Introduction

Fournier’s gangrene (FG) is a rare, life-threatening, rapidly progressive, polymicrobial, and synergistic form of infective necrotizing fasciitis of the perineal, genital, or perianal regions. It leads to thrombosis of the small subcutaneous vessels and necrosis of the overlying skin. It was initially described by Baurienne in 1764; however, it was named by Jean Alfred Fournier, a Parisian dermatologist and venerologist, who reported it in 1883.¹ The treatment of FG basically consists of hemodynamic resuscitation, aggressive surgical debridement, and administration of broad-spectrum antibiotics.^2,3

Reported overall mortality rates for FG vary between 0% and 88%.^4,5 However, studies published during the last three decades report a mortality rate ranging from 20% to 40%. In 2000, Eke⁶ reviewed 1,726 cases of FG from literature written in English and reported a mortality rate of 16%. The study by Furr et al.⁷, which included the largest patient population in the literature, reported a 4.7% inpatient mortality.

Since FG is a rare disease, designing a prospective clinical study may not be feasible. To overcome this limitation, which is associated with the nature of FG, the authors aimed to conduct a retrospective study with a large patient population. Thus, the authors retrospectively reviewed published literature reporting FG mortality and risk factors in the Turkish population during the last two decades.

Materials and Methods

A database search was conducted via PubMed Central^® using the keywords “FG” and “Turkey” between January 2000 and December 2020. The search revealed 95 articles. Articles that included <20 patients and those published in a country other than Turkey were excluded. In the case of consecutive publications from the same first author and institution, only the article with the largest patient number was included. A total of 41 studies were finally included. A flow chart showing the included papers is presented in Figure 1, and a full list of manuscripts is presented in Appendix 1. Approval from the institutional review board was obtained for this study.

Data regarding the etiological origin of FG, patient demographics, comorbidities, treatment methods, and mortality rates were collected from the reviewed articles. The overall data and the subgroups including two decades (2000-2010 and 2010-2020) were analyzed for factors affecting mortality. The authors aimed to evaluate whether there were differences between the patient characteristics and, in particular, the outcomes (mortality) between the two decades, as the authors believed that the outcomes may have improved with a better understanding of the disease and the advances in treatment modalities.

Statistical Analysis

Statistical analyses were performed using SPSS for Windows version 23.0 (IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp). A normality check for the data was performed using the Shapiro-Wilk test. Normally distributed variables were reported as mean ± standard deviation, and two independent groups were compared using the t-test. Non-normally distributed variables were reported as the median (minimum-maximum), and two independent groups were compared using the Mann-Whitney U test. The correlations between the variables were analyzed using the Spearman correlation coefficient. An a-value of <0.05 was accepted as statistically significant.

Results

The median patient number was 38 (20-120). The distribution of the patient numbers based on the publication date are presented in Figure 2. The reported median mortality was 6 (1-129) patients; mortality rates were calculated for every single study, and the median mortality rate was 17.39% (2.89-40.54). The distributions of mortality rates by year are shown in Figure 3. The number of patients with diabetes mellitus (DM) were reported in all studies except two; the rate of patients with DM was 50.02%±16.59% among the overall population.

A total of 16 (39%) studies were published in the first decade (2000-2010), and 25 (61%) were published in the second decade (2010-2020). The mortality rate was 22.46%±11.62% for the studies published in the first decade and 14.72%±7.10% for studies published in the second decade. The mortality rate was significantly high for the first decade (p=0.011). Furthermore, the rate of patients with DM was higher in the second decade than in the first decade (p=0.022). The comparison of mortality rates and patients with DM between the two decades is presented in
Figure 4. A summary of the comparison of the data obtained from reviewed articles, as well as the differences between the two decades are shown in Table 1.

The respective associations between the mortality rate and other variables were analyzed. The mortality rate was negatively correlated with the cutaneous origin and positively correlated with chronic renal failure (CRF) and fecal diversion (Table 2).

The studies were classified into two groups based on the median mortality rate (<17.39 “low mortality” vs. >17.39 “high mortality”). Female patients, CRF and anorectal origin rates were common in the high-mortality group, and the cutaneous origin rate was common in the low-mortality group (Table 3).

Discussion

FG is a devastating disease that can rapidly progress to sepsis, septic shock with multi-organ failure, and death.⁸ In the present study, data collected from previously published articles from Turkish institutions between 2000 and 2020 were analyzed to determine the related risk factors and mortality in the Turkish population. It was shown that FG is still associated with a significant mortality rate (17.39%) and that the female gender, anorectal origin, CRF, and fecal diversion may be associated with a poor outcome.

