A 57-year-old man with diabetes presents with toe pain. He states that it started two days before with a blister on his toe that he thinks he acquired from boots that were too tight. He has increased swelling and drainage from the toe with pain “crawling into my leg.”
He is febrile, hypotensive, and ill-appearing. What condition are you concerned about, and how would you evaluate and treat this patient's condition? See p. 12.
Necrotizing fasciitis is a rare infection (approximately 3.5 cases per 100,000) characterized by aggressive destruction of deep space fascia and fat. (Emerg Infect Dis 1995;1:69.) It is known in the lay press as “flesh-eating bacteria syndrome,” but this is a misnomer because bacterial pathogens do not literally consume the tissue, despite the fact that aggressive devitalization of previously healthy tissue occurs. Prior to early and aggressive antibiotic and surgical treatment, mortality rates were as high as 25 percent to 50 percent. (Minerva Chir 2010;65:347.)
Necrotizing infections of the skin and fascia are a family of conditions that share clinical features but not surgical pathology characteristics. (Clin Infect Dis 2007;44:705.) They are loosely categorized as necrotizing cellulitis, myositis, and fasciitis. Although the pathophysiology of tissue destruction may vary, it is thought that exposure to “bacterial superantigens” result in hyperactive cytokine production and subsequent aggressive and extensive tissue destruction, blood vessel thrombosis, bacterial spread along fascial plans, systemic symptoms (fever, hypotensive, tachycardia), organ failure, and shock. (Virchows Arch 2009;455:87.) Patients with immunocompromising states (cancer, organ transplants, HIV, neutropenia), diabetes, peripheral vascular disease, obesity, and intravenous drug use are predisposed to this condition.
Clinical features of necrotizing infections include tense tender (54%), indurated (66%), edematous (80%), fluctuant (35%) skin, pain out of proportion to examination, subcutaneous gas/crepitous (10%), hemorrhagic blisters/bullae (11%), and skin necrosis (23%). (Intern Med 2010;49:1051; Clin Infect Dis 2007;44:705.) By the time bullae formation occurs, significant deep tissue devitalization has occurred, and patients typically have abnormal vital signs (LR 3.5 necrotizing fasciitis vs. nonsevere soft tissue infection). (Intern Med 2010;49:1051.) Involved tissue may be dusky, purplish, pale, friable, black, and gangrenous. Cutaneous tissue may not be involved at the time of presentation, despite significant subcutaneous involvement. Pain out of proportion to exam of the soft tissue is an early indicator of likely severe deep space infection. Diabetic patients, however, may have limited pain because of peripheral neuropathy, making clinical recognition very challenging.
It is thought that the infection starts with an inciting trauma to the skin, which can be on the continuum from major (surgery) to incidental to idioopathic. Nearly any soft tissue of the body can be affected, but it is more common on the extremities (36%-55%), trunk (18%-64%) and perineum (36%). (Intern Med 2010;49:1051.) Necrotizing infections in certain anatomical regions are referred to as distinct syndromes including Ludwig's angina (submandibular and sublingual spaces) and Fournier's gangrene (perineal area).
Necrotizing fasciitis is categorized as either Type I (polymicrobial) or Type II (monomicrobial) infection. Type I infections tend to occur after surgical procedures in immunocompromised patients, and are a mixed aerobic and anaerobic infection of pathogens including Staphylococcus aureus, Vibrio vulnificus, Clostridium perfringens, Bacteroides fragilis, Streptococci, Enterococci, Escherichia coli, Peptostreptococcus,Proteus, Pseudomonas, and Klebsiella, among others, with an average of five isolates. While Type II infections were predominantly Group A Streptococcus (Streptococcus pyogenes), cases of methicillin-resistant Staphylococcus aureus (MRSA) (J Burn Care Res 2008;29:790) and very aggressive gram-negative monobacterial pathogens (BMC Infect Dis 2011;11:5) have been reported. Type II infections typically occur in previously healthy individuals of any age group (post-childbirth, varicella infections, burns or penetrating injuries, or via hematogenous spread of pharyngeal infection). Most cases (80%) are community acquired. (Clin Infect Dis 2007;45:450; Lancet 1994;344:1111.)
