Necrotizing fasciitis

Description

Necrotizing fasciitis is a rare and rapidly progressive infection of the subcutaneous tissue that presents a surgical emergency. The infection moves along fascial planes, destroying fascia and fat, while sparing the underlying muscle tissue, and can affect any part of the body. Prompt diagnosis and aggressive treatment are of utmost importance due to a high degree of morbidity and mortality associated with necrotizing fasciitis.

Clinical Manifestations

History: Patients typically have a prior history of trauma or surgery, even minor, but idiopathic cases are not uncommon. On initial presentation, the patient is often in severe pain or there is tenderness of the underlying tissue and muscle. It is not uncommon for patients to mistake the pain for a torn muscle. Unexplained pain, or pain out of proportion to injury, may be the first presenting symptom of necrotizing fasciitis. Over hours to days, pain progresses to local anaesthesia due to destruction of peripheral nerves. These signs and symptoms are often seen before those of infection, such as fever or malaise. Due to the paucity of initial symptoms, a high index suspicion is required when evaluating patients on initial presentation.                        

Physical Exam: Many times, physical examination findings do not correlate with the extent of disease or patient discomfort, which can lead to a delay in diagnosis and treatment. In a study done by Wong et al, the absence of cutaneous findings early on can make the diagnosis of necrotizing fasciitis difficult. Only 15% of the patients studied were accurately diagnosed at the time of admission. On physical exam, tenderness beyond the margins of infection, erythema, warmth of the skin upon palpation, and pain out of proportion to physical findings were common features.

Initial signs and symptoms are non-specific and are generally related to inflammation and systemic toxicity – swelling, erythema, fever, exquisite pain and tachycardia. Additionally, thrombosis of vessels can occur and cause local anaesthesia due to necrosis of the nerve fibers. Erythema is typically seen first and over hours to days, the overlying skin becomes increasingly erythematous and tense. As the infection progresses, tense edema, crepitus, pain out of proportion to appearance, subcutaneous gas, bullae and necrosis develop. Bullae filled with serous fluid should raise clinical suspicion of necrotizing fasciitis and can be an important diagnostic clue. While these are considered typical clinical features of necrotizing fasciitis, their sensitivity is low and they are only present in 10-40% of patients.

Necrotizing fasciitis can present with a somewhat typical progression. Initially, the involved skin may change color from a red-purple to dusky blue, which is followed by bullae formation. Bullae contain clear fluid at first, but the fluid progresses to a blue/maroon color and becomes necrotic and hemorrhagic. The presence of bullae signifies extensive deep soft tissue destruction.

If the skin is open, exploration by a gloved hand may reveal yellow-green necrotic fascia. In such cases, fingers can be passed between fascial layers with ease, a positive "finger test". If the skin remains intact, a scalpel may be used to open the skin and perform a finger test. Underlying muscle generally remains healthy, signalled by a red and bleeding appearance, and can be visualized under the yellow-green fascial layer. However, if left untreated, infection can spread to involve the underlying muscle, leading to myositis or myonecrosis.

Red Flags

Patients presenting with a history of trauma or surgery, pain out of proportion to physical findings, and signs of infection should be evaluated for necrotizing fasciitis and considered for prompt surgical exploration with debridement. Additionally, persistence or rapid progression of infection, despite intravenous antibiotic use, is an important sign in the early stages of necrotizing fasciitis. Surgical exploration should never be delayed for imaging, especially if there is crepitus or evidence of a spreading soft tissue infection.

Epidemiology

There are approximately 500-1500 cases of necrotizing fasciitis each year in the United States. The mean age at onset is 38-44, with males being affected more often than females. Most patients who develop necrotizing fasciitis have a predisposing comborbidity or history of trauma rendering them susceptible to disease. Possible trauma causes include an insect bite, scratch, abrasion or surgery. Pre-existing medical conditions resulting in immunosupression include diabetes mellitus, vascular disease, advanced age, cancers, HIV infection and IV drug use are predisposing risk factors.

Pathology and Pathophysiology

Necrotizing fasciitis is characterized by widespread infection of the subcutaneous tissue and fat. It has traditionally been thought that group A Streptococcus (GAS) is the most common organism involved. However, according to Hasham et al, only 15% of cases of necrotizing fasciitis were caused by a single pathogen, GAS or otherwise. Most commonly the cause is polymicrobial, with anaerobic and aerobic gram negative organisms being the most likely causative agents.

