Thursday, December 3, 2020

Platelet-Lymphocyte Ratio and Neutrophil-Lymphocyte Ratio: Updates in Prognosticating Fournier Gangrene in the Emergency Department

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Authors: Alessandra Della Porta, EMT-B, MSIIIUniversity of Miami School of Medicine
Kasha Bornstein, Msc Pharm, EMT-P, MSIV
AAEM/RSA Modern Resident Blog Copy Editor
University of Miami School of Medicine

Bottom Line Up Front:
Fournier gangrene (FG) is a necrotizing soft tissue infection (NSTI) associated with high mortality rates, particularly when it is not suspected early, or interventions are initiated late in the course. Diagnosis is clinical and challenged by overlap with more superficial skin infections (i.e. cellulitis) and the need for thorough examination of the genital region. Imaging and laboratory analysis are not able to consistently rule out FG. While risk calculators exist, they are also limited in their utility for ruling out severity of illness. This brief article discusses use of the monocyte-lymphocyte ratio, neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio; recently innovated, simple, and effective biomarkers for prognosticating NSTIs. 

While cases of genital gangrene were documented as early as 980 CE, the condition we know today as FG was coined in the 1880’s by French venerologist, Jean Alfred Fournier.1 His description of cases of life-threatening infections in the perineal, genital or perianal regions were thought to be idiopathic in previously healthy men. Today, the underlying etiology for patients presenting with genital gangrene can be identified a majority of the time.2 A better understanding of the demographics of FG indicate that it can present in any sex and at any age. While uncommon—representing less than 0.02% of hospital admissions—FG is associated with significant morbidity, and mortality rates as high as 88% when not suspected and treated early. Rapid recognition and time to surgical intervention are the single greatest factors impacting survival.3-5 Fournier gangrene is a type of necrotizing soft tissue infection, which can be categorized into four types based on the infectious organism involved and other features (Table 1).

NSTI TypeImplicated organismsCommon associations
Type I

Bacteroides fragilis
Escherichia coli
Klebsiella pneumonia
Staphylococcus aureus
Clostridium species
Commensal flora of the GI/GU tract, mixed anerobic and anerobic bacteria6,7
Type II
Streptococcus pyogenes
Group A streptococcus
Complicated by toxic shock syndrome in > 50% of cases8
Type III
Clostridium perfringens
Aeromonas hydrophila
Vibrio vulnificus
Marine related infections following traumatic injury9
Type IV
Candida albicans
Rhizopus microspores
Lactobacillus gasseri
Often in immunocompromised or following traumatic burns10,11
Table 1: Classification of necrotizing soft tissue infections

FG is most common in patients with diminished host defenses, including diabetes mellitus, human immunodeficiency virus (HIV), immunosuppression, malignancy, and/or liver failure, as well as, those with a history of chronic alcohol use, but up to 30% of patients may have no other comorbidities.12,13 Proximal risk factors for development of FG include trauma to the perineal area, including iatrogenic/procedural trauma or injection of drugs (cocaine, heroin, other injection drug use) into the surrounding vasculature.14,15 Infections are often polymicrobial and a mixture of aerobes and anaerobic bacteria from the gastrointestinal tract, genitourinary tract or skin flora.16 Up to 80% of cases of FG are polymicrobial and synergistic interactions between bacteria allow for rapid progression from cellulitis to critical ischemia to gangrene.6,13,17

Challenges in Diagnosis:
The diagnosis of Fournier’s gangrene is clinical: There are no laboratory or imaging studies that can be used to definitively rule out disease. Diagnosis is often challenging, due to both the indolent course of some cases, and that deep infections can be severe despite minimal cutaneous findings. Onset of symptoms can vary widely, as some patients present from days to weeks, while others present with rapid progression to sepsis and multiorgan failure.18 In patients presenting early, tenderness, erythema, or edema of the perineal area is common, and thorough physical exam of the genital region may be necessary to appreciate findings, especially in obese or obtunded patients.19 More specific findings for FG, as opposed to cellulitis or other soft tissue infections, include crepitus upon palpation, bulla formation, putrid odor, purulent discharge and pain out of proportion to examination.20,21 Imaging may be helpful in diagnosis or surgical planning but cannot rule out NSTI and may delay definitive surgical management. Conventional radiography may demonstrate presence of tissue emphysema but this finding has low sensitivity (49%) and may not be present in NSTI types II or IV that do not commonly contain clostridium species.22 Computed tomography (CT) with IV contrast has a better sensitivity and specificity for NSTI, 88.5% and 93.3%, respectively, and findings include fluid collection, fat stranding and abscess.23-26 While point-of-care ultrasound has a similar sensitivity and specificity to CT and the advantage of rapid nature of a bedside exam, CT is preferred if the patient is able due to ability to detect extent of necrosis and benefit potential benefit to surgical planning.22,27

Multiple risk calculators currently exist to aid in the clinical diagnosis of FG, relying primarily on vital signs and bloodwork to predict likelihood of FG, overall prognosis, or need for specific interventions. The sensitivity of these scores range, but they cannot exclude FG diagnosis and may have lower sensitivity when used for prediction in ED patient populations.28 When specifically assessing mortality, the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) are newer validated markers of physiologic stress that have been applied to a wide variety of inflammatory conditions.29 In patients with FG, a PLR >140 and a NLR >8 have been associated with an 11.6 and 4.66-fold increased odds of mortality, respectively.30 An MDcalc assessment tool exists for NLR, requiring the absolute (cells/μL) or % neutrophil and lymphocyte counts, and classifies patients based on physiologic stress levels, ranging from normal to severe.31 Additionally, the monocyte-lymphocyte ratio (MLR) can be used to follow patients as higher MLR have been used to predict repeat surgical debridement.32 Relying on easily and rapidly obtained information, these simple and low-cost tools may be particularly useful in low resource settings and in cases where time or severity of patient presentation does not permit additional workup.

Positive outcomes in diagnosis and management of FG rely on rapid intervention as soon as it is suspected. A thorough physical exam, imaging, and laboratory studies can assist, but definitive diagnosis can only be made in the operating room. Newer validated scoring tools, such as the PLR, NLR, and MLR, may be some of the first results returned and offer faster risk stratification in FG, when time is of the essence.


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