Early operative debridement of necrotising fasciitis is a major outcome determinant. Identification and diagnosis of such patients can be clinically difficult. The Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score first published in 2004 is based on routinely performed parameters and offers a method for identifying early cases. No literature review has yet been performed on the application of such a score.
A systematic review of English-language literature was performed from 2004 to 2014 to identify articles reporting use of LRINEC score and the incidence of necrotising fasciitis. We performed a critical review of PubMed, Medline and Embase in line with the PRISMA statement. A meta-analysis was performed with a random effects model and 95% confidence interval. Suitable correlation coefficient and receiver operating characteristic (ROC) curves were also calculated.
After application of inclusion criteria, 16 studies with 846 patients were included. The mean LRINEC score in patients with necrotising fasciitis was 6.06. Two papers reported LRINEC score in patients without necrotising fasciitis with a mean 2.45. All six studies with a reported coefficient of variance were < 1; Pearson correlation coefficient was r = 0.637 (P = 0.011). An ROC curve showed an area under the curve of 0.927.
Necrotising fasciitis is a rare, potentially life-threatening infection involving the fascia and subcutaneous tissues. This can progress to necrosis, leading to a systemic inflammatory response syndrome (SIRS), shock and even death. Features of necrotising fasciitis include purpura, subcutaneous bleeding, bullae, necrosis and gangrene. Mortality from this disease is up to 40%, with around 500 cases per year.1,2 Necrotising fasciitis infection is categorised as type 1 (infection from both aerobic and anaerobic bacteria) and type 2 (group A beta-haemolytic Streptococcus and Staphylococcus aureus).3
The high morbidity and mortality associated with necrotising fasciitis has not changed markedly since its description over 50 years ago.4,5 Early clinical differentiation between necrotising fasciitis and cellulitis is important when considering surgical management. Delayed recognition is a key factor when considering the high mortality.6 Imaging modalities such as computed tomography, magnetic resonance imaging and frozen section biopsy have been previously used in the discrimination between necrotising fasciitis and other soft tissue infections but these methods have been limited by cost and availability.2,7,8
The Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) is a clinical tool first described by Wong C et al.9 The tool is based on six common serum parameters at the time of presentation: C-reactive protein (CRP), total white cell count, haemoglobin, serum sodium, creatinine and glucose (Table 1). An LRINEC of six or greater confers a higher risk of necrotising fasciitis.9 The LRINEC scoring system has been controversial, with papers questioning its role as a scoring system for prognostic identification.10,11
|White cells (10^9/L)||<15||0|
aScore ≤5 = <50% risk (low); 6–7 = intermediate risk; ≥8 = >75% risk (high).
Diagnostic scoring has the potential to prevent marked morbidity and mortality in the accurate diagnosis of necrotising fasciitis. There have been no papers to date offering a comprehensive review of the literature to reach consensus regarding the LRINEC score. Our principle objective is to provide the reader with a critical analysis of the literature and LRINEC score for future use.
A systematic review of publications in English was conducted of the following electronic databases: EMBASE, MEDLINE and the Cochrane Database of Systematic Reviews. The key words used were (necrotising OR necrotising) AND (fasciitis) AND (score). The inclusion date range was 1 January 2004 to 1 June 2015.
Two researchers (JB and GF) independently selected papers from the databases. Papers were selected through two levels of screening. The first level entailed the review of abstracts satisfying the inclusion and exclusion criteria. The second level of screening involved the review of the articles in full, with the same application of inclusion and exclusion criteria. Only studies which passed both the first and second levels of screening were included in our analysis. Articles were included if a subgroup of patients fulfilling the inclusion and exclusion criteria could be extracted. Our procedure for assessing data within papers was in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria.12 Articles (not letters or case reports) were included if they met the criteria (Table 2).
|Adults (>18yrs)||Non-tissue infection/NF|
|Soft tissue infection||Non-English|
|Any country of origin||Review articles|
|Full article||Conference proceedings|
|Intervention||LRINEC score||No LRINEC score|
|Comparator||LRINEC score to necrotising fasciitis and soft-tissue infections||–|
|Outcomes||Confirmed necrotising fasciitis||Necrotising fasciitis not confirmed|
|Study design||Any clinical studya||Non-clinical study|
a Comparative or non-comparative, randomised or non-randomised
Assessment of methodological quality was made according to the Consolidated Standards of Reporting Trials.13 The methodological quality of non-randomised studies was assessed using the Methodological Index for Non-Randomised Studies (MINORS) tool.14
Extracted data (Table 2) were recorded in a Microsoft Excel® spreadsheet. A Kappa statistic was used to measure the agreement between reviewers for included articles. We performed multiple statistical analyses to pooled proportions. All statistical models were produced and presented using Stats Direct (StatsDirect Ltd, Cheshire, UK). Comparisons between groups was made using confidence intervals. Further values were compared using means, standard deviations, Pearson Correlation coefficient (r), two-tailed student T test, two-tailed single-sample T test and receiver operator curve (ROC) plots. The threshold for significance was P < 0.05.
The literature search identified 77 articles. After the application of inclusion and exclusion criteria at the first and second level of screening, 16 articles were included in the final analysis (Kappa 0.72; Fig 1).9,16–19,21–31 The mean MINORS score for comparative studies was 8.6 and 7.0 for non-comparative studies.
