Necrotizing Fasciitis

Necrotizing fasciitis, also known as flesh-eating disease, is a rapidly progressive bacterial infection of the subcutaneous tissue. Prompt recognition is potentially lifesaving, but early identification can be challenging given the lack of skin findings in the first 24 hours of infection. Therefore, the pediatrician needs a high index of suspicion.Necrotizing fasciitis is rare in children compared with adults. The incidence in children is 0.08 to 0.13 per 100,000 per year, with a case fatality of 10%, compared with 0.4 per 100,000 per year in adults, with fatality ranging from 25% to 75%. Males are affected slightly more commonly than females. Although it can affect any part of the body, most infections in children affect the trunk and lower extremities.A sudden onset of severe pain out of proportion to the cutaneous signs is the hallmark of necrotizing fasciitis. The infection typically spreads along the muscle fascia, with its relatively scant blood supply; the muscle tissue itself is frequently spared because of its generous blood supply. The course is often fulminant, as with the 17-year-old athletic teenager with underlying eczema seen in Fig A. He presented with right-sided chest pain, minimal chest wall swelling, and no skin changes. During the next 24 hours he developed toxic shock syndrome and later required multiple debridements and reconstructive surgeries over his chest and right upper and lower extremities. Tissue culture grew group A β-hemolytic streptococcus (Streptococcus pyogenes).Otherwise healthy, immunocompetent children often have a history of recent trauma, eczema, surgery, or varicella infection. Necrotizing fasciitis was commonly reported as a complication of varicella infection in the era of high prevalence of varicella. It also occurs after group A streptococcus (GAS) pharyngitis, with or without evidence of associated trauma or local infection. In addition, insect bites, perirectal abscesses, incarcerated hernias, and subcutaneous insulin injections are reported as predisposing factors. In neonates, necrotizing fasciitis can complicate omphalitis or circumcision. Nonsteroidal anti-inflammatory drugs have been implicated as a predisposing factor, although the association is controversial.Necrotizing fasciitis can be classified into 3 types based on the underlying infectious microbiology (Table). Type I, more common in adults, is the polymicrobial form and often occurs postoperatively or in patients with diabetes mellitus or peripheral vascular disease. Type II, the most common in children, is caused by infection with GAS, especially after skin breakdown. Type III, which is the rarest, results from infection with Vibrio species.The clinical manifestations typically occur 1 to 4 days after trauma. Children might even appear well at the initial presentation, although often they have significant fever. When associated with varicella infection, the findings usually manifest within 3 to 4 days after onset of the exanthem. Infants may present with profound irritability without localized skin involvement, requiring a careful physical examination for early recognition. Toddlers and young children might refuse to bear weight or move the affected extremity. Swelling of the soft tissue usually is noted, but erythema may be lacking. Feeling crepitus can serve as an important physical sign. The key discovery on examination is intense pain on manipulation of the involved site out of proportion to the cutaneous findings. Skin changes that occur during the subsequent 24 to 48 hours include blistering with bleb formation and a dusky appearance of the involved site (Fig C). Without adequate treatment, within 4 or 5 days, extension of the infection along fascial planes leads to necrosis of the superficial fascia and the deeper layers of the dermis. Destruction and thrombosis of the small blood vessels in the area lead to necrosis of the surrounding tissues. The extensive tissue damage often leads to systemic symptoms, including multiorgan failure and shock, signaling a poor prognosis.Recognition of toxic shock syndrome is crucial with necrotizing fasciitis because mortality of up to 60% is reported. The M protein is an important virulence determinant of GAS. Necrotizing infection caused by GAS strains with M types 1 and 3 are associated with toxic shock syndrome in approximately 50% of patients. Children with necrotizing fasciitis associated with streptococcal toxic shock syndrome often have nonspecific complaints of vomiting, diarrhea, and severe myalgias early in the course of infection. Renal and hepatic dysfunction occur typically, often with signs and symptoms of acute respiratory distress.During the past decade, GAS has been reported widely as the single pathogen in most cases of pediatric necrotizing fasciitis. Less commonly, a polymicrobial etiology has been noted, particularly in patients with so-called Fournier gangrene, or necrotizing