Necrotizing fasciitis

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Necrotizing fasciitis
Other namesFlesh-eating bacteria, flesh-eating bacteria syndrome, [1] necrotizing soft tissue infection (NSTI), [2] fasciitis necroticans
Necrotizing fasciitis left leg.JPEG
Person with necrotizing fasciitis. The left leg shows extensive redness and tissue death.
Specialty Infectious disease
Symptoms Severe pain, fever, purple colored skin in the affected area [3]
Usual onsetSudden, spreads rapidly [3]
CausesMultiple types of bacteria, [4] occasional fungus [5]
Risk factors Poor immune function such as from diabetes or cancer, obesity, alcoholism, intravenous drug use, peripheral artery disease [2] [3]
Diagnostic method Based on symptoms, medical imaging [4]
Differential diagnosis Cellulitis, pyomyositis, gas gangrene [6]
Prevention Wound care, handwashing [3]
Treatment Surgery to remove the infected tissue, intravenous antibiotics [2] [3]
Prognosis ~30% mortality [2]
Frequency0.7 per 100,000 per year [4]

Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the body's soft tissue. [3] It is a severe disease of sudden onset that spreads rapidly. [3] Symptoms usually include red or purple skin in the affected area, severe pain, fever, and vomiting. [3] The most commonly affected areas are the limbs and perineum. [2]


Typically, the infection enters the body through a break in the skin such as a cut or burn. [3] Risk factors include poor immune function such as from diabetes or cancer, obesity, alcoholism, intravenous drug use, and peripheral artery disease. [2] [3] It is not typically spread between people. [3] The disease is classified into four types, depending on the infecting organism. [4] Between 55 and 80% of cases involve more than one type of bacteria. [4] Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of cases. [4] Medical imaging is often helpful to confirm the diagnosis. [4]

Necrotizing fasciitis may be prevented with proper wound care and handwashing. [3] It is usually treated with surgery to remove the infected tissue, and intravenous antibiotics. [2] [3] Often, a combination of antibiotics is used, such as penicillin G, clindamycin, vancomycin, and gentamicin. [2] Delays in surgery are associated with a much higher risk of death. [4] Despite high-quality treatment, the risk of death is between 25 and 35%. [2]

Necrotizing fasciitis occurs in about 0.4 people per 100,000 per year in the US, and about 1 per 100,000 in Western Europe. [4] Both sexes are affected equally. [2] It becomes more common among older people and is rare in children. [4] It has been described at least since the time of Hippocrates. [2] The term "necrotizing fasciitis" first came into use in 1952. [4] [7]

Signs and symptoms

Symptoms may include fever, swelling, and complaints of excessive pain. The initial skin changes are similar to cellulitis or abscess, thus making the diagnosis at early stages difficult. Hardening of the skin and soft tissue and swelling beyond the area of skin changes are commonly present in those with early necrotizing changes. [2] The redness and swelling usually blend into surrounding normal tissues. The overlying skin may appear shiny and tense. [8] Other signs which are more suggestive of necrotizing changes (but present in later stages in 7 to 44% of the cases) are: formation of bullae, bleeding into the skin which is present before skin necrosis [2] (skin turning from red to purple and black due to thrombosis of blood vessels), [8] presence of gas in tissues, and reduced or absent sensation over the skin [2] (due to the necrosis of the underlying nerves). [8] Rapid progression to shock despite antibiotic therapy is another indication of necrotizing fasciitis. Necrotizing changes affecting the groin are known as Fournier gangrene. [2]

However, those who are immunocompromised (have cancer, use corticosteroid, on radiotherapy, chemotherapy, HIV/AIDS, or prior organ or bone marrow transplantation) may not show typical symptoms. Immunocompromised persons also have twice the risk of death from necrotizing infections, so higher suspicion should be maintained in this group. [2]


