FOURNIER S GANGRENE: RELATION OF DISEASE OUTCOMES WITH LRINEC (LABORATORY RISK INDICATOR FOR NECROTIZING FASCIITIS) SCORE AND NECROTIC AREA WIDTH

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1 Acta Medica Mediterranea, 2015, 31: 17 FOURNIER S GANGRENE: RELATION OF DISEASE OUTCOMES WITH LRINEC (LABORATORY RISK INDICATOR FOR NECROTIZING FASCIITIS) SCORE AND NECROTIC AREA WIDTH ABDULLAH KISAOGLU 1, BUNYAMI OZOGUL, SALIH KARA 1, ATIF BAYRAMOGLU 2, NURHAK AKSUNGUR 1, SABRI SELCUK ATAMANALP 1, ¹Department of General Surgery, School of Medicine, Ataturk University, Erzurum - 2 Department of Emergency Medicine, School of Medicine, Ataturk University, Erzurum, Turkey ABSTRACT Introduction: Fournier s gangrene (FG) is a rapidly progressive, synergistic polymicrobial necrotizing fasciitis of mostly the scrotum, vulva, genital or perianal region. Aim of our study is to investigate the relation of disease outcomes with Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score and necrosis width by examining the characteristics of the patients. Materials and methods: The width of necrotic area and LRINEC score were calculated for all patients by retrospective investigation of the records of 57 subjects who had an operation due to FG in our clinics and all the information about patients were studied. Results: 52 patients (91.2%) were male and mean age was 51.3 years (range 21-74). The most common accompanying risk factor was diabetes mellitus and most commonly isolated microbial agent was Escherichia coli. LRINEC score had a positive correlation with the average duration of complaints and average number of debridements, whereas no relation with mortality was observed. Additionally, there was a significant relation between the width of necrotic area and mortality rate. Discussion: Fournier s gangrene is a rare synergistic polymicrobial infection, characteristically leads to vascular thrombosis and tissue necrosis. Mortality rate is ranging from 3 to 67%. Mortality rate of patients with a width of necrotic area 5% is significantly increased. Having more than one risk factor in patients with FG negatively affects the disease locally and systemically, and it causes a significant increase in mortality rates. Key words: Fournier s gangrene, LRINEC score, necrotic area width, outcome. Received May 18, 2014; Accepted September 02, 2014 Introduction Fournier s gangrene (FG) is a disease characterized by rapidly progressive, fatal, synergistic polymicrobial necrotising fasciitis of mostly the scrotum, penis, vulva, perineal, genital or perianal region resulting with the gangrene of subcutaneous tissue and skin due to obliterative endarteritis of subcutaneous arteries (1). Incidence of this rare but life-threatening disease is 1/7500-1/750,000 and mortality rate is 3-67%. It has been reported that some systemic diseases, are closely related with FG, especially diabetes mellitus (DM) but it is controversial whether it is related with increased mortality or not (2). Most common isolated microorganisms are Escherichia coli (43-80%), Klebsiella pneumoniae, Bacteroides, Pseudomonas, Staphylococcus, Streptococcus, Clostridium and Enterobacter (3-5). Early surgical debridement of necrotic tissues, appropriate use of broad spectrum antibiotics and intensive care supply are the main principles of FG treatment (1-3, 5). Fournier s Gangrene Severity Index, Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) and affected area calculation are the prognostic factors for FG (2). Although LRINEC score has been designed to make a distinction between the necrotising soft tissue infections and to be used for early diagnosis of necrotising fasciitis, in our study we aimed to evaluate the relation of LRINEC score and width of necrotic area with the characteristics and outcomes of FG patients by examining our patients characteristics.

