How do we misdiagnose and mismanage necrotizing fasciitis?

Authors: Paul Cohen (EM Resident Physician, Alpert Medical School of Brown University) and Nicholas Musisca, MD (Assistant Professor of Emergency Medicine, Alpert Medical School of Brown University) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Case

A 53-year-old male with a past medical history of diabetes and obesity presents with two days of fever and left leg pain. The patient states that three days ago he was in his normal state of health when he had a mechanical fall and sustained a small abrasion over the left anterior leg.  The next day he noticed that the area was swollen and red, and the pain has worsened to the point that he has difficulty walking.  On exam, the patient’s vital signs are T 101.7, HR 104, BP 118/70, RR 18, and SpO2 98%. He has a 6 cm area of erythema without sharply demarcated margins on the left anterior leg. The area is minimally swollen, exquisitely tender to palpation, and without crepitus. The patient’s plain films demonstrate no underlying fracture. He has a blood sugar of 330, bicarbonate of 19, and anion gap of 17. He is given two liters of 0.9% saline, started on IV antibiotics and an insulin drip, and admitted to the medicine intermediate unit. Over the next several hours, his pain intensifies despite IV pain medication, and a violaceous hue develops over his leg.

Background

Necrotizing fasciitis is a destructive infection of subcutaneous tissues that spreads rapidly along fascial planes. Infection is generally caused by bacterial incursion through some external trauma or spread directly from a perforated viscus such as the colon.  Necrotizing fasciitis is exceedingly rare with an incidence of roughly 0.04 cases/1000 person-years,¹ yet it carries a high mortality.

There are two classic forms of necrotizing fasciitis:

1. Type I infections are the most common form and are polymicrobial, involving aerobic and anaerobic bacteria.² Risk factors for patients whom develop these infections include diabetes, peripheral vascular disease, obesity, CKD, HIV, ethanol abuse, and trauma.³ Notable examples of Type I infections include Fournier’s gangrene (male perineal necrotizing infection) and Ludwig’s angina (sublingual necrotizing infection).
2. Type II infections are monomicrobial infections most commonly caused by group A Strep infection (often referred to as flesh-eating) either alone or in conjunction with Staph aureus. As opposed to type I infections the majority of type II infections involve otherwise healthy and immunocompetent patients.⁴

This post will evaluate pitfalls in the diagnosis and management of necrotizing fasciitis, discussing common mistakes. A little knowledge of these potential pitfalls can go a long way towards improving care.

How is necrotizing fasciitis missed?

1. Unreliable history

The classic risk factors for necrotizing fasciitis aren’t always present. Necrotizing fasciitis is assumed to be a disease of the obese, diabetic, and immunocompromised. Though more prevalent in those populations, necrotizing fasciitis also occurs in the young and otherwise healthy patient.⁴ There is no age or sex prediction. Moreover, it is often thought that the patient history would reveal a provoking factor such as an abscess, IVDU, insect bite, or surgical incision that led to necrotizing infection. However, studies have shown no such inciting event in up half of patients.⁵

2. Unreliable exam and anchoring on cellulitis

Necrotizing fasciitis is a challenging diagnosis as not only is it a rare disease, but classic signs and symptoms are often not seen early in the disease. A systematic review found that the more advanced findings –bullae, skin necrosis, and crepitus were only found 25.6%, 24.1%, and 20.3%, respectively.⁶ The most common signs of necrotizing infection were swelling (80.8%), pain (79%), and erythema (70.7%). As these signs are indistinguishable to those found in non-necrotizing cellulitis and abscesses, necrotizing fasciitis is frequently misdiagnosed, especially in the early stages. A review of patients with necrotizing fasciitis over a 6-year period found that only 14% were initially admitted with the diagnosis of necrotizing fasciitis – the majority were originally diagnosed with cellulitis or abscess.⁷ The authors noted that the only findings shared by a majority of patients were erythema and tenderness and/or edema beyond the apparent boundaries of infection. The classic findings of shock, mental status changes, crepitus, and skin ecchymosis often occur later in the disease and are each found in less than 25% of patients.⁶

3. Failure to complete a full skin exam, especially in those unable to provide a history

Frequently, elderly patients are brought to the Emergency Department and are unable to provide a history secondary to dementia or encephalopathy. These patients may have pressure sores, trauma from an indwelling foley, or vulvar skin infections, placing them at greater risk for necrotizing infection of the perineal and inguinal regions. Therefore, a thorough skin inspection for findings necrotizing infection must occur in these patients.