Risk factors

More than 70% of cases are recorded in people with at least one of these clinical situations: immunosuppression, diabetes, alcoholism/drug abuse/smoking, malignancies, and chronic systemic diseases. For reasons that are unclear, it occasionally occurs in people with an apparently normal general condition. [9]

Necrotizing fasciitis can occur at any part of the body, but it is more commonly seen at the extremities, perineum, and genitals. Only a few of such cases arise from the chest and abdomen. Trauma is the usual cause of the infection, such as from intravenous drug injection, insulin injection, animal and insect bites, catheter insertion over the skin, or a fistula connecting skin to the internal body organs. Skin infections such as abscess and ulcers can also complicate necrotizing fasciitis. Spreading of infection through blood has been suggested for those with streptococcal pharyngitis. For infection of the perineum and genitals (Fournier gangrene), trauma, surgery, urinary tract infection, stones, and Bartholin gland abscess are the usual causes. [2]

The risk of developing necrotizing fasciitis from a wound can be reduced by good wound care and handwashing. [3]


Types of soft-tissue necrotizing infection can be divided into four classes according to the types of bacteria infecting the soft tissue. This classification system was first described by Giuliano and his colleagues in 1977. [4] [2]

Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. [4] This type of infection is usually caused by various species of Gram-positive cocci, ( Staphylococcus aureus , Streptococcus pyogenes , and enterococci), Gram-negative rods, ( Escherichia coli , Pseudomonas aeruginosa ), and anaerobes, ( Bacteroides and Clostridium species). [4] Populations of those affected are typically older with medical comorbidities such as diabetes mellitus, obesity, and immunodeficiency. [4] Usually, trauma is not the cause of such infections. Previous history of abscess infection or gut perforation with bacterial translocation may be elicited. Clostridial infection accounts for 10% of type I infection. Clostridium species involved are Clostridium perfringens , Clostridium septicum , and Clostridium sordellii , which typically cause gas gangrene (also known as myonecrosis). Clostridium perfringens produces two deadly toxins: alpha-toxin and theta-toxin. Alpha-toxin causes excessive platelet aggregation which blocks blood vessels and deprives the vital organs of oxygen supply. This creates an acidic, oxygen-deficient environment for the proliferation of bacteria. When alpha-toxin is absorbed by soft tissues, it can inhibit the migration of white blood cells from blood vessels into the soft tissue, thus impairing phagocyte function. The two toxins together can cause destruction of red blood cells in blood vessels, damage to the integrity of the blood vessels, and suppression of heart function.[ citation needed ]

Clostridium sordellii can also produce two major toxins: all known virulent strains produce the essential virulence factor lethal toxin (TcsL), and a number also produce haemorrhagic toxin (TcsH). TcsL and TcsH are both members of the large clostridial cytotoxin (LCC) family. [10] The key Clostridium septicum virulence factor is a pore-forming toxin called alpha-toxin, though it is unrelated to the Clostridium perfringens alpha-toxin. Myonecrotic infections caused by these clostridial species commonly occur in injecting heroin users. Those with clostridial infections typically have severe pain at the wound site, where the wound typically drains foul-smelling blood mixed with serum (serosanguinous discharge). Shock can progress rapidly after initial injury or infection, and once the state of shock is established, the chance of dying exceeds 50%. Another bacterium associated with similar rapid disease progression is group A streptococcal infection (mostly Streptococcus pyogenes). Meanwhile, other bacterial infections require two or more days to become symptomatic. [2]

Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. [4] [11] This mainly involves Streptococcus pyogenes bacteria, alone or in combination with staphylococcal infections. Both types of bacteria can progress rapidly and manifest as toxic shock syndrome. Streptococcus species produce M protein, which acts as a superantigen, stimulating a massive systemic immune response which is not effective against the bacterial antigen, precipitating shock. Type II infection more commonly affects young, healthy adults with a history of injury. [2]

Type III infection: Vibrio vulnificus , a bacterium found in saltwater, is a rare cause of this infection, which occurs through a break in the skin. Disease progression is similar to type II but sometimes with little visible skin changes. [2]