2 18 Abdullah Kisaoglu, Bunyami Ozogul et Al Materials and methods Records of 57 patients who had an operation between 2004 and 2012 due to FG in our clinics were retrospectively studied. Age, gender, duration of complaints, wound localization, predisposing factors, etiology, isolated microbial agents, number of debridements, width of necrotic area and data of mortality were recorded. Patients with tenderness, edema, erythema, cyanosis, gangrene, foul-smelling discharge, crepitation and skin necrosis in local wound examination after general physical examination were considered as FG and they were taken to surgical operation under general anaesthesia following a rapid preoperative preparation. Aggressive necessary debridement and drainage was applied to infected and necrotic tissues until bleeding viable tissues appear after having a wound culture from all the patients. This procedure was repeated several times in requiring patients. During debridement and wound dressing, irrigation with hydrogen peroxide and povidone-iodine was performed. According to the results of culture antibiogram, parenteral single or combination antibiotic therapy was applied to all the patients. In patients with rectum perforation or loss of anal sphincter function, systemic sepsis or whom faecal contamination can not be prevented due to a large wound in perianal region, a colostomy was opened for diversion. After obtaining clinical improvement and a health granulation tissue, a reconstructive surgical intervention has been planned. Stoma of patients with intestinal diversion were closed after 3 months. Width of necrotic area was measured based on the first debridement. The extent of the necrotic area was measured by using a modified body surface area nomogram used routinely to assess the extent of burns. Width of the penis, scrotum, and perineum were considered as 1% and the ischiorectal fossa was considered as 2.5%. LRINEC score includes C-reactive protein concentration, white blood cell count, sodium, haemoglobin, creatinine and glucose levels. Maximum value of LRINEC is 13 and it was calculated based on the laboratory values obtained during admission to our clinic which were studied in our emergency service. Patients were divided into 3 groups as <6 (Group I), 6-7 (Group II) and 8 (Group III) according to the LRINEC score. Groups were compared by means of duration of complaints, width of necrotic area, number of risk factors, number of debridements and mortality. Additionally, all the patients were divided into 2 groups as having necrotic area 5% and 5% and data were compared again. In addition to these, it was investigated whether there is a relation between the number of risk factors with the number of debridements and mortality. Statistical Package for the Social Sciences (SPSS) 20.0 package program (SPSS 20.0, IBM SPSS Statistics, Armonk, NY, USA) was used in the statistical analysis of data. Categorical measurements were summarized as the number and percentage, whereas digital measurements were summarized as mean and Standard deviation. Chi-Square test was used for comparison of categorical measures among groups. In the comparison of digital measures among groups, independent samples T test and one-way Analysis of Variance (ANOVA) was used if assumptions are provided. Statistical significance level were taken as 0.05 in all tests. Results 52 patients (91.2%) were male, 5 patients (8,8%) were females, mean age was 51.3 years (range 21-74). Time to onset of complaints was 2-13 days (mean 4.7). Most common complaint was the pain in perianal region (91.2%), whereas foulsmelling discharge (93.0%), hyperaemia (89.5%), cyanosis (87.7%) and hyperpigmentation of the skin (84.2%) were the most common symptoms. Most common accompanying risk factor was DM as it was found alone in 9 patients (15.8%) and in a total of 15 (26.3%) patients. Other risk factors were smoking, hypertension (HT) and chronic heart disease. Undetermined risk factor was found in 32 patients (56.1%) and more than one risk factor was found in 12 (21%) patients (Table 1). Risk factor Number of patients, n=57, n(%) Diabetes mellitus 9(15.8) Diabetes mellitus+smoking Diabetes mellitus+hypertension 3(5.3) 3(5.3) Smoking+ hypertension 6(10.5) Hypertension 2(3.5) Chronic cardiac disease 2(3.5) Undetermined 32(56.1) Table 1: Distribution of risk factors for patients.

3 Fournier s Gangrene: relation of disease outcomes with LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) Examining the etiology of FG in our patients, colorectal/anorectal diseases were at the top of the list with 73.7% (n=42) followed by urogenital, cutaneous and gynaecologic diseases (Table 2). Number of patients, n=57, n(%) Colorectal/Anorectal 42(73.7) Perianal abscess 31(54.4) Hemorrhoid 5(8.8) Fistula in ano 2(3.5) Malignancy 2(3.5) Rectal or anal surgery/trauma 2(3.5) Average number of debridements were 2.7 (1-5). An additional colostomy was performed for diversion in 5 (8.8%) patients. Four patients (7.0%) died due to sepsis. Duration of hospitalization changes between 7-59 days. However the rate of patients with necrotic area width >5% and the rate of patients with >1 risk factor increase in parallel to an increase in LRINEC score but they were not statistically significant (p=0.108, p=0.385, respectively). In addition, there was no relation between mortality and LRINEC score (p=0.07). A positive correlation was found between LRINEC score with average duration of complaints and average number of debridements (p=0.037, p<0.001, respectively) (Table 4). Urogenital 7(12.3) Urethral strictures 3(5.3) Malignancy 2(3.5) Duration of complaints (day) Group I, n=8 (LRINEC<6) Group II, n=20 (LRINEC 6-7) Group III, n=29 (LRINEC 8) p-value 3.8± ± ± Epididymitis 2(3.5) Cutaneous 6(10.5) Scrotal carbuncle/abscess 4(7.0) Chronic skin infection 2(3.5) Gynecologic 2(3.5) Bartholin abscess 2(3.5) Width of necrotic area %5 8(%100) 18(%90) 23(%79.3) %5 0 2(%10) 6(%20.7) Number of risk factors 1< 0 3(%15) 9(%31) 1 8(%100) 17(%85) 20(%69) Table 2: Etiology of FG in patients. Most common isolated microbial agents were Escherichia coli in 29 patients (50.9%), Staphylococcus aureus in 19 patients (33.3%) and Pseudomonas in 11 patients (19.3%). Multiple microorganisms were produced in the cultures of 23 (40.4%) patients. Other agents produced in cultures were Enterococcus, Streptococcus, Clostridium perfringens and Bacteroides fragilis (Table 3). Number of debridements 1.8± ± ± 0.7 <0.001 Mortality 0 0 4(%13.8) 0.07 Table 4: Characteristics of the groups according to LRI- NEC score. A positive correlation was defined between the width of necrotic area with average duration of complaints, having multiple risk factors, average number of debridements and mortality rates (p=0.011, p=0.002, p=0.004 and p<0.001, respectively) (Table 5). Number of patients, n=57, n(%) Escherichia coli 29(50.9) Duration of complaints (day) %5, n=49 %5, n=8 p-value 4.4± ± Staphylococcus aureus 19(33.3) Pseudomonas 11(19.3) Enterococcus 5(8.8) Streptococcus 4(7.0) Clostridium perfringens 3(5.3) Bacteroides fragilis 2(3.5) Polymicrobial 23(40.4) Table 3: Wound culture results of 57 patients. Number of risk factors < 7(%14.3) 5(%62.5) 1 42(%85.7) 3(%37.5) Number of debridements 2.6± ± Mortality 1(%2) 3(%37.5) <0.001 Table 5: Characteristics according to the width of necrotic area.

