Streptococcal Toxic Shock Syndrome

Streptococcal toxic shock syndrome is shock and multi-organ failure caused by invasive infection with group A Streptococcus (Streptococcus pyogenes), driven by superantigen exotoxins (SpeA, SpeB, SpeC) and by the M protein. It is often linked to necrotising soft tissue infection.

Epidemiology. Invasive group A streptococcal disease occurs in about 3 to 4 cases in 100,000 each year, and toxic shock syndrome complicates up to 10 to 15%. Mortality is 30 to 60%.

Causes and associations. Skin and soft tissue infection, often after minor trauma, surgery, varicella, injection drug use or childbirth. Others are pharyngitis, pneumonia with empyema, puerperal sepsis and bone or joint infection. Risk factors include diabetes, alcohol use, immunosuppression, age extremes, and recent NSAID use.

Pathophysiology. Exotoxins act as superantigens, activating up to 20% of T cells, with cytokine storm, vasodilation and capillary leak. Tissue destruction occurs with necrotising fasciitis through proteases and streptolysins.

Presentation is severe pain (often out of proportion) at a site of soft tissue injury, fever, hypotension, tachycardia, confusion, renal failure, ARDS, coagulopathy, liver dysfunction, and a diffuse macular rash with desquamation in about 10% or fewer. Signs of necrotising infection are tense swelling, bullae, skin discolouration, crepitus and anaesthesia of the skin.

Red flags.

• Pain out of proportion to appearance, or rapidly spreading erythema.
• Hypotension with soft tissue infection, bullae or skin necrosis.
• Recent varicella, childbirth or surgery with fever.

Blood cultures (positive in about 60%), cultures of tissue, wound, and throat, rapid antigen test for group A streptococcus, creatine kinase, creatinine, liver tests, lactate, coagulation, platelets, blood gas and CT or MRI of the affected area (but do not delay surgery). Operative findings of fascial necrosis confirm necrotising infection.

Differential diagnosis. Staphylococcal toxic shock syndrome, cellulitis, gas gangrene, meningococcaemia, leptospirosis, drug reaction and other septic shock.

Urgent source control. Surgical exploration and wide debridement for suspected necrotising infection without waiting for imaging, with repeat debridement every 24 to 48 hours as needed.

Antibiotics (within 1 hour).

• Benzylpenicillin 2.4 g (4 million units) IV every 4 hours (adjust in severe renal impairment).
• Clindamycin 900 mg IV every 8 hours for toxin suppression (600 to 900 mg).
• Add vancomycin 25 to 30 mg/kg IV loading then 15 to 20 mg/kg every 8 to 12 hours (monitor levels), or meropenem 1 g IV every 8 hours, until the organism is known and polymicrobial or methicillin resistant infection is excluded.
• Continue until no further debridement is needed, the patient is afebrile and well for 48 to 72 hours, and usually for a minimum of 10 to 14 days.

Immunoglobulin. Intravenous immunoglobulin 1 g/kg on day 1 followed by 0.5 g/kg on days 2 and 3 (or 2 g/kg once), for shock or necrotising infection, with monitoring of renal function.

Supportive care. Early noradrenaline 0.05 to 1 microgram/kg/min with fluid resuscitation (large volumes because of capillary leak), ventilation, renal replacement therapy and treatment of coagulopathy. Corticosteroid (hydrocortisone 50 mg IV every 6 hours) only for refractory shock.

Avoid NSAIDs.

Hyperbaric oxygen. Not shown to help and must not delay surgery.

Contacts. Notify public health, and assess household contacts for antibiotic prophylaxis.

Monitoring. Haemodynamics, wound, creatinine, creatine kinase, platelets, coagulation, lactate and blood cultures.

Referral and escalation. Surgery, intensive care and infection specialists at once.

Special groups. In postpartum infection, evacuate the uterus or remove infected tissue. In pregnancy, treat early with obstetric input. In children, weight based dosing and exclude varicella.