4. Failure to consider if patient’s pain is uncontrollable and anchoring on the “pain seeker”

Many of these patient’s will present with severe pain that does not fit with the physical exam findings. This finding alone should be taken as a red flag and not brushed off as another opioid abuser. Studies have found that “pain out-of-proportion” was one of the most prominent clinical features that helped to identify necrotizing fasciitis patients.⁸

5. Reliance on lab scoring and LRINEC score

Unfortunately, laboratory findings seldom aid in the diagnosis of necrotizing fasciitis. The most common scoring system for necrotizing fasciitis is the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC). The score was developed from data on 89 patients diagnosed with necrotizing fasciitis and 314 patients diagnosed with severe cellulitis or abscess.⁹ Patients with skin infection are risk stratified based on 6 laboratory values (CRP, WBC, Hgb, sodium, creatinine, and glucose). The initial data was promising and a recent meta-analysis demonstrated a statistically positive correlation between the LRINEC score and a true diagnosis of necrotizing fasciitis.¹⁰ However, many other studies have produced less ideal results with sensitivities of 48%-83% and specificities of 60-84%.^11–15 Additionally, the score has yet to be validated prospectively in Western nations.¹⁶  However, prospective studies in North America do suggest that two components of the LRINEC score may aid in early diagnosis – elevated WBC above 15.4 and hyponatremia below 135. One study demonstrated all of their patients met either the WBC or the Na criterion with 90% meeting the sodium criterion, 90% meeting the WBC criterion, and 81% meeting both criteria.¹⁷

6. Too much reliance on imaging for ruling out disease

Similarly, imaging has limited value. Subcutaneous emphysema, a classic finding for necrotizing fasciitis, is often not found, especially when infection does not involve clostridium. A systematic review with a total of 1463 patients found that the overall incidence of finding gas in the soft tissue on plain films was only 24.8%.⁶ CT imaging is more sensitive as it may demonstrate fascial thickening and soft-tissue gas. However, it more often demonstrates non-specific soft tissue swelling. Ultrasound has been proposed to aid in diagnosis as it can be performed quickly at the bedside. Significant findings include fascial and subcutaneous tissue thickening, abnormal fluid accumulation in the deep fascia layer, and, in advanced cases, subcutaneous air. The mnemonic STAFF reminds you what to evaluate for: Subcutaneous Thickening, Air, and Fascial Fluid. Picking up on these ultrasound findings and separating them from other soft tissue infections requires ultrasound expertise and is unable to safely rule out a diagnosis of necrotizing fasciitis if not present.^18,19

7. Being told this can’t be necrotizing fasciitis after surgical consultation

The diagnosis of necrotizing fasciitis requires a high degree of suspicion and clinical acumen. Our surgical consultants are invaluable in the ultimate management of patients with this infection; however, they can succumb to the same difficulties with diagnosis as others. The definitive diagnosis of necrotizing fasciitis requires surgical exploration, thus one must have a more detailed discussion with their surgical consultants if there is a high index of suspicion.

Where do we fail in management?

1. Forgetting this is a surgical disease

Surgical exploration is the lone means to conclusively diagnose necrotizing fasciitis. Surgical findings include malodourous, ‘dishwater’ appearing discharge, lack of bleeding from necrotic tissue, and limited resistance to finger dissection of fascia.²⁰ 

Just as surgical exploration is the lone means to conclusively diagnose necrotizing fasciitis, surgical debridement is the only treatment demonstrated to decrease mortality. Multiple studies have shown that mortality increases greater than 9-fold when debridement is delayed more than 24 hours.^7,21 Thus, high suspicion for necrotizing fasciitis should prompt early surgical management for both definitive diagnosis and treatment.

