Necrotizing fasciitis is an uncommon but life-threatening soft tissue infection characterized by rapidly spreading inflammation and necrosis of the skin, subcutaneous fat, and fascia. 1 Rapid early intervention may prevent morbidity and mortality; however, left untreated, the mortality rate may reach over 70%.
The earliest reference to this condition was made in the 15th century BC by Hippocrates, who spoke of it as a complication of erysipelas. 1,2 The term necrotizing fasciitis (NF) was not coined until 1952. Terms for NF have included flesh-eating bacteria syndrome, suppurative fasciitis, hospital gangrene, and necrotizing erysipelas, among others. 3,4,5
The incidence of NF has been reported to be 0.40 cases per 100,000 population. 3 Although NF is rare, certain conditions can predispose patients to developing the disease, including immunocompromised states such as diabetes mellitus, AIDS, and malignancy. 1–4,6–10,11 Necrotizing fasciitis may also occur as a result of trauma, such as burns and lacerations. Even minor trauma, such as insect bites and needle sticks, may lead to NF. Simply put, the entrance of bacteria can occur from any break in the skin and can occur in patients with preexisting skin conditions such as psoriasis, pressure ulcers, or perirectal abscesses.
Necrotizing fasciitis is categorized as Type 1 or Type 2 depending on which organisms are cultured (Table 1). 1,2,6,12,13 Type 1 NF is a polymicrobial infection from aerobic and anaerobic bacteria such as Clostridium and Bacteroides species. Type 2 NF consists of group A Streptococcus (S. pyogenes) with or without a coexisting Staphylococcal infection.
Clinically, NF can be divided into 3 groups based on the length and extent of the disease 14:
- fulminant NF—Patients with fulminant disease present with rapid disease progression and are often in shock. They have typically had symptoms for only several hours.
- acute NF—Patients with acute disease have symptoms for several days. In most cases, large areas of their skin are involved.
- subacute NF—Patients with subacute disease may have symptoms for several weeks. Only a localized area of skin is generally affected.
Necrotizing fasciitis can affect any area of the body, but it most commonly occurs on the extremities. Involvement of the genitalia is referred to as Fournier’s gangrene and usually results from a polymicrobial infection. There is a higher mortality rate when the head, neck, chest, and abdomen are involved because those areas tend to be refractory and, as such, are more difficult to treat.
Early on, patients generally present with a clinical picture similar to cellulitis. As with less aggressive cases of cellulitis, redness and edema can be seen at the site, with a spreading, diffuse inflammatory reaction that blends into the surrounding tissue. The overlying skin is shiny and tense without any clear lines of demarcation. However, patients’ complaints of severe pain are usually out of proportion to the clinical lesion. This characteristic clue of NF may be the only hint of a deeper, more aggressive infection. It is critical to be alert for this because the earlier the NF diagnosis is made, the earlier treatment can be instituted and the better the chance that the patient will survive.
In acute and subacute cases, the infection progresses for 2 to 3 days, the redness of the skin turning purple or purple-black as tissue necrosis occurs. The necrosis is presumably a direct result of thrombosis of the skin’s underlying nutrient vessels. If necrosis involves the cutaneous nerves, numbness may occur in the affected skin. Clear or hemorrhagic bullae may develop, but the serous or hemorrhagic fluid turns into gray foul-smelling fluid termed “dishwater pus” (Figure 1). When bullae rupture (Figure 2), a dry, often black eschar may develop.
Over time, frank cutaneous gangrene may extend beyond the skin and into the subcutaneous fat and fascial planes below. Separation of the necrotic tissue along the fascial planes with suppuration may occur. Myonecrosis develops in the underlying muscle. Lymphadenitis, lymphangitis, crepitation, and venous thrombosis are seen less often.
Metastatic abscesses have been reported in the liver, lung, spleen, brain, and pericardium, but they are rare. 2 When they do present, they are painless, subcutaneous abscesses in areas of pressure points. 15
In addition to cutaneous manifestations of NF, there are systemic findings as well (Table 2). 1,10,16–18 With progression of disease, patients usually appear toxic with high fever, chills, and constitutional symptoms. In fulminant cases, multiorgan system failure will occur.
The pathogenesis of NF is multifactorial, involving local and systemic host factors and bacterial virulence factors. 9 First, there is a decrease in tissue resistance, often due to immunosuppression. This allows the bacteria to be introduced into the skin. Bacterial toxins and enzymes facilitate the spread of the bacteria through the skin, especially through the subcutaneous tissue and fascial planes. These enzymes—including hyaluronidase, collagenase, streptokinase, and lipase—result in extensive tissue necrosis.
Recent research has found that certain superantigens secreted by beta hemolytic Streptococcus (SPE-A, SPE-B, SPE-C) can activate clones of T-helper lymphocytes. These, in turn, activate a host of cytokines, including tumor necrosis factor alpha and beta, as well as clotting factors and complement. 1,5,8,18 This results in the production of oxygen-free radicals and nitrous oxide that may ultimately cause shock, immunosuppression, depression of myocardial function, and multiorgan failure. Streptococcus also produces other virulence factors, such as M protein type 1 and 3, which decrease neutrophilic phagocytosis and decrease the body’s ability to rid itself of the bacteria.
The more the bacteria spread and release toxins, the more they decrease the normal local protective tissue factors. 9 In addition, thrombosis of the vasculature occurs when bacteria spread, leading to a decrease in oxygen supply and nutrients.
