US Pharm. 2016;41(8):HS6-HS11.
ABSTRACT: Fournier gangrene (FG), a polymicrobial necrotizing infection of the perineal, perianal, or genital area, can affect any age group and either gender, but is most common in older males. Persons with impaired immunity and those who have experienced genital trauma are at increased risk. Symptoms include redness, swelling, and pain in the genital region; fever may also be present. The virulence of infectious microorganisms promotes the rapid spread of FG, leading to vascular necrosis and tissue ischemia. FG is considered a urologic emergency because it spreads aggressively, requiring prompt surgical consultation for debridement, empirical treatment with broad-spectrum antibiotics, wound management, and possible reconstructive surgery. Despite advances in diagnosis and treatment, FG continues to have a high mortality rate.
Fournier gangrene (FG) is a polymicrobial necrotizing infection of the perineal, perianal, or genital area originally identified and described in 1883 by the French venereologist Jean Alfred Fournier.1 Fournier’s initial description indicated that the disease was limited to young people, males in particular; however, it is now known that any age group and either gender may be affected, but most commonly older males. Persons with impaired immunity (e.g., diabetes) and those who have experienced genital trauma are at increased risk for developing this infection.1
FG is considered a urologic emergency because it spreads aggressively, requiring prompt surgical consultation for debridement and empirical treatment with broad-spectrum antibiotics.
Etiology and Predisposing Factors
FG is classified as a type I necrotizing fasciitis of polymicrobial etiology. FG was originally described as idiopathic; however, based on newer research, the number of cases classified as idiopathic is presently <25%.1,2 In many instances, patients with FG have impaired immunity (for example, from diabetes mellitus, chronic alcoholism, or advanced age).2 It has been reported that 20% to 70% of patients who present with FG also have diabetes. The relatively high incidence of diabetes in patients with FG is believed to be due to small-vessel disease, defective phagocytosis, neuropathy, and immunosuppression.3
Frequently cited causes of FG include genital trauma that allows a site of entry for bacteria; colorectal sources; urogenital sources; and cutaneous infections.2,4 Genital trauma may be accidental, intentional, or surgical in nature, including superficial soft-tissue injury, genital piercings, penile self-injection with cocaine, instrumentation, penile implants, IM injection, and rectal foreign bodies.4-6 Colorectal sources of FG include perianal, perirectal, and ischiorectal abscesses, as well as anal fissures, colonic perforations, diverticulitis, hemorrhoidectomy, inflammatory bowel disease, and malignancy.2,7-9 Urogenital sources of FG include urethral strictures, epididymitis, orchitis, chronic urinary tract infection, and neurogenic bladder.2,10 Dermatologic causes include scrotal ulceration from pressure and inadequate perianal hygiene.
Symptoms and Pathophysiology
The etiology of, and predisposing factors for, FG provide a favorable environment for infection. FG exists because of synergism between multiple bacteria that together are highly aggressive; these organisms are species that normally exist in the genitalia and perineum.11 Redness of the skin, swelling and pain in the genital region, and fever are the most common symptoms of FG. Crepitus of the inflamed tissues is a common feature because of the presence of gas-forming organisms.2,12
The infection usually starts as cellulitis that is adjacent to the portal of entry and has an insidious presentation.2 The affected area commonly is dark and is covered by macerated skin, and there is characteristically a feculent odor that is caused by anaerobes.13 The average number of isolates cultured in FG per case is four; the most common aerobic organisms cultured are Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus, and the most commonly cultured anaerobic organism is Bacteroides. Other commonly identified microorganisms are Proteus, aerobic and anaerobic Streptococcus, Pseudomonas, Enterococcus, and Clostridium species.
Rarely, necrotizing fasciitis due to Candida species, as well as Lactobacillus gasseri, has been reported.2,4 The virulence of the microorganisms promotes the rapid spread of FG from a localized infection to an obliterative endarteritis with both cutaneous and subcutaneous vascular necrosis, leading to ischemia and further bacterial proliferation.2,12 The complexity of the external male genitalia influences how FG initiates and spreads. Often, the deep muscular structures are spared, and to a variable degree, the overlying skin is spared as well. This has implications for the initial debridement and required reconstructions, making it critical for those treating FG to have expert knowledge of the male lower urinary tract and external genitalia.
Diagnosis
The diagnosis of FG is primarily clinical. Imaging modalities are used to assist in cases with an atypical presentation or to investigate the full extent of the disease.14 It is important not to delay surgery for imaging. Conventional radiography may be used to detect air in the soft tissues in the area over the scrotum and perineum before the detection of clinical crepitus.