4 20 Abdullah Kisaoglu, Bunyami Ozogul et Al Additionally, having multiple risk factors is found to be related to a significant increase in average number of debridements and mortality rates (p=0.001, p<0.001, respectively) (Table 6). Discussion 1, n=45 1<, n=12 p-value Number of debridements 2.5± ± Mortality 0 4(%33.3) <0.001 Table 6: Characteristics according to the number of risk factors. Fournier s gangrene is a rare synergistic polymicrobial infection usually affecting genital region and perineum, commonly associated with fulminant necrotising (5-8). This infection in which the rate of fascial necrosis can be high as 2-3 cm/hour, characteristically leads to vascular thrombosis and tissue necrosis in cutaneous and subcutaneous tissues (9). This infection could be seen in both genders and at all ages (10) but it is more commonly seen at years and in males (3, 11, 12). In our study, 91.2% of patients were male and mean age was 51.3 years. Patients with Fournier s gangrene usually have major predisposing factors (1, 2, 5, 7, 8, 10). Among known risk factors are DM, immunosuppression, local trauma, genitourinary infections, alcoholism, advanced age, chronic liver disease, chronic kidney failure, smoking, HT and systemic diseases (1, 2, 7, 13). DM is the most common related and reported predisposing factor for FG. Its prevalence is about 20-70% (1-4, 11). In parallel to literature, DM was the most common risk factor among defined risk factors in our study. However McGeehan et al. (14) have reported that DM is associated with bad prognosis in patients with FG whereas it has been indicated in other studies that DM is an important risk factor but does not affect prognosis (12, 13). In addition, Altarac et al. (15) have notified that DM does not affect prognosis in patients with FG and also have reported that having multiple risk factors is not related with mortality. On the contrary, it has been defined in our study that having multiple risk factors is significantly associated with increased mortality. In our study, it is very striking that no mortality was defined in the patients with only DM as a risk factor whereas in all of 4 patients who died, DM was a associated risk factor with HT or smoking. Etiology can be discovered in about 95% of the patients with Fournier s gangrene (2). Most common etiologic factors in patients are anorectal infections, genitourinary infections, local trauma or local skin infections (2, 12, 16, 17). Eke (1) have reported the source of infection as idiopathic in 36% of patients, skin in 24%, colorectal in 21% and urogenital origin in 19%. On the contrary, Ersay et al. (17) have reported the most common etiologic factor of FG as perianal abscess in 40%, primary scrotal abscess in 34.3% and they have indicated that 11.4% is due to trauma. In the same study, source of infection has been determined as anorectal diseases in 54.3% and genitourinary diseases in 45.7%. Basoglu et al. (7) have reported the most common etiologic factor as perirectal abscess and FG was due to colorectal diseases in 48.9% and cutaneous diseases in 33.3%. Similarly, the most common etiologic factor was perianal abscess in our study. In the wound culture of FG, considered as a bacterial synergistic infection, all species can not always be identified. Type and number of isolated microorganisms may show difference in FG including both aerobic and anaerobic organisms and usually being a polymicrobial infection (1-5, 7, 12, 13). In the wound culture of % of the patients, multiple microorganisms have been cultivated (12, 13, 18). 3 or more microorganisms usually lead to infection and the most common ones are Escherichia coli, Proteus and Enterococcus. Most commonly isolated anaerobic microorganism is Bacteroides fragilis (2). Jeong et al. (12), Ersay et al. (17), Basoglu et al. (7) and Benjelloun et al. (19) have reported that the most common isolated microorganism in FG is Escherichia coli. Escherichia coli was also the most common isolated microorganism in our study (50.9%) and it was followed by Staphylococcus aureus and pseudomonas. Multiple microorganisms have been defined in 40.4%. LRINEC score composed of 6 quick and useful laboratory parameters, is a scoring system designed to differentiate necrotising tissue infection from other soft tissue infections and to be used for early prediction of a severe necrotising soft tissue infection (20-22). Wong et al. (22) have divided the patients into three groups as low (LRINEC score 5), moderate (LRINEC score 6-7) and high risk (LRINEC score 8) in terms of necrotising soft tissue infection in their study. They have reported that patients with a LRINEC score 5 have a low risk of necrotising fasciitis, a score 8 is a powerful indicator of necrotising fasciitis and the possibility of necrotising soft tissue infection is <50% and 75%, respectively.