A total of 846 patients was included from the selected papers (range 7–209). The continents of origin were Europe for nine papers, Asia for five papers, North America for one paper and Oceania for one paper. The mean number of years of study was 6.5 years (range 1–15 years). The mean LRINEC score for patients with necrotising fasciitis was 6.06. The mean LRINEC score for patients without necrotising fasciitis was 2.45. The Pearson correlation coefficient between LRINEC score and positive diagnosis of necrotising fasciitis was r = 0.637 (P = 0.01). A two-tailed student T test was used to compare patients with a positive diagnosis of necrotising fasciitis and patients with a negative diagnosis. A two-tailed analysis was chosen to accommodate patients with LRINEC scores at the extremes of the range. This revealed t = 2.98 (P = 0.01). A two-tailed single-sample T test was used to determine the value at which the LRINEC score was statistically significant in patients with necrotising fasciitis; with an LRINEC score of 6, t = 0.14 (P = 0.44). An LRINEC score of 7.1 was significant (t = –1.93, P = 0.03). Figure 2 illustrates an ROC curve for patients with and without necrotising fasciitis with calculated LRINEC scores. The fitted ROC area was 0.927. Figure 3 shows a forest plot of papers for LRINEC means, with score range and confidence intervals where indicated.
It has been suggested that the LRINEC score is capable of detecting early cases of necrotising fasciitis among patients with severe soft tissue infections. Wong et al. suggest a LRINEC threshold of ≥ 6 for patients with a suspicion of necrotising fasciitis and a score of ≥ 8 for patients with a strong prediction for the disease.9 The importance of adopting an evidence-based approach for the diagnosis of necrotising fasciitis has the potential to lead to early diagnosis, surgical intervention and improved morbidity and mortality. Mortality rates vary widely, from over 50% to as low as 8.6%,15 with the low mortality figures being attributed to a low comparative patient age (less than 62 years) in some studies. The average LRINEC score reported in our study was 6.06, over the threshold of 6 reported by Wong et al.9 The score also varied markedly for the part of the body affected with necrotising fasciitis, with limbs scoring 6, groin 6.8 and chest/trunk 7.3.
The number of studies that reported an LRINEC score in patients without necrotising fasciitis were comparatively few, with only Chao et al.16 and Holland et al.17 reporting scores of 1.1 and 3.8, respectively. Chao et al. reported the use of the LRINEC score uniquely in patients with necrotising fasciitis and soft tissue infection with the atypical microorganism Vibrio vulnificus. The retrospective study examined 125 consecutive patients with this microorganism over 8 years. The LRINEC score in soft tissue infections (necrotising fasciitis negative) may have been biased owing to the atypical nature of this organism. The paper by Holland et al.17 retrospectively examined 28 patients with the possibility of a necrotising fasciitis diagnosis on admission. Of these, 17 were found to have severe soft tissue infections with a low LRINEC of 3.8. The small numbers of both of these patient groups for a negative necrotising fasciitis LRINEC score lends to a perceived low sensitivity. Of the 16 studies included in this review, only four detailed a coefficient of variance ranging from 0.2 described by Citak et al.18 to 0.7 by Chao et al.16 This suggests a small range of LRINEC scores for a given patient with necrotising fasciitis. Only two papers demonstrated a range of LRINEC scores with confidence intervals (Fig 3).
Swain et al.19 retrospectively studied patients with necrotising fasciitis over a five-year period, recruiting 15 patients with the disease between 2006 and 2011. Of these patients, the mean LRINEC score varied for patients who survived and those who died. The LRINEC score was comparatively higher for patients who died (LRINEC 9) versus those who survived (LRINEC 6.5) with necrotising fasciitis. The paper also examined the comorbidities associated with necrotising fasciitis. The authors found the highest associated comorbidities were diabetes, hypertension, obesity and hypercholesterolaemia.19
The LRINEC score examines six laboratory-based parameters but makes no consideration for patient age, comorbidities, clinical observations and other blood parameters (e.g. lactate) as do other scoring systems such as APACHE II and GLASGOW scoring in pancreatitis. Other perceived criticisms of the LRINEC score are the relatively small cohort used to devise the score, an over-reliance on non-specific CRP (given a maximal score of 4 compared with other parameters). Borschitz et al.20 conducted an observational study which recruited 29 patients with necrotising fasciitis and 59 matched comparators. Of the additional parameters, patients with necrotising fasciitis compared with control have statistically increased pain. Patients with renal failure and chronic venous insufficiency also showed a higher risk of diagnosis for necrotising fasciitis. The authors suggested an addition of several parameters (Table 3). Further studies need to be performed to validate the additional parameters suggested by Borschitz et al.20 This may take the form of a prospective comparative study, with all patients with suspected cellulitis, abscess and necrotising fasciitis being enrolled with timed follow-up to resolution. This would elucidate the scores apparent better sensitivity and specificity as compared with the standard LRINEC score.
|C-reactive protein||>150 mg/dl||4|
|Total white cell count||<15 × 106/mm3||0|
|Total white cell count||15–25 × 106/mm3||1|
|Total white cell count||>25 × 106/mm3||2|
|Erthrocyte count||<4 × 10^6/μl||1|
|Fibrinogen levels||>750 mg/dl||2|
|Signs of acute renal injury||No||0|
a ≥8 = strong suspicion for necrotising fasciitis 6–7 = suspicion; ≤no suspicion
The LRINEC score is a useful adjunct in the clinical diagnosis of necrotising fasciitis with a statistically positive correlation. The score, however, is amenable to further development, with the possible addition of clinical perimeters such as pain, pyrexia and comorbidities.
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