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Fournier’s gangrene is a fulminating, polymicrobial, necrotising fasciitis

of the anogenital region, which spreads rapidly along the deep fascial planes. This eponymous syndrome was first mentioned by venereologist Jean Alfred Fournier in 1883 when he described an idiopathic, rapidly spreading genital gangrene occurring in five healthy young males.1

Fournier’s gangrene is rare, accounting for <0.02% of hospital admissions2 and is now understood to be the result of opportunistic infection, most commonly arising from the ano-rectum (30–50%), uro-genitalia (20–40%) or genital skin (20%).3 A resultant obliterative endarteritis ultimately leads to tissue ischaemia and necrosis. Immunocompromised populations are most at risk, with males over 50 years old being the most commonly affected. The disease has a significant associated morbidity, and mortality rates lie between 20–40%.2 Early identification, resuscitation, and

administration of broad-spectrum antibiotics and timely surgical debridement are the basic principles of successful management.

Clinical presentationFournier’s gangrene should be considered in anyone with painful swelling of the scrotum or perineum with features of sepsis. The most common presenting feature, in over 75% of patients, is perianal/scrotal pain and swelling.4 Systemic features such as pyrexia and tachycardia are frequently present and may be associated with end organ dysfunction and increased mortality.5 The onset of Fournier’s appears to be insidious in nature, with the average time from initial symptoms

to presentation being five to seven days - hence patients may present with late features such as skin hyperaemia or necrosis6 (Figure 1). Purulent, foul smelling discharge and crepitus have been described in the late stages of the disease process.4

Risk factorsAny condition that is likely to decrease the host immunity can predispose a patient to Fournier’s gangrene. Common precipitants include diabetes and chronic alcohol abuse, present in 20–70% and 20–50% of cases, respectively.7 Other risk factors include obesity, steroid use and malnutrition.7 Low socio-economic status has also been found to be an important predisposing factor.9

The diagnosis and management of Fournier’s gangreneAndrew Brown, CT2 Urology; Nadine Coull, Consultant Urologist, Kingston Hospital NHS Foundation Trust, London

Fournier’s gangrene is a life-threatening condition and, although rare, should be considered in anyone with painful swelling of the scrotum or perineum with features of sepsis. In this article the author discusses risk factors, diagnosis and management of Fournier’s gangrene and the importance of early diagnosis and treatment.

Figure 1. Skin ischaemia and necrosis in late presentation of Fournier’s gangrene8 (© 2017 Medicalhelplines.com Inc. and John Wiley & Sons Ltd.)

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DiabetesPatients with diabetes are more likely to develop Fournier’s gangrene; however, the overall length of hospital stay and mortality does not appear to be affected.2,5,10 Diabetes appears to be associated with younger age at presentation5 and patients may require significantly more debridements than those without diabetes.10 Patients with poorly controlled diabetes, indicated by a high HbA1c, have been found to require longer hospital stays, larger surface area involvement and higher severity index scores.11 Fungal organisms should be considered in diabetic patients as an important causative pathogen.12

Human immunodeficiency virusHuman immunodeficiency virus (HIV) invades CD4+ T cells and ultimately leads to their destruction, lowering the host immunity and increasing its susceptibility to opportunistic infections. The age at presentation appears to be lower in patients with HIV; however, the virus does not have any influence on disease progression or outcome.10

AlcoholismChronic alcoholism is consistently indicated as a risk factor for developing Fournier’s gangrene. Low albumin, an indicator of synthetic liver failure, has shown a trend toward worse prognosis.8 However, alcoholism appears to have no bearing on outcome.2,8

Causative organisms Once considered to be the result of streptococcal infection alone, Fournier’s gangrene is now understood to be polymicrobial in nature13,14 and is typically caused by the opportunistic invasion of commensal bacteria. Commonly found organisms include Staphylococcus aureus, Streptococcus species, Escherichia coli and Acinetobacter.6,8,13 In this regard, antibiotic resistance may be a growing concern in Fournier’s gangrene with methicillin-resistant Staphylococcus aureus (MRSA) being the most commonly cultured resistant organism.15 Patients with multiple drug resistant organisms have shown a trend towards having poorer outcomes.15

Risk stratification and laboratory investigationsWong et al. described the laboratory risk indicator for necrotising fasciitis using white cell count, C-reactive Protein, haemoglobin, sodium, glucose and creatinine measurements, with a cumulative score ≥6 having a 92% positive predictive value for necrotising infection versus cellulitis, with a narrow confidence interval.16