5 Fournier s Gangrene: relation of disease outcomes with LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) It has been reported that a LRINEC score of 5, 6 and 8 has a positive predictive value for necrotising fasciitis as 40%, 92% and 93.4%, respectively. Beyond these, it is not very clear whether there is a relation between LRINEC score and outcomes of necrotising fasciitis and there are few studies on this subject in the literature. Su et al. (20) have indicated that having a LRINEC score greater than 6 is related with increased mortality and higher rates of amputations in patients with necrotising fasciitis. On the contrary Tilkorn et al. (23) have reported that there is no significant relation between LRINEC score and mortality in patients with necrotising soft tissue infection. Although all the patients who died was in Group III in our study, there was no relation between LRINEC score and mortality. Fournier s gangrene begins with nonspecific symptoms in the affected region such as a local erythema, edema and pruritus and these inflammatory changes progress quickly to a necrosis in skin, subcutaneous tissue and fascia. It leads to an impaired general condition rapidly and even leads to septic shock in about 50% of patients. As laboratory findings; anaemia, leucocytosis, hyponatremia, hypokalaemia, hypocalcaemia, thrombocytopenia, hyperglycaemia, azotaemia and increased serum creatinine levels can be seen (2). In parallel to increased duration of complaints, an increase in LRINEC score, being an indicator of severe sepsis due to progression of local inflammatory changes to sepsis, is actually an expected result. As a result of our study, we associated the significant relationship between LRINEC score and average duration of complaints with that. Early aggressive debridement has been reported to decrease the mortality rates in Fournier s gangrene (1, 2). Residual necrotic tissues in wound site or a failure in the prevention of necrosis will lead to a continuous septic condition. In cases when correction of impaired general condition is not possible or delayed, we persistently want to ensure that all the necrotic tissue is removed from the environment. Because we believe that serial and aggressive debridement in FG is life-saving, we strongly perform re-debridement in required patients. Su et al. (20) have reported in their study that there is no relation between LRINEC score and the number of debridements in patients with necrotising fasciitis. In our study, there was a positive correlation between LRINEC score and the average number of debridements in patients with FG. This outcome shows that we perform serial debridements in patients with impaired general condition. We also associated our low rates of mortality (7.0%, n=4) with this. Chawla et al. (24) have defined that the affected body area is not an influential factor on prognosis in patients with FG. Jeong et al. (12) have detected a relationship between prognosis and duration of complaints with the width of necrotic area and they have indicated that a necrotic area of more than 6% leads to significant increase in mortality rates and duration of complaints. Also in our study, a positive correlation between the width of necrotic area with the duration of complaints and mortality rates have been detected. Similarly, there are studies reporting that a wide area of gangrenous body surface is related with a significant increase in mortality rates (15, 25, 26). Additionally, a significant relationship has been detected between the width of necrotic area with having more than one risk factor and average number of debridements and it has been seen that having more than one risk factor is related with a significant increase in average number of debridements and mortality rates. We think that the relation between a wide necrotic area and average number of debridements is originated from the effort to protect important functional structures. We assert that having multiple risk factors leads to a more aggressive progression of the disease locally and systemically and leads to more difficulty in controlling necrosis and sepsis despite serial debridements and parenteral systemic antibiotic therapy. In conclusion, no significant relation has been determined between LRINEC score and mortality in patients with FG. Although the rate of patients with a width of necrotic area >5% increases in parallel to an increase in LRINEC score, this was not statistically significant. In patients with a width of necrotic area %5, mortality rates and average number of debridements increase significantly. Having more than one risk factor in patients with FG negatively affects the disease locally and systemically (we believe that DM is the principal risk factor being a common risk factor in patients who died in our study) and it leads to a significant increase in average number of debridements and mortality rates. References 1) Eke N. Fournier s gangrene: a review of 1726 cases. Br J Surg 2000; 87: ) Shyam DC, Rapsang AG. Fournier s gangrene. Surgeon 2013; 11:

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