Missing the Mark: Utility of Clinical Signs in Necrotizing Soft Tissue Infections

By Melissa Smith

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Case

53y.o. male presents to triage with primary complaint of gluteal rash. Pt experiences syncope at triage and is found to be diaphoretic, hot, pale, and weak. He is urgently taken by stretcher to room with suspicion of sepsis. He is found to be hypotensive and febrile. On examination pt demonstrates exquisitely painful area of mottling of the left buttock and hip without bullae, crepitus, or hypoesthesia. CT demonstrates fat stranding, seen in figure 1. After stabilization and starting broad spectrum antibiotics, the patient is taken for emergent surgical resection of grossly necrotic tissue and diagnosis of necrotizing soft tissue infection is confirmed. As of this writing the patient remains hospitalized for surgical revisions and intravenous antibiotics.

Clinical Question: What are the utility of clinical signs as indicators of necrotizing soft tissue infection (NSTI) and how can we improve early recognition of the disease.

Figure 1: Pt CT scan demonstrating fat stranding associated with left gluteal Fournier’s gangrene

Summary of the Evidence

Necrotizing soft tissue infections (NSTIs) represent a rare but fatal disease. Early recognition and treatment can improve levels of morbidity and mortality. Due to poor sensitivity of clinical signs, early recognition is often missed. The rarity of the disease can result in clinicians lacking specific expertise in NSTI recognition resulting in delay of treatment.

The CDC reports that incidence in the US has remained stable since 2010 at an estimated 0.4 per 100,000 persons or 700-1150 cases annually.5,10 Incidence increases with age >50 years to a maximum of 12 per 100,000 persons at age 80 years.5 Incidence may be underestimated due to limitations of surveillance and missed diagnoses. Some reports indicate that incidence may be increasing in response to rising rates of associated co-morbidities.8 Surveillance in the US is typically limited to type II NSTI’s, those caused by Group A Strep, and does not include polymicrobial type I infections. Other classifications include type III infections with Vibrio or Clostridium and type IV infections with fungal species. One study suggests that monomicrobial infections are increasing in frequency and may be associated with higher mortality.7 The bulk of infections, 85%, are community acquired; 14% occur in health care facilities.5

NSTIs cause significant morbidity and mortality. Of cases, 15.9% result in amputation. Mortality rates have been unchanged for almost 100 years at 21.5-30%.2,3,5 When recognized and treated early, survival rate for NSTI is 93.2%. Delays in treatment of even 24 hours reduce survival rate by 18% to 75.2%.2 Despite this, early diagnosis and treatment is missed in 75-100% of cases.2,4 This is due in part to the absence of specific signs and symptoms in early disease.

NSTIs begin with entry of bacteria through disruptions in the skin. The bacteria first invade the mucosa and then the epithelium and are sometimes taken up to the lymphatics and spread from the source with evident lymphadenitis. Bacteria then seeds fascia and replication occurs with expression of virulence factors leading to inflammation and frustrated phagocytosis. Impaired microbial clearance in turn causes localized coagulation and cytotoxicity. Increased pressure, compartment syndrome and decreased perfusion ensue producing tissue necrosis.4 The pathogenesis of NSTIs demonstrate that clinical signs are specific only temporally to the disease course. For instance, direct cytotoxicity leads to bullae and dusky discoloration only in late illness. Physical signs of NSTI and their chronology can be visualized in Figure 2.

Early signs and symptoms of redness, warmth and swelling are imperceptible from those of other soft tissue infections contributing to the high miss rate of early NSTIs. In early disease pain is the most common symptom occurring in 79% of NSTI.4 Pain out of proportion to exam and extending beyond the borders of poorly demarcated skin findings is the most common and specific early physical finding in NSTI.2,4,5 Lymphadenitis is rare and thus poorly sensitive for NSTI.

Figure 2: Physical findings in NSTI by stage4

In intermediate and late disease, bullae, crepitus, hypoesthesia, and dusky skin discoloration are very specific for NSTI and considered “hard signs”.4,5,12 These signs are only present in 10-40% of cases, however, making them poorly sensitive.5 Furthermore, bullae are only found at presentation in 25.6-41% of cases. Their presence is positively correlated to increased amputation and mortality.2,5 Signs of systemic toxicity, such as fever, may also be poorly sensitive as they are only present in 40% of patients at presentation. Their presence has a positive correlation with mortality.2,3,4

There are multiple studies which have developed scoring systems for NSTI recognition via laboratory findings. These tools are considered by some as unvalidated and having limited diagnostic performance. 4,5 Others note that use of scoring systems may introduce delay to treatment.3 A tool developed by Wall et al. utilizes white blood cell count and serum sodium to evaluate the presence of NSTI.11 It was identified that WBC count >115,400 cells/mm3 and serum sodium level <135 mmol/L was associated with NSTI with a NPV of 99%, though a PPV of only 26%. The sensitivity of this tool makes it useful for ruling out NSTI.1 When considering WBC alone, a WBC >14 has a sensitivity of 81% and specificity of 76%.3 The second tool, the LRINEC, utilizes WBC count, hemoglobin, sodium, glucose, creatinine, and C-reactive protein to determine the likelihood of NSTI. A score of >6 on the LRINEC is specific for NSTI with a PPV or 92% and NPV of 96%.13 Notably, this score was internally validated and is only useful in patients with high pre-test probability of NSTI.1 Some suggest that findings of pain out of proportion to exam and a CRP >150mg/L are comparable to the LINREC score.3

