Indian J Pediatr DOI 10.1007/s12098-013-1272-8
CLINICAL BRIEF
Streptococcal Toxic Shock Syndrome Vidya Krishna & Shuba Sankaranarayan & Rajakumar Padur Sivaraman & Krithika Prabaharan
Received: 8 July 2013 / Accepted: 10 October 2013 # Dr. K C Chaudhuri Foundation 2013
Abstract Streptococcal Toxic Shock syndrome (STSS) is a serious complication caused by exotoxins of Group A Streptococcus (GAS). It presents with fulminant shock and rash, is rapidly progressive with Multi-Organ Dysfunction Syndrome (MODS) and requires aggressive therapy with fluids, antibiotics and source control. Keywords Streptococcal Toxic Shock Syndrome . Group A Streptoccus . Multi Organ Dysfunction Syndrome . Renal Replacement Therapy
Introduction GAS infections can range from cellulitis to necrotizing fasciitis, myositis, empyema, bacteremia and endocarditis. A fatal complication is Toxic- shock syndrome, an exotoxin mediated illness presenting with rash, shock and multi-organ dysfunction. Incidence is especially higher in North America and Europe [1]. The authors report two cases of Streptococcal Toxic Shock syndrome (STSS) encountered in their setting and discuss their presentations, management and outcomes.
Case Reports Case 1 A 5-y-old boy presented with fever for 3 d, cough, respiratory distress and loose stools for 1 d. He was in compensated shock
V. Krishna : S. Sankaranarayan (*) : R. P. Sivaraman : K. Prabaharan Department of Pediatrics, Sri Ramachandra Medical College and Hospital, Porur, Chennai 600116, India e-mail: [email protected]
with irritability, diffuse erythematous rash all over the body and severe mottling. He required large volume of fluid for resuscitation and inotropes and ventilation. Chest radiograph showed left sided pneumonia with effusion and inter-costal drainage was done. Laboratory examination showed decreased total leucocyte counts (1,750 cells/cu mm), elevated renal and liver parameters and altered coagulation profile. Toxic Shock syndrome was suspected due to the rapid course, rash and multi-organ dysfunction. Antibiotics and intravenous immunoglobulin (IVIG) were given. Pleural fluid and blood cultures grew Streptococcus pyogenes. He developed Rhabdomyolysis with myoglobinuria and grossly elevated CPK (2,38,400 u/L). Acute Kidney Injury (AKI) worsened and Renal Replacement Therapy (RRT) was started. He eventually succumbed to the Multi-Organ Dysfunction syndrome (MODS) and coagulopathy. Case 2 A 16-y-old girl, a known case of Juvenile Idiopathic Arthritis on Etanercept, got admitted with fever and joint pain for 4 wk. She had vomiting and swelling of the right thigh since 2 d prior to admission. She had undergone branding for arthritis. She was in compensated shock with diffuse erythema over the body, cellulitis of right thigh and arthritis right knee. She developed hypotension within 4 h and was resuscitated appropriately. She had elevated liver enzymes and renal parameters. Fasciotomy done showed subcutaneous tissue necrosis. Blood cultures grew Streptococcus mitis. As she developed brainstem dysfunction, IVIG and RRT were deferred. She succumbed to the illness after 2 d.
Discussion Toxic shock syndrome (TSS) is a multisystem disease caused by toxin producing strains of Staphylococcus/Streptococcus.
Indian J Pediatr
Streptococcal M types 1, 3, 12, and 28 have been the most common isolates from patients with shock and multiorgan failure [1]. Group A streptococcus (e.g., Streptococcus pyogenes), an aerobic gram-positive coccus, enters the body via skin, usually following trivial trauma or varicella [2]. GAS can cause pharyngitis, soft tissue infections and bacteremia. It is more common in children under 10 y [3]. TSS usually presents with fever, chills, vomiting, loose stools, myalgia and diffuse macular erythroderma. The patient has hypotension at presentation or develops it within 4– 8 h. Some degree of renal dysfunction is known to precede shock [1]. Incidence may vary from 0.7 to 4.16/1,00,000 population [3]. Specific diagnostic criteria are listed below. Diagnostic Criteria for Streptococcal TSS (CDC 2010) [4] & &
Hypotension- Systolic blood pressure less than the fifth percentile by age for children aged less than 16 y. Multi-organ involvement characterized by two or more of the following: – – – – – –
&
Renal impairment: Creatinine greater than or equal to twice the upper limit of normal for age. Coagulopathy: Platelets less than or equal to 100,000/mm3 (less than or equal to 100×106 /L) or disseminated intravascular coagulation. Liver involvement: Alanine aminotransferase, Aspartate amino-transferase or total bilirubin levels greater than or equal to twice the upper limit of normal. Acute respiratory distress syndrome A generalized erythematous macular rash that may desquamate. Soft-tissue necrosis, including necrotizing fasciitis or myositis, or gangrene.
