The patient is a female in her 50s who presented with bilateral lower extremity swelling and right foot pain.

Figure 1. Right ankle xray showing multiple foci of subcutaneous gas within the ankle and subcutaneous gas tracking up the leg. — Figure 1. Right ankle xray showing multiple foci of subcutaneous gas within the ankle and subcutaneous gas tracking up the leg.

The patient states that approximately two weeks ago she began noticing swelling in her feet. Over the subsequent two weeks, she has noted worsening swelling and redness of the right foot that now extends up her leg. The patient also remarks that she noticed some bleeding from her right heel at the same time the symptoms started. She has had worsening pain in the right foot and lower leg. She has still been able to ambulate despite these symptoms, but does note that she is generally very sedentary. The patient does not know how long she has had the wound on her foot. She endorses some numbness in her bilateral feet, but states that this has been a chronic problem for her that has not worsened during this current illness. She denies fever, chills, chest pain, shortness of breath, cough, abdominal pain, nausea, vomiting, diarrhea, or dysuria. The patient admits that she has stopped taking all of her medications, including her insulin, for at least one month.

Past Medical History: Hypertension, Type 2 Diabetes Mellitus, Hyperlipidemia

Medications: None

Physical Exam

The patient is an alert, obese, unkempt female in no apparent distress. Her pupils are equal, round, and reactive. Mucous membranes are moist. She has clear breath sounds with good air entry bilaterally and normal respiratory effort. Her cardiovascular exam reveals a normal rate and rhythm and 2+ dorsalis pedis and posterior tibial pulses bilaterally. Her abdomen is soft, obese, and non-tender. Examination of her lower extremities reveals bilateral non-pitting edema to the level of the mid-shin, greater in the right leg than the left. She has tenderness over the right heel, dorsal right foot, and right shin. There is warmth and erythema of the right foot extending up to the level of the mid-calf/shin. There is a large ulceration encompassing the entire right heel with a considerable amount of eschar. There is no palpable crepitus or purulent drainage. She has 5/5 strength in the bilateral lower extremities.

Diagnostics

Glucose 657, Na 125, BUN 53, Cr 2.98, Anion Gap 19

Lactate 2.8

pH 7.34, pCO2 35, HCO3 19

WBC 24.2, Neutrophils 92.3%

CRP 373.5, ESR 74. CK 262

X-ray as above

Hospital Course

The patient’s history, exam and imaging studies were most consistent with a diagnosis of necrotizing fasciitis. In addition, her laboratory studies indicated that she was in DKA with an AKI. She was resuscitated with normal saline and started on broad-spectrum IV antibiotics (piperacillin-tazobactam, vancomycin, and clindamycin). The patient was admitted to the SICU where a central line was placed and she was started on an insulin drip to improve glucose control prior to operative management. As an inpatient, she underwent a right below knee amputation, which was ultimately followed two weeks later by a right above the knee amputation. Wound culture and blood cultures grew MSSA. She completed a 10-day course of doxycycline and ceftriaxone. After 10 days, the ceftriaxone was discontinued due to concern for HUS and doxycycline was changed to nafcillin at the recommendation of Infectious Disease. Her DKA resolved, but her renal function did not recover. It was believed patient likely had chronic underlying CKD, and she was ultimately started on intermittent hemodialysis that was continued after discharge. After a 3-week hospitalization, she was discharged to a SNF where she continued nafcillin for 10 more days to complete a total of a 4-week course.

Necrotizing Fasciitis

Necrotizing fasciitis is a dreaded diagnosis. Fortunately, it is an extremely rare condition, with an estimated annual incidence of only 1000 cases in the United States.[1] Most clinicians will only see a few true cases during their careers. A rapidly progressive infection of the subcutaneous tissues, its aggressiveness accounts for its significant mortality rate of 20% or higher. Untreated, its mortality rate approaches 100%. As such, it is crucial that EM physicians recognize the early signs of necrotizing fasciitis and treat appropriately.

Although necrotizing fasciitis can occur anywhere on the body, the most common location is the lower leg. Patients at increased risk for this clinical presentation include those with diabetes, vascular insufficiency and immunosuppression. In 80% of cases, necrotizing fasciitis is the result of direct extension from a skin lesion. The type of skin lesion is quite variable and includes penetrating trauma, surgical incisions, diabetic eschars, pressure ulcers, IV drug injection sites, burn injuries, varicella infection, and from childbirth.[2] When infection occurs in the perineal, genital or perianal regions, it is referred to as Fournier's gangrene. This is more commonly seen in males, diabetics, the immunosuppressed, and chronic alcohol abusers.[3]

Once bacteria have breached the skin, infection sets in in the superficial fascia. The bacteria produce and release proteins, enzymes, and exotoxins that trigger an inflammatory response and cause breakdown and necrosis of the fascial layers. Exotoxins also inhibit neutrophils which can facilitate bacterial growth. As the bacteria multiply, they spread horizontally along the fascial planes, which is why initially there may not be significant overlying skin changes. The bacterial enzymes and toxins also result in thrombosis of the arteries and veins, causing tissue ischemia and further necrosis.[4]

There are three main types of necrotizing fasciitis. Type I is polymicrobial and is usually seen in the elderly, diabetics, or those with chronic medical illnesses. This typically affects the trunk and perineum. Often there is no history of trauma, but rather breakdown in the skin secondary to pre-existing abscesses, perforations or bacterial translocation from the GI or GU tracts. Type II is caused by Group A strep or staphylococci and is commonly referred to as “flesh-eating disease.” Type III is due to Clostridia perfringens and is commonly called “gas gangrene.” Some reports will also describe a Type IV that is caused by fungal infections (candida and zygomecetes), but this is by far the least common. There is no difference in the clinical course, morbidity, or mortality between these different types. For EM physicians, timely recognition and treatment is more important than identifying the type of infection or the causative agent.