Radiography can show swelling of the scrotal tissue as well as subcutaneous emphysema extending from the scrotum and perineum to the inguinal regions, anterior abdominal wall, and thighs. It is important to note that the lack of subcutaneous air does not exclude a diagnosis of FG. The major pitfall of radiography in the diagnosis and evaluation of FG is that it does not detect deep fascial gas.2,15
Contrary to other conditions that can cause acute scrotal pain, the scrotal contents, testes, and epididymides are normal in FG. Ultrasound (US) effectively demonstrates specific features of FG, but CT does so with a greater specificity. US findings include a thickened edematous scrotal wall and air in the subcutaneous tissues.16
Because most FG cases are secondary to other conditions, CT plays a role in diagnosis and in the evaluation of disease extent to guide appropriate surgical intervention. CT may be used to evaluate superficial and deep fascia and to distinguish FG from soft-tissue edema or cellulitis, which can appear similar to FG on physical examination.2 The underlying cause of FG may be shown on CT as well, including perianal abscess or an intraabdominal or retroperitoneal infectious process. MRI is more useful than radiography and US, and some argue that it is more helpful than CT in guiding surgical interventions.2
Commonly, laboratory results are nonspecific and may demonstrate anemia, leukocytosis, thrombocytopenia, electrolyte abnormalities, hyperglycemia, elevated serum creatinine, azotemia, and hypoalbuminemia.2 Notably, abnormal laboratory parameters at admission have been shown to have a significant impact on mortality. The laboratory results with the most predictive value for poor prognosis include increased leukocytes, creatinine, creatine kinase, urea, lactate dehydrogenase, and alkaline phosphatase and decreased levels of bicarbonate, sodium, potassium, calcium, total protein, and albumin; anemia also has predictive value.2
Management and Treatment
As was previously stated, the mainstays of treatment of FG include urgent surgical debridement of necrotic tissue, broad-spectrum antibiotics, and fluid resuscitation for hemodynamic support.2,11,12 FG should be considered a surgical emergency since the rate of fascial necrosis has been noted to be up to 2 to 3 cm per hour.11,17
Broad-Spectrum Antibiotics: Empirical broad-spectrum antibiotics should be initiated as soon as possible and continued until culture results are available to guide therapy. The selected antibiotic regimen must have activity against gram-positive, gram-negative, and anaerobic bacteria, as the etiology can be polymicrobial or monomicrobial.18 A recent retrospective cohort study that examined the most common microbiologic isolates involved in FG determined the following to be the most common pathogens: polymicrobial microorganisms (54%); E coli (46.6%); Streptococcus (36.8%), Bacteroides (35.5%), Enterobacter (30.9%), Staphylococcus (19.7%), Enterococcus (15.9%), Pseudomonas (12.7%), and Corynebacterium (8%) species; and K pneumoniae (3%).19 See TABLE 1 for a survey of empirical antimicrobial therapy options for FG.18,20
Surgical Debridement: In addition to treatment with broad-spectrum antibiotics, radical surgical debridement should be performed as soon as possible. Most patients require multiple procedures during their hospital course, as antibiotics alone are typically associated with a higher mortality rate. Debridement of the deep fascia, muscle, and testes is not usually required, as these areas are rarely involved. In some cases, orchiectomy has been performed because of suspected severe infection in the peritesticular tissues; however, following pathologic review, the testes were found not to be involved. It is sometimes possible to place the testes in a temporary SC pouch until healing or reconstruction is complete.1,18,21
Wound Management: After debridement, an open wound must be managed, usually with sterile dressings or negative-pressure wound therapy (NPWT). A retrospective review of 14 patients assessed the efficacy of daily povidone-iodine dressing or sodium hypochlorite (Dakin’s solution) for wound management. The length of hospitalization was significantly shorter in patients managed with Dakin’s solution than in those managed with iodine dressing (8.9 days vs. 13 days), which it was suggested may have been due to the known antimicrobial effects of Dakin’s solution on aerobic and anaerobic organisms.22 NPWT, also known as vacuum-assisted wound closure, refers to wound-dressing systems that consistently or intermittently apply subatmospheric pressure to the surface of a wound to promote debridement and healing. NPWT has been studied in the postoperative management of FG. One study prospectively collected data on 35 patients with FG to assess the efficacy of NPWT versus daily polyhexanide dressings.23 Patients treated with NPWT had significantly longer hospitalizations (27.8 days +/– 27.6 days vs. 96.8 days +/– 77.2 days) and lower mortality (37.5% vs. 5.3%). The study also found that significantly more patients in the NPWT group required fecal-diversion systems because of the need to reapply the vacuum dressing after each bowel movement. The need for fecal-diversion systems may also have been responsible for a higher mean number of surgical interventions in patients treated with NPWT compared with conventional dressings that were more easily changed. It was concluded that NPWT is not superior to conventional dressings in terms of length of stay or clinical outcomes; however, it is still clinically effective and may be successfully used in the management of large wounds.23
Reconstructive Surgery: The extensive debridement required in many cases of FG leads to skin and soft-tissue defects that necessitate reconstructive surgery for wound closure and acceptable functional and cosmetic results.2 Differing techniques have been used to achieve these results, including the transplantation of testes, free skin grafts, and groin and myocutaneous flaps. The primary goal of reconstruction in patients who have experienced genital skin loss from FG is wound coverage; other goals include acceptable appearance and preservation of penile function (i.e., erection, ejaculation, and ability to urinate). Ideally, these goals would be achieved quickly and with low associated morbidity and mortality.
As mentioned previously, involvement of the testes is rare in FG.11 As stated previously, a temporary thigh pouch may be created to store the testes in the acute setting, allowing the patient time to recover prior to scrotal reconstruction. The implantation of the testicles in an adjacent subcutaneous thigh flap can reduce length of hospital stay and recovery time.24
Owing to its versatility, skin grafting is advantageous in FG. There are several types of skin grafts, including full-thickness skin graft (FTSG) and split-thickness skin graft (STSG). FTSG procedures harvest an entire layer of skin as the graft and are thought to be superior in terms of cosmetic results; however, STSG transfers a portion of donor-site skin (epidermis and some of the underlying dermis) and is preferred in cases of contaminated wounds because these grafts have been shown to take better in such cases.2
Conclusion
FG is a rare, aggressive polymicrobial necrotizing infection of the perineal, perianal, or genital area. The predisposing and etiologic factors of FG provide the perfect environment for infection to thrive. The mainstays of FG treatment are urgent surgical debridement of necrotic tissue, broad-spectrum antibiotics, supportive care, wound management, and reconstructive surgery. Despite advances in diagnosis and management, FG continues to have a high rate of mortality and requires a multidisciplinary approach to management.
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