Laboratory criteria for diagnosis – Isolation of group A Streptococcus from sterile site
Case Classification Probable A case that meets the clinical case definition in the absence of another identified etiology for the illness and with isolation of group A Streptococcus from a non-sterile site. Confirmed A case that meets the clinical case definition and with isolation of group A Streptococcus from a normally sterile site (e.g., blood or cerebrospinal fluid or less commonly, joint, pleural, or pericardial fluid). Streptococcal TSS is caused by super-antigen toxin mediated injury [1]. Super antigens do not require processing by antigen dependent cells and cause non-specific binding of Major Histo-compatibility Complex (MHC) class II to T-cell receptors resulting in polyclonal T-cell activation. The
resultant cytokine storm causes the multi-system involvement [1]. Treatment includes rapid resuscitation with fluids, vasoactive agents and treatment for MODS, including dialysis for renal failure. Source control should be done early. Antibiotic therapy should include Clindamycin in addition to betalactams. Clindamycin’s action does not depend on inoculum size, is a potent suppressor of bacterial toxin synthesis, facilitates phagocytosis and has a longer post-antibiotic effect than beta-lactams. Penicillin can fail when microbiological load is large [1, 3]. Although IVIG has been used early in Streptococcal TSS its role has not been firmly established [5]. RRT has been found to be useful by removing streptococcal exotoxins and inflammatory mediators [6]. Mortality rates are 30–70 % despite adequate intensive care [7]. Differential diagnoses include Staphylococcal Toxic Shock syndrome, Gram-negative septic shock and Severe Dengue. In a multi-centric, retrospective study of children in Spain all patients developed shock and variable organ dysfunction. The median PICU stay was 7 d (0–41). 65.8 % of patients survived, 26.8 % with sequelae. The cause of death was refractory shock and multi-organ failure [8]. Toxic Shock syndrome requires early identification, aggressive management with fluids, antibiotics and source control. Contributions All the authors were involved in case management. VK wrote the initial draft and shall act as the guarantor. KP helped in draft writing. SS and RPS gave intellectual inputs in case management and edited the draft. All authors approved the final draft. Conflict of Interest None. Role of Funding Source None.
References 1. Stevens DL. Streptococcal toxic-shock syndrome: Spectrum of disease, pathogenesis, and new concepts in treatment. Emerg Infect Dis. 1995;1:69–78. 2. Abuhammour W, Hasan RA, Unuvar E. Group A beta-hemolytic streptococcal bacteremia. Indian J Pediatr. 2004;71:915–9. 3. Morales MV, Navarro CJS, Lletí MS, Alonso MM, Bellés CP, Aldeguer JL, et al. Group A streptococcal bacteremia: Outcome and prognostic factors. Rev Esp Quimioter. 2006;19:367–75. 4. Streptococcal Toxic Shock Syndrome (STSS). CDC Case definition 2010. Available from:http://wwwn.cdc.gov/NNDSS/script/casedef. aspx?CondYrID=858&DatePub=1/1/2010%2012:00:00%20AM. Accessed on 06/08/2013. 5. Shah SS, Hall M, Shrivastava R, Subramony A, Levin JE. Intravenous immunoglobulin in children with streptococcal toxic shock syndrome. Clin Infect Dis. 2009;49:1369–76. 6. Wiles 3rd CE, Reynolds HN, Bar-Lavie Y. Flush resuscitation for group A streptococcus toxic shock : A possible role for continuous renal resuscitation therapy and plasmapheresis. Md Med J. 1998;47: 188–90.
Indian J Pediatr 7. Demers B, Simor AE, Velland H, Schlievert PM, Byrne S, Jamieson F, et al. Severe invasive group A streptococcal infections in Ontario, Canada: 1987–1991. Clin Infect Dis. 1993;16:792–800. discussion 801–2.
8. Rodríguez-Nuñez A, Dosil-Gallardo S, Jordan I. Clinical characteristics of children with group A streptococcal toxic shock syndrome admitted to pediatric intensive care units. Eur J Pediatr. 2011;170: 639–44.
