157Archivio Italiano di Urologia e Andrologia 2016; 88, 3 REVIEW Fournier’s gangrene. A clinical review Ariana Singh, Kamran Ahmed, Abdullatif Aydin, Muhammad Shamim Khan, Prokar Dasgupta MRC Centre for Transplantation, King’s College London; Department of Urology, Guy’s and St. Thomas’ NHS Foundation Trust - King’s Health Partners, London, United Kingdom. Introduction and Hypothesis: Fournier’s gangrene is a rare, necrotising fasciitis of the external genitalia, perineal or perianal regions. The dis- ease has a higher incidence in males and risk factors for development include diabetes, HIV, alcoholism and other immune-compromised states. The aggressive disease process is associated with a high mortality rate of 20-30%. In addi- tion, the increasing age and prevalence of diabetes in the population, begs the need for increased clinical awareness of Fournier’s gangrene with emphasis on early diagnosis and management. This review aims to highlight the relevant research surrounding Fournier’s gangrene, in particular the various prognostic indicators and management strategies. Methods: A search was conducted on the MEDLINE database for all applicable research; clinical reviews, retrospective studies and case reports. In addition to which a search of the European Association of Urology, the British Association for Urological Surgeons and the British Medical Journal was conducted for the most recent recommendations. Results: Immediate broad-spectrum antibiotic therapy and urgent surgical debridement are the core managerial princi- ples of Fournier’s gangrene. The use of adjunctive therapies such as hyperbaric oxygen and vacuum assisted closure are supported in some aspects of the literature and disputed in others. The lack of randomized controlled studies limits the use of these potential additional therapies to patients unre- sponsive to conventional management. The value of unprocessed honey as a topical antimicrobial agent has been highlighted in the literature for small lesions in uncomplicat- ed patients. Conclusion: Fournier’s gangrene is a urological emergency with a high mortality rate despite advances in the medical and surgical fields. The aggressive nature of the infection advocates the need for early recognition allowing immediate surgical intervention. The opposing results of available research as well as the lack of high quality evidence sur- rounding emergent therapies prevents their routine use in the management of Fournier’s gangrene. The absence of a specif- ic care pathway may hinder efficient management of Fournier’s gangrene, thus based on current guidelines a man- agement pathway is suggested. KEY WORDS: Fournier’s gangrene; Necrotizing fasciitis; Fournier’s gangrene severity index (FGSI); Surgical debride- ment. Submitted 20 March 2015; Accepted 28 March 2015 Summary No conflict of interest declared. talia. However, the Parisian venereologist, Jean Alfred Fournier is more commonly associated with the epony- mous condition. In his 1883 manuscript, he described a fulminant gangrene of idiopathic nature and abrupt onset, of the scrotum and penis, in a series of 5 young males (1). Since then our understanding of the aetiology and pathophysiology of this condition has grown to reveal a more indolent nature and identifiable cause in the majority of cases. Contrary to the earlier descrip- tions, the disease is not restricted to young males, but has been reported to occur in women and children, although at a lower incidence. Basic management of Fournier’s gangrene employs a multi-disciplinary team approach and the three fundamental principles of urgent haemodynamic stabilization and crucial surgical debridement with or without plastic reconstruction, under the cover of antibiotic therapy. DEFINITION Fournier’s gangrene is a type I necrotizing fasciitis of the perineal, perianal or genital areas. Over the years, Fournier’s gangrene has been referred to by several names, such as “streptococcus gangrene”, “synergistic necrotizing cel- lulitis” and “peri-urethral phlegmon”, all of which describe a soft tissue disease that is infective, destructive and fatal (2). EPIDEMIOLOGY Fournier’s gangrene is a relatively uncommon condition, representing a mere 0.02% of hospital admissions according to a recent epidemiological study, although its incidence is increasing with the ageing population and higher prevalence of diabetes. Sorensen et al. highlighted an overall incidence rate of 1.6 cases per 100,000 males/year and showed a peak in incidence past the age of 50 at 3.3 cases