fasciitis of the perineum. In these cases, Staphylococcus aureus, GAS, and 1 or more anaerobes, including Peptostreptococcus and Bacteroides fragilis, have been implicated. Necrotizing fasciitis caused by Pseudomonas aeruginosa or Clostridium septicum has been seen in neutropenic patients.Diagnosis can be challenging in the first 24 to 48 hours. The tip-off is pain out of proportion to the cutaneous findings. Plain radiographs usually are normal. Computed tomography scan is the initial imaging of choice. It delineates the extent of soft-tissue involvement. The most useful finding on a computed tomography scan is the presence of gas in the soft tissue (Figure B). Magnetic resonance imaging is the preferred technique to detect soft-tissue involvement, with visualization of soft-tissue edema infiltrating the fascial planes. Magnetic resonance imaging can demarcate different structures involved such as fascia, fat, muscle, and bone. However, surgical intervention should not be delayed while awaiting magnetic resonance imaging confirmation: if the index of suspicion for necrotizing fasciitis is high, immediate surgical exploration is appropriate. Laboratory findings suggestive of streptococcal toxic shock syndrome should be sought in any pediatric patient with fasciitis. Typically, the white blood cell count is normal, but most affected patients have a significant increase in immature neutrophils or bandemia greater than 50%. Electrolyte abnormalities such as hypoalbuminemia and hypocalcemia are common. Thrombocytopenia and evidence of coagulopathy are also seen. Laboratory findings associated with myocardial dysfunction, renal failure, and acute respiratory distress syndrome may develop during the first 48 to 72 hours. A microbiological diagnosis can be made by isolating the bacteria from the blood, tissue, or wound culture.Timely identification allows for early antibiotic treatment coupled with surgical intervention. Empirical treatment should include a broad spectrum penicillin, such as piperacillin-tazobactam, plus vancomycin for methicillin-resistant Staphylococcus aureus and clindamycin for its potential antitoxin effect. Surgical debridement of necrotic tissue is the key to managing necrotizing fasciitis. Increase in mortality has been reported when debridement is delayed for more than 24 hours. In addition to prompt administration of appropriate parenteral antimicrobial therapy, careful management of fluids, attention to pain control, and anticipation of multisystem organ failure are crucial.The recommended therapy for Clostridium necrotizing fasciitis is penicillin plus clindamycin. In neutropenic patients, P aeruginosa and gram-negative enterics are potential pathogens, and coverage with a fourth-generation cephalosporin such as cefepime or a carbapenem such as meropenem should be considered. In severe GAS infections or toxic shock syndrome, adjunctive therapy with high-dose intravenous immunoglobulin has been proposed. The mechanism of action of intravenous immunoglobulin in this setting is thought to include inhibition of superantigen activity through the presence of neutralizing antibodies, opsonization through M-specific antibodies, and a general anti-inflammatory effect. Although the role of hyperbaric oxygen is controversial, this therapy may serve an adjunctive role by inhibiting α-toxin production, increasing oxidative killing by host neutrophils, and, in the case of anaerobic infection, retarding growth of the organism.Response to therapy is assessed by careful serial examination. In addition, meticulous pain control, attention to nutritional support, and physical therapy are necessary in most patients.S pyogenes has a long-recognized predilection for the skin, and when that barrier is broken, the bacteria can cause a spectrum of lesions moving from superficial to deep. Most superficial is impetigo, which affects the stratum corneum, the outermost layer of the epidermis composed of keratin cells, and manifests with its typical honey-colored crusts. Although not in itself a risk for spread, impetigo can initiate an immune response that produces poststreptococcal glomerulonephritis. When the infection moves a bit deeper into the epidermis, the result is the bright red, well-demarcated lesion of erysipelas, which can spread into the lymphatic system. Moving deeper, into the dermis and subcutaneous fat, cellulitis is characterized by its warm, painful, red, spreading lesion and its risk of bacteremia. With spread to the underlying fascial planes, the result is the necrotizing fasciitis described in this In Brief. Without rapid and aggressive treatment, infection can invade the muscle itself, causing life-threatening myonecrosis.Careful management of the way we use antibiotics can hopefully prevent the emergence of resistance that would set us back to times when the morbidity and mortality from streptococcal skin diseases was far higher than what we see today.