast reconstruction. Ann Plast Surg 2005; 54:553.
- Okumura K, Schroff R, Campbell R, et al. Group A streptococcal puerperal sepsis with retroperitoneal involvement developing in a late postpartum woman: case report. Am Surg 2004; 70:730.
- Laupland KB, Davies HD, Low DE, et al. Invasive group A streptococcal disease in children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group. Pediatrics 2000; 105:E60.
- Zachariadou L, Stathi A, Tassios PT, et al. Differences in the epidemiology between paediatric and adult invasive Streptococcus pyogenes infections. Epidemiol Infect 2014; 142:512.
- Imöhl M, van der Linden M, Reinert RR, Ritter K. Invasive group A streptococcal disease and association with varicella in Germany, 1996-2009. FEMS Immunol Med Microbiol 2011; 62:101.
- Patel RA, Binns HJ, Shulman ST. Reduction in pediatric hospitalizations for varicella-related invasive group A streptococcal infections in the varicella vaccine era. J Pediatr 2004; 144:68.
- Stevens DL. Could nonsteroidal antiinflammatory drugs (NSAIDs) enhance the progression of bacterial infections to toxic shock syndrome? Clin Infect Dis 1995; 21:977.
- Auerbach SB, Schwartz B, Facklam RR, et al. Outbreak of invasive group A streptococcal (GAS) disease in a nursing home (abstract). In: ICAAC, Atlanta, GA 1990.
- Hohenboken JJ, Anderson F, Kaplan EL. Invasive group A streptococcal (GAS) serotype M-1 outbreak in a long-term care facility (LTCF) with mortality (abstract). In: ICAAC, Atlanta, GA 1994.
- Centers for Disease Control and Prevention (CDC). Nosocomial group A streptococcal infections associated with asymptomatic health-care workers--Maryland and California, 1997. MMWR Morb Mortal Wkly Rep 1999; 48:163.
- Ye C, Zheng H, Zhang J, et al. Clinical, experimental, and genomic differences between intermediately pathogenic, highly pathogenic, and epidemic Streptococcus suis. J Infect Dis 2009; 199:97.
- Kanetake K, Hayashi M, Hino A, et al. Primary peritonitis associated with streptococcal toxic shock-like syndrome: report of a case. Surg Today 2004; 34:1053.
- Hung TY, Wang LY, Chen CT, Chen TJ. Streptococcal toxic shock syndrome with initial manifestation of abdominal pain and cholecystitis. Acta Paediatr Taiwan 2005; 46:106.
- Khateeb OM, Osborne D, Mulla ZD. Gastrointestinal symptomatology as a predictor of severe outcomes of invasive group A streptococcal infections. Epidemiol Infect 2010; 138:534.
- Chiang MC, Jaing TH, Wu CT, et al. Streptococcal toxic shock syndrome in children without skin and soft tissue infection: report of four cases. Acta Paediatr 2005; 94:763.
- Karakousis PC, Page KR, Varello MA, et al. Waterhouse-Friderichsen syndrome after infection with group A streptococcus. Mayo Clin Proc 2001; 76:1167.
- Gourlay M, Gutierrez C, Chong A, Robertson R. Group A streptococcal sepsis and ovarian vein thrombosis after an uncomplicated vaginal delivery. J Am Board Fam Pract 2001; 14:375.
- Chuang I, Van Beneden C, Beall B, Schuchat A. Population-based surveillance for postpartum invasive group a streptococcus infections, 1995-2000. Clin Infect Dis 2002; 35:665.