Fournier Gangrene

In 1764, Baurienne originally described an idiopathic, rapidly progressive soft-tissue necrotizing process that led to gangrene of the male genitalia. However, the disease was named after Jean-Alfred Fournier, a Parisian venereologist, on the basis of a transcript from an 1883 clinical lecture in which Fournier presented a case of perineal gangrene in an otherwise healthy young man, adding this to a compiled series of 4 additional cases.[7] He differentiated these cases from perineal gangrene associated with diabetes, alcoholism, or known urogenital trauma, although these are currently recognized risk factors for the perineal gangrene now associated with his name.

This manuscript outlining Fournier’s initial series of fulminant perineal gangrene provides a fascinating insight into both the societal background and the practice of medicine at the time. In anecdotes, Fournier described recognized causes of perineal gangrene, including placement of a mistress’ ring around the phallus, ligation of the prepuce (used in an attempt to control enuresis or as an attempted birth control technique practiced by an adulterous man to avoid impregnating his married lover), placement of foreign bodies such as beans within the urethra, and excessive intercourse in diabetic and alcoholic persons. He calls upon physicians to be steadfast in obtaining confession from patients of “obscene practices.”

The complex anatomy of the male external genitalia influences the initiation and progression of Fournier gangrene. This infectious process involves the superficial and deep fascial planes of the genitalia. As the microorganisms responsible for the infection multiply, infection spreads along the anatomical fascial planes, often sparing the deep muscular structures and, to variable degrees, the overlying skin, making the extent of involvement difficult to appreciate.

This phenomenon has implications for both initial debridement and subsequent reconstruction. Therefore, a working knowledge of the anatomy of the male lower urinary tract and external genitalia is critical for the clinician treating a patient with Fournier gangrene.

Skin and superficial fascia

Because Fournier gangrene is predominately an infectious process of the superficial and deep fascial planes, understanding the anatomic relationship of the skin and subcutaneous structures of the perineum and abdominal wall is important.

The skin cephalad to the inguinal ligament is backed by Camper fascia, which is a layer of fat-containing tissue of varying thickness and the superficial vessels to the skin that run through it. Scarpa fascia forms another distinct layer deep to Camper fascia. In the perineum, Scarpa fascia blends into Colles fascia (also known as the superficial perineal fascia), while it is continuous with Dartos fascia of the penis and scrotum (see the image below).

Fascial envelopment of the perineum (male). Note how Colles fascia completely envelops the scrotum and penis. Colles fascia is in continuity cephalad to the level of the clavicles. In the inguinal region, this fascial layer is known as Scarpa fascia. Familiarity with this fascial anatomy, along with recognition that necrotizing fasciitis tends to spread along fascial planes, makes it easy to understand how a process that starts in the perineum can spread to the abdominal wall, the flank, and even the chest wall.

Several important anatomic relationships should be considered. A potential space between the Scarpa fascia and the deep fascia of the anterior wall (external abdominal oblique) allows for the extension of a perineal infection into the anterior abdominal wall. Superiorly, Scarpa and Camper fascia coalesce and attach to the clavicles, ultimately limiting the cephalad extension of an infection that may have originated in the perineum.

Colles fascia is attached to the pubic arch and the base of the perineal membrane, and is continuous with the superficial Dartos fascia of the scrotal wall. The perineal membrane is also known as the inferior fascia of the urogenital diaphragm and, together with Colles fascia, defines the superficial perineal space.

This space contains the membranous urethra, bulbar urethra, and bulbourethral glands. In addition, this space is adjacent to the anterior anal wall and ischiorectal fossae. Infectious disease of the male urethra, bulbourethral glands, perineal structures, or rectum can drain into the superficial perineal space and can extend into the scrotum or into the anterior abdominal wall up to the level of the clavicles.

Vascular supply to the skin of the lower abdomen and genitalia

Branches from the inferior epigastric and deep circumflex iliac arteries supply the lower aspect of the anterior abdominal wall. Branches of the external and internal pudendal arteries supply the scrotal wall. With the exception of the internal pudendal artery, each of these vessels travels within Camper fascia and can therefore become thrombosed in the progression of Fournier gangrene.

