What causes necrotizing fasciitis, including its pathophysiology, particularly in immunocompromised patients or those with chronic conditions like diabetes?

Causes and Pathophysiology of Necrotizing Fasciitis

Necrotizing fasciitis is caused by bacterial invasion of subcutaneous tissues and fascia, with polymicrobial infections (Type I) involving mixed aerobic and anaerobic bowel flora, and monomicrobial infections (Type II) predominantly caused by Streptococcus pyogenes, particularly affecting immunocompromised patients including those with diabetes, HIV/AIDS, and cancer. 1

Bacterial Etiology

Type I: Polymicrobial Necrotizing Fasciitis

• Polymicrobial infections involve up to 15 different organisms with an average of 5 pathogens per wound, predominantly originating from bowel flora including coliforms and anaerobic bacteria. 2
• These infections occur in four specific clinical settings: perianal abscesses, penetrating abdominal trauma or bowel surgery, decubitus ulcers, and injection sites in illicit drug users. 2
• Streptococci and enterobacteriaceae are the most common isolates in polymicrobial infections. 3
• Polymicrobial synergistic infection represents the most common cause, accounting for approximately 54% of cases. 3

Type II: Monomicrobial Necrotizing Fasciitis

• Streptococcus pyogenes (Group A Streptococcus) is the predominant pathogen in monomicrobial infections, particularly arising after varicella or trivial injuries such as minor scratches and insect bites. 2
• Group A streptococcal necrotizing fasciitis carries mortality rates of 30-70% when accompanied by hypotension and organ failure. 2
• Staphylococcus aureus (including MRSA) occurs less frequently as a primary organism but can occur simultaneously with streptococci. 2
• Other monomicrobial causes include Vibrio vulnificus (water exposure), Aeromonas hydrophila (water-related exposures), and anaerobic streptococci (Peptostreptococcus species). 4, 2

Type III: Rare Gram-Negative Infections

• Type III necrotizing fasciitis is caused by Gram-negative strains such as Clostridium difficile or Vibrio species. 5

Pathophysiology

The infection spreads along fascial planes with obliterative endarteritis causing vessel thrombosis and profound tissue ischemia, beginning at the superficial fascia along subcutaneous soft tissues and progressing into deeper fascial layers between muscle planes. 6, 4

Mechanism of Tissue Destruction

• The pathophysiology begins with localized infection allowing entrance of normally commensal bacteria into subcutaneous tissues. 1
• An inflammatory response results in obliterative endarteritis with thrombosis of surrounding vessels and critical reduction in blood flow. 1
• The infection causes necrosis by microvascular occlusion along fascial tissues, with fascial necrosis typically preceding muscle and skin involvement. 4, 7
• This process leads to soft tissue inflammation and liquefactive necrosis. 4
• Violaceous/mottled purpura and necrotic patches indicate vascular thrombosis and tissue necrosis. 6

Risk Factors and Predisposing Conditions

Diabetes Mellitus: The Primary Risk Factor

• Diabetes mellitus is the most frequently associated comorbidity, present in 70.8% of cases, representing the single most important risk factor. 1, 3
• Diabetic patients often present with atypical symptomatology due to neuropathy and immunocompromise, leading to high rates of misdiagnosis in emergency departments. 5
• In diabetic patients, soft tissue gas may not be present or detectable early in the disease process. 4

Immunocompromised States

• Conditions resulting in impaired host resistance from reduced cellular immunity increase risk, including alcoholism, HIV/AIDS, leukemia, and other malignancies. 1
• Immune-compromised patients present with atypical symptomatology, explaining the high percentage of misdiagnosed cases. 5

Other Risk Factors

• Advanced age and two or more associated comorbidities adversely affect outcomes. 3
• Penetrating trauma, crush injuries with interruption of blood supply, and surgical procedures involving the bowel are predisposing factors. 4
• Peripheral vascular disease, decubitus ulcers, and spontaneous mucosal tears of the gastrointestinal or genitourinary tract (Fournier gangrene) increase risk. 4

Critical Diagnostic Considerations

Microbiological Diagnosis

• Surface cultures of wounds are not valuable as they represent colonizing microbes rather than the underlying etiologic agent; tissue biopsies from deep tissues after thorough debridement or specimens obtained during operation provide definitive bacteriologic diagnosis. 2
• Gram stain of deep tissue exudate provides early clues to the causative pathogen, with gram-positive cocci in chains suggesting Streptococcus organisms. 1, 2

Clinical Pitfalls

• The paucity of cutaneous findings early in the course of disease makes diagnosis difficult, with only 15% of patients receiving the correct diagnosis at admission. 3
• Preadmission treatment with antibiotics modifies the initial clinical picture and often masks the severity of underlying infection. 3
• Pain disproportionate to physical findings is a critical early sign that distinguishes necrotizing fasciitis from simple cellulitis. 6