Necrotizing fasciitis (NF), also known as flesh-eating disease or flesh-eating bacteria, is an infection that kills the body's soft tissue. It is a serious disease that begins and spreads quickly. It is sometimes incorrectly labeled flesh-eating virus. Symptoms include red or purple or black skin, swelling, severe pain, fever, and vomiting. The most commonly affected areas are the limbs and perineum.
Bacterial infection is by far the most common cause of necrotizing fasciitis. Despite being called a "flesh-eating disease", bacteria do not eat human tissue. Rather, they release toxins that cause tissue death. Typically, the infection enters the body through a break in the skin, such as a cut or burn. Risk factors include recent trauma or surgery and a weakened immune system due to diabetes or cancer, obesity, alcoholism, intravenous drug use, and peripheral artery disease. It does not usually spread between people. The disease is classified into four types, depending on the infecting organisms. Medical imaging is often helpful to confirm the diagnosis.
Necrotizing fasciitis is treated with surgery to remove the infected tissue, and antibiotics. It is considered a surgical emergency. Delays in surgery are associated with a much higher risk of death. Despite high-quality treatment, the risk of death remains 25–35%.
Signs and symptoms Signs and symptoms emerge very quickly, often within hours. Manifestations include:
Redness and swelling Induration (hardening of the skin and soft tissue) Excessive pain Systemic symptoms, including high fever > 102 °F/39 °C, fatigue, muscle pains Large amounts of smelly pus and discharge, especially at a surgical site
The initial skin changes are similar to cellulitis or abscess, so diagnosis in early stages may be difficult. The redness and swelling usually blend into the surrounding normal tissues. The overlying skin may appear shiny and tense as well.
Later signs more suggestive of necrotizing changes (but only present in less than half of cases) are:
Bullae (blisters) Crepitus (palpable gas in tissues) Reduced or absent sensation over the skin of the affected area Ecchymosis (bruising) that progresses to skin necrosis. This is because the skin changes color from red to purple and black due to clotting blood vessels
Rapid progression to shock despite antibiotic therapy is another indication of necrotizing fasciitis. However, those who are immunocompromised may not show typical symptoms. This includes but is not limited to patients with:
Cancer or malignancy Corticosteroid use Current radiotherapy or chemotherapy HIV/AIDS History of organ or bone marrow transplant
Immunocompromised persons are twice as likely to die from necrotizing infections compared to the general population, so higher suspicion should be maintained in this group.
Causes
Risk factors Vulnerable populations are typically older with medical comorbidities such as diabetes mellitus, obesity, and immunodeficiency. Other documented risk factors include:
Any trauma or lacerations Injection drug use Recent surgery Injury of mucous membranes, including hemorrhoids, rectal fissures Peripheral artery disease Cancer Alcohol use disorder Pregnancy or recent childbirth
For unclear reasons, it can also infect healthy individuals without medical history or injury.
NSAIDs may increase the rates of necrotizing infections by impairing the body's immune response. NSAIDs inhibit the production of prostaglandins responsible for fever, inflammation, and pain. In theory, it also prevents white blood cells from migrating to infected areas, thus increasing the risk of soft-tissue infections.
Skin infections such as abscesses and ulcers can also complicate NF. A small percentage of people can also get NF when bacteria from streptococcal pharyngitis spreads through the blood. For infection of the perineum and genitals (Fournier gangrene), urinary tract infection, renal stones, and Bartholin gland abscess may also be implicated.
Prevention Good wound care and handwashing reduce the risk of developing necrotizing fasciitis. It is unclear if people with a weakened immune system would benefit from taking antibiotics after being exposed to a necrotizing infection. Generally, such a regimen entails 250 mg of penicillin four times daily for 10 days.
Bacteria Necrotizing fasciitis is classified into four groups based on the type of bacteria causing the infection. This classification system was first described by Giuliano and his colleagues in 1977.
Type I infection: This is the most common type of infection, and accounts for 70–80% of cases. It is caused by a mixture of bacterial types, usually in the abdominal or groin areas. These bacterial species include:
Gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes, and Enterococci) Gram-negative rods (Escherichia coli, Pseudomonas aeruginosa, Klebsiella species, Bacteroides species, Prevotella species) Clostridium species (Clostridium perfringens, Clostridium septicum, and Clostridium sordellii)
In polymicrobial (mixed) infections, Group A Streptococcus (S. pyogenes) is the most commonly found bacterium, followed by S. aureus. However, when the infection is caused solely by S. pyogenes and/or S. aureus, it is classified as a Type II infection.
Gram-negative bacteria and anaerobes, such as Clostridia, are more often implicated in Fournier gangrene. This is a subtype of Type I infections affecting the groin and perianal areas. Clostridia account for 10% of overall Type I infections and typically cause a specific kind of necrotizing fasciitis known as gas gangrene or myonecrosis.
Type II infection: This infection accounts for 20–30% of cases, mainly involving the extremities. This involves Streptococcus pyogenes, alone or in combination with staphylococcal infections. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of Type II infections. Infection by either type of bacteria can progress rapidly and manifest as shock. Type II infection more commonly affects young, healthy adults with a history of injury.