Studies published in the last three decades report mortality rates of between 0% and 43%.^5,9 However, studies with high patient numbers published during the last two decades reported mortality rates as low as 4.7%-16%.^6,7,10 The median mortality rate was 17.39% in the present study; this rate is comparable with that reported in Eke’s⁶ study (16%) but higher than those in the studies published in North America. However, the authors determined a higher mortality rate in the first decade (2000-2010) than in the second decade (2010-2020). The emerging technologies and advances in medical knowledge appear to have improved the outcome of FG by providing better surgical and medical care.

Two previously published studies with the largest patient populations reported different gender rates in FG. Eke⁶ reported a 10:1 rate dominancy of men, while Sorensen et al.¹⁰ reported that 2.32% of the included 1,680 patients were women. In the present study, the majority of the 1,919 included patients were men, with the women-patient rate 16.88%. The impact of gender on the prognosis of FG is controversial; several studies report female gender either as a risk factor or as inconsequential to the prognosis.^11-13 In the present study, the rate of women patients was higher in the high-mortality group than in the low-mortality group. The association between gender and mortality in FG might be explained by the anatomical features of the female pelvis, which allow for widespread necrotizing fasciitis.¹² However, there is a need for further studies to establish a precise explanation.

Major sources of infection are the local skin, colon, anus and rectum, and the lower urinary tract.⁶ The infection has a polymicrobial and synergistic pattern and includes both Gram-positive and Gram-negative aerobe and anaerobic bacteria.¹⁴ Colonic, anal, and rectal sources are associated with a bad prognosis.^2,6 Perianal infection is the most common of these (19%-50%), either as a primary infection or infection secondary to perianal surgical interventions.² In the present study, the cutaneous origin was negatively correlated with mortality, while the anorectal origin rate was higher in the high-mortality group than in the low-mortality group; these results were in line with previously published data.

Comorbidities such as DM, obesity, alcoholism, smoking, CRF, liver failure, malignancy, and HIV infection play an important role in the prognosis of FG. All these conditions may impair microcirculation and/or immunity.¹⁵ Specifically, DM is a well-defined risk factor that may influence the frequency and the prognosis of the disease.¹⁶ In the present study, the rate of patients with DM was significantly higher in the last decade (2010-2020) than in the first (2000-2010). The study failed to show a correlation between DM and the mortality rate, much like the previously published studies from our department;^13,17 however, the study did reveal a positive correlation between CRF and the mortality rate.

The gold standard treatment of FG includes aggressive and repeated debridement of necrotic tissue in conjunction with the administration of broad-spectrum antibiotics and hemodynamic supportive measures in the intensive care unit.¹³ Recurrent surgical debridement may cause wide perianal tissue defects and impair anal sphincter functions due to direct trauma. As a result of these factors, fecal contamination of the wound may be unavoidable. Fecal diversion is an option for such patients for facilitating wound care. However, fecal diversion does not improve the treatment outcome and increases morbidity and the cost of treatment.¹⁸ In addition, the mortality rate was reported to be relatively high in patients with a diverting stoma.¹⁹ Similarly, the present study found a positive correlation between fecal diversion and the mortality rate. However, the need for a stoma is common in patients with extensive diseases, and it should be borne in mind that extensive disease may be another factor impairing the treatment outcome.

Study Limitations

The major limitation of this study is its retrospective nature. Since every article has its original study design, reviewing variables from previously published articles may be associated with missing data, which may affect the results of the study. Another important issue is that the manuscripts were published by different specialties from different centers, and there may be differences in disease management among the centers and specialties, which again may have affected the study outcomes. However, the high patient number provides this study with clinical value. Furthermore, this is the first study reflecting data on patients with FG in the Turkish population.

Conclusion

In conclusion, FG remains a fatal disease. The mortality rate and correlated risk factors of FG in the Turkish population appear to be comparable with the literature data. The cutaneous origin may be associated with better outcomes, and female gender, CRF, and the need for fecal diversion may be associated with a poor prognosis.

Ethics

Ethics Committee Approval: The study was approved by the Bursa Uludağ University Local Ethics Committee (approval number: 2023-17/43, date: 19.09.2023).

Informed Consent: Retrospective study.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: Ö.I., T.Y., Concept: T.Y., Design: Ö.I., M.Ş., T.Y., Data Collection or Processing: Ö.I., M.Ş., D.S., T.Y., Analysis or Interpretation: Ö.I., D.S., T.Y., Literature Search: Ö.I., M.Ş., D.S., T.Y., Writing: Ö.I., D.S., T.Y.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.