Multiple imaging findings have been found to be specific for NSTI though most are poorly sensitive. While MRI is the gold standard of imaging for NSTI, authors agree that imaging should not delay treatment. Specific features on MRI include hyperintense signal on T2-weighted images at the deep fascia and within muscles, thickened fascia (>3 mm), and deep fascial fluid collections.1,4,5 CT has a questionable 80-100% sensitivity for signs of NF as it can show inflammatory changes such as abscesses or fascial thickening. Specific findings are presence of gas, fluid collections, and involvement of fascia with asymmetrical fascial thickening and lack of enhancement after contrast injection.1,3,4 A large prospective study is ongoing which may help to provide additional information on CT sensitivity.3 XR is considered less sensitive than CT as subcutaneous gas, a specific finding, it is only found in 17-29% of patients.1,4 Additionally, XR has a <25% accuracy in identifying gas.3 Ultrasound is considered by most authors to be neither sensitive or specific for NSTI. Imaging findings associated with NSTI include thickening and distortion of the deep fascia and fluid collections.1,5,12 Alternate studies have shown higher sensitivities for ultrasound with thickening of subcutaneous tissue at 100%, thickening of fascia at 85.7% and cobble stoning at 78.5%.9

In small studies, frozen section pathology with 1cm3 of tissue resection is a promising area of future development in diagnosing NSTI within 21 hours of clinical signs. Biopsies may be obtained during a bedside “finger test” of fascial planes. It is noted, however, that this method is a highly invasive diagnostic and results in high numbers of negative biopsies. It will also require increased pathologist support for development.6,11

Recommendations

Pain out of proportion to exam and extending beyond the boundaries of skin findings appears to be the only clinically specific finding in early stage NSTI. As “hard signs” of NSTI do not present until intermediate stages of disease, are not highly sensitive, and are associated with higher rates of morbidity and mortality it is crucial to raise our index of suspicion for NSTI in all soft tissue infections. It is important to note that the absence of hard signs does not rule out NSTI. It is suggested that due to the rarity of the illness and absence of clear diagnostic tools, senior decision makers should be involved early. Laboratory scoring systems are most useful in ruling out NSTI but should be used cautiously due to concerns regarding their validity. More research should be pursued in this area. MRI is the most specific imaging modality for NSTI but is time consuming and should not delay operative management. Most imaging is poorly sensitive. Future directions in clinical diagnosis include frozen tissue pathology but more support is needed for this area of research.

References

1. Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management. Clin Infect Dis. 44 (2007), pp. 705-710

2. Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br J Surg. 2014 Jan;101(1):e119-25. doi: 10.1002/bjs.9371. Epub 2013 Nov 29. PMID: 24338771.

3. Henry SM, Davis KA, Morrison JJ, et al. Can necrotizing soft tissue infection be reliably diagnosed in the emergency department? Trauma Surgery & Acute Care Open 2018;3:e000157. doi: 10.1136/tsaco-2017-000157

4. Hua C, Urbina T, Bosc R, Parks T, Sriskandan S, de Prost N, Chosidow O. Necrotising soft-tissue infections. Lancet Infect Dis. 2023 Mar;23(3):e81-e94. doi: 10.1016/S1473-3099(22)00583-7. Epub 2022 Oct 14. PMID: 36252579.

5. Lancerotto L, Tocco I, Salmaso R, Vindigni V, Bassetto F. Necrotizing fasciitis: classification, diagnosis, and management. J Trauma Acute Care Surg. 2012 Mar;72(3):560-6. doi: 10.1097/TA.0b013e318232a6b3. PMID: 22491537.

6. Majeski, J., & Majeski, E. (1997). Necrotizing fasciitis: Improved survival with early recognition by tissue biopsy and aggressive surgical treatment. Southern Medical Journal, 90(11), 1065. https://doi-org.proxy.hsl.ucdenver.edu/10.1097/00007611-199711000-00001

7. Naamany E, Shiber S, Duskin-Bitan H, et al. Polymicrobial and monomicrobial necrotizing soft tissue infections: comparison of clinical, laboratory, radiological, and pathological hallmarks and prognosis. A retrospective analysis. Trauma Surgery & Acute Care Open 2021;6:e000745. doi: 10.1136/tsaco-2021-000745

8. Pelletier J, Gottlieb M, Long B, Perkins JC. Necrotizing Soft Tissue Infections (NSTI): Pearls and Pitfalls for the Emergency Clinician. The Journal of Emergency Medicine. Volume 62, Issue 4, 2022, Pages 480-491. Doi: 10.1016/j.jemermed.2021.12.012

9. Stoianovskyi IV, Khimich SD, Chemerys OM. Point-of-care Ultrasound in the Early Diagnosis of Necrotizing Fasciitis. Wiad Lek. 2022;75(10):2471-2475. doi: 10.36740/WLek202210129. PMID: 36472282.

10. “Type II Necrotizing Fasciitis: Information for Clinicians.” Centers for Disease Control and Prevention, 27 June 2022, www.cdc.gov/groupastrep/diseases-hcp/necrotizing-fasciitis.html#epidemiology.

11. Wall DB, Klein SR, Black S, de Virgilio C. A simple model to help distinguish necrotizing fasciitis from non-necrotizing soft tissue infection, J Am Coll Surg, 2000, vol. 191 (pg. 227-31).

12. Wong CH, Wang YS. The diagnosis of necrotizing fasciitis. Curr Opin Infect Dis. 2005 Apr;18(2):101-6. doi: 10.1097/01.qco.0000160896.74492.ea. PMID: 15735411.

13. 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. doi: 10.1097/01.ccm.0000129486.35458.7d. PMID: 15241098.