Triple diagnostics for early detection of ambivalent necrotizing fasciitis

Necrotizing fasciitis is a relatively rare disease, which describes a group of infections that comprises skin, soft tissue and muscle and swiftly can spread through fascial planes [1‐3]. The disease can be rapidly progressive and can have devastating outcome with many patients not surviving the infection (up to 70 % mortality rate reported in past series) [2]. Early diagnosis followed by immediate and thorough surgical debridement of affected tissue is necessary to prevent mortality and curb the systemic effects from resultant sepsis. However, diagnosis in the early stages can be challenging [4, 5]. Patients with necrotizing fasciitis might be brought to the ICU because of their sepsis without known cause and later prove unresponsive to resuscitation therapy [6, 7]. In a systematic review, a close correlation between the percentage of initially missed cases and the mortality rate in the presented cohort series has been described [8]. A 75 % mortality reduction has been reported if operated within 12 h after onset [9‐13]. Moreover, a mismatch between external signs and affected fascia has been mentioned. Thus, early recognition, timely surgery and thorough initial debridement are mandatory for survival [6, 8].

Over the last decade, mortality rate has decreased to 20-40 % in reported series [14‐17]. Some have attributed this to the improved awareness for necrotizing fasciitis at general practitioners and ED-physicians, probably due to the attention that has been given to this disease in medical journals and general media [18]. Due to this improved awareness, patients are presented to the different surgical specialties in more early stages of their disease. This is a challenge for the treating surgeon, as local signs can be minimal and only become more prominent as the disease progresses [19]. In these early stages of necrotizing fasciitis, triple diagnostics is suggested to be a useful adjunct in obtaining a diagnosis [20]. We provide an algorithm that contributes in the early phases of these patients in which a fresh frozen section and Gram staining can be of paramount importance to the treating surgeon. Implementation of this algorithm was analysed.

In a three year period, 21 non-transferred cases were presented to the emergency department who underwent incision biopsy or operative debridement. Their average age was 53 (range 34–75) and most patients suffered from severe comorbidities (6 ASA I, 4 ASA II, 2 ASA III and 9 (47 %) ASA IV patients). In 11 patients, diagnoses was confirmed based on intra-operative macroscopic findings of fascial necrosis. There were 10 ambivalent cases with only macroscopic peri-fascial oedema or necrosis of the subcutaneous fatty tissue, in which fresh frozen section and Gram staining resulted in a change in treatment strategy in six patients. Based on macroscopic findings the surgeon would have ended the surgical procedure, but instead extended the incisional area and focal necrosis was found at a distant side in all 6 patients. Follow-up proved that 4/21 patients did not have necrotizing fasciitis (Fig. 2). Group A Streptococcus were found in 8 of the 17 patients with confirmed necrotizing fasciitis. Mortality due to necrotizing fasciitis was the outcome in two patients (12.5 %) and 2 additional patients died within the first 30 days after admission due to other pre-existing conditions (25 % total 30 day mortality).

In this cohort series we present the results of an algorithm which uses triple diagnostics for ambivalent cases of necrotizing fasciitis in the very early stages of the disease. In patients with an ambivalent presentation and no clear macroscopic necrosis of the fascia during incisional biopsy, the combination of a fresh frozen section and Gram staining altered treatment in 60 % of the cases. All of which later proved to be necrotizing fasciitis based on clinical follow-up. Mortality due to necrotizing fasciitis in this series was 12.5 % and overall mortality was 25 %, which is a fair result considering the large number of ASA IV classified patients.

The mortality rate in the present series is identical to the first report (12.5 %) on the use of histology in necrotizing fasciitis [20]. It was discussed if the relative low mortality was the result of the early operative debridement or could be attributed to the histology [19]. We feel that the use of histology and Gram staining results in more timely decision making and therefore early debridement and source control.

Necrotizing fasciitis is rare and heterogeneous in its presentation for body region as it can occur in every fascia and mimic many other infectious and non-infectious diseases. As a result, numbers per treating physician and expertise gained with this disease are often limited. In addition, physicians frequently find it a “scary” disease, because of its rapid progression and the necessary thorough debridement that might result in bad function and appearance [24].