The suspicion that NF is developing is based on clinical findings. 1 Because NF evolves rapidly, the ability to recognize the condition—based on appearance of the skin, extreme pain, fever, and toxic appearance—and initiate therapy may prevent mortality. Once NF is suspected, laboratory and radiologic tests and histopathology can aid in diagnosis (Table 3). 1,3,6,10,15,17–20
Leukocytosis with left shift; normochromic, normocytic anemia; and elevated sedimentation rate can be present. A positive gram stain result from infected tissue and/or blood culture findings can aid in diagnosis and the choice of antibiotic treatment regimen. The rapid strep screen is a fast way of specifically diagnosing the presence of Group A Streptococcus (GAS). This noninvasive, inexpensive test measures the presence of the Streptococcal antigen; however, a negative test result does not exclude the presence of GAS infection. Because gas-producing organisms may be responsible, searching for air in the tissue via clinical exam and/or radiographic assessment through computed tomography (CT) or magnetic resonance imaging (MRI) may be helpful. Although gas can be seen on plain radiographs, the extent of damage is better visualized on a CT scan and even better through MRI, which does not depend on contrast. Fine needle aspiration, fascial biopsy, and surgical exploration are extremely helpful in diagnosing NF. Surgical exploration may be therapeutic as well. Pathognomonic for NF is the ability to introduce a hemostat into the wound and slide it easily along the fascial planes. Additional findings during surgical exploration include the presence of liquefactive necrotic tissue and/or pus in between the fascial planes.
The mainstay of NF treatment includes intravenous antibiotics, surgical debridement, and supportive care in an intensive care unit. 1–10,14–18 Both medical and surgical treatments are usually needed. A combination of broad-spectrum antibiotics, such as a penicillin, an aminoglycoside, or a third-generation cephalosporin, and clindamycin or metronidazole are needed to cover all potential bacteria until culture, gram stain, and sensitivity results are obtained and the antibiotic regimen can be adjusted accordingly.
After the diagnosis of NF is made, emergent surgical debridement and/or fasciotomy should be considered in the presence of deep infection. 1–10,14–18 After initial debridement, subsequent debridements should be done, 2,3,6,8 preferably beyond the margins of visible infection/necrosis. Fasciotomies may need to be performed at the time of debridement. 8,21 In extreme cases, when the infection cannot be controlled, amputation may be needed to prevent the patient’s death.
Supportive care in an intensive care unit is critical to survival of patients with NF. This involves fluid resuscitation, cardiac monitoring, and adequate nutritional support. 1,8,16 Patients with NF are in a catabolic state and require extra calories via oral or intravenous hyperalimentation. Caloric intake that is double what is normally required has been correlated with a lower complication rate. 1 Hyperalimentation should begin within 24 to 72 hours of diagnosis. 16 Laboratory values for albumin, prealbumin, transferrin, blood urea nitrogen, and triglycerides can be obtained to ensure that the patient is receiving adequate nutrition.
The use of hyperbaric oxygen (HBO) in the treatment of NF has been controversial. 1,2,5,6,8,17,18,21 It is postulated that HBO, by increasing the partial pressure of oxygen in tissues, will increase the killing ability of leukocytes, increase the killing of anaerobes, reduce tissue edema, stimulate fibroblast growth, increase collagen formation, reduce ischemia, enhance the action of antibiotics, stimulate angiogenesis, and promote granulation tissue. 5,8,18,21 Riseman et al 22 reported that HBO significantly reduced mortality in NF patients from 66% to 23%; however, Brown et al 23 showed that there was no significant reduction in mortality rates in NF patients (30% in the HBO group versus 42% in the non-HBO group).
Intravenous immunoglobulin (IVIg) has been shown to be an effective treatment for patients with Streptococcal toxic shock syndrome (STTS) by neutralizing the superantigens involved. 3 Because STTS and NF are mediated by the Streptococcal toxins, it is postulated that IVIg would be as effective in NF as it is in STTS. In addition, IVIg has been shown to decrease the hyperproliferation of T cells by binding Streptococcal toxin and opsonizing bacteria. 1,18 The reduction in T cells decreases the production of tumor necrosis factor, which is implicated in the progression of NF. While there have not been any prospective trials on the use of IVIg for treatment of NF, there have been sporadic reports on its benefit. 1–3,5,18 Kaul et al 24 reported a significant decrease in mortality in the group of patients receiving IVIg.
Hemorrhagic cellulitis, also known as bullous hemorrhagic cellulitis, is a variant of NF that has recently been described. 25 This condition has been associated with Gram-positive and Gram-negative infections of cutaneous and noncutaneous origins and preexisting systemic diseases, such as diabetes mellitus or malignancy. With this syndrome, there is an acute onset of painful erythema localized to dependent areas with hemorrhage (Figure 3). Blistering and sloughing of the necrotic areas follow. It is believed that the pathogenesis of this condition is related to lipopolysaccharide-induced or bacterial mitogen-induced tumor necrosis alpha (TNFa) secreted by activated macrophages. TNFa injures endothelial cells and epidermal keratinocytes via neutrophil degranulation and DNAse activation. Effective treatment for this condition includes a combination of antibiotics and corticosteroids. Corticosteroids act by inhibiting the secretion of TNFa and by blocking the cytotoxic effects of TNFa through membrane stabilization, preventing neutrophil degranulation.
Necrotizing fasciitis has the potential to be a severe life-threatening condition. Heightened clinician awareness is needed to ensure early diagnosis and rapid treatment.
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