Early in the disease course, symptoms may be vague with pain in the affected area and possibly some associated flu-like symptoms (e.g., fever, nausea, general malaise). Within several hours to days, the site will start to swell and may develop a purplish/reddish rash. Distinguishing between necrotizing fasciitis and simple cellulitis can be challenging. However, there are some findings that are suggestive of more serious infection, including systemic toxicity, severe pain, pain out of proportion to exam findings, and crepitus. Alternatively, there may be the absence of pain once necrosis destroys the peripheral nerves. Unfortunately, these findings can be nonspecific and have low sensitivity. Although subcutaneous air and crepitus are traditionally taught to be classic findings, they are actually rarely seen. Quite possibly the most important information a physician can obtain on initial history and physical exam is the chronicity. Unlike simple cellulitis, necrotizing fasciitis usually advances at a much more rapid pace. Significant progression will be noted over the order of several hours rather than several days.

Beyond the initial assessment, there have been studies to look at more objective findings for predicting the diagnosis of necrotizing fasciitis. In two studies by Wall et al., they demonstrated that a white blood cell count <15,000 cells/mm3 and a sodium level >135 mmol/L had a 99% negative predictive value and 90% sensitivity for ruling out necrotizing fasciitis.[5,6]

Table 1: Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score Parameters. Wong et al, 2004.

A few years later, Wong et al. proposed a scoring tool for predicting whether a patient was likely to have necrotizing fasciitis. Known as the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), it factors in CRP, WBC count, hemoglobin, serum sodium, creatinine, and glucose, assigning point values as shown in Table 1. Ninety two percent of patients with a LRINEC score of six or more were found to have true necrotizing fasciitis. Furthermore, of all the patients with a total score of less than six, only 4% had necrotizing fasciitis.[7] The disadvantage of this tool that clinicians must bear in mind is that it is derived from a single study and has never been validated. It is plausible that other conditions could produce the same abnormal lab values, and this makes it especially difficult to apply in conditions where other inflammatory states are present. As such, while this can be a useful tool to take into consideration in a diagnostic dilemma, it should be interpreted with caution within the context of the entire clinical picture and should not be the sole determinant in clinical decision-making.

Once the clinician has determined that there is significant concern for possible necrotizing fasciitis, the most important immediate actions are to contact surgery and start empiric broad-spectrum antibiotic coverage. Imaging studies may be obtained but there are two disadvantages to doing so. First, if obtaining the imaging creates any delay to antibiotic administration or surgical management, they are more likely to be of more harm than utility. Second, there are no well-designed or adequately powered studies to compare what is the best imaging modality to aid in this diagnosis. Plain films are the most commonly obtained to assess for subcutaneous gas; however, despite this being a specific finding, it is not particularly sensitive and cannot be used to definitely rule out necrotizing infection.

The initial choice for antibiotics should include coverage of gram-positive, gram-negative and anaerobic organisms. A typical regimen includes vancomycin and clindamycin, along with a broad-spectrum β-lactam (i.e., piperacillin-tazobactam or ampicillin-sulbactam). Intravenous immunoglobulin (IVIG) has been proposed as an adjunctive therapy, with the theory that it binds exotoxins and super antigens produced by staphylococcal and streptococcal bacteria, thereby limiting the systemic inflammatory response.[8]The evidence that exists supporting the use of IVIG comes mostly from underpowered and non-randomized studies and there have been no randomized controlled trials that have confirmed its benefit.[9] There does not appear to be significant harm associated with its use, however, and may be worth consideration in a critically ill patient who continues to deteriorate despite appropriate antibiotics and large surgical debridement.

Ultimately, the most important intervention is surgery. Therefore, the goal of the EM physician should be to minimize the delay in getting the patient to the OR. There have been multiple studies over the years that have demonstrated that an increase in the amount of time from admission to surgical intervention is associated with increased mortality.[10,11] The same authors who developed the LRINEC score reported that there was a nine-fold increase in the mortality risk if surgical treatment was delayed by >24 hours from the time of diagnosis. In a more recent study, it was found that a delay of>12 hours to initial surgical debridement was associated with an increase in the number of surgical procedures required, as well as a higher incidence of septic shock and acute renal failure.[12]

In sum, necrotizing fasciitis is a rarely seen condition with high morbidity and mortality that relies on rapid recognition and prompt intervention. Emergency Department physicians must be able to identify the findings by history and on physical exam that point toward a higher risk for necrotizing infection, including rapid progression, pain out of proportion to exam, peripheral anesthesia, and possibly skin findings such as erythema, bullae, ecchymosis, and crepitus. They may also apply the LRINEC score if the clinical diagnosis is more ambiguous. While laboratory and imaging studies may provide further support of the diagnosis, administering appropriate antibiotics and getting surgery involved should never be postponed if there is high clinical suspicion based on history and physical alone. Ultimately, the final diagnosis can only be made by inspection in the OR. Given the severe consequences of delaying treatment, it is always better to err on the side of caution if this deadly diagnosis is on the differential.

Authored by Alexa Sabedra, MD Posted by Grace Lagasse, MD