Pediatrics

Necrotizing fasciitis

OVERVIEW: What every practitioner needs to know

Are you sure your patient has necrotizing fasciitis? What are the typical findings for this disease?

Necrotizing fasciitis is an invasive skin and soft tissue infection, which involves rapidly spreading necrosis from the subcutaneous tissue, through fascial planes, and occasionally to the muscle. Often referred to as a "flesh-eating" bacterial infection by the lay public, necrotizing fasciitis is a result of superficial skin entry and infection from a gram-positive bacteria (e.g., group A streptococcus), often a toxin-producing strain, which results in necrosis, rapid extension, and clinical instability. Co-infection from anaerobic bacteria is possible, as well.

Affected patients are toxic upon presentation, and often manifest tachycardia, hypotension, and pain out of proportion to clinical findings at the site of infection. For the clinician, prompt recognition, resuscitative efforts, antimicrobial therapy, and surgical consultation are paramount, as necrotizing fasciitis carries a high risk of morbidity and mortality.

Most common clinical manifestations of necrotizing fasciitis

Local findings affecting any part of the body:

  • Erythema

  • Swelling and induration

  • Exquisite pain and tenderness over the affected area, which is often out of proportion to the overt clinical appearance

  • Systemic toxicity

Other Local findings in necrotizing fasciitis:

  1. Skin discoloration (red-purple, dusky blue)

  2. Crepitance

  3. Skin bullae

Systemic Toxicity:

  1. Fever

  2. Tachycardia

  3. Hypotension

  4. Altered mental status

  5. Systemic inflammatory response syndrome

  6. Fulminant shock and multiorgan failure

Body sites most often affected by necrotizing fasciitis:

  1. Lower extremities

  2. Perineum and genitourinary region (Fournier's gangrene)

  3. Upper extremities

  4. Abdomen and trunk

What other disease/condition shares some of these symptoms?

  • Erysipelas

  • Cellulitis

  • Necrotizing staphylococcal abscess

  • Spider bite (brown recluse)

  • Toxic Shock Syndrome

  • Septicemia

What caused this disease to develop at this time?

  • Introduction of offending bacteria into the skin is the most common precipitant to necrotizing fasciitis. Inoculation may occur through multiple mechanisms:

    • Blunt or penetrating trauma

    • Overlying soft tissue infection

    • Recent surgical wounds

    • Burns

    • Intravenous drug abuse

  • Comorbid conditions may increase the risk for development of necrotizing fasciitis in children

    • Immunosuppression, congenital or acquired

    • Corticosteroid use

    • Malnutrition

    • Diabetes

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

The diagnosis of necrotizing fasciitis is a primarily clinical one, and maintenance of a high index of suspicion is paramount. Management and therapy should not be delayed awaiting diagnostic studies or their results. Laboratory testing yields non-specific results; elevated markers of inflammation may only assist clinicians in decision regarding advanced imaging and surgical consultation. Obtaining culture of affected tissue and fluid can typically be obtained during debridement, and remains the gold-standard.

  • Inflammatory markers

    • Complete blood count (CBC) for leukocytosis

    • C-reactive protein (CRP)

    • Erthyrocyte sedimentation rate (ESR)

  • Signs of advanced, systemic disease

    • Metabolic panel and /or blood gas

    • Coagulation profile

  • Blood cultures

  • Wound cultures (from surgical debridement)

Would imaging studies be helpful? If so, which ones?

  • Owing to the difficulty in clinical diagnosis, imaging is often employed in securing the diagnosis of necrotizing fasciitis.

    • Plain radiograph

    • Advanced Imaging: Computed tomography (CT) and magnetic resonance imaging (MRI)

  • Caution should be used in cases where radiographs or advanced imaging are normal; none of the aforementioned modalities has optimal sensitivity, and continued monitoring or empiric surgical exploration and debridement may be indicated.

Plain films of the affected area, although easy to obtain and inexpensive, are only adjunctive in securing the diagnosis of necrotizing fasciitis. Soft tissue gas may be visualized on the radiograph in up to 60% of cases, and has a high association with necrotizing fasciitis in the appropriate clinical setting; the absence of gas is very insensitive and cannot exclude the diagnosis.

Although CT may be useful, MRI is the preferred modality of imaging for necrotizing fasciitis, as soft tissues and edema are better visualized using MRI. In addition, CT carries increased radiation load for detection of fasciitis, as thin cuts are required. MRI is associated with good sensitivity and is highly specific for necrotizing fasciitis. Enhancement of the affected areas, including fascial planes and local soft tissues, can detect the presence and extent of infection.

Confirming the diagnosis

No established, validated clinical decision algorithms exist for diagnosis or management of necrotizing fasciitis.

If you are able to confirm that the patient has necrotizing fasciitis, what treatment should be initiated?

