Fournier’s gangrene (FG) can be defined as a rapidly progressive polymicrobial necrotising fasciitis of the perineal, genital and/or perianal areas, leading to gangrene and necrosis of tissues and a concomitant systemic sepsis1,2. Fournier’s Gangrene is an urological emergency and if it is not diagnosed and treated promptly could be a life-threatening condition3 . Although it can be considered a rare disease (1.6 cases per 100,000), the mortality rate is high (3% up to 88%)4. FG is more prevalent in male patients, with a M/F ratio of 10:1 and its incidence increases with age with a peak in the 5th- 6th decades5.
RISK FACTORS AND ETIOLOGY
An infection of urinary, genital, anorectal and skin origin or a local trauma are usually the entry door for the subcutaneous tissues6. Most uro-genital, anorectal and cutaneous infection can be the origin of gangrene. Many condition may predispose to FG, with impairment of host immunity and microcirculation as common denominator7,8 (Box 1).
Fournier’s Gangrene is typically a polymicrobic infection sustained by different organisms9 , both Gram + and Gram -, aerobic and anaerobic. The synergistic action of aerobic and anaerobic bacteria can be considered as responsible of thrombosis and tissue necrosis10,11. Local thrombosis determines ischemia and decrease in tissue oxygenation that yield spreading of the infection, leading to necrotising fasciitis12. E. coli is the most commonly pathogen detected (48%), followed by Enterococcus fecalis (28%)10-13 (Box 2).
Clinical recognition of Fournier’s Gangrene signs and symptoms is essential for early diagnosis and treatment. Some prodromal symptoms can be noticed from 2 to 7 days before the onset of gangrene such as fever, asthenia, nausea and vomiting, tachycardia, perineal, perianal and/or scrotal pain, itching, edema and/or erythema of tissue surface14,15. Subsequently and suddenly the clinical picture evolves to necrosis and gangrene of tissues with possible concomitant discharge of purulent materials. The presence of subcutaneous crepitus due to emphysema can be detected and it is considered pathognomonic for anaerobic bacteria involvement10-14. It has been estimated that the gangrenous area spreads to nearest tissues at a speed of 2/3 cm per hour, making crucial early diagnosis for patients’ survival. In this phase, signs and symptoms of septic shock can be detected16,17. Potential life-threatening complication of FG is unresolved sepsis that leads to multiple organ failure (heart, lung, kidney, liver). Other possible severe complications can be coagulopathy, cholecystitis and cerebrovascular accidents14-17.
Diagnostic criteria for Fournier’s Gangrene are18:
- Infection of soft tissues that involves perineum, genitalia (usually scrotum) or anal region
- Finding of air in subcutaneous tissue at clinical or radiological examination
- Presence of necrotic tissues at surgical intervention and histological diagnosis of necrotizing fasciitis
Most of laboratory findings in FG are quite aspecific. Anemia, leukocytosis and thrombocytopenia can be usually detected in blood examination. Electrolyte impairments like hyponatremia, hypokalemia, hypocalcaemia are frequently present. Other common findings are hyperglycemia, elevated creatinine and azotemia19,20. Blood culture resulted positive in about 20% of patients21.
X-rays of the abdomen and pelvis, can be useful to recognize the presence of air in soft tissues and subcutaneous emphysema22. Computed Tomography (CT) can be helpful for evaluating the extension of gangrene, as unlike x-rays, it allows to evaluate also the deep fascia23. Magnetic Resonance (MRI) provides more detailed information on extension of necrotic fasciitis and it is the gold standard for planning surgical intervention24,25.
Some prognostic scores have been developed to evaluate the outcomes of Fournier’s Gangrene:
- Fournier’s Gangrene Severity Index (FGSI) (Box 3): The score is calculated including patients’ vital signs and metabolic parameters. It has been estimated that score > 9 have a 75% probability of death and an index score ≤ 9 is associated with 78% survival26-28.
- Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC): this score stratifies patients into three different risk class for Necrotising Soft-Tissue Infection (low, moderate or high risk) according to blood parameters (C-reactive proteins, WBC, Haemoglobin, Serum sodium, Serum creatinine, Plasma glucose)29.
- Affected area calculation/Extension of the necrosis: It has been estimated that an affected area of less than 3% have a low risk of progression while if the area is above 5% the risk raises30.
FG requires a multimodal therapy including intensive care, antibiotics and surgery16.
Anemia, hypotension, hyperglycemia and electrolytic impairment should be corrected and patient should be addressed to surgery that represents the cornerstone of FG treatment31.
When possible, antibiotic therapy should be targeted to culture results. Timing of antibiotic therapy is crucial for positive outcome. An empiric therapy with penicillins (for gram positive), clindamycin or metronidazole (for anaerobes) and cephalosporine with aminoglycosides or fluoroquinolones (for gram negative) or, as alternative, monotherapy with carbapenems or piperacillinetazobactam can be started in these patients46.
Surgical debridement is crucial for reduce mortality in FG patients33 (Fig. 1). Main goals of surgery are to remove all the infected tissues. Intervention is performed under general anesthesia, with patient in lithotomic position. A midline perineal and scrotal incision allows a good exposition of necrotic tissues. Debridement should be extended until the affected fascia is no longer easily dissociable from deep fascia and muscle34. In about 25% of patients, orchiectomy is needed. In some cases a second time reconstructive surgery with skin flap or grafts can be required35. Early surgery (first 12-24 hours) has a significantly better outcome in terms of survival when compared to delayed surgery36.
Hyperbaric Oxygen Therapy In Fournier’s Gangrene
Hypoxia is one of the most important pathogenetic mechanisms of necrotizing infection. Hyperbaric oxygen therapy (HBOT) has been proposed as a possible adjuvant therapy in FG management37,38. Combined with local wound care, hyperbaric oxygen seems to be able to improve viability of tissues and wound healing in necrotizing fasciitis39. Recent emerging evidences have demonstrated efficacy and safety of HBOT for treatment of Fournier’s Gangrene.
HBOT consists in the inhalation 100% O2 with a pressure superior to atmospheric pressure at sea level, in a dedicated chamber. The European Committee for Hyperbaric Medicine recommends application of HBOT for anaerobial or mixed bacterial infections (LoE 1 grade C)40. It exerts a bacteriostatic and bactericidal effect. This anti-infectious effect is carried out through several mechanisms (Box 4)41. It has been demonstrated that HBOT can significantly reduce disease related mortality and that hyperbaric treatment is an independent predictor of lower mortality in FG patients38. Taking together all published studies regarding HBOT as adjuvant therapy in FG treatment, the mortality rate in patients treated with hyperbaric therapy is 16.6% versus 25.9% in patients who do not receive treatment42.
The correct timing for HBOT administration is still not standardized, but it is reasonable to start the treatment as soon as possible, with the specific aim of avoiding infection spreading and the subsequent progression to necrosis43. The characteristics of treatments varies with the severity of illness. The suggested therapeutic scheme is twice daily for 4-7 days and daily thereafter depending on wound healing. HBOT should be administered at a pressure ranging from 2.4 to 2.8 ATM for a time ranging from 50 to 90 minutes38.
To date, it is not possible to predict which patient will benefit of HBOT, as FG is still a very complex disease and many factors can affect the outcomes. Nevertheless, based on the above mentioned findings, HBOT should be considered, whenever available, in the setting of multimodal treatment together with surgery and antimicrobial therapy.
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