What is the role of Intravenous Immunoglobulin (IVIG) in the treatment of toxic streptococcal infections?

From the Guidelines

Intravenous Immunoglobulin (IVIG) may be considered in the treatment of toxic streptococcal infections, particularly in cases of necrotizing infections caused by Group A Streptococcus (GAS) or streptococcal toxic shock syndrome (STSS).

Role of IVIG in Toxic Streptococcal Infections

• IVIG therapy has been postulated to improve outcomes in a selected population of patients with necrotizing soft-tissue infections (NSTIs) 1.
• The efficacy and safety of high-dose IVIG as adjunctive therapy in STSS were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial, which found a significant decrease in the sepsis-related organ failure assessment score and an increase in plasma neutralizing activity against superantigens expressed by autologous isolates in the IVIG group 1.
• Other prospective studies have also demonstrated the role of IVIG in improving survival in STSS 1.

Evidence and Recommendations

• The 2018 WSES/SIS-E consensus conference recommends considering IVIG therapy in patients with necrotizing infections caused by GAS (recommendation 2B) 1.
• A Cochrane review on intervention for NSTIs found no clear difference between IVIG and placebo in terms of mortality within 30 days or serious adverse events experienced in the ICU 1.
• The Surviving Sepsis Campaign International Guidelines for the management of septic shock and sepsis-associated organ dysfunction in children suggest that polyclonal IVIG may have clinical utility in patients with toxic shock syndrome, especially those with streptococcal etiology 1.

Clinical Utility and Potential Benefits

• IVIG therapy may be beneficial in boosting passive immunity through neutralization of bacterial toxins, promoting opsonization of bacteria, and inhibition of immune cell proliferation and inflammatory mediators 1.
• However, the true biologic activity of IVIG is not clear, and there are no high-quality studies of IVIG in critically ill children with sepsis 1.

From the Research

Role of IVIG in Toxic Streptococcal Infections

• IVIG has been used as an adjunct therapy in the treatment of streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis, with some studies suggesting a beneficial effect on mortality 2, 3, 4.
• The mechanism of action of IVIG in STSS is thought to be related to its ability to neutralize superantigen toxins and modulate the inflammatory response 5, 4.
• Several studies have reported improved survival rates in patients with STSS who received IVIG therapy compared to those who did not 3, 4.
• A comparative observational study found that IVIG therapy was associated with a significantly improved 28-day survival rate in patients with STSS, with an odds ratio of 5.6 (P = .030) 3.
• Another study found that IVIG therapy enhanced the ability of patient plasma to neutralize bacterial mitogenicity and reduced T cell production of interleukin-6 and tumor necrosis factor alpha 4.
• However, the use of IVIG in STSS is not without controversy, and its definitive role remains unclear due to the lack of high-level evidence 2.
• Adverse reactions to IVIG are generally mild and transitory, and occur during or immediately after drug infusion 2.

Clinical Evidence

• A study published in 2014 found that IVIG therapy was associated with improved survival in patients with STSS, with a 28-day survival rate of 67% compared to 34% in patients who did not receive IVIG therapy (P = .02) 4.
• A study published in 2006 found that IVIG neutralized superantigenicity of S. pyogenes in vitro and enhanced bacterial killing in a whole blood assay 5.
• A case report published in 1992 described a patient with toxic strep syndrome who experienced dramatic clinical improvement after receiving IVIG therapy 6.

Limitations

• The evidence for the use of IVIG in STSS is largely based on observational studies and case reports, and there is a need for randomized controlled trials to confirm its efficacy 2, 3, 4.
• The optimal dose and duration of IVIG therapy in STSS are unclear, and further studies are needed to determine the most effective treatment regimen 2, 3, 4.