  • Stabilization and Resuscitation of the patient is the first step in management, and frequently is necessary. Necrotizing fasciitis is often accompanied by systemic toxicity that may mimic clinical sepsis. Therefore, Airway, Breathing, and Circulation must be supported. Among these, circulatory support is most often necessary, as toxins lead to vasodilation, myocardial suppression, and capillary leak.

    • Crystalloid intravenous fluid bolus (20 cc/kg) using normal saline or lactated ringers solution, repeated as necessary to improve or maintain hemodynamic instability.

    • Vasopressor support is indicated for refractory hypotension.

  • Antibiotic Therapy

  • Emergency Surgical Consultation is indicated in suspected cases of necrotizing fasciitis, as operative management and debridement are required for definitive care.

  • Cases of suspected necrotizing fasciitis require hospital admission, often for ongoing intravenous antibiotic therapy, fluid management and monitoring. Sequential operative wound debridement may be indicated, as necrotizing fasciitis may continue to extend even after initial therapies.

Vasopressors:

  1. Dopamine is often the initial choice, titrated from 10-20 mcg/kg/hour.

  2. Dobutamineprovides additional myocardial support and may be added to dopamine in refractory cases.

  3. Epinephrineis an excellent choice for peripheral vasopressive support in toxin-mediated processes.

Antibiotics:

Initial antimicrobial therapy is broad-spectrum, but principally directed toward both Gram-positive and anaerobic organisms, therefore combination antibiotic therapy is necessary. Penicillins inhibit cell wall synthesis in growing organisms, and may not be as effective in necrotizing tissue, whereas clindamycin inhibits protein synthesis, and may have additional benefit by reducing elicitation of bacterial toxin in streptococcal species.

  • Gram-positive coverage: Streptococcal species, particularly group A streptococcus (GABHS), and Staphylococcus aureus are the most common causes of necrotizing faciitis.

    • Synthetic penicillins (e.g. oxacillin, nafcillin) are often an initial choice, although they are ineffective versus community associated methicillin-resistant S. aureus(CA-MRSA), which has been described as an etiologic agent of necrotizing fasciitis.

    • Vancomycin is often an initial choice and provides excellent coverage for most streptococcal and staphylococcal species.

    • Clindamycin often has adequate coverage for streptococcal and staphylococcal species, including CA-MRSA, although it is not sufficient as monotherapy in invasive, systemic disease.

  • Gram-negative coverage

    • Gentamycin is effective against many gram-negative enterics, but may not used as monotherapy

  • Anaerobic coverage:

    • Clindamycin

    • Metronidazole

What are the adverse effects associated with each treatment option?

The aforementioned therapies are not optional, and are necessary for treatment. Typical adverse events from antibiotic therapy include allergic reactions. Increased incidence of diarrhea is common, including Clostidium difficile enteritis, particularly with use of clindamycin.

What are the possible outcomes of necrotizing fasciitis?

Most adverse outcomes from necrotizing fasciitis occur from delays in diagnosis; therefore clinicians must maintain a high index of suspicion for the illness.

A clinical presentation of fulminant shock is associated with poor outcomes as well, and requires immediate critical care therapies.

Mortality from necrotizing fasciitis has been reported to be as low as 6% with optimal therapy, and as high as 76% in some situations, although the recent estimates suggest a case-fatality rate of approximately 25%. Therefore rapid diagnosis, antibiotic administration, surgical debridement, and intensive care therapies must be instituted when clinical suspicion is high.

Even with optimal therapies and successive debridements, necrotizing fasciitis may lead to severe systemic inflammatory response syndrome, multi-system organ failure, and death.

What causes this disease and how frequent is it?

  • Necrotizing fasciitis is the result of bacterial infection of the deep soft tissue spaces, leading to necrosis along the fascial planes with relative sparing of the muscular compartment.

    • Microbiology: Most infections are polymicrobial in nature (up to 70%), with aerobic and anaerobic bacteria playing a role in pathogenesis. Gram-positive organisms, specifically group A β-hemolytic streptococcus, are most commonly isolated, and Staphylococcus aureus is often implicated as well. Gram-negative enterics may produce infection, especially in the perineal and gluteal region. Anaerobic pathogens often co-infect tissue as necrosis occurs, and Clostridium and Bacteriodes species are often implicated.

    • Toxin-mediated processes contribute significantly to the pathogenesis of necrotizing fasciitis.

    • The actual incidence of necrotizing fasciitis is not known, although it appears to be a relatively rare clinical entity. A single report from the United Kingdom estimated that 500 cases are diagnosed annually.

    • The most common mode of transmission of bacteria into the deep soft tissues is via penetrating trauma of the skin, or from recent surgical wounds.

  • The underlying genetics of host inflammatory response in necrotizing fasciitis is not well known.

How do these pathogens/genes/exposures cause the disease?

Direct Infection: Similar to other soft tissue infections, introduction of the offending bacterium into the skin via minor trauma is the most common method of entry. Local spread of infection into the deep tissues is then followed by rapid multiplication and spread via the fascial planes. Via infection, local inflammatory processes produce increased amounts of purulence, local edema, and eventually necrosis in the deep tissues, leading to pain out of proportion to clinical findings, edema, and eventually skin discoloration and surface findings. Necrosis allows for co-infection with anerobic organisms, which may be gas producing, leading to the crepitance and soft-tissue gas classically associated with the disease.

Toxin-mediated: Through M-proteins, exotoxins, streptolyisin, and superantigens, which enhance local inflammation via cytokine release, Gram-positive organisms, particularly GABHS can mediate a "toxic-shock syndrome". The resultant capillary leak, hypotension, and myocardial suppression produces the clinical picture of toxic shock.

Other clinical manifestations that might help with diagnosis and management

In the setting of fever and compartment syndrome affecting an extremity, the clinician should consider the diagnosis of necrotizing fasciitis. Fever is not a usual finding with compartment syndrome. Moreover, the increased pressure from inflammation deep in the fascial compartments of the lower extremities can produce pain out of proportion to clinical findings, similar to that of compartment syndrome from injury.

What complications might you expect from the disease or treatment of the disease?

Surgical therapy and extensive wound debridement is necessary for cases of necrotizing fasciitis. Although highly interventional, and with significant risk, surgical management is the mainstay of therapy, despite the risk incurred.

Reconstructive surgery, including skin grafting of the affected area is often necessary after effective treatment of the infection. In the most severe cases, when necrosis and spread of the infection is rapid, extremity amputation may be necessary.

Are additional laboratory studies available; even some that are not widely available?

No additional laboratory studies are available.

How can necrotizing fasciitis be prevented?

At present, there are no specific preventative therapies for necrotizing fasciitis.

What is the evidence?

Etiology:

Elliott, D, Kufera, JA, Myers, RA. "The microbiology of necrotizing soft tissue infections". Am J Surg. May. vol. 179. 2000. pp. 361-366.

Miller, LG, Perdreau-Remington, F, Rieg, G. "Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles". N Engl J Med. vol. 352. Apr 7 2005. pp. 1445-1453.

Owing to rarity of necrotizing fasciitis, descriptions of the bacteriology have been limited to retrospective reviews, case series, and case reports. Moreover, the difficulties of isolating many anaerobic organisms in culture makes true estimates of organism prevalence nearly impossible. However, the common occurrence of co-infection with Gram-positive, Gram-negative, and anaerobic bacteria was documented in a retrospective study (Elliot, 2000), emphasizing the need for broad-spectrum antibiotic coverage. In addition, community-associated strains of methicillin-resistant Staphylococcus aureus have been implicated in recent years, and Gram-positive coverage should also include this organism (Miller, 2005). (Evidence Level: D)

Treatment:

Riseman, JA, Zamboni, WA, Curtis, A, Graham, DR, Konrad, HR, Ross, DS. "Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements". Surgery. Nov. vol. 108(5). 1990. pp. 847-850.

Jallali, N, Withey, S, Butler, PE. "Hyperbaric oxygen as adjuvant therapy in the management of necrotizing fasciitis". Am J Surg. vol. 189. 2005 Apr. pp. 462-6.

Randomized clinical trials of treatment of necrotizing fasciitis are exceedingly difficult, owing the rarity of the disease, and ethics of subjecting critically-ill patients to unknown treatment. Surgical debridement and antimicrobial therapy remain the mainstay of therapy, and evidence is derived from etiologic studies and retrospective assessments of patient outcome (Evidence Level: D).The role of adjunctive hyperbaric oxygen therapy has been debated, with initial studies showing promise in terms of mortality and need for repeated surgical procedures (Riseman, 1990). Recent systematic reviews have not demonstrated definitive benefit of hyperbaric oxygen therapy, although it appears that the treatment does not result in harm, and has a trend towards benefit in cases of necrotizing fasciitis (Jallali, 2005). (Evidence Level: D).

Ongoing controversies regarding etiology, diagnosis, treatment

Hyperbaric oxygen therapy has been suggested as beneficial therapy for necrotizing fasciitis in some studies, although its utility and availability are often questionable. Theoretical benefits include forced oxygenation to deep necrotic tissue and hypoxic zones as a method to reduce need for multiple debridements and improve survival.

Intravenous gamma-globulin (IVIG) may be used as an adjunctive therapy in cases with evidence of systemic toxicity, through immune modulation. Randomized clinical trials have not been conducted to show true benefits in cases of necrotizing fasciitis.

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