Thrombosis jeopardizes the viability of the skin of the anterior scrotum and perineum. Since the internal pudendal artery is not contained within Camper fascia, it is less susceptible to thrombosis; therefore, its vascular territory—the posterior aspect of the scrotal wall—remains viable and can be used in the reconstruction following resolution of the infection.

Penis and scrotum

The contents of the scrotum, namely the testicles, epididymides, and cord structures, are invested by several fascial layers distinct from the Dartos fascia of the scrotal wall. Again, several important anatomic relationships should be considered.

The most superficial layer of the testis and cord is the external spermatic fascia, which is continuous with the external aponeurosis of the superficial inguinal ring (external abdominal oblique). The next deeper layer is the internal spermatic fascia, which is continuous with the transversalis fascia. A deep fascia termed Buck fascia covers the erectile bodies of the penis, the corpora cavernosa, and the anterior urethra. Buck fascia fuses to the dense tunica albuginea of the corpora cavernosa, deep in the pelvis.

The fascial layers described in this section do not become involved with an infection of the superficial perineal space and can limit the depth of tissue destruction in a necrotizing infection of the genitalia. The corpora cavernosa, urethra, testes, and cord structures are usually spared in Fournier gangrene, while the superficial and deep fascia and the skin are destroyed.

Localized infection adjacent to a portal of entry is the inciting event in the development of Fournier gangrene. Ultimately, an obliterative endarteritis develops, and the ensuing cutaneous and subcutaneous vascular necrosis leads to localized ischemia and further bacterial proliferation. Rates of fascial destruction as high as 2-3 cm/h have been described.

Infection of superficial perineal fascia (Colles fascia) may spread to the penis and scrotum via Buck and Dartos fascia, or to the anterior abdominal wall via Scarpa fascia, or vice versa. Colles fascia is attached to the perineal body and urogenital diaphragm posteriorly and to the pubic rami laterally, thus limiting progression in these directions. Testicular involvement is rare, as the testicular arteries originate directly from the aorta and thus have a blood supply separate from the affected region. Far-advanced or fulminant Fournier gangrene can spread from the fascial envelopment of the genitalia throughout the perineum, along the torso, and, occasionally, into the thighs.

The following are pathognomonic findings of Fournier gangrene upon pathologic evaluation of involved tissue:

• Necrosis of the superficial and deep fascial planes<
• Fibrinoid coagulation of the nutrient arterioles
• Polymorphonuclear cell infiltration
• Microorganisms identified within the involved tissues

Infection represents an imbalance between (1) host immunity, which is frequently compromised by one or more comorbid systemic processes, and (2) the virulence of the causative microorganisms. The etiologic factors allow the portal for entry of the microorganism into the perineum; the compromised immunity provides a favorable environment to initiate the infection; and the virulence of the microorganism promotes the rapid spread of the disease. See the image below.

Necrotizing infection results when the pathogen is extremely virulent or, most commonly, when a combination of microorganisms act synergistically in a susceptible immunocompromised host.

Microorganism virulence results from the production of toxins or enzymes that create an environment conducive to rapid microbial multiplication.[8] Although Meleney in 1924 attributed the necrotizing infections to streptococcal species only,[9] subsequent clinical series have emphasized the multiorganism nature of most cases of necrotizing infection, including Fournier gangrene.[10, 11, 12, 13, 14]

Presently, recovering only streptococcal species is unusual.[15] Rather, streptococcal organisms are cultured along with as many as 5 other organisms.

The following are common causative microorganisms:

• Streptococcal species
• Staphylococcal species
• Enterobacteriaceae
• Anaerobic organisms
• Fungi

Most authorities believe that polymicrobial involvement is necessary to create the synergy of enzyme production that promotes rapid multiplication and spread of Fournier gangrene.[8] For example, one microorganism might produce the enzymes necessary to cause coagulation of the nutrient vessels. Thrombosis of these nutrient vessels reduces local blood supply; thus, tissue oxygen tension falls.