Type IV infection: Some authors have described the type IV infection as fungal in nature. [4]


Necrotizing fasciitis producing gas in the soft tissues as seen on CT scan Pnecrotisingfasc.png
Necrotizing fasciitis producing gas in the soft tissues as seen on CT scan
Necrotizing fasciitis as seen on ultrasound [12]
Micrograph of necrotizing fasciitis, showing necrosis (center of image) of the dense connective tissue, i.e. fascia, interposed between fat lobules (top-right and bottom-left of image), H&E stain Necrotizing fasciitis - intermed mag.jpg
Micrograph of necrotizing fasciitis, showing necrosis (center of image) of the dense connective tissue, i.e. fascia, interposed between fat lobules (top-right and bottom-left of image), H&E stain

Early diagnosis is difficult, as the disease often looks early on like a simple superficial skin infection. [4] While a number of laboratory and imaging modalities can raise the suspicion for necrotizing fasciitis, none can rule it out. [13] The gold standard for diagnosis is a surgical exploration in a setting of high suspicion. When in doubt, a small incision can be made into the affected tissue, and if a finger easily separates the tissue along the fascial plane, the diagnosis is confirmed and an extensive debridement should be performed. [2]

Medical imaging

Imaging has a limited role in the diagnosis of necrotizing fasciitis. The time delay in performing imaging is a major concern. Plain radiography may show subcutaneous emphysema (gas in the subcutaneous tissue), which is strongly suggestive of necrotizing changes, but it is not sensitive enough to detect all the cases, because necrotizing skin infections caused by bacteria other than clostridial infections usually do not show subcutaneous emphysema. If the diagnosis is still in doubt, computed tomography (CT) scans and magnetic resonance imaging (MRI) are more sensitive modalities than plain radiography. However, both the CT scan and MRI are not sensitive enough to rule out necrotizing changes completely. [2] CT scan may show fascial thickening, edema, subcutaneous gas, and abscess formation. [2] In MRI, when fluid collection with deep fascia involvement occurs, thickening or enhancement with contrast injection, necrotizing fasciitis should be strongly suspected. Meanwhile, ultrasonography can show superficial abscess formation, but is not sensitive enough to diagnose necrotizing fasciitis. [2] CT scan is able to detect about 80% of cases, while MRI may pick up slightly more. [14]

Scoring system

A white blood cell count greater than 15,000 cells/mm3 and serum sodium level less than 135 mmol/l have a sensitivity of 90% in detecting the necrotizing soft tissue infection.[ citation needed ] It also has a 99% chance of ruling out necrotizing changes if the values have shown otherwise. Various scoring systems are being developed to determine the likelihood of getting necrotizing fasciitis, but a scoring system developed by Wong and colleagues in 2004 is the most commonly used. It is the laboratory risk indicator for necrotizing fasciitis (LRINEC) score, which can be used to stratify by risk those people having signs of severe cellulitis or abscess to determine the likelihood of necrotizing fasciitis being present. It uses six laboratory values: C-reactive protein, total white blood cell count, hemoglobin, sodium, creatinine, and blood glucose. [2] A score of 6 or more indicates that necrotizing fasciitis should be seriously considered. [15] The scoring criteria are:

However, the scoring system has not been validated. The values would be falsely positive if any other inflammatory conditions are present. Therefore, the values derived from this scoring system should be interpreted with caution. [2] About 10% of patients with necrotizing fasciitis in the original study still had a LRINEC score <6. [15] A validation study showed that patients with a LRINEC score ≥6 have a higher rate of both death and amputation. [17]


Necrotizing fasciitis can be partly prevented by good wound care and handwashing. [3]


Surgical debridement (cutting away affected tissue) is the mainstay of treatment for necrotizing fasciitis. Early medical treatment is often presumptive; thus, antibiotics should be started as soon as this condition is suspected. Tissue cultures (rather than wound swabs) are taken to determine appropriate antibiotic coverage, and antibiotics may be changed in light of results. Besides blood pressure control and hydration, support should be initiated for those with unstable vital signs and low urine output. [2]