Type III infection: Vibrio vulnificus is a bacterium found in saltwater. It occasionally causes NF after entering the body through a break in the skin. One in three patients with a V. vulnificus infection develop necrotizing fasciitis. Disease progression is similar to type II but sometimes with few visible skin changes.
Type IV infection: This type of NF accounts for less than 1% of cases. It is mostly caused by the Candida albicans fungus. Risk factors include age and immunodeficiency.
Diagnosis
Early diagnosis is difficult, as the disease often first appears like a simple superficial skin infection. While several labs and imaging can raise the suspicion for necrotizing fasciitis, none can rule it out. The gold standard for diagnosis is a surgical exploration and subsequent tissue biopsy. When in doubt, a 2-cm incision can be made into the affected tissue under local anesthesia. If a finger easily separates the tissue along the fascia, then the finger test is positive. This confirms the diagnosis, and an extensive debridement should be performed.
Medical imaging
Necrotizing fasciitis is ideally a clinical diagnosis based on symptoms. Due to the need for rapid surgical treatment, the time delay in performing imaging is a major concern. Hence, imaging may not be needed if signs of a necrotizing infection are clear. However, due to the vague symptoms associated with the earlier stages of this disease, imaging is often useful in clarifying or confirming the diagnosis.
Both CT and MRI scans are used to diagnose NF, but neither is sensitive enough to rule out necrotizing changes completely.
Computed tomography (CT)
If available, computed tomography (CT) is the most convenient tool in diagnosing NF due to its speed and resolution (detects about 80% of NF cases). CT scan may show fascial thickening, edema, or abscess formation. CT can pick up on gas within tissues better than MRI, but it is not unusual for NF to present without gas on imaging. In addition, CT helps evaluate complications due to NF and find possible sources of infections. Its use may be limited in pregnant patients and patients with kidney issues.
Magnetic resonance imaging (MRI)
Magnetic resonance imaging (MRI) is considered superior to computed tomography (CT) to visualize soft tissues and can detect about 93% of NF cases. It is especially useful in finding fluid in the deep fascia, which can distinguish between NF and cellulitis. When fluid collects in the deep fascia, or thickening or enhancement with contrast, necrotizing fasciitis should be strongly suspected. However, MRI is much slower than CT and not as widely available. There may also be limitations on its use in patients with kidney problems.
Point-of-care ultrasonography (POCUS)
Point-of-care ultrasound (POCUS) may be useful in the diagnosis of NF when MRI and CT are unavailable. It can also help rule out diagnoses that mimic earlier stages of NF, including deep vein thrombosis (DVT), superficial abscesses, and venous stasis. Linear probes are generally preferred for the assessment, especially in the extremities.
Findings characteristic of NF include abnormal thickening, air, or fluid in the subcutaneous tissue. This can be summarized as the mnemonic "STAFF" (Subcutaneous irregularity or Thickening, Air, and Fascial Fluid). The official diagnosis of NF using ultrasound requires "the presence of BOTH diffuse subcutaneous thickening AND fascial fluid more than 2 mm." Gas in the subcutaneous tissue may show "dirty acoustic shadowing." However, similar to other imaging modalities, the absence of subcutaneous free air does not definitively rule out a diagnosis of NF, because this is a finding that often emerges later in the disease process.
Of note, the quality and accuracy of POCUS are highly user-dependent. It may also be difficult to visualize NF over larger areas, or if there are many intervening layers of fat or muscle. It is still unclear whether POCUS improves the speed of diagnosis of NF or if it reduces the time to surgical intervention as a whole.
Plain radiography (X-ray) It is difficult to distinguish NF from cellulitis in earlier stages of the disease using plain radiography. X-rays can detect subcutaneous emphysema (gas in the subcutaneous tissue), which is strongly suggestive of necrotizing changes. However, air is often a late-stage finding, and not all necrotizing skin infections create subcutaneous emphysema. Hence, radiography is not recommended for the initial diagnosis of NF. However, it may be able to identify the source of infection, such as foreign bodies or fractures, and thus aid in subsequent treatment.
Scoring system Correlated with clinical findings, a white blood cell count greater than 15,000 cells/mm3 and serum sodium level less than 135 mmol/L are predictive of necrotizing fasciitis in 90% of cases. If lab values do not meet those values, there is a 99% chance that the patient does not have NF. There are various scoring systems to determine the likelihood of getting necrotizing fasciitis. The laboratory risk indicator for necrotizing fasciitis (LRINEC) scoring system developed by Wong and their colleagues in 2004 is the most common. It evaluates people with severe cellulitis or abscesses to determine the likelihood of necrotizing fasciitis.
LRINEC uses six laboratory values: C-reactive protein, total white blood cell count, hemoglobin, sodium, creatinine, and blood glucose. A score of 6 or more indicates that there is a 50–75% probability of necrotizing fasciitis. A score of 8 or more represents over 75% likelihood of NF. Patients with a LRINEC score ≥6 may have a higher rate of both death and amputation as well. The scoring criteria are: