Point-of-care ultrasonography in diagnosing necrotizing fasciitis—a literature review

Introduction Necrotizing fasciitis (NF) is a rapidly progressive necrosis of the fascial layer with a high mortality rate. It is a life-threatening medical emergency that requires urgent treatment. Lack of skin finding in NF made diagnosis difficult and required a high clinical index of suspicion. The use of ultrasound may guide clinicians in improving diagnostic speed and accuracy, thus leading to improved management decisions and patient outcomes. This literature search aims to review the use of point-of-care ultrasonography in diagnosing necrotizing fasciitis. Method We searched relevant electronic databases, including PUBMED, MEDLINE, and SCOPUS, and performed a systematic review. Keywords used were “necrotizing fasciitis” or “necrotising fasciitis” or “necrotizing soft tissue infections” and “point-of-care ultrasonography” “ultrasonography” or “ultrasound”. No temporal limitation was set. An additional search was performed via google scholar, and the top 100 entry was screened. Results Among 540 papers screened, only 21 were related to diagnosing necrotizing fasciitis using ultrasonography. The outcome includes three observational studies, 16 case reports, and two case series, covering the period from 1976 to 2022. Conclusion Although the use of ultrasonography in diagnosing NF was published in several papers with promising results, more studies are required to investigate its diagnostic accuracy and potential to reduce time delay before surgical intervention, morbidity, and mortality.


Introduction
Necrotizing fasciitis (NF), also known as necrotizing soft tissue infections, is defined as rapidly progressive necrosis of the fascial layer, often sparing the overlying skin and underlying muscle. NF is difficult to diagnose in its early stages due to a lack of skin findings, requiring a high clinical index of suspicion [1]. NF of the limbs accounts for a 30% mortality rate, despite new advancements in treatment and critical care management [2]. Early diagnosis of NF is vital for surgical intervention, reducing a patient's morbidity and mortality [3].
The clinical feature of NF includes fever, edema, pain, and redness with rapid deterioration into dusky-blue discoloration, with or without serosanguineous blister and crepitus. The definitive diagnosis of NF is invasive, which requires surgical exploration of the tissues [4]. Laboratories Risk Indicator for Necrotizing Fasciitis (LRINEC) may help assess a patient's risk of NF. However, LRINEC has low sensitivity and is not recommended to be used to rule out NF [5].
Advanced imaging, such as magnetic resonance imaging (MRI), is currently the gold standard for diagnosing necrotizing fasciitis, with a sensitivity of 93% [6]. Other options, such as computed tomography (CT) scan, also has high sensitivity (80%) in diagnosing NF [6]. However, MRI and CT scans are costly and not readily available in all emergency department settings. Furthermore, the use of MRI requires hours from arrangement until the results are available [7]. In addition, there is a case reported by Kehrl et al. on necrotizing fasciitis detected by ultrasonography which was missed by using CT and MRI scans [8].
Although MRI and CT scans are mainstream diagnostic modalities, point-of-care ultrasonography (POCUS) could also be handy. POCUS is defined as ultrasonography performed by the provider to obtain real-time images [9]. The nature of POCUS allows it to be easily performed and repeated anytime when required [9]. POCUS is convenient, relatively affordable, and non-invasive. POCUS will enable clinicians to obtain real-time dynamic images that could guide clinicians in diagnosing NF. The ultrasonographic findings of necrotizing fasciitis are described as STAFF-Subcutaneous irregularity or Thickening, Air and Fascial Fluid [10].
This literature search aims to review the use of pointof-care ultrasonography in diagnosing necrotizing fasciitis.

Materials and methods
A literature review was performed to collect all the relevant publications, such as original research, reports, review, and case series concerning the use of POCUS in diagnosing NF. PubMed, MEDLINE, and SCOPUS databases were searched to locate studies that meet the objectives of this literature review. The research strategy used was: ((necrotizing fasciitis) OR (necrotising fasciitis) OR (necrotizing soft tissue infection)) AND ((point-of-care ultrasonography) OR (ultrasonography) OR (ultrasound)). No time limitation was set. An additional search was performed via Google Scholar, and the top 100 entry was screened manually.
The search included all articles that appeared in the literature until June 2022. First, full articles were retrieved and assessed for their suitability for review. The resulting studies were then screened initially based on their respective titles and abstracts. The flow of information in this literature review isshown in fig. 1.
The exclusion criteria were: 1. Incomplete documentation of the use of ultrasound in the diagnosis.
In the eligibility stage, the selected articles were: 1. English language reports. 2. the use of ultrasonography diagnosis for necrotizing fasciitis.
The eligible articles were extracted by two authors (the first and second) independently using predefined criteria. After the screening, the results were compared. The third reviewer resolved disharmonies between the first two authors. Next, duplicated data were removed using End-Note. The information was then extracted based on the PICO (patient, intervention, comparison, and outcome) structure. Finally, we analyzed ultrasound findings from case reports and case series using Microsoft Excel to obtain prevalence proportion and relative frequency for specific USG findings in NF. The flow of information in this literature review is shown in fig. 1.
The prevalence proportion formula is as follows: The relative frequency formula is as follows:

Results
Among papers concerning diagnosing necrotizing fasciitis by ultrasonography, only 21 met the inclusion criteria. We found three observational studies, 16 case reports, and 2 case series covering the period from 1976 to June 2022. The three observational studies are described in Table 1.
The three observational study's location was based on the emergency department in the United States and two different emergency departments in Taiwan. All three papers adopted a convenience sampling strategy. However, studies varied in terms of the disease spectrum, prevalence, and ultrasound operator experience. All three articles utilize linear probes in performing POCUS to diagnose NF.
Our literature review also revealed 17 case reports and 2 case series, which contained 5 case reports within. The age range of all patients is from 32 to 80 years old, with an average of 53 years old. In all the case reports, only a single anatomical region was involved. The most commonly affected anatomical locations were lower limbs; 15 case reports include the thigh, leg, and foot. Followed by upper limbs, 4 cases were reported, 1 case reported on the gluteal region and another one on the breast (Fig. 3, Table 2). All 16 case reports and 2 case series with 5 cases within described the use of ultrasound to screen for necrotizing fasciitis. Amongst the ultrasound findings, 13 of the case reported subcutaneous thickening and air. In addition, 17 of the case reported fascial fluid, and 2 of the case reported fascial irregularity. Other than that, 2 of the case reported fascial thickening, 1 case reported fluid collections around tendons, 1 case reported fluid collection around femurs, 1 case reported reduced vascularization via doppler, and 1 case reported hypo-anechoic small area with blurred contours, with marked edge shadowing which suggesting fat necrosis (Fig. 4).
The literature review revealed the most common ultrasound probe used for the purpose of diagnosing NF is a linear probe. In addition, 12 out of 21 case reports screened mentioned the use of linear probes in their diagnosis.
The most common ultrasonographic findings in NF were fascial fluid, with 33.33% of relative frequency and 0.81 prevalence proportion from the case reports analysis. Regarding the amount of fascial fluid, 2 mm depth has the best accuracy of 72.7%, 75% sensitivity, 70.2% specificity, and a positive and negative predictive value of 71.7% and 72.7%, respectively [7].
There were subcutaneous thickening findings in 13 out of 21 of the case reports screened. Moreover, Yen et al. (2002) found subcutaneous thickening accompanied by In relation to air/subcutaneous emphysema, no article was published mentioning the sensitivity and specificity of its finding in ultrasonography of necrotizing fasciitis patients. Among our case reports, 13 out of 21 cases reported air in their ultrasonographic finding, giving rise to a prevalence proportion of 0.62 and relative frequency of 25.5%. Interestingly, Butcher et al. [13], the cadaver ultrasonography test for subcutaneous emphysema yielded a sensitivity of 100% and specificity of 87.5%. In Lin et al. (2019), 3 out of 48 patients with necrotizing fasciitis had air/subcutaneous emphysema from the ultrasonographic findings. Even Though subcutaneous emphysema is pathognomonic for necrotizing fasciitis, it is often presented in very late stages where the air accumulation is significant enough to be visible (Fig. 5). Thus, their absence should not exclude the diagnosis and cause a delay in referral to related specialty and treatment [14] (Table 3).