The resultant tissue hypoxia allows for the growth of facultative anaerobes and microaerophilic organisms. These latter microorganisms, in turn, may produce enzymes (eg, lecithinase, collagenase), which lead to digestion of fascial barriers, thus fueling the rapid extension of the infection.

Fascial necrosis and digestion are hallmarks of this disease process; this is important to appreciate because it provides the surgeon with a clinical marker of the extent of tissue involvement. Specifically, if the fascial plane can be separated easily from the surrounding tissue by blunt dissection, it is quite likely to be involved with the ischemic-infectious process; therefore, any such dissected tissue should be excised.

Although originally described as idiopathic gangrene of the genitalia, Fournier gangrene has an identifiable cause in 75-95% of cases.[16] The necrotizing process commonly originates from an infection in the anorectum, the urogenital tract, or the skin of the genitalia.[17]

Anorectal causes of Fournier gangrene include perianal, perirectal, and ischiorectal abscesses; anal fissures; anal fistula; and colonic perforations. These may be a consequence of colorectal injury or a complication of colorectal malignancy,[18, 19] inflammatory bowel disease,[20] colonic diverticulitis, or appendicitis.

A case of Fournier gangrene was reported in a patient with COVID-19 following prolonged and repeated ventilation in prone position.[21]

Urogenital tract causes include the following:

• Infection in the bulbourethral glands
• Urethral injury
• Iatrogenic injury secondary to urethral stricture manipulation
• Epididymitis
• Orchitis
• Lower urinary tract infection (eg, in patients with long-term indwelling urethral catheters)

Dermatologic causes include hidradenitis suppurativa, ulceration due to scrotal pressure, and trauma. Inability to practice adequate perineal hygiene, such as in paraplegic patients, results in increased risk.

Accidental, intentional, or surgical trauma[22] and the presence of foreign bodies may also lead to the disease. The following have been reported in the literature as precipitating factors:

• Blunt thoracic trauma
• Superficial soft-tissue injuries
• Genital piercings
• Penile self-injection with cocaine ^[23]
• Urethral instrumentation
• Prosthetic penile implants
• Intramuscular injections
• Steroid enemas (used for the treatment of radiation proctitis)
• Rectal foreign body ^[24]

In women, septic abortions, vulvar or Bartholin gland abscesses, hysterectomy, and episiotomy are documented sources. A comprehensive literature review of 134 women with Fournier gangrene reported that perineal abscess was the most common etiology (n=41, 35%).[2] In men, anal intercourse may increase risk of perineal infection, either from blunt trauma to the area or by spread of rectally carried microbes.

In children, the following have led to the disease:

• Circumcision
• Phimosis
• Strangulated inguinal hernia
• Omphalitis
• Insect bites
• Trauma
• Urethral instrumentation
• Prematurity ^[25]
• Perirectal abscesses
• Systemic infections
• Diaper rash ^[25]
• Secondary immunodeficiency

A case report by Numoto et al describes Fournier gangrene that developed after surgical repair of a strangulated inguinal hernia in a 2-month-old boy. The boy was receiving adrenocorticotropic hormone (ACTH) therapy for infantile spasms, and the authors suggest that immune suppression from the ACTH may have contributed to the development of Fournier gangrene.[26]

Pathogens

Wound cultures from patients with Fournier gangrene reveal that it is a polymicrobial infection with an average of 4 isolates per case. Escherichia coli is the predominant aerobe, and Bacteroides is the predominant anaerobe.

Other common microflora include the following:

• Proteus
• Staphylococcus
• Enterococcus
• Streptococcus (aerobic and anaerobic)
• Pseudomonas
• Klebsiella
• Clostridium ^[27]

Rarely, Candida albicans has been reported as the pathogen in cases of Fournier gangrene.[28, 29, 30]

Predisposition to disease

Any condition that depresses cellular immunity may predispose a patient to the development of Fournier gangrene. Examples include the following:

• Diabetes mellitus (present in as many as 60% of cases) ^{[31, 27]}
• Morbid obesity
• Alcoholism
• Cirrhosis
• Extremes of age
• Vascular disease of the pelvis
• Malignancy (eg, acute leukemia) ^{[32, 33]}
• Systemic lupus erythematosus ^[34]
• Crohn disease
• HIV infection ^[35] ref34}
• Malnutrition
• Iatrogenic immunosuppression (eg, from long-term corticosteroid therapy or chemotherapy ^[36] )