2. Failure to provide broad spectrum antibiotics including clindamycin or linezolid for toxin inhibition

Patients should be placed on IV antibiotics to mitigate the spread of infection; however, antibiotics are limited in their ability to infiltrate the infected necrotic tissue, thus necessitating early and extensive surgical debridement. Moreover, there is considerable variation in antibiotic duration between centers with expertise in the care of these infections.²² The clinician should take into account particular exposures and culture sensitivities when available; however, current recommendations from the IDSA for empiric antibiotic treatment includes broad spectrum antibiotics such as vancomycin or linezolid (given its effect on exotoxin production) plus piperacillin-tazobactam or a carbapenem as well as clindamycin, given it suppresses streptococcal toxin and cytokine production.²³

3. Failure to resuscitate appropriately with fluids and vasopressors to ensure end organ perfusion

Patients with necrotizing fasciitis may decompensate quickly despite an initial non-toxic presentation. Fluid resuscitation up to a 30 cc/kg bolus should begin promptly and septic shock should be anticipated. These patients will often undergo multiple debridements and must be admitted to the ICU.

4. Believing that IVIG and hyperbaric oxygen are cornerstones of therapy

Therapies such as IVIG and hyperbaric oxygen remain controversial and should never delay operative management. Studies evaluating the use of IVIG therapy for patient with necrotizing fasciitis are limited and either show no significance or are flawed.^24,25 Hyperbaric oxygen therapy is more promising, and it has been shown to inhibit anaerobic bacteria and limit clostridium toxin release. However, human studies are mixed on its efficacy and its use will be institution and multi-disciplinary specific.^26–28

Take Home Points

-Necrotizing fasciitis is a challenging diagnosis as it is exceedingly rare and classic findings are often not seen early in the disease.

-Laboratory and imaging data may aid the diagnosis but are often neither sensitive nor specific and should never replace clinical suspicion.

-Early diagnosis is essential but difficult to separate from more common diagnoses such as cellulitis. Key early findings include:

• Tenderness and edema that spreads beyond the apparent boundaries of infection
• Pain out of proportion to skin findings
• Ill-defined margins of involvement
• Rapid progression of infection

-If a patient presents with the classic findings (shock, bullae, crepitus, skin necrosis, and skin anesthesia), the infection has likely progressed and they need prompt surgical consultation.