Awareness is advocated in patients with sudden onset and rapid progression of a suspected infectious disease. Disproportional pain is often referred to as the common denominator in this disease and should trigger further investigation. More classical symptoms for necrotizing fasciitis, such as erythema, oedema, blisters, crepitus, and skin necrosis have been described in only 10–40 % of the cases and are seldom seen within the first 24 h [22, 32, 33]. The difficulty in recognition is further stretched by underlying conditions, for instance trauma, vascular disease, diabetic wounds or drug abuse [24]. Co-morbidities are found in nearly 50 % of patients with necrotizing fasciitis and frequently some form of trauma (blunt or penetrating) preceded symptoms. In the present series 55 % suffered severe co-morbidities such as congestive heart failure, renal insufficiency or acute leukemia. Although heterogeneous in its presentation, the philosophy of early identification and aggressive holistic treatment is uniform. This is often referred to as the “search and destroy” strategy [7, 21, 31, 34, 35]. In the presented cohort, a total of 4 patients were brought to the operation room based on clinical suspicion, who did not prove to have necrotizing fasciitis, This demonstrates the low threshold for incisional biopsy when necrotizing fasciitis is suspected, leading to a relative over treatment of patients with a less severe condition (i.e. erysipelas).

Proposed classifications are universal and either based on location or microbiology [36, 37]. Locations which are often affected are the trunk, extremities and the maxillofacial region. Frequently encountered specific locations include Fournier (perineum), Ludwig’s angina (submandibular) and Meleney’s synergistic gangrene (abdominal wall and/or post-operative) [24, 25, 38].

Classification by microbiology covers all locations, although some locations are more associated with a specific type than others. Type 1 accounts for 55–90 % of all cases and consists of a polymicrobial flora [24, 26, 38, 39]. Fournier is often associated with type 1 necrotizing fasciitis. Type 2 consists of a mono-microbial flora, of which necrotizing fasciitis with Group A Haemolytic Streptococcus (GAS, also called Streptococcus pyogenes) is the most important one. Other suggested classification groups are type 3 for virulent Gram negative bacilli (i.e. Vibrio species) and type 4 for fungi and yeasts (i.e. Cryptococcus or Candida species) [40]. Microbiological findings, and thus classification types, are highly geographically dependant. For instance, Vibrio species is mostly situated in Asia, while methicillin-resistant Staphylococcus aureus (MRSA) is seldom seen in the northern region of Europe [41, 42]. In order to combine multiple aetiologies, it has been proposed to integrate all types of necrotizing fasciitis like entities in the diagnose of severe necrotizing soft tissue disease as therapy is similar [43]. In addition, the potential whole body presentation causes many different medical specialties to be confronted with necrotizing fasciitis, resulting in more scattered experience. This stretches the need for a universal treatment algorithm [34, 44, 45].

To aid in the identification of patients with necrotizing fasciitis, several adjuncts have been described. A large base deficit or high Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score have been suggested to increase the possibility of a patient having necrotizing fasciitis, however, they are not tools to provide a definitive diagnosis [16, 32, 33, 46, 47]. Their values may provide insight in the severity of disease, however, sensitivity remains low [7, 48, 49].

Imaging studies might provide additional information. Although air in the fascial planes is seldom present in the early stages and fascial fluid collections are not always seen. Moreover, CT-scanning might provide information about underlying conditions in cases for necrotizing fasciitis in the maxillo-facial area or trunk (Fournier), such as diverticulitis or abscesses. Some clinics have incorporated CT-scanning in their standard work-up for hemodynamic stable patients with fasciitis to screen for underlying pathology. In certain cases CT helps to evaluate the extent of tissue infection showing swelling, inflammation and gas formation.

MRI scanning proves to have the highest sensitivity and specificity [50]. However, MRI scanning may not be desirable in all patients or available in all hospitals. Furthermore, the exact contribution of imaging modalities in the early stages of necrotizing fasciitis is still under debate and should always be correlated with the clinical presentation [48, 51, 52]. In more advanced cases treatment should not be delayed for imaging. Taken together, clinical suspicion should outweigh both laboratory and imaging adjuncts for the diagnosis of necrotizing fasciitis, especially in the early stages of the disease, where the therapeutic yield of debridement is the greatest [9]. Clinical suspicion can be supported by fresh frozen section and Gram staining during incisional biopsy and might result in more timely identification of this life threatening condition.