The US Food and Drug Administration (FDA) has noted an increased risk for Fournier gangrene in patients with type 2 diabetes mellitus treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors were first approved in 2013, and by 2019, 55 cases of Fournier gangrene had been reported in patients receiving these agents. By comparison, only 19 cases of Fournier gangrene have been reported over 35 years in patients taking other diabetes drugs.[37]

Details of Fournier gangrene cases associated with SGLT2 inhibitors included the following[37] :

• Patients ranged in age from 33 to 87 years; 39 were men, 16 were women.
• Onset of Fournier gangrene after initiation of SGLT2 inhibitors ranged from 5 days to 49 months.
• Complications included diabetic ketoacidosis, sepsis, and kidney injury.
• Eight patients underwent fecal diversion surgery, two patients required amputation of a lower extremity due to  necrotizing fasciitis, and three patients died.

Fournier gangrene is relatively uncommon, but the exact incidence of the disease is unknown. In a review of Fournier gangrene in 1992, Paty et al calculated that approximately 500 cases of the infection had been reported in the literature since Fournier’s 1883 report, yielding a rate of 1 case in 7500 persons.[38] A retrospective case review revealed 1726 cases documented in the literature from 1950-1999, with an average of 97 cases per year reported from 1989-1998.[39] A review of National Inpatient Sample data from 2004-2012 identified a total of 9249 patients with Fournier gangrene.[6]

A review using the US State Inpatient Database in 2009 estimated that among 25.8 million hospital admissions from 2001 and 2004, Fournier gangrene constituted only 0.02% of hospital admissions. In this same database, 66% of the hospitals reported no patients with Fournier gangrene, and among high volume centers, the admission frequency was only 1 patient every few months.[40]

The frequency of Fournier gangrene has not likely changed appreciably. Rather, the apparent increase in the number of cases in the literature most likely results from increased reporting.

No seasonal variation occurs. Fournier gangrene is not indigenous to any region of the world, although the largest clinical series originate from the African continent.[41]

Sex- and age-related differences in incidence

The typical patient with Fournier gangrene is an elderly man in his sixth or seventh decade of life with comorbid diseases. The male-to-female ratio is approximately 10:1. The lower incidence in females may reflect better drainage of the perineal region through vaginal secretions.[2]

Men who have sex with men may be at higher risk, especially for infections caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA).[42]

Most reported cases occur in patients aged 30-60 years. A literature review found only 56 pediatric cases, with 66% of those in infants younger than 3 months.

Large scrotal, perineal, penile, and abdominal wall skin defects may require reconstructive procedures; however, the prognosis for patients following reconstruction for Fournier gangrene is usually good. The scrotum has a remarkable ability to heal and regenerate once the infection and necrosis have subsided. However, approximately 50% of men with penile involvement have pain with erection, often related to genital scarring. Consultation with a psychiatrist may help some patients deal with the emotional stress of an altered body image.

If extensive soft tissue is lost, lymphatic drainage may be impaired; thus, dependent edema and cellulitis may result. Use of external support may be beneficial to minimize this postoperative problem.

To date, the majority of studies of Fournier gangrene have been retrospective reviews.[43, 44] Therefore, the utility of drawing reliable prognostic information from these studies is very limited.

In 1995, Laor and colleagues introduced the Fournier Gangrene Severity Index (FGSI).[45] The FGSI is based on deviation from reference ranges of the following clinical parameters:

• Temperature
• Heart rate
• Respiratory rate
• White blood cell count (WBC)
• Hematocrit
• Serum sodium
• Serum potassium
• Serum creatinine
• Serum bicarbonate

Each parameter is assigned a score between 0 and 4, with the higher values indicating greater deviation from normal. The FGSI represents the sum of all the parameters’ values.

Laor and colleagues determined that an FGSI greater than 9 correlated with increased mortality.[45] The FGSI has been validated in several retrospective studies.[46, 47, 48] In a retrospective review of 20 patients with Fournier gangrene, the average FGSI was 9 overall and 14 for fatal cases. An increased FGSI was predictive of having an increased mortality rate or hospital stay longer than the median (>25 days) (P=0.0194).[49]

In 2010, Yilmazlar and colleagues updated the FGSI (UFGSI), adding two additional parameters—age and extent of disease—to further refine the prognostic utility of the FGSI.[50]

These two groups concluded that the mortality risk in general may be directly proportional to the age of the patient and the extent of disease burden and systemic toxicity upon admission. Factors associated with an improved prognosis included the following[50, 51, 52] :

• Age younger than 60 years
• Localized clinical disease
• Absence of systemic toxicity (eg, low FGSI)
• Sterile blood cultures

Most recently, Roghmann et al queried whether these increasingly complex scoring systems actually outperformed two existing and less burdensome morbidity scoring systems, the age-adjusted Charlson Comorbidity Index (ACCI) and the surgical APGAR score (sAPGAR).[53] They assessed this retrospectively then prospectively with a 30-day follow-up. They noted that ACCI and sAPGAR performed as well as the FGSI and UFGSI and were easier to calculate at the bedside. Again, increasing age and medical comorbidities were associated with increased risk of death.[53]

Bozkurt et al reached a similar conclusion in their comparison of the FGSI; the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), which is based on the WBC, hemoglobin, serum sodium, glucose, serum creatinine, and C-reactive protein levels; and the neutrophil/lymphocyte ratio (NLR)—a marker for inflammation that has been studied as a prognostic indicator in a variety of conditions, primarily cancer and heart disease. In their retrospective cohort studies, higher scores in all three scoring systems (FGSI ≥4, LRINEC ≥6, NLR ≥10) identified patients with a worse prognosis, including need for mechanical ventilation requirement and mortality. However, the NLR had the advantages of speed, simplicity, and low cost.[54]  

In a retrospective case series that included 19 patients with a median age of 70 years, Morais et al reported that the percentage of body surface area (BSA) affected proved to be a useful prognostic factor. Combining the LRINEC model with a BSA >3.25% led to a major improvement in the accuracy of the scores.[51]

In a retrospective review of 54 patients with a mean age of 49.3 years and a mean body mass index (BMI) of 28.6 kg/m2, patients on average were hospitalized for 37.5 days, with a mean intensive care unit stay of 8.3 days. Three patients (5.6%) died during their hospital stay, and 33 (61%) required reconstructive surgery. Multivariate logistic modeling showed that BMI (P=0.001) and alkaline phosphatase (P< 0.001) correlated with decreasing length of stay, while age at admission was not significantly correlated (P=0.369).[55]

This study also developed a novel scoring system, the Combined Urology and Plastics Index (CUPI), designed to predict length of stay in Fournier gangrene patients. CUPI parameters include the following:

• Age at admission
• Hematocrit
• Plasma CO ₂ (serum bicarbonate)
• Blood urea nitrogen
• Serum calcium
• Alkaline phosphatase
• Albumin
• International normalized ratio (INR)
• Lactate
• Total bilirubin

The CUPI scoring system has a minimum score of 0 and a maximum score of 15. Patients with CUPI scores ≤5 had an average length of stay of 25 days (standard deviation [SD], 15.6), while those with CUPI scores >5 had an average length of stay of 71 days (SD 49.8).[55]

Interestingly, obesity is independently associated with reduced in-hospital mortality in patients with severe soft tissue infections (SSTIs) regardless of the obesity classification, according to a review of 2868 patients with SSTIs, which found that obese patients were less likely to die in hospital than nonobese patients (odds ratio = 0.42, 95% confidence index, 0.25 to 0.7, P=0.001).[56]

Surprisingly, diabetes and HIV infection are not associated with higher mortality. In some studies, Fournier gangrene that originates from anorectal diseases carries a worse prognosis than cases caused by other factors.

The reported mortality rates for Fournier gangrene have varied widely, ranging as high as 75%. Joseph Jones, a Confederate army surgeon, was the first person to describe the mortality of Fournier gangrene in a large population of men. He reported a mortality rate of 46% in 2642 affected Confederate soldiers during the Civil War.[57]

Using National Surgical Quality Improvement Program data from 2005 to 2009, Kim et al determined that the overall 30-day mortality rate for Fournier gangrene and necrotizing fasciitis of the genitalia was 10.1% (64 of 636 patients)—a rate about half that of historically published estimates, but similar to that in recent studies.[58] A review of 25.8 million hospital admission in 2001 and 2004, using the US State Inpatient Database, estimated that Fournier gangrene constituted only 0.02% of hospital admissions and carred a 7.5% case fatality rate.[40] A review by Furr et al of National Inpatient Sample data on Fournier gangrene from 2004 to 2012 found that inpatient mortality was 4.7%.[6]

Factors associated with high mortality include an anorectal source, advanced age, extensive disease (involving abdominal wall or thighs), shock or sepsis at presentation, renal failure, and hepatic dysfunction.[59]  In a Turkish study of 50 patients, Acinetobacter baumannii and Klebsiella pneumoniae were significantly more common in patients who required mechanical ventilation, but A baumannii was the only microorganism associated with an increased mortality rate.[60]

Death usually results from systemic illness, such as sepsis (usually gram negative), coagulopathy, acute kidney injury, diabetic ketoacidosis, or multiple organ failure. Fatal tetanus associated with Fournier gangrene has been reported in the literature.

The hallmark of Fournier gangrene is intense pain and tenderness in the genitalia. The clinical course usually progresses through the following phases:

1. Prodromal symptoms of fever and lethargy, which may be present for 2-7 days
2. Intense genital pain and tenderness that is usually associated with edema of the overlying skin; pruritus may also be present
3. Increasing genital pain and tenderness with progressive erythema of the overlying skin
4. Dusky appearance of the overlying skin; subcutaneous crepitation
5. Obvious gangrene of a portion of the genitalia; purulent drainage from wounds

Early in the course of the disease, pain may be out of proportion to physical findings. As gangrene develops, pain may actually subside as nerve tissue becomes necrotic.

Systemic effects of this process vary from local tenderness with no toxicity to florid septic shock. In general, the greater the degree of necrosis, the more profound the systemic effects.

The physician should direct particular attention to palpation of the genitalia and perineum and to the digital rectal examination, to assess for signs of the disease and to seek a potential portal of entry. Fluctuance, soft-tissue crepitation, localizing tenderness, or occult wounds in any of these sites should alert the examiner to possible Fournier gangrene. See the image below.

Photograph of a morbidly obese male with long-standing phimosis. This condition led to urinary incontinence, perineal diaper rash–like dermatitis, and urinary tract infection. Ultimately, he presented with exquisite perineal pain. An examination with the patient under anesthesia was necessary to discover the necrotizing infection that appeared to originate in the right bulbourethral gland. Courtesy of Thomas A. Santora, MD.

Skin overlying the affected region may be normal, erythematous, edematous, cyanotic, bronzed, indurated, blistered, and/or frankly gangrenous. Skin appearance often underestimates the degree of underlying disease.

A feculent odor may be present secondary to infection with anaerobic bacteria. Crepitus may be present, but its absence does not exclude the presence of Clostridium species or other gas-producing organisms.

Systemic symptoms (eg, fever, tachycardia, hypotension) may be present.

Diagnosis of Fournier gangrene is based primarily on clinical findings, and treatment is based on those findings. Incisional biopsy may ultimately confirm the diagnosis.

The following studies are indicated:

• Complete blood cell count (CBC)
• Arterial blood gas (ABG) sampling
• Blood and urine cultures
• Disseminated intravascular coagulation (DIC) panel
• Cultures of any open wound or abscess

Pelvic imaging studies can be extremely valuable, although sensitivities and specificities of different radiologic modalities are not established. Plain radiography should be the initial imaging study, while computed tomography (CT) should be considered the imaging study of choice. With either technique, the presence of subcutaneous air is very suggestive of the diagnosis in a patient with an appropriate clinical history. In addition, any test deemed necessary to assess exacerbation of a comorbid condition (eg, electrocardiogram and cardiac enzyme evaluation in patients with coronary artery disease) is warranted.