As a result of their metabolism, anaerobic and aerobic organisms produce gases. These gases accumulate in soft tissues, due to reduced water solubility, which can lead to subcutaneous gas formation and crepitus. Additionally, anaerobic organisms thrive in the hypoxic environment created by a patients pre-existing medical condition or injury. Furthermore, in hypoxic environments, the function of polymorphonuclear leukocytes decreases, allowing facultative aerobes to proliferate. The subsequent abundance of organisms further lowers the oxidation/reduction potential leading to an even greater proliferation of the anaerobic organisms and furthering disease. Moreover, toxins and enzymes released by the bacteria involved, further facilitates the spread of the organism along superficial and deep fascia. The result is a deep seeded infection with vascular occlusion, superficial nerve damage, ischemia, and tissue necrosis (Medscape).

There are two clinical types of necrotizing fasciitis:

Type I Necrotizing Fasciitis accounts for the majority of cases, and is a polymicrobial infection by non-GAS aerobic and anaerobic bacteria. The most common species involved are streptococcal, staphycoccal, enterococci and enterobacteriaceae. This infection occurs most commonly after a surgical procedure or in patients with coexisting comorbidities such as diabetes mellitus, peripheral vascular disease, or other causes of immunosupression. Necrotizing fasciitis secondary to a surgical wound infection has a characteristic appearance of profuse dishwater drainage, crumbly subcutaneous tissue and debilitated fascia.

Fournier’s Gangrene is an aggressive variant of type I necrotizing fasciitis that affects the perineal area. Organisms penetrate the gastrointestinal or urethral mucosa, beginning abruptly and causing severe pain. Infection can spread rapidly to gluteal muscles, anterior abdominal wall and, in males, the scrotum and penis.

Another variant of type I necrotizing fasciitis is Saltwater Necrotizing Fasciitis, which occurs when a minor skin wound becomes contaminated with saltwater containing Vibrio species.

Type II Necrotizing Fasciitis is typically a monomicrobial infection caused by GAS alone or with Staphylococcus and tends to occur in patients with no underlying comorbidities. Predisposing factors include those that allow for skin entry of GAS, such as surgical procedures, infection with varicella, a history of blunt trauma, injection drug use, child birth and burns. M protein, an important virulence factor of GAS, produces pyrogenic exotoxins that act as superantigens causing a rapid proliferation of T cells. The T cells cause stimulation of the host immune system resulting in production of cytokines like TNF-a, leading to shock, tissue destruction, and possible organ failure.

Differential Diagnosis

Several other cutaneous infections can present similarly to necrotizing fasciitis such as cellulitis, gas gangrene, pyomyositis, myositis, and toxic shock syndrome. And, as previously mentioned, any illness or disease that suppresses ones immune system can be associated with necrotizing fasciitis by pre-disposing a patient, and eventually allowing for disease.

Etiology

Although the etiology of necrotizing fasciitis is not entirely known, most patients have a comorbidity of some sort rendering them susceptible to disease. 20–40% of patients who develop necrotizing fasciitis have diabetes mellitus, but up to half can be previously young and healthy.

Patients frequently have a history of trauma that causes disruption of skin integrity. Possible examples include:

• an insect bite that introduces Streptococcus into a wound
• a decubitus ulcer in a patient with spinal cord injury
• a surgical procedure causing local tissue damage and invasion by bacteria
• systemic illness causing ischemia and hypoxia

Radiographic and Laboratory Findings

Imaging and laboratory studies are important in the workup of necrotizing fasciitis. A risk score to asses the severity of necrotizing fasciitis was established retrospectively. Using six different laboratory values, the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) measures six variables found in necrotizing fasciitis: white cell count, CRP, hemoglobin, serum sodium, serum glucose, and serum creatinine concentration. The maximum score is 13; scores >6 raise suspicion of necrotizing fasciitis and a score of >8 is strongly predictive of disease.

Variable, Units	Score	Variable, Units	Score
C-Reactive Protein, mg/L		Sodium, mmol/L
<150	0	>135	0
>150	4	<135	2
Total WBC Count, per mm3		Creatinine, mg/dL
<15	0	<141	0
15-25	1	>141	2
>25	2	Glucose, mmol/L
Hemoglobin, g/dL		<10	0
>13.5	0	>10	1
11-13.5	1
<11	2

• 50-75% of patients with a score of >6 developed necrotizing fasciitis, with a positive predictive value (PPV) of 92%
• Greater than 75% of patients with a score of >8 developed necrotizing fasciitis, with a PPV of 93.4%

The LRINEC is useful not only because of it’s high positive predictive value, but also because other soft tissue infections, such as cellulitis and abscesses, do not cause enough of an inflammatory response to have the same effect on the variables included in the calculation.