References/Further Reading

1. Ellis Simonsen SM, Van Orman ER, Hatch BE, et al. Cellulitis incidence in a defined population. Epidemiol Infect. 2006;134(2):293-299.
2. Childers BJ, Potyondy LD, Nachreiner R, et al. Necrotizing fasciitis: a fourteen-year retrospective study of 163 consecutive patients. Am Surg. 2002;68(2):109-116.
3. Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing Fasciitis: Current Concepts and Review of the Literature. J Am Coll Surg. 2009;208(2):279-288.
4. Hakkarainen TW, Kopari NM, Pham TN, Evans HL. Necrotizing soft tissue infections: Review and current concepts in treatment, systems of care, and outcomes. Curr Probl Surg. 2014;51(8):344-362.
5. Roje Z, Roje Ž, Matić D, Librenjak D, Dokuzović S, Varvodić J. Necrotizing fasciitis: literature review of contemporary strategies for diagnosing and management with three case reports: torso, abdominal wall, upper and lower limbs. World J Emerg Surg WJES. 2011;6:46.
6. Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br J Surg. 2014;101(1):119-125.
7. Wong C-H, Chang H-C, Pasupathy S, Khin L-W, Tan J-L, Low C-O. Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am. 2003;85-A(8):1454-1460.
8. Borschitz T, Schlicht S, Siegel E, Hanke E, Stebut E von. Improvement of a Clinical Score for Necrotizing Fasciitis: “Pain Out of Proportion” and High CRP Levels Aid the Diagnosis. PLOS ONE. 2015;10(7):0132775.
9. Wong C-H, Khin L-W, Heng K-S, Tan K-C, Low C-O. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med. 2004;32(7):1535-1541.
10. Bechar J, Sepehripour S, Hardwicke J, Filobbos G. Laboratory risk indicator for necrotising fasciitis (LRINEC) score for the assessment of early necrotising fasciitis: a systematic review of the literature. Ann R Coll Surg Engl. 2017;99(5):341-346.
11. Chao W-N, Tsai S-J, Tsai C-F, et al. The Laboratory Risk Indicator for Necrotizing Fasciitis score for discernment of necrotizing fasciitis originated from Vibrio vulnificus infections. J Trauma Acute Care Surg. 2012;73(6):1576-1582.
12. Bernal NP, Latenser BA, Born JM, Liao J. Trends in 393 necrotizing acute soft tissue infection patients 2000-2008. Burns J Int Soc Burn Inj. 2012;38(2):252-260. doi:10.1016/j.burns.2011.07.008.
13. Swain R, Hatcher J, Azadian B, Soni N, De Souza B. A five-year review of necrotising fasciitis in a tertiary referral unit. Ann R Coll Surg Engl. 2013;95(1):57-60.
14. Su Y-C, Chen H-W, Hong Y-C, Chen C-T, Hsiao C-T, Chen I-C. Laboratory risk indicator for necrotizing fasciitis score and the outcomes. ANZ J Surg. 2008;78(11):968-972.
15. Thomas AJ, Meyer TK. Retrospective evaluation of laboratory-based diagnostic tools for cervical necrotizing fasciitis. The Laryngoscope. 2012;122(12):2683-2687.
16. Holland MJ. Application of the Laboratory Risk Indicator in Necrotising Fasciitis (LRINEC) score to patients in a tropical tertiary referral centre. Anaesth Intensive Care. 2009;37(4):588-592.
17. Chan T, Yaghoubian A, Rosing D, Kaji A, de Virgilio C. Low sensitivity of physical examination findings in necrotizing soft tissue infection is improved with laboratory values: a prospective study. Am J Surg. 2008;196(6):926-930.
18. Castleberg E, Jenson N, Dinh VA. Diagnosis of Necrotizing Fasciitis with Bedside Ultrasound: the STAFF Exam. West J Emerg Med. 2014;15(1):111-113.
19. Buttar S, Cooper D, Olivieri P, et al. Air and its Sonographic Appearance: Understanding the Artifacts. J Emerg Med. 2017;53(2):241-247.
20. Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;44(5):705-710.
21. Bilton BD, Zibari GB, McMillan RW, Aultman DF, Dunn G, McDonald JC. Aggressive surgical management of necrotizing fasciitis serves to decrease mortality: a retrospective study. Am Surg. 1998;64(5):397-400; discussion 400-401.
22. Faraklas I, Yang D, Eggerstedt M, et al. A Multi-Center Review of Care Patterns and Outcomes in Necrotizing Soft Tissue Infections. Surg Infect. 2016;17(6):773-778.
23. Stevens DL, Bisno AL, Chambers HF, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):10-52.
24. Madsen MB, Hjortrup PB, Hansen MB, et al. Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT): a randomised, blinded, placebo-controlled trial. Intensive Care Med. April 2017.
25. Kadri SS, Swihart BJ, Bonne SL, et al. Impact of Intravenous Immunoglobulin on Survival in Necrotizing Fasciitis With Vasopressor-Dependent Shock: A Propensity Score-Matched Analysis From 130 US Hospitals. Clin Infect Dis Off Publ Infect Dis Soc Am. 2017;64(7):877-885.
26. Brown DR, Davis NL, Lepawsky M, Cunningham J, Kortbeek J. A multicenter review of the treatment of major truncal necrotizing infections with and without hyperbaric oxygen therapy. Am J Surg. 1994;167(5):485-489.
27. Shupak A, Shoshani O, Goldenberg I, Barzilai A, Moskuna R, Bursztein S. Necrotizing fasciitis: an indication for hyperbaric oxygenation therapy? Surgery. 1995;118(5):873-878.
28. Hollabaugh RS, Dmochowski RR, Hickerson WL, Cox CE. Fournier’s gangrene: therapeutic impact of hyperbaric oxygen. Plast Reconstr Surg. 1998;101(1):9