The Fournier’s gangrene severity index (FGSI) (Table 1) utilises physiological and laboratory parameters, which are individually graded 0–4. A cumulative score of greater than 9 was associated with a 75% chance of mortality.17 The reliability of this score as an outcome predictor has been validated in several studies since its conception.13,18,19 Although widely quoted in the literature, the FGSI has a limited clinical role and, due to its cumbersome nature, it is difficult to calculate quickly at the bedside. Lin et al. proposed a simplified FGSI including only haematocrit, potassium and creatinine, which was demonstrated to be a similarly reliable predictor of outcome.19

Variables High abnormal values Low abnormal values

+4 +3 +2 +1 0 +1 +2 +3 +4

Temperature (0C) >41 39–40.9 – 38.5–38.9 36–38.4 34–35.9 32–33.9 30–31.9 <29.9

Heart rate >180 140–179 110–139 – 70–109 – 55–69 40–54 <39

Respiration rate >50 35–49 – 25–34 12–24 10–11 6–9 – <5

Serum Na (mmol/L) >180 160–179 155–159 150–154 130–149 – 120–129 111–119 <110

Serum K (mmol/L) >7 6–6.9 – 5.5–5.9 3.5–5.4 3–3.4 2.5–2.9 – <2.5

Serum creatinine (mg/100mL) x2 for acute renal failure

>3.5 2–3.4 1.5–1.9 – 0.6–1.4 – <0.6 – –

Haemotocrit (%) >60 – 50–59.9 46–49.9 30–45.9 – 20–29.9 – <20

White blood cell count (x1000/mm3)

>40 – 20–39.9 15–19.9 3–14.9 – 1–2.9 – <1

Serum bicarbonate (mmol/L)

>52 41–51.9 – 32–40.9 22–31.9 – 18–21.9 15–17.9 <15

Table 1. Fournier’s Gangrene Severity Index17

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In addition, other factors such as chronic kidney disease, surface area involved and serum albumin have all been found to differ significantly between survivors and non-survivors of Fournier’s gangrene.18 The Uludag FGSI is an updated scoring system that utilises age and extent of disease parameters. Patients scoring over 9 have a 94% incidence of mortality.20

ImagingImaging plays a limited role in Fournier’s gangrene. If necrotising infection is suspected then urgent surgical debridement should be performed. A plain X-ray has low sensitivity and specificity but it may show gas in the soft tissues (Figure 2).

UltrasoundUltrasound may be beneficial in patients where the diagnosis is unclear. It is readily available, quick to perform and can even be utilised at the bedside. Hyperechoic foci with reverberation artifact and ‘dirty’ shadowing represents gas in the soft tissue and is highly suggestive of Fournier’s gangrene.21 However, 10% of patients will not have subcutaneous emphysema. Furthermore, although an ultrasound may allow quick diagnosis and rapid definitive treatment, its success is operator dependent.

Computed tomography and magnetic resonance imagingComputed tomography and magnetic resonance imaging (MRI), unlike ultrasound, will demonstrate the nidus of infection and delineate the extent of soft tissue and fascial involvement. The main findings include soft tissue and fascial thickening with or without subcutaneous emphysema (Figure 3). MRI results in greater soft tissue detail and resolution; however, its use is seldom reported due to its cost and relative lack of availability.

ManagementAntibioticsEmpirical broad-spectrum antibiotics are administered when a diagnosis of Fournier’s gangrene is suspected. Given the polymicrobial nature of the disease, the typical regimens will include a penicillin-based agent and anaerobic cover with metronidazole or clindamycin. The European Association of Urology (EUA) has suggested antimicrobial regimens (Table 2).18 Treatment should always be guided by local policy and culture results.

Surgical debridementOverlying skin changes may not necessarily reflect fascial or deep tissue involvement and surgical debridement is the mainstay of successful management of Fournier’s gangrene. Urgent debridement should be performed within 24 hours to prevent worsening mortality. Tissue resection should include a cuff of healthy tissue and as a result will hopefully halt disease progression. However, patients may require multiple debridements, with an average of 1.5 debridements per

admission.2 Repeated procedures have been associated with increased mortality, and correlate with a high FGSI score.4

To encourage perineal wound healing and prevent any faecal contamination a diverting colostomy may be indicated and is performed in the presence of anal sphincter involvement and/or faecal incontinence.7 The formation of a diverting stoma has been found to increase mortality2 and overall length of hospital stay and therefore the risk / benefit of this procedure should be made on a case-by-case basis. An alternative to a diverting stoma is a faecal management system – a catheter inserted into the rectum that navigates faeces away from the wound. These devices have been shown to decrease hospital stay while successfully maintaining wound integrity.23 Urinary contamination can be prevented by urethral catheterisation in the majority of cases, though (rarely) cystectomy may be indicated.