Imaging: Plain radiograph studies are very specific, but not sensitive, and may merely delay treatment if necrotizing fasciitis is indeed present. Plain films only help to identifying subcutaneous gas, which does not necessarily indicate infection since some organisms produce subcutaneous gas under normal conditions (i.e. Escherichia coli, Peptostreptococcus, Bacteroides). Perforations of the esophagus or abdominal organs may also appear as gas on radiograph.

Computed tomography (CT) and magnetic resonance imaging (MRI) are useful in checking for the absence of deeper tissue involvement in cases where the suspicion of necrotizing fasciitis is raised, but is clinically unlikely. A study looking at four elements of necrotizing fasciitis on CT.  The four elements were: asymmetrical and diffuse soft tissue inflammation and ischemia; muscle necrosis; gas in tissue planes; fluid collections. The study found CT imaging to be 100% sensitive and 81% specific, and when positive, correlated with disease 76% of the time. This study suggested that CT can reliably exclude disease and, as a result, prevent unnecessary surgical exploration. By comparison, MRI has been found to be overly sensitive due to overestimation of the extent of deep fascial involvement. This can lead to mislabelling cellultis as necrotizing fasciitis and resulting in unnecessary surgical exploration.

In all situations, surgical exploration should never be delayed for imaging, especially if there is crepitus or evidence of a spreading soft tissue infection.

Finger Test and Frozen Section Analysis: The finger test is a procedure that can be done surgically or as a bedside procedure. After application of local anaesthesia, a 2 cm incision is made down to the deep fascia. A gloved index finger is then used to probe down at the level of the deep fascia. A positive finger test is signified by a lack of resistance of tissues to blunt dissection, lack of bleeding, gray necrotic tissue, and “dishwater” pus, and suggests a diagnosis of necrotizing fasciitis. Some use these signs as a definitive diagnosis for necrotizing fasciitis.

Frozen section analysis can be done from the tissue obtained during the finger test. On examination, characteristic histological appearances seen with necrotizing fasciitis include: subcutaneous tissue necrosis, vessel obliteration, and acute inflammation.

Risk Factors and Prevention

Unfortunately, true risk factors for necrotizing fasciitis have not been established. Nevertheless, maintaining a healthy lifestyle, and thus preventing possible comorbidities that can predispose one to necrotizing fasciitis, is recommended. However, there are comorbidities that are unavoidable, (i.e. diabetes mellitus, cancer) no matter how healthy of a lifestyle an individual maintains. Additionally, avoiding the use of needles, especially for use of elicit drugs, is strongly recommended.

The single most important preventative measure is maintenance of skin integrity. Any break in the skin, even a small needle prick, can be enough to allow for infection and subsequent necrotizing fasciitis. In the event that a wound or infection does develop, it is imperative to properly cover and treat them in a timely manner. Some important considerations to help minimize the risk of developing necrotizing fasciitis from a pre-existing wound include cleaning and washing any wounds and applying an antibiotic ointment or seeking medical treatment. That being said, there is no true certain measure for prevention for necrotizing fasciitis.

Treatment Options

Once necrotizing fasciitis has been diagnosed, treatment must be initiated immediately as it is a surgical emergency. A team approach should be utilized consisting of a surgeon, microbiologist, and infectious disease specialist.  A plastic surgeon and urologist may be needed depending on the location and extent of infection. The mainstay of treatment is organ support, broad spectrum intravenous antibiotics, and complete surgical debridement of infection. When treatment consists of only organ support and antimicrobial therapy, mortality is nearly 100%. Control of infection and subsequent recovery are only accomplished by complete surgical debridement of the infected tissue.

Surgery: Early and thorough surgical debridement of necrotic tissue greatly improves the chances of recovery and can be life, and limb, saving. Additionally, any delay of surgery for more than 24 hours after admission has been found to be the only independent predictor of mortality. Surgery not only provides debridement of the infected areas, but can also be used to establish a definitive diagnosis. Definitive diagnosis can be evidenced by the following findings during operation: gray necrotic tissue, lack of resistance to blunt dissection ("positive finger test), absence of bleeding of the fascia during dissection, and the presence of foul-smelling “dishwater” pus.