Aggressive wound debridement should be performed early, usually as soon as the diagnosis of necrotizing soft tissue infection (NSTI) is made. Surgical incisions often extend beyond the areas of induration (the hardened tissue) to remove the damaged blood vessels that are responsible for the induration. However, cellulitic soft tissues are sometimes spared from debridement for later skin coverage of the wound. More than one operation may be used to remove additional necrotic tissue. In some cases when an extremity is affected by a NSTI, amputation may be the surgical treatment of choice. After the wound debridement, adequate dressings should be applied to prevent exposure of bones, tendons, and cartilage so that such structures do not dry out and to promote wound healing. [2]

For necrotizing infection of the perineal area (Fournier's gangrene), wound debridement and wound care in this area can be difficult because of the excretory products that often render this area dirty and affect the wound-healing process. Therefore, regular dressing changes with a fecal management system can help to keep the wound at the perineal area clean. Sometimes, colostomy may be necessary to divert the excretory products to keep the wound at the perineal area clean. [2]


Empiric antibiotics are usually initiated as soon as the diagnosis of NSTI has been made, and then later changed to culture-guided antibiotic therapy. In the case of NSTIs, empiric antibiotics are broad-spectrum, covering gram-positive (including MRSA), gram-negative, and anaerobic bacteria. [18]

While studies have compared moxifloxacin (a fluoroquinolone) and amoxicillin-clavulanate (a penicillin) and evaluated appropriate duration of treatment (varying from 7 to 21 days), no definitive conclusions on the efficacy of treatment, ideal duration of treatment, or the adverse effects could be made due to poor-quality evidence. [18]

Add on therapy


Necrotizing fasciitis affects about 0.4 in every 100,000 people per year in the United States. [4] About 1,000 cases of necrotizing fasciitis occur per year in the United States, but the rates have been increasing. This could be due to increasing awareness of this condition, leading to increased reporting, or bacterial virulence or increasing bacterial resistance against antibiotics. [2] In some areas of the world, it is as common as one in every 100,000 people. [4]

Higher rates of necrotizing fasciitis are seen in those with obesity or diabetes, and those who are immunocompromised or alcoholic, or have peripheral artery disease. However, the disease may also occur in young, healthy adults with no underlying illnesses. NSAIDs may increase the rates of necrotizing infections due to the modification of immune response in the body, because NSAIDs inhibit the cycloxygenase-1 and cycloxygenase-2 enzymes which are important in producing thromboxane and prostaglandin E2. Prostaglandin has been responsible for fever, inflammation, and pain. The inhibition of prostaglandin E2 production reduces inflammatory response and leukocyte adhesion, and thus reduces immune response against bacterial invasion, giving rise to soft-tissue infection. [2]


In the fifth century BC, Hippocrates described necrotizing soft tissue infection as a disease where those affected would have "erysipelas all over the body while the cause was only a trivial accident. Bones, flesh, and sinew (cord, tendon, or nerve) would fall off from the body and there were many deaths". The first English description for necrotizing soft-tissue infection was by British surgeon Leonard Gillespie and British physicians Gilbert Blaine and Thomas Trotter in the 18th century. At that time, necrotizing soft-tissue infections were known variously as "phagedaenic ulcer" (ulceration that spreads and destroys surrounding tissue), "gangrenous phagedena", "gangrenous ulcer", "malignant ulcer", "putrid ulcer", "fulminating gangrene", "necrotizing erysipelas", "gangrenous erysipelas", "crepitant cellulitis", "gangrenous cellulitis", "Meleney cellulitis", "necrotizing synergistic cellulitis", "hemolytic streptococcal gangrene", "progressive bacterial synergistic gangrene", "necrotizing abscess", "galloping gangrene", or "hospital gangrene". [19] Later, "hospital gangrene" became more commonly used. In 1871 Confederate States Army surgeon Joseph Jones reported 2,642 cases of hospital gangrene with a mortality rate of 46%. In 1883, Dr Jean-Alfred Fournier described the necrotizing infection of the perineum and scrotum, now called Fournier gangrene. The term "necrotizing fasciitis" was first coined by Wilson in 1952. Its definition has become broader, to include not only infection of fascia, but also other soft-tissue infection. [2] Despite being disfavored by the medical community, the term "galloping gangrene" is frequently used in sensationalistic news media to refer to outbreaks of necrotizing fasciitis. [20]