CLINICAL BRIEF
Streptococcal Toxic Shock Syndrome Vidya Krishna & Shuba Sankaranarayan & Rajakumar Padur Sivaraman & Krithika Prabaharan
Received: 8 July 2013 / Accepted: 10 October 2013 # Dr. K C Chaudhuri Foundation 2013
Abstract Streptococcal Toxic Shock syndrome (STSS) is a serious complication caused by exotoxins of Group A Streptococcus (GAS). It presents with fulminant shock and rash, is rapidly progressive with Multi-Organ Dysfunction Syndrome (MODS) and requires aggressive therapy with fluids, antibiotics and source control. Keywords Streptococcal Toxic Shock Syndrome . Group A Streptoccus . Multi Organ Dysfunction Syndrome . Renal Replacement Therapy
Introduction GAS infections can range from cellulitis to necrotizing fasciitis, myositis, empyema, bacteremia and endocarditis. A fatal complication is Toxic- shock syndrome, an exotoxin mediated illness presenting with rash, shock and multi-organ dysfunction. Incidence is especially higher in North America and Europe [1]. The authors report two cases of Streptococcal Toxic Shock syndrome (STSS) encountered in their setting and discuss their presentations, management and outcomes.
Case Reports Case 1 A 5-y-old boy presented with fever for 3 d, cough, respiratory distress and loose stools for 1 d. He was in compensated shock
V. Krishna : S. Sankaranarayan (*) : R. P. Sivaraman : K. Prabaharan Department of Pediatrics, Sri Ramachandra Medical College and Hospital, Porur, Chennai 600116, India e-mail: [email protected]
with irritability, diffuse erythematous rash all over the body and severe mottling. He required large volume of fluid for resuscitation and inotropes and ventilation. Chest radiograph showed left sided pneumonia with effusion and inter-costal drainage was done. Laboratory examination showed decreased total leucocyte counts (1,750 cells/cu mm), elevated renal and liver parameters and altered coagulation profile. Toxic Shock syndrome was suspected due to the rapid course, rash and multi-organ dysfunction. Antibiotics and intravenous immunoglobulin (IVIG) were given. Pleural fluid and blood cultures grew Streptococcus pyogenes. He developed Rhabdomyolysis with myoglobinuria and grossly elevated CPK (2,38,400 u/L). Acute Kidney Injury (AKI) worsened and Renal Replacement Therapy (RRT) was started. He eventually succumbed to the Multi-Organ Dysfunction syndrome (MODS) and coagulopathy. Case 2 A 16-y-old girl, a known case of Juvenile Idiopathic Arthritis on Etanercept, got admitted with fever and joint pain for 4 wk. She had vomiting and swelling of the right thigh since 2 d prior to admission. She had undergone branding for arthritis. She was in compensated shock with diffuse erythema over the body, cellulitis of right thigh and arthritis right knee. She developed hypotension within 4 h and was resuscitated appropriately. She had elevated liver enzymes and renal parameters. Fasciotomy done showed subcutaneous tissue necrosis. Blood cultures grew Streptococcus mitis. As she developed brainstem dysfunction, IVIG and RRT were deferred. She succumbed to the illness after 2 d.
Discussion Toxic shock syndrome (TSS) is a multisystem disease caused by toxin producing strains of Staphylococcus/Streptococcus.
Indian J Pediatr
Streptococcal M types 1, 3, 12, and 28 have been the most common isolates from patients with shock and multiorgan failure [1]. Group A streptococcus (e.g., Streptococcus pyogenes), an aerobic gram-positive coccus, enters the body via skin, usually following trivial trauma or varicella [2]. GAS can cause pharyngitis, soft tissue infections and bacteremia. It is more common in children under 10 y [3]. TSS usually presents with fever, chills, vomiting, loose stools, myalgia and diffuse macular erythroderma. The patient has hypotension at presentation or develops it within 4– 8 h. Some degree of renal dysfunction is known to precede shock [1]. Incidence may vary from 0.7 to 4.16/1,00,000 population [3]. Specific diagnostic criteria are listed below. Diagnostic Criteria for Streptococcal TSS (CDC 2010) [4] & &
Hypotension- Systolic blood pressure less than the fifth percentile by age for children aged less than 16 y. Multi-organ involvement characterized by two or more of the following: – – – – – –
&
Renal impairment: Creatinine greater than or equal to twice the upper limit of normal for age. Coagulopathy: Platelets less than or equal to 100,000/mm3 (less than or equal to 100×106 /L) or disseminated intravascular coagulation. Liver involvement: Alanine aminotransferase, Aspartate amino-transferase or total bilirubin levels greater than or equal to twice the upper limit of normal. Acute respiratory distress syndrome A generalized erythematous macular rash that may desquamate. Soft-tissue necrosis, including necrotizing fasciitis or myositis, or gangrene.
Laboratory criteria for diagnosis – Isolation of group A Streptococcus from sterile site
Case Classification Probable A case that meets the clinical case definition in the absence of another identified etiology for the illness and with isolation of group A Streptococcus from a non-sterile site. Confirmed A case that meets the clinical case definition and with isolation of group A Streptococcus from a normally sterile site (e.g., blood or cerebrospinal fluid or less commonly, joint, pleural, or pericardial fluid). Streptococcal TSS is caused by super-antigen toxin mediated injury [1]. Super antigens do not require processing by antigen dependent cells and cause non-specific binding of Major Histo-compatibility Complex (MHC) class II to T-cell receptors resulting in polyclonal T-cell activation. The
resultant cytokine storm causes the multi-system involvement [1]. Treatment includes rapid resuscitation with fluids, vasoactive agents and treatment for MODS, including dialysis for renal failure. Source control should be done early. Antibiotic therapy should include Clindamycin in addition to betalactams. Clindamycin’s action does not depend on inoculum size, is a potent suppressor of bacterial toxin synthesis, facilitates phagocytosis and has a longer post-antibiotic effect than beta-lactams. Penicillin can fail when microbiological load is large [1, 3]. Although IVIG has been used early in Streptococcal TSS its role has not been firmly established [5]. RRT has been found to be useful by removing streptococcal exotoxins and inflammatory mediators [6]. Mortality rates are 30–70 % despite adequate intensive care [7]. Differential diagnoses include Staphylococcal Toxic Shock syndrome, Gram-negative septic shock and Severe Dengue. In a multi-centric, retrospective study of children in Spain all patients developed shock and variable organ dysfunction. The median PICU stay was 7 d (0–41). 65.8 % of patients survived, 26.8 % with sequelae. The cause of death was refractory shock and multi-organ failure [8]. Toxic Shock syndrome requires early identification, aggressive management with fluids, antibiotics and source control. Contributions All the authors were involved in case management. VK wrote the initial draft and shall act as the guarantor. KP helped in draft writing. SS and RPS gave intellectual inputs in case management and edited the draft. All authors approved the final draft. Conflict of Interest None. Role of Funding Source None.
References 1. Stevens DL. Streptococcal toxic-shock syndrome: Spectrum of disease, pathogenesis, and new concepts in treatment. Emerg Infect Dis. 1995;1:69–78. 2. Abuhammour W, Hasan RA, Unuvar E. Group A beta-hemolytic streptococcal bacteremia. Indian J Pediatr. 2004;71:915–9. 3. Morales MV, Navarro CJS, Lletí MS, Alonso MM, Bellés CP, Aldeguer JL, et al. Group A streptococcal bacteremia: Outcome and prognostic factors. Rev Esp Quimioter. 2006;19:367–75. 4. Streptococcal Toxic Shock Syndrome (STSS). CDC Case definition 2010. Available from:http://wwwn.cdc.gov/NNDSS/script/casedef. aspx?CondYrID=858&DatePub=1/1/2010%2012:00:00%20AM. Accessed on 06/08/2013. 5. Shah SS, Hall M, Shrivastava R, Subramony A, Levin JE. Intravenous immunoglobulin in children with streptococcal toxic shock syndrome. Clin Infect Dis. 2009;49:1369–76. 6. Wiles 3rd CE, Reynolds HN, Bar-Lavie Y. Flush resuscitation for group A streptococcus toxic shock : A possible role for continuous renal resuscitation therapy and plasmapheresis. Md Med J. 1998;47: 188–90.
Indian J Pediatr 7. Demers B, Simor AE, Velland H, Schlievert PM, Byrne S, Jamieson F, et al. Severe invasive group A streptococcal infections in Ontario, Canada: 1987–1991. Clin Infect Dis. 1993;16:792–800. discussion 801–2.
8. Rodríguez-Nuñez A, Dosil-Gallardo S, Jordan I. Clinical characteristics of children with group A streptococcal toxic shock syndrome admitted to pediatric intensive care units. Eur J Pediatr. 2011;170: 639–44.