Discussion
The literature review identified many research articles, case reports, and case series that illustrate the usefulness of POCUS in helping physicians establish the diagnosis of NF. NF is a life-threatening medical emergency that requires urgent treatment. Any delay in the treatment of NF is associated with increased morbidity and mortality [18]. POCUS is non-invasive, does not require intravenous contrast, and is free of ionizing radiation. It is also readily available in the emergency department, especially under limited resources settings.
Fozard et al. 2020 [30], recommend Sonographic exploration for fascial exploration (SEFE) examination as a systematic evaluation of the extremities for necrotizing fasciitis. However, the same principles may also apply to other body parts.
SEFE examinations include 4 steps as followings: Step 1: Scan all fascial compartments using a linear transducer (i.e., anterior, lateral, superficial posterior, and deep posterior in the lower extremity) even if there are no obvious skin changes.
Step 2: The presence of BOTH diffuse subcutaneous thickening AND fascial fluid more than 2 mm is the diagnostic of necrotizing fasciitis.
Step 3: Look for supporting findings such as subcutaneous air or abnormal muscle tissue structure.
Step 4: Mark the area of US findings on the patient skin and consult surgery for exploration.
Castleberg et al. [10], recommend looking for Subcutaneous Thickening, Air and Fascial fluid (STAFF) examination POCUS has also been reported to diagnose non-infective necrotizing fasciitis. Martínez-Doménech et al. [22] described the use of POCUS in NF caused by the envenomation of the Loxosceles rufescens spider, which has necrotoxin property [31]. Suggest the possibility of using POCUS in monitoring the progress of envenomation and diagnosis of non-infective NF. Figure 6 shows the ultrasonographic evolution of necrotizing fasciitis recovering over time.
The differential diagnosis to be considered for subcutaneous thickening and fascial fluid will be cellulitis and other causes of soft tissue edema, such as simple stasis edema, as shown in Fig. 7. For soft tissue air collection, differential diagnosis of gas-related trauma or iatrogenic causes should be considered, especially in patients with a history of surgery or trauma who did not show symptoms of sepsis. Deep vein thrombosis, foreign bodies, and abscesses could also be assessed by using ultrasonography.  High-frequency ultrasound probes greater than 8 MHz are recommended for skin and soft tissue ultrasound because they allow for good image resolution when scanning superficial structures. In addition, linear ultrasound probes enable optimum contact with the skin, and ample ultrasound gel will decrease the amount of air between the transducer and the patient's skin, resulting in an optimum image [32].
Hence, the summary of Ultrasonography findings in diagnosing Necrotizing fasciitis is as follows [

Limitation
This study also has several limitations. There are disadvantages to the usage of POCUS as a diagnostic tool for NF.
The findings and quality of the examination are operatordependent. POCUS examination also provides a limited field of vision and is not suitable for large anatomical areas of study. In the case of an obese or very muscular patient, tissue resolution may be compromised for deeper tissue depth visualization [34].
The availability of data published on the diagnostic accuracy of POCUS in the diagnosis of NF is limited. More robust quality data are needed for the purpose of metaanalysis. The case report available mainly focuses on NF of extremity, except for 2 case reports describing NF on breast and gluteal, again reinforcing the difficulty of POCUS in large anatomical areas of study.

Conclusion
Although the use of ultrasonography in diagnosing necrotizing fasciitis was published in several papers with promising results, more studies are required to investigate its diagnostic accuracy and potential to reduce time delay before surgical intervention, morbidity, and mortality.

Conflict of interest
The authors have no financial or other interests that should be known to readers related to this study.
Ethical approval This article utilized secondary data. We collected written permission from authors for the utilization of ultrasonographic images.
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