Notable cases

See also

Related Research Articles

Abscess Localized collection of pus that has built up within the tissue of the body

An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends beyond the swelling. Carbuncles and boils are types of abscess that often involve hair follicles, with carbuncles being larger.

Necrosis Unprogrammed cell death caused by external cell injury

Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.

Gangrene Type of tissue death by a lack of blood supply

Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the gangrene is caused by an infectious agent it may present with a fever or sepsis.

<i>Clostridium perfringens</i> Species of bacterium

Clostridium perfringens is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus Clostridium. C. perfringens is ever-present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil. It has the shortest reported generation time of any organism at 6.3 minutes in thioglycolate medium.

Cellulitis Bacterial infection of the skin

Cellulitis is a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of the area of redness are generally not sharp and the skin may be swollen. While the redness often turns white when pressure is applied, this is not always the case. The area of infection is usually painful. Lymphatic vessels may occasionally be involved, and the person may have a fever and feel tired.

Gas gangrene Human bacterial infection

Gas gangrene is a bacterial infection that produces tissue gas in gangrene. This deadly form of gangrene usually is caused by Clostridium perfringens bacteria. About 1,000 cases of gas gangrene are reported yearly in the United States.

<i>Peptostreptococcus</i> Genus of bacteria

Peptostreptococcus is a genus of anaerobic, Gram-positive, non-spore forming bacteria. The cells are small, spherical, and can occur in short chains, in pairs or individually. They typically move using cilia. Peptostreptococcus are slow-growing bacteria with increasing resistance to antimicrobial drugs. Peptostreptococcus is a normal inhabitant of the healthy lower reproductive tract of women.

Lymphangitis Medical condition

Lymphangitis is an inflammation or an infection of the lymphatic channels that occurs as a result of infection at a site distal to the channel. The most common cause of lymphangitis in humans is Streptococcus pyogenes, hemolythic streptococci, and in some cases, mononucleosis, cytomegalovirus, tuberculosis, syphilis, and the fungus Sporothrix schenckii. Lymphangitis is sometimes mistakenly called "blood poisoning". In reality, "blood poisoning" is synonymous with sepsis.

Blackleg (disease)

Blackleg, black quarter, quarter evil, or quarter ill is an infectious bacterial disease most commonly caused by Clostridium chauvoei, a Gram-positive bacterial species. It is seen in livestock all over the world, usually affecting cattle, sheep, and goats. It has been seen occasionally in farmed bison and deer. The acute nature of the disease makes successful treatment difficult, and the efficacy of the commonly used vaccine is disputed.

<i>Aeromonas</i> Genus of bacteria

Aeromonas is a genus of gram-negative, facultative anaerobic, rod-shaped bacteria that morphologically resemble members of the family Enterobacteriaceae. Most of the 14 described species have been associated with human diseases. The most important pathogens are A. hydrophila, A. caviae, and A. veronii biovar sobria. The organisms are ubiquitous in fresh and brackish water.

Orbital cellulitis inflammation of eye tissues

Orbital cellulitis is inflammation of eye tissues behind the orbital septum. It is most commonly caused by an acute spread of infection into the eye socket from either the adjacent sinuses or through the blood. It may also occur after trauma. When it affects the rear of the eye, it is known as retro-orbital cellulitis.

