What is the role of Intravenous Immunoglobulin (IVIG) in the treatment of severe sepsis and perineal fasciitis?

Role of IVIG in Severe Sepsis and Perineal Fasciitis

IVIG therapy should be considered as an adjunctive treatment specifically for necrotizing fasciitis caused by Group A Streptococcus (GAS), especially when associated with streptococcal toxic shock syndrome (STSS), but is not recommended for routine use in all cases of severe sepsis or septic shock. 1

Initial Management Priorities

1. Early Aggressive Resuscitation

• Immediate fluid resuscitation with balanced/buffered crystalloids (at least 30 mL/kg within first 3 hours)
• Vasopressor support with norepinephrine as first-line agent targeting MAP ≥65 mmHg
• Early blood cultures before antibiotic administration (but do not delay antibiotics) 1, 2

2. Source Control

• Urgent surgical debridement is paramount and should never be delayed
• Radical debridement of all involved tissues is essential for successful management
• Multiple surgical interventions are often required (typically >4 procedures) 1, 3
• Consider diverting colostomy in perineal cases to prevent fecal contamination 4, 3

3. Antimicrobial Therapy

• Administer broad-spectrum antibiotics within 1 hour of recognition for septic shock 2
• Include clindamycin in the regimen for suspected toxic shock syndromes to inhibit toxin production 1
• Tailor antibiotics based on culture results and local resistance patterns

IVIG Therapy Decision Algorithm

When to Consider IVIG:

1. Confirmed or strongly suspected GAS infection with one of the following:
   • Streptococcal toxic shock syndrome (STSS)
   • Rapidly progressive necrotizing fasciitis
   • Refractory hypotension despite adequate fluid resuscitation and vasopressors 1

When NOT to Use IVIG:

• Routine sepsis or septic shock without GAS involvement
• Stable patients responding to standard therapy
• Non-streptococcal necrotizing infections 1

Dosing and Administration:

• High-dose IVIG: 25 g/day for three consecutive days 1
• Administer early in the disease course (within first 48 hours) 1, 5

Evidence Analysis for IVIG Use

Supporting Evidence:

• Small randomized trials showed significant decrease in sepsis-related organ failure assessment scores at days 2 (p=0.02) and 3 (p=0.04) with IVIG use 1
• Increased plasma neutralizing activity against superantigens was noted after IVIG treatment (p=0.03) 1
• Case reports demonstrate successful outcomes when IVIG is used as adjunctive therapy in STSS with necrotizing fasciitis 6, 5

Contradictory Evidence:

• A 2017 retrospective study of 4,127 cases found no mortality difference between matched IVIG and non-IVIG groups (27.3% vs 23.6%; adjusted HR 1.00 [95% CI, 0.55-1.83]) 1
• A Cochrane review found no clear difference between IVIG and placebo in terms of 30-day mortality (RR=1.17; 95% CI, 0.42-3.23) 1
• The Surviving Sepsis Campaign explicitly recommends against using IV immunoglobulins in adult patients with severe sepsis or septic shock (grade 2B) 1

Monitoring and Ongoing Management

• Reassess patient every 30-60 minutes during initial resuscitation 2
• Monitor for signs of clinical improvement:
  • Decreasing vasopressor requirements
  • Improving organ dysfunction
  • Decreasing lactate levels
• Continue surgical reassessment every 24-48 hours to evaluate need for additional debridement 3

Pitfalls and Caveats

• Delay in surgical debridement significantly increases mortality - never delay surgery while waiting for IVIG administration
• IVIG should be considered an adjunct, not a replacement for standard care (surgery, antibiotics, supportive care)
• The high cost of IVIG without definitive mortality benefit makes it difficult to recommend for all cases
• Perineal necrotizing fasciitis has a particularly high mortality (18-27%) and requires especially aggressive surgical management 4, 3
• Failure to include clindamycin in antibiotic regimens for suspected toxic shock can lead to continued toxin production despite bacterial killing

IVIG remains a therapy with mixed evidence but may benefit selected patients with GAS-related necrotizing infections and toxic shock syndrome. The decision to use IVIG should be made early in the course of illness for patients not responding to standard therapies.