Vacuum assisted closureNegative pressure dressings are thought to reduce oedema, increase blood flow and hence improve wound healing when compared to conventional healing by secondary intention. Negative pressure therapy encourages the formation of

Figure 2. Plain abdominal X-ray demonstrating scrotal swelling and air locules suggestive of Fournier’s gangrene. Image courtesy of Dr Ahmed Abdrabou24

Figure 3. Axial, portal venous phase CT demonstrating air in the soft tissues secondary to perforated rectal cancer. Image courtesy of Dr Chris O’Donnell25

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granulation tissue by removal of bacterial contamination and exudate, and may be used to decrease the size of broad defects prior to definitive reconstructive surgery.26 Although Vacuum assisted closure therapy (Figure 4) reduces wound surface area significantly quicker than conventional therapy,26 the total length of hospital stay does not appear to be significantly altered.27

Hyperbaric oxygen therapyHyperbaric oxygen therapy (HBOT) involves exposing patients to increasing atmospheric pressure while inhaling 100% oxygen. Hypoxia due to small vessel thrombosis provides an ideal environment for

proliferation of anaerobic bacteria, hence providing tissues with a surplus of oxygen aims to counteract this.28 Furthermore, HBOT is thought to up-regulate the body’s immune system, stimulate collagen formation and increase intra-cellular transport of antibiotics.7,28 Indeed, HBOT has been found to reduce mortality in a study of 341 patients.29 However, overall the evidence is inconsistent and HBOT is not recommended in the EUA guidelines.18

Reconstructive proceduresIdeally, wounds following debridement would be primarily closed; however, in large defects this is unlikely to be possible. Healing by secondary

intention, although feasible, can lead to skin contracture and poor cosmesis7 – though it may be considered for wounds confined to less than 50% of the scrotal area.30 However, for the majority of cases the defect is too large and reconstruction is generally achieved using a full thickness skin graft, or flap reconstruction. SummaryFournier’s gangrene remains a surgical emergency with a high mortality if it is not diagnosed early in its progression. The scoring systems predict mortality accurately but play a small role in clinical practice. Rapid administration of broad-spectrum antibiotics and urgent surgical debridement remain the mainstay of successful treatment, despite the emergence of adjuvant therapy such as HBOT. Survival rates of >70% are achievable depending on the patient group and availability of higher level care.18

Declarations of interests: none declared

References1. Fournier JA. Jean-Alfred Fournier 1832–1914. Gangrene foudroyante de la verge (overwhelming gangrene). Sem Med 1883. Dis Colon Rectum 1988;31:984–8. 2. Sorensen MD, Krieger JN. Fournier’s Gangrene: Epidemiology and Outcomes in the General US Population. Urol Int 2016;97(3):249–59. 3. Eke N. Fournier’s gangrene: a review of 1726 cases. Br J Surg 2000;87(6):718–28.4. Ersay A, Yilmaz G, Akgun Y, Celik Y. Factors affecting mortality of Fournier’s gangrene: review of 70 patients. ANZ J Surg 2007;77(1–2):43–8.5. Nisbet AA, Thompson IM. Impact of diabetes mellitus on the presentation and outcomes of Fournier’s gangrene. Urology 2002;60(5):775–9.6. Aridogan IA, Izol V, Abat D, et al. Epidemiological characteristics of Fournier’s gangrene: a report of 71 patients. Urol Int 2012;89(4):457–61. 7. Chennamsetty A, Khourdaji I, Burks F, Killinger KA. Contemporary diagnosis and

Antimicrobial Dosage

Piperacillin-tazobactam plus vancomycin

3.37g every 6–8 hours (h) iv15mg/kg every 12h

Imipenem-cilastatin 1g every 6–8h iv

Meropenem 1g every 8h iv

Ertapenem 1g once daily

Cefotaxime plus metronidazole or clindamycin

2g every 6h iv500mg every 6h iv600–900mg every 8h iv

Table 2. Suggested regimens for antimicrobial therapy for Fournier’s gangrene of mixed microbiological aetiology; European Association of Urology18

Figure 4. Use of vacuum assisted closure device for large perineal wound31 (© Meyer Ganz et al.; licensee BioMed Central Ltd 2012)