<i>Aeromonas hydrophila</i> Species of heterotrophic, Gram-negative, bacterium

Aeromonas hydrophila is a heterotrophic, Gram-negative, rod-shaped bacterium mainly found in areas with a warm climate. This bacterium can be found in fresh or brackish water. It can survive in aerobic and anaerobic environments, and can digest materials such as gelatin and hemoglobin. A. hydrophila was isolated from humans and animals in the 1950s. It is the most well known of the species of Aeromonas. It is resistant to most common antibiotics and cold temperatures and is oxidase- and indole-positive. Aeromonas hydrophila also has a symbiotic relationship as gut flora inside of certain leeches, such as Hirudo medicinalis.

Fournier gangrene Medical condition

Fournier gangrene is a type of necrotizing fasciitis or gangrene affecting the external genitalia or perineum. It commonly occurs in older men, but it can also occur in women and children. It is more likely to occur in diabetics, alcoholics, or those who are immunocompromised.

Clostridial necrotizing enteritis (CNE) is a severe and potentially fatal type of food poisoning caused by a β-toxin of Clostridium perfringens, Type C. It occurs in some developing regions, particularly in New Guinea, where it is known as pig-bel. The disease was also documented in Germany following World War II, where it was called Darmbrand. The toxin is normally inactivated by certain proteolytic enzymes and by normal cooking, but when these protections are impeded by diverse factors, and high protein is consumed, the disease can emerge.

Open fracture Medical condition

An open fracture, also called a compound fracture, is a type of bone fracture in orthopedics that is frequently caused by high energy trauma. It is a bone fracture associated with a break in the skin continuity which can cause complications such as infection, malunion, and nonunion. Gustilo open fracture classification is the most commonly used method to classify open fractures, to guide treatment and to predict clinical outcomes. Advanced trauma life support is the first line of action in dealing with open fractures and to rule out other life-threatening condition in cases of trauma. Cephalosporins are generally the first line of antibiotics. The antibiotics are continued for 24 hours to minimize the risk of infections. Therapeutic irrigation, wound debridement, early wound closure and bone fixation are the main management of open fractures. All these actions aimed to reduce the risk of infections.

<i>Clostridium septicum</i> Species of bacterium

Clostridium septicum is a gram positive, spore forming, obligate anaerobic bacterium.

Skin and skin structure infections (SSSIs), also referred to as skin and soft tissue infections (SSTIs), or acute bacterial skin and skin structure infections (ABSSSIs), are infections of skin and associated soft tissues. Historically, the pathogen involved has most frequently been a bacterial species—always, since redescription of SSSIs as ABSSSIs—and as such, these infections require treatment by antibiotics.

Clostridium histolyticum is a species of bacteria found in feces and the soil. It is a motile, gram-positive, aerotolerant anaerobe. C. histolyticum is pathogenic in many species, including guinea pigs, mice, and rabbits, and humans. C. histolyticum has been shown to cause gas gangrene, often in association with other bacteria species.

Anaerobic infections are caused by anaerobic bacteria. Obligately anaerobic bacteria do not grow on solid media in room air ; facultatively anaerobic bacteria can grow in the presence or absence of air. Microaerophilic bacteria do not grow at all aerobically or grow poorly, but grow better under 10% carbon dioxide or anaerobically. Anaerobic bacteria can be divided into strict anaerobes that can not grow in the presence of more than 0.5% oxygen and moderate anaerobic bacteria that are able of growing between 2 and 8% oxygen. Anaerobic bacteria usually do not possess catalase, but some can generate superoxide dismutase which protects them from oxygen.

<i>Clostridium tertium</i> Species of bacterium

Clostridium tertium is an anaerobic, motile, gram-positive bacterium. Although it can be considered an uncommon pathogen in humans, there has been substantial evidence of septic episodes in human beings. C. tertium is easily decolorized in Gram-stained smears and can be mistaken for a Gram-negative organism. However, C.tertium does not grow on selective media for Gram-negative organisms.


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