per 100,000 males/year (3). A retro- spective case review of 1726 cases, revealed a mean of 97 cases per year during the period of 1989-1998 (4). AETIOLOGY J.A. Fournier described the condition as an idiopathic process, however, Fournier’s gangrene is rarely truly idio- pathic and with diligent observation and investigation an underlying cause can be identified in the majority of cases. The necrotizing fasciitis frequently stems from an infection DOI: 10.4081/aiua.2016.3.157 INTRODUCTION In 1764 Baurienne described an idiopathic, fatal, necro- tizing process with resultant gangrene of the male geni- Kamran_Stesura Seveso 21/09/16 13:35 Pagina 157 Archivio Italiano di Urologia e Andrologia 2016; 88, 3 A. Singh, K. Ahmed, A. Aydin, M.S. Khan, P. Dasgupta 158 of the ano-rectum (30-50%), uro-genitalia (20-40%) or genital skin (20%) (4). Trauma to these regions, whether intentional or accidental has been reported in the literature as a possible source of infection. Fournier’s gangrene has been shown to be strongly associated with diabetes, chron- ic alcoholism, human immunodeficiency virus (HIV), lym- pho-proliferative diseases, chronic steroid abuse and cyto- toxic drugs (5). The underlying principle of all these con- ditions being compromised host immunity creating a favourable environment to establish infection. Malnutrition and lower socio-economic status have also been shown to be associated with the development of Fournier’s gangrene. These two factors potentially associated with poor perineal hygiene and lower immunity accounting for their associa- tion with the development of Fournier’s gangrene (5). PREDISPOSING FACTORS Diabetes The insistent nature of Fournier’s gangrene poses a threat to the immuno-competent host so that patients suffering from systemic disorders such as diabetes mellitus are at an additional risk. Sustained hyperglycaemia has detrimental effects on host immunity via its adverse effect on cellular adherence, chemotaxis and phagocyte activity (6). Diabetes has been indicated as a predisposing factor in 32% to 66% of cases of Fournier’s gangrene (6). An eval- uation of cases of Fournier’s gangrene in diabetics has shown that this co-morbid condition has an impact on the clinical course of the soft-tissue infection. Primarily, the patient profile tends to be of a younger age and wound cultures reveal different bacterial colonies. Candida albi- cans has been identified in the cultures of diabetic patients (7). Rarely, Fournier’s gangrene has been reported as the initial manifestation of diabetes in a previously undiag- nosed diabetic (8, 9). The degree of diabetic control has been shown to correlate directly with the extent of the dis- ease and therefore the patient prognosis. Hence, uncon- trolled diabetics will have a poorer prognosis requiring more aggressive wound care and extensive debridement. Human Immunodeficiency Virus Human Immunodeficiency Virus (HIV) is a retrovirus that infects and destroys the host’s immune system by invad- ing CD4+ cells, which are at the very core of the immune response. It is therefore not surprising these patients are more susceptible to opportunistic infections. Accordingly, it is logical to propose that these patients are more prone to developing Fournier’s gangrene than a HIV negative group. HIV has been reported as a comorbidity in 4% of patients with Fournier’s gangrene (10). Various studies have documented a significant rise in the prevalence of cases of Fournier’s gangrene since the advent of the HIV epidemic (11). A handful of cases have reported Fournier’s gangrene as the initial presentation of the HIV infection (11, 12). Notably, although the presence of comorbid HIV may predispose to Fournier’s gangrene, it does not seem to adversely affect the natural course of the disease or patient prognosis. The fundamental principles of early recognition and timely initiation of treatment have been highlighted in the literature repeatedly as the ideals to a successful outcome. The identical principles apply to the prognosis of patients infected with HIV. PATHOPHYSIOLOGY The presence of a localized infection adjacent to the por- tal of entry, Table 1, allows the entry of normally com- mensal bacteria, such as Staphylococcus spp., and Escherichia coli, into the perineum. Essentially the infec- tious organisms trigger an inflammatory response result- ing in an obliterative endarteritis of the surrounding vas- culature. Subsequent thrombosis of the nutrient vessels and a resultant reduction in blood flow to this region leads to tissue ischaemia. The reduced oxygen tension of the tissues promotes further anaerobic bacteria prolifera- tion and fascial necrosis and digestion. CAUSATIVE MICROORGANISMS It was previously suggested that the necrotizing fasciitis could be attributed to infection by streptococcal species alone however; later clinical investigations have high- lighted the polymicrobial nature of this infection (13). Wound cultures from patients with Fournier’s gangrene show an average of 4 different microorganisms per case (14). Streptococcus, Staphylococcus and Escherichia are commonly identified species. SPREAD Advanced Fournier’s gangrene can extend through the fas- Uro-genital Ano-rectal Cutaneous Traumatic Men (26, 50-58) Urethral strictures, calculi, Peri-anal, peri-rectal, Ulceration due to scrotal Inguinal hernia repair (52), prostatic massage ischio-rectal abscesses, pressure (51), hidradenitis prostatic biopsy, vasectomy (53), anal fissures, diverticulitis, suppurative, poor perineal diathermy for genital warts, appendicitis, colonic hygiene e.g. paraplegics anal perforation (foreign body), malignancy (50), rectal cancer penile prosthesis (54), genital piercings (55), penile injection (56), steroid enemas (57), urethral instrumentation Women (58) Septic abortions, vulval HPV lesions (58) Hysterectomy. Episiotomy abscess, Bartholin’s abscess Children (59) Circumcision, strangulated Post-varicella rash (59) Urethral instrumentation congenital inguinal hernia Table 1. Reported cases in men, women and children of various portals of entry leading to Fournier’s gangrene. Kamran_Stesura Seveso 21/09/16 13:35 Pagina 158 cial planes ascending as high as the torso and descending to the thigh. The location of the por- tal of entry and anatomy of the fascial planes determines the extent of the infection (15). The deep layer of superficial perineal fascia, Colles’ fascia, is continuous with Scarpa’s fascia of the anterior abdominal wall and Buck and Dartos’ fascia of the penis and scrotum. Therefore, infec- tion can spread via these routes. Colles’ fascia is attached to the perineal body and urogenital diaphragm posteriorly and the pubic rami later- ally (15). Thus limiting the progression of infec- tion in these directions. Testicular involvement is rare and this has been attributed to their non- perineal blood supply. CLINICAL ASSESSMENT Patient presentation The most common symptoms of Fournier’s gan- grene include scrotal pain, swelling and erythe- ma (16). Systemic features such as fever, rigor and tachycardia are often present. Although originally described to be of sudden onset, experience has shown the condition 159Archivio Italiano di Urologia e Andrologia 2016; 88, 3 Fournier’s gangrene. A clinical review Figure 1. The imbalance between host defenses and the virulence of microorganisms in Fournier’s gangrene (12, 14). Figure 2. Potential care pathway for Fournier’s gangrene. 1 Pain may be out of proportion to clinical findings early in disease process; 2 Early on skin changes are a poor reflection of the infectious process. Kamran_Stesura Seveso 21/09/16 13:35 Pagina 159 Archivio Italiano di Urologia e Andrologia 2016; 88, 3 A. Singh, K. Ahmed, A. Aydin, M.S. Khan, P. Dasgupta 160 more frequently has an indolent onset. The symptoms of pruritus, pain and general discomfort tend to worsen over 3-5 days before hospital admission. In up to 40% of cases, the onset of the disease is more insidious resulting in delayed diagnosis and management (17). Examination may reveal purulent discharge, crepitus, and patches of necrotic tissue with surrounding oedema. Cutaneous manifestations tend to appear later in the disease process as these patches progress to florid gangrene (17). A thor- ough history, revealing diabetes, chronic alcohol abuse, steroid abuse, HIV, malignancy, lympho-proliferative dis- ease as well as recent catherisation, instrumentation and perineal trauma, should all increase the index of suspi- cion for a soft-tissue necrotizing infection. INVESTIGATIONS Although the diagnosis of Fournier’s gangrene is only certain after surgical exploration, laboratory studies and radiological evaluation are invaluable tools in risk assess- ment and in cases of diagnostic uncertainty. RISK STRATIFICATION Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) & Fournier’s Gangrene Severity Index (FGSI) Necrotising fasciitis is a complicated disease with a com- plex patient presentation, making early recognition a dif- ficult task. The LRINEC has been highlighted in the lit- erature as a system capable of differentiating necrotizing fasciitis from other soft tissue infections enabling early intervention (18). More specific to Fournier’s gangrene, the (FGSI) is a numerical scoring system, put forward by Laor et al. in 1995, to determine patient outcome and risk of mortality (19). The FGSI score is based on 9 phys- iological variables, Table 3, taken on admission includ- ing, temperature, heart rate, respiratory rate, These parameters similar to those of the LRINEC, represent the state of equilibrium and any deviation has been high- lighted in the literature as the key factor predictive of outcome. These researchers determined that a score of greater than 9 was a sensitive indicator of mortality, with a 75% probability of death (19). RENAL FUNCTION Lin et al. proposed a simplified FGSI with a focus on 3 parameters; serum potassium, serum creatinine and haematocrit (20). Their study showed a non-inferior pre- dictive value for patient outcome utilizing this 3 score index in their patient series. It is acknowledged that abnormalities in these variables are commonly found in renal failure. A mortality rate of 83.3% in patients with renal pathology, in this study, implores the concept of early risk assessment and aggressive management to improve survival in this group of patients (20). A num- ber of studies of patients with Fournier’s gangrene have highlighted that renal function is an important prognos- tic indicator and that dysfunction is associated with a higher mortality. Dysfunction of the key elements of the immune system such as neutrophils, monocytes and alterations to the elements of the inflammatory cascade, accumulate to increase the severity of sepsis and risk of death in these patients (20). An appreciation of these risks to patients with renal pathology, allowing early recognition and aggressive management such as dialysis, may improve the patient’s chance of survival. IMAGING If a soft-tissue necrotizing infection is suspected urgent surgical exploration is required nevertheless, there is a place for imaging in the investigation and management of these patients. Plain radiographs, ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) may demonstrate air in the soft tissue planes as well as help determine the extent of the disease. The use of imaging modalities must not delay surgical intervention. Conventional radiography Radiography may reveal subcutaneous emphysema extending from the perineum and external genitalia to the inguinal regions, thigh and anterior abdominal wall (12). The presence of subcutaneous air is not pathog- nomic but should increase the index of suspicion of a soft-tissue necrotizing infection. 90% of patients with Fournier’s gangrene have been reported to have subcuta- neous emphysema (12). Radiography may also reveal significant swelling of the scrotal tissue. Ultrasonography (US) US investigation may reveal subcutaneous emphysema, seen as echogenic areas demonstrating reverberation artifact with ‘dirty’ shadowing, in the scrotal or perineal regions (22). Another ultrasound finding in Fournier’s gangrene may be a thickened, oedematous scrotal wall. Complete blood count • Leucocytosis; WBC count > 15.4 x 109 L • Haemoglobin < 11 g/dL • Haematocrit < 20/> 60% Biochemistry panel • Serum Na < 135 mmol/L • Glucose level >10 mmol/L • Serum creatinine > 141 μmol/L • Serum K < 2.5/> 7 mmol/L • Bicarbonate < 15/> 52 mmol/L • Reduced serum Mg Raised inflammatory markers • CRP > 150 mg/L Raised serum lactate Urea > 18 mg/dL DIC panel • Sepsis induced coagulopathy Arterial blood gas • Acidosis (possibly due to hypo/hyperglycaemia or septic disturbance) * LRINEC -Laboratory Risk Indicator for Necrotising Fasciitis. WBC count, Haemoglobin, CRP, Serum Na, Glucose, Creatinine. FGSI Table 2. Common investigation findings and prognostic factors in Fournier’s gangrene (14, 18). Kamran_Stesura Seveso 21/09/16 13:35 Pagina 160 In cases of diagnostic doubt, quick and efficient radio- logical evaluation allows for timely treatment. Morrison et al. emphasized that the diagnosis of Fournier’s gangrene can be made with bedside ultrasound, at a very high sen- sitivity (23). US is also useful in differentiating a soft-tis- sue necrotizing infection from other scrotal pathology. In this context, US is superior to radiography. Computed Tomography (CT) Soft-tissue thickening, inflammation and subcutaneous emphysema are the CT features found in Fournier’s gan- grene. The main role of CT in soft-tissue necrotizing infections however is in identifying the infectious origin and in delineating the extent of the disease (22). The extent of fascial destruction on CT has been shown to correlate with the total affected tissue at surgery (22). Magnetic Resonance Imaging (MRI) Only a few cases in the literature describe the use of MRI in Fournier’s gangrene even though it yields greater soft tissue detail than the other imaging modalities. The rea- son for this may be its limited availability in many hos- pitals as well as a longer scan time, reducing its practical usefulness. However, a number of cases have detailed the use of MRI in the diagnosis of Fournier’s gangrene show- ing subcutaneous emphysema, scrotal wall thickening and fluid accumulation (24, 25). MRI enables a wider field of view, allowing the spread of the infection to be assessed and is suggested to be advantageous in advanced lesions (25). DIFFERENTIAL DIAGNOSIS The differential diagnosis of Fournier’s gangrene may include scrotal, perineal, intra-abdominal or systemic disorders (Table 3). MANAGEMENT The cornerstones of management in this life-threatening condition are urgent patient resuscitation, broad-spec- trum antibiotic therapy and surgical debridement. The goal of treatment is to reduce systemic toxicity, halt pro- gression of the infection and eliminate the causative microorganisms. Antibiotic coverage A parenteral broad-spectrum antibiotic regime is required, Table 4, on presentation in the management of Fournier’s gangrene. Subsequent culture and sensitivity results may modify the choice of antibiotics. Currently there are no recommendations for optimal antibiotic therapy in Fournier’s gangrene and patient management depends on local hospital guidelines. Surgical debridement The early and radical removal of necrotic and devitalized tissue is the crucial step in halting progression of the infec- tion. The necessity for rapid surgical debridement is appreciated, with even a few hours delay increasing the risk of death (26). In a retrospective analysis of 72 patients with Fournier’s gangrene, Kabay et al. highlighted that a time delay in surgical debridement was associated with significant mortality (27). Removal of the deep fascia and underlying muscle is not usually necessary and these structures are rarely involved in the disease process. Nonetheless, it is important to highlight that the magni- tude of the infection cannot be judged by the degree of cutaneous necrosis and surgical exploration is imperative (12). The initial debridement, with adequate resection of the non-viable tissues, is considered the most important factor for survival (26). Extensive debridement, including a slim window of healthy adjacent tissue, has been advo- cated in the literature. Close observation of the wound and repeated debridement are necessary measures to control the infection. A mean of 3.5 debridement operations per patient has been suggested to be necessary for adequate infection control (28). Plastic reconstruction The rapid and aggressive pathological process underly- ing Fournier’s gangrene can result in large scrotal, per- ineal and abdominal defects. The choice of surgical reconstruction is based on the characteristics of the defect, that is, the size, location and depth as well as the availability of local tissue (29). The use of local skin flaps, split-thickness skin grafts, fasciocutaneous perfora- tor flaps and myocutaneous flaps have all been described in the literature. The ideal reconstructive technique would occur as a single procedure, yield optimal func- tion, a natural appearance of the wound and minimal post-operative and donor site complications. Primary closure of the wound is the closest to this ideal, provid- ing the best functional and cosmetic results, but is only useful in small to medium sized lesions. 161Archivio Italiano di Urologia e Andrologia 2016; 88, 3 Fournier’s gangrene. A clinical review Vancomycin/linezolid • MRSA positive Clindomycin • Streptococcal spp Fluoroquinolone • Broad spectrum both gram negative spp and gran positive spp Cephalosporin • Gram positive spp Metronidazole • Anaerobic bacteria * Antibiotic regime accounting for gram positive, gram negative and anaerobic bacteria Table 4. European Association of Urology (EAU) suggested initial antibiotic options* (49). Scrotal cellulitis Inguino-scrotal strangulated hernia Testicular torsion/abscess/haematoma Gonococcal balantis Acute epididymitis Vasculitis Polyarteritis nodosum Table 3. Differential diagnosis of Fournier’s gangrene. Kamran_Stesura Seveso 21/09/16 13:35 Pagina 161 Archivio Italiano di Urologia e Andrologia 2016; 88, 3 A. Singh, K. Ahmed, A. Aydin, M.S. Khan, P. Dasgupta 162 Scrotal advancement flap The scrotum is involved in the majority of cases and scro- tal advancement flaps are suitable in small-medium size lesions. A recent review of 43 reconstructive cases revealed the need for scrotal reconstruction in 93% of the cases (29). Scrotal advancement flaps apply the surgical principle of “replace like with like” providing coverage from local scrotal tissue. Advancement flaps have been used to repair scrotal deficits up to 96 cm2 (30). The larg- er the skin defect, the longer advancement distance required and therefore the more stress on the tissue and greater risk of reconstructive complications. The higher tension in the flap may compromise the blood supply leading to wound edge necrosis and flap failure, yet it has been shown that as little as one third of healthy scrotal skin can be expanded to provide complete scrotal cover- age, possibly due to the expandable and resilient nature of scrotal tissue (29). This reconstructive technique, where suitable, provides excellent clinical and aesthetic results. In more complicated cases, involving perineal and/or abdominal wall defects after debridement, local scrotal flaps may be insufficient to provide wound coverage. Split Thickness Skin Grafts (STSG) Maguina et al. described four cases of scrotal reconstruc- tion by meshed split thickness skin grafts (STSG) (31). These cases illustrated both the efficiency and effective- ness of STSG by the reduction in recovery time and excellent functional and aesthetic results. Various studies have highlighted the similarities in colour, shape and thickness of the neo-scrotum to normal scrotal tissue (32, 33). Post-operative complications of scrotal skin grafting including bleeding, shearing and infection have been reported. Some studies reported cases of graft con- tracture and undesirable cosmetic results. Chen et al. applied STSG to nine patients with good clinical and cos- metic results. These authors recommend this method in scrotal defects with abdominal wall involvement (30). Skin grafts in the perineal region have been reported unsatisfactory due to continuous wound contamination. Fasciocutaneous/perforator flap Various fasciocutaneous flaps have been used for scrotal and perineal reconstruction. These tissue flaps provide a large surface area of wound coverage and are used in cases where skin graft coverage is insufficient (34). The literature also reports superior functional and cosmetic outcomes compared to reconstruction with split thick- ness skin grafts, possibly due to the reduced incidence of skin contracture (34). Superomedial thigh, pudendal, inguinal and anterolateral thigh fasciocutaneous flaps have been described in the reconstruction of the scrotum and perineum. These flaps have the advantage of having a reliable blood supply, minimal donor site morbidity and preservation of the underlying muscle (35). The tis- sue flaps can be harvested as sensate flaps, with preser- vation of the nerve supply, to allow sensation to the scro- tal and perineal skin. Myocutaneous/muscle flap In cases of radical debridement and deep pocket forma- tion, a muscle flap is the recommended reconstructive method of choice, to eliminate the empty space. A gra- cilis muscle flap has been used to provide wound cover- age for large, deep perineal defects. The close proximity of the muscle to the perineal region and its highly vas- cularized tissue providing a greater resistance to wound contamination, make the technique ideal for this region (35). A number of cases have reported successful func- tional and aesthetic outcomes after gracilis myocuta- neous flap reconstruction of the scrotum and perineum (36, 37). Notably, the anterolateral thigh flap can be har- vested as a myocutaneous flap, with fibres of the vastus lateralis muscle within its core. This allows coverage of the deep wound, with an adjustable muscle mass, with- out compromising the integrity of the quadriceps femoris muscle (37). Fibrin tissue sealant Fibrin sealant has been reported in a number of cases as a useful adjunct in the management of complicated wounds of the perineum and external genitalia. It has been suggested that the fibrin adhesive strengthens the wound site, supports closure and provides a route for the slow release of growth factors and antibiotics (38). In regards to reconstruction of defects in Fournier’s gan- grene, fibrin sealant has been shown to promote effective closure of thigh fasciocutaneous flaps and other large flaps, with decreased infection and resultant clinically stable wounds without further complications (39). SURGICAL ADJUNCTS Fecal & urinary diversion In certain cases of perineal involvement, faecal contami- nation may be prevented by colostomy formation. Cases of anal sphincter insufficiency, fecal incontinence and continuous contamination of the wound affecting healing necessitate fecal diversion (40). Diversion colostomy is a surgical operation and therefore carries additional risks to the patient. Stoma site infection, stoma ischaemia and evisceration have been reported. Korkut et al. emphasized a significantly higher mortality, 38%, in patients that required colostomy compared to the mortality, 7%, of those that did not require colostomy (41). The Flexi-Seal Fecal management system is a form of fecal diversion that may serve as an alternative to colostomy. The catheter maneuvers faecal material away from the wound, pre- venting contamination and promoting healing. A recent study highlighted the use of bowel catheter over that of colostomy revealing a reduction in hospital stay and expenses (42). However, the use of the catheter was lim- ited to those patients without anal sphincter and rectum involvement. Clear contraindications to the use of this device include rectal neoplasms, penetrating rectal injuries and fistulas (42). Urinary diversion may be nec- essary in cases of urethral inflammation or penile involve- ment (43). Urethral catherisation may suffice but in more severe cases, cystostomy is indicated. Vacuum assisted closure Vacuum Assisted Closure (VAC) is a method employed to accelerate the healing of surgical wounds and compli- Kamran_Stesura Seveso 21/09/16 13:35 Pagina 162 cated wounds that fail primary healing. The open wound is exposed to negative pressure, which is thought to reduce oedema of the tissues, increase blood flow and thereby promote healing and debridement. There is some evidence that suggests VAC is advantageous over conventional wound treatment in certain patients. Assenza et al. found that VAC reduced hospitalization, patient morbidity and allowed early reconstructive sur- gery (44). EMERGING THERAPIES Honey Recently the antimicrobial properties of unprocessed honey and its ability to stimulate epithelial cell growth have been recognized in the management of Fournier’s gan- grene. A low pH of 3.6, a high osmotic pressure and enzy- matic activity, are the properties, which allow honey to digest necrotic tissue and bacteria. Tahmaz et al. compared the classic triad of management of Fournier’s gangrene to that of topical unprocessed honey and triple antibiotic therapy, without debridement, in 33 male patients (45). These researchers showed better clinical and cosmetic out- comes in the group of patients treated with unprocessed honey and antibiotic therapy. Notably, this group of patients was younger, healthier and had less severe lesions. A recent review of 25 trials analyzing the use of topical unprocessed honey and its impact on wound healing con- cluded that honey dressings, do not impact healing and in some cases may delay the healing process (46). Hyperbaric oxygen therapy Hypoxia due to arterial vessel thrombosis results in tissue ischaemia, necrosis and creates a favourable environment for anaerobic bacteria. Therefore, the creation of an envi- ronment with optimal oxygen uptake by tissues, is a sen- sible adjunct to surgical debridement and triple antibiotic therapy. Hyperbaric oxygen therapy is thought to hasten tissue healing by optimizing the immune system’s activity through fibroblast proliferation, maximizing neutrophil function, reducing oedema and increasing intracellular transport of antibiotics (47). Indeed the use of hyperbaric oxygen has yielded promising clinical and cosmetic results. However, the most recent review examining 42 patients with Fournier’s gangrene highlighted a higher morbidity and mortality with HBO. Although it was acknowledged to possibly be due to patient selection bias. HBO therapy is indicated in those patients unresponsive to conventional treatment, in Clostridial or severe anaero- bic infection or deep tissue involvement (48). CONCLUSIONS Fournier’s gangrene remains a surgical emergency and urgent, complete debridement is at the foundation of patient survival (49). The management of Fournier’s gangrene focuses on patient monitoring for sepsis, broad-spectrum antibiotics and surgical removal of unvi- able tissue. 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