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management of Fournier’s gangrene. Ther Adv Urol 2015;7(4):203–15. 8. Hong KS, Yi HJ, Lee RA, et al. Prognostic factors and treatment outcomes for patients with Fournier’s gangrene: a retrospective study. Int Wound J 2017;14(6):1352–8. 9. Bhatnagar AM, Mohite PN, Suthar M. Fournier’s gangrene: a review of 110 cases for aetiology, predisposing conditions, microorganisms, and modalities for coverage of necrosed scrotum with bare testes. N Z Med J 2008;121(1275):46–56.10. Elsaket AE, Maharajh S, Urry RJ. The presentation, management and outcomes of Fournier’s gangrene at a tertiary urology referral centre in South Africa. S Afr Med J 2018;108(8):671–6. 11. Sen H, Bayrak O, Erturhan S, et al. Is hemoglobin A1c level effective in predicting the prognosis of Fournier gangrene? Urol Ann 2016;8(3):343–7. 12. Perkins TA, Bieniek JM, Sumfest JM. Solitary Candida albicans Infection Causing Fournier Gangrene and Review of Fungal Etiologies. Rev Urol 2014;16(2):95–8.13. Tarchouli M, Bounaim A, Essarghini M, et al. Analysis of prognostic factors affecting mortality in Fournier’s gangrene: A study of 72 cases. Can Urol Assoc J 2015;9(11-12):E800–4. 14. Bjurlin MA, O’Grady T, Kim DY, et al. Causative Pathogens, Antibiotic Sensitivity, Resistance Patterns, and Severity in a Contemporary Series of Fournier’s Gangrene. Urology 2013;81(4):752–8.

15. Chia L, Crum-Cianflone NF. Emergence of multi-drug resistant organisms (MDROs) causing Fournier’s gangrene. J Infect 2018;76(1):38–43. 16. Wong CH, Khin LW, Heng KS, et al. 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):1535–41.17. Laor E, Palmer LS, Tolia BM, et al. Outcome prediction in patients with Fournier’s gangrene. J Urol 1995;154(1):89–92.18. Grabe M, Bartoletti R, Bjerklund Johansen TE, et al. Guidelines on Urological Infections. Arnhem, The Netherlands: European Association of Urology, 2015. (www.uroweb.org/wp-content/uploads/19-Urological-infections_LR2.pdf; accessed 14 December 2018).19. Lin TY, Ou CH, Tzai TS, et al. Validation and simplification of Fournier’s gangrene severity index. Int J Urol 2014;21(7):696–701. 20. Yilmazlar T, Ozturk E, Ozguc H, et al. Fournier’s gangrene: an analysis of 80 patients and a novel scoring system. Tech Coloproctol 2010;14(3):217–23. 21. Kim DJ, Kendall JL. Fournier’s Gangrene and its Characteristic Ultrasound Findings. J Emerg Med 2013;44(1):e99–101. 22. Misiakos EP, Bagias G, Patapis P, et al. Current concepts in the management of necrotizing fasciitis. Front Surg 2014;1:36. 23. Levenson RB, Singh AK, Novelline RA. Fournier Gangrene: Role of Imaging.

Radiographics 2008;28(2):519–28. 24. Ahmed A. Founier gangrene. Radiopedia (radiopaedia.org/cases/founier-gangrene; accessed 19 December 2018).25. O’Donnell C. Fournier gangrene - spontaneous perforation of rectal cancer. Radiopedia (radiopaedia.org/cases/fournier-gangrene-spontaneous-perforation-of-rectal-cancer; accessed 19 December 2018). 26. Mouës CM, van den Bemd GJ, Heule F, Hovius SE. Comparing conventional gauze therapy to vacuum-assisted closure wound therapy: a prospective randomised trial. J Plast Reconstr Aesthet Surg 2007;60(6):672–81. 27. Ozkan OF, Koksal N, Altinli E, et al. Fournier’s gangrene current approaches. Int Wound J 2016;13(5):713–6. 28. Singh A, Ahmed K, Aydin A, et al. Fournier’s gangrene. A clinical review. Arch Ital Urol Androl 2016;88(3):157–64. 29. Devaney B, Frawley G, Frawley L, Pilcher DV. Necrotising soft tissue infections: the effect of hyperbaric oxygen on mortality. Anaesth Intensive Care 2015;43(6):685–92.30. Karian LS, Chung SY, Lee ES. Reconstruction of Defects After Fournier Gangrene: A Systematic Review. Eplasty 2015;15:e18. 31. Ganz O, Gumener R, Gervaz P, et al. Management of unusual genital lymphedema complication after Fournier’s gangrene: a case report. BMC Surg. 2012;12:26