Laboratory findings are typically nonspecific and consistent with severe systemic infection, including leukcytosis with a left shift, coagulopathy, elevated serum lactate, and creatine kinase. In 2004, the LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score was introduced to help distinguish necrotizing fasciitis from other soft tissue infections. (Crit Care Med 2004;32:1535; Opin Infect Dis 2005;18:101.)
- Serum C-reactive protein $150 mg/L (4 points).
- White blood cell count 15,000 to 25,000/microL (1 point) or >25,000/microL (2 points).
- Hemoglobin 11.0 to 13.5 g/dL (1 point) or #11 g/dL (2 points).
- Serum sodium < 135 meq/L (2 points).
- Serum creatinine > 1.6 mg/dL (141 mmol/L) (2 points)
- Serum glucose > 180 mg/dL (10 mmol/L) (1 point)
Total possible score is 13 points. A score of 8 or higher is highly predictive (>75%) for necrotizing fasciitis, and a score of 5 or 6 or higher is suspicion. (Ann Dermatol Venereol 2010;137:5; ANZ J Surg 2008;78:968; Intern Med 2010;49:1051.) But the score has been found to be sensitive only for severe infections, and requires assignment of significant (but not quantified) clinical pretest probability for necrotizing fasciitis.
The presence of gas along the facial plan can be visualized by soft tissue radiographs or noncontrast CT scans (demonstrate necrosis with asymmetric fascial thickening), which is highly specific but not sensitive. Radiographs are notoriously falsely negative for necrotizing fasciitis. MRI and local biopsy are more time-consuming (biopsy), more costly (MRI), and overestimate tissue involvement (MRI), and thus are utilized less commonly as a diagnostic tool. (Intern Med 2010;49:1051.) Soft tissue edema is more common, especially early in the disease progression, and intraoperative gross and tissue pathogen culture diagnosis is sometimes required. The differential diagnosis of necrotizing fasciitis includes erysipelas, cellulitis, gas gangrene, pyomyositis, and myositis.
The mainstay of treatment is early and aggressive antibiotic therapy and surgical debridement. Early surgical exploration should not be delayed by imaging studies if there is a high degree of suspicion for necrotizing fasciitis, as delay of surgery for even hours can negatively affect the risk of mortality. (Ann Surg 1995;221:558; discussion: 563.) Standard resuscitation protocols should be followed in the hemodynamically unstable patient. Broad coverage empiric antibiotics should cover aerobes and anaerobe pathogens. Gram-negative coverage should be expanded for recently hospitalized patients. Bacteremia is present 20 percent to 60 percent of the time, but serum or blister aspiration pathogens may not be the same as tissue pathogens, so care should be taken when tailoring antibiotics based on these results. (J Bone Joint Surg Am 2003;85-A:1454.)
Guidelines for treatment are available from the Infectious Disease Society of America. The use of intravenous immunoglobulin G (IVIG), hyperbaric oxygen, and vacuum-assisted closure have also been discussed in the literature, but are not currently considered standard of care, although they may be appropriate in certain patients at high risk of death. (Minerva Chir 2010;65:347.) There have been no studies to date concerning the role of post-exposure group A Streptococcus necrotizing fasciitis prophylaxis with penicillin.
Patients should be admitted to critical care after operative intervention for close monitoring because many require surgical re-exploration and debridement within 12 to 24 hours (Ann Surg 1987;206:661), with patients requiring an average of 33 debridements and grafting procedures. (Cleve Clin J Med 1998;65:241.) Early and aggressive antibiotic therapy and surgical debridement has decreased the mortality rate to 10 percent to 16 percent (Minerva Chir 2010; 65:347), but as high as 25 percent in other recent studies. (Intern Med 2010;49:1051.)
This patient had emergent surgical exploration with amputation of the lower leg. He survived to discharge.
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