Perform a chemistry panel to evaluate for possible electrolyte disturbances; to look for laboratory evidence of dehydration (elevated blood urea nitrogen [BUN]/creatinine ratio), which tends to occur as the disease progresses; and to evaluate for glucose intolerance, which may be due to preexisting diabetes or sepsis-induced metabolic disturbance.

Arterial blood gas (ABG) sampling provides a more accurate assessment of acid/base disturbance. Acidosis with hyperglycemia or hypoglycemia may be present.

Obtain a CBC to assess the immunologic stress induced by the infectious process, check the adequacy of the red blood cell mass, and evaluate the potential for sepsis-induced thrombocytopenia.

A coagulation profile (ie, prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen level) is helpful to look for sepsis-induced coagulopathy.

Blood samples should be drawn for culture to assess for septicemia. Consider type and screen if surgical exploration is undertaken.

Radiography should be considered to evaluate for the presence and extent of Fournier gangrene, especially when the clinical examination findings are inconclusive.[61, 62] Gas within the soft tissues is detected more commonly with imaging modalities than with the physical examination. (Note that in the setting of a clinical suspicion of Fournier gangrene, demonstration of soft-tissue gas or detection of subcutaneous crepitation is an absolute indication for surgical exploration.)

Plain radiography should be the initial imaging study. It may reveal moderate-to-large amounts of soft-tissue gas, foreign bodies, or scrotal tissue edema. Soft-tissue gas collections, which manifest as areas of hyperlucency, may be evident on radiography before they become clinically apparent. However, the absence of air on plain films does not exclude the diagnosis.

CT scanning is readily available in most hospitals and should be considered the imaging study of choice, as it defines the extent of the disease more specifically than plain films or ultrasound. CT scanning can reveal smaller amounts of soft-tissue gas than plain radiography and can demonstrate fluid collections that track along the deep fascial planes.[63, 64]

Findings include soft-tissue and fascial thickening, fat stranding, and soft-tissue gas collections. CT scan often identifies the underlying cause of the infection (eg, perirectal abscess). The findings may assist in surgical planning.

Ultrasonography can be used to detect fluid or gas within the soft tissues.[65] Gas in the scrotal wall is the "sonographic hallmark" of Fournier gangrene. Air may be appreciated in perineal and/or perirectal areas. Scrotal wall edema may be seen. The testes and epididymides are usually normal.

Ultrasonography may reveal other causes of acute scrotal pain, including the following:

• Intratesticular injury
• Scrotal cellulitis
• Epididymo-orchitis
• Testicular torsion
• Inguinal hernia

The drawback of ultrasonography is the need for direct pressure on the involved tissue; patients with Fournier gangrene probably will not be able to tolerate this procedure.

Use of MRI in Fournier gangrene is not well described in the literature. MRI yields greater soft tissue detail than does CT scanning; however, MRI requires greater time, with limited ability for patient monitoring during testing. These logistical challenges, which are not shared by CT scanning, limit the practical usefulness of MRI, especially in patients with critical illness. Use of MRI should not delay operative intervention if the diagnosis is highly suspected.

An incisional biopsy at the time of surgical debridement allows pathological distinction of Fournier gangrene (ie, necrotizing infection) from severe cellulitis. The former would benefit from excisional debridement, while the latter rarely requires surgical excision.

The biopsy sample should be taken from the point of maximal tenderness, and it should include skin and superficial and deep fascia. This sample may be sent for frozen-section analysis to assess for fascial necrosis. Early fascial involvement may appear as edematous fascia on gross inspection but may appear as frank necrosis on microscopic analysis.

Pathologic evaluation of the involved tissue may reveal the following pathognomonic findings of Fournier gangrene:

• Necrosis of the superficial and deep fascial planes
• Fibrinoid thrombosis of the nutrient arterioles
• Polymorphonuclear cell infiltration
• Microorganisms identified within the involved tissues

Fibrinoid thrombosis of the nutrient vessels that supply the superficial