Due to thrombosis of surrounding vessels, delivery of antimicrobial medications to the infected area is often ineffective. As a result, surgical debridement of all necrotic tissue is extremely important. An incision should be made down to the deep fascial layer, and all non-viable tissue, including fascia, removed. The surrounding tissue should be excised until healthy, bleeding tissue is seen at the wound margins. The wound should then be irrigated well, left open, and the patient managed in an intensive care unit for close monitoring. Surgical debridement should be repeated at intervals of 6-48 hours, depending on extent of infection, to ensure that all necrotic tissue has been removed and the infection has not spread. Surgical excisions may be necessary earlier than scheduled if there is an increase in peripheral leukocytes or evidence of physiologic decline.

Antimicrobial Treatment: Antimicrobial treatment is a good adjunct to control infection and can help during the acute phase of infection. Broad spectrum antibiotics should be started early and include coverage for gram positive cocci, gram negative rods, and anaerobic organisms, and then narrowed based on culture and sensitivity studies of the organism. Treatment should be continued until the patient is physiologically stable and for several days following the last surgical debridement. While the use monotherapy agents is acceptable, a multidrug regimen such as penicillin G, gentamicin (if renal function allows), plus clindamycin or metronnidazole, is suggested. Vancomycin should also be included until it is known that methicillin-resistant Staphylococcus aureus (MRSA) is not involved.

Organ Support: Close monitoring in an intensive care unit and physiologic support is mandatory. Many patients with necrotizing fasciitis develop organ failure, including acute kidney failure or acute respiratory distress syndrome, and require resuscitation. Patients may also require blood replacement following surgery. Furthermore, intravenous fluids, sometimes in very large amounts, may be needed due to persistent hypotension and capillary leak. Early nutritional support, via an enteral feeding tube, is important to offset the catabolic response seen in these patients. Careful control of glucose and fluid levels are important as well.

Once all necrotic tissue has been debrided, soft tissue reconstruction can be considered. If less than 25% of the body surface area is involved, skin grafts and flaps can provide adequate coverage. Otherwise, alternative skin grafting measures should be considered, such as integra artificial skin and AlloDerm.

Outcomes

Necrotizing fasciitis has a high mortality rate of about 21%. The mean age of survivors is 35, and of non-survivors, 49. Untreated, or without surgical debridement, mortality is nearly 100%. According to a study done by Wong et al, the three factors that predicted poor survival were advanced age, the presence of two or more associated comorbidities, and a delay of greater than 24 hours from admission to surgery.

Other complications associated with necrotizing fasciitis include:

• Renal failure
• Septic shock with cardiovascular collapse
• Scarring with cosmetic deformity
• Sepsis
• Toxic Shock Syndrome

Limb loss is another important complication of necrotizing fasciitis. While the need for amputation may occur in anyone, but there is a much higher risk in patients with coexisting diabetes mellitus or other vascular disease.

Holistic Medicine

Non-pharmacologic measures are important for prior health of the patient and in recovery. Post-infection deformity, can have considerable psychosocial and economic effects on the patient. Loss of a limb could prevent the return to a specific profession, or work in general, and place a substantial financial burden on the patient.

Miscellany

Key Terms

• Necrotizing fasciitis
• Flesh eating bacteria
• Sepsis

Skills and Competencies

• Have a high index of suspicion in anyone with exquisite pain and a cutaneous infection
• Know the components of LRINEC and how it is interpreted
• Know which broad spectrum antimicrobial agents to use initially and how to adjust the regimen once an organism has been identified
• Awareness and management of possible resultant organ failure

References

1. Wong CH, Khin LW, Heng KS, Tan KC, Low CO. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: A tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med. 2004 Jul;32(7):1535-41 ???PubMed

2. Wong CH, Chang HW, Pasupathy S, Khin LW, Tan JL, Low CO. Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am. 2003 Aug;85-A(8):1454-60 ?PubMed

3. Hasham S, Matteucci P, Stanley PR, Hart NB. Necrotizing fasciitis. BMJ. 2005 Apr 9;330(7495):830-3 ?PubMed

4. Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management. Clin Infect Dis. 2007 Mar 1;44(5):705-10 ?PubMed

5. Zacharias N, Velmahos GC, Salama A, Alam HB, de Moya M, King DR, Novelline RA. Diagnosis of necrotizing soft tissue infections by computed tomography. Arch Surg. 2010 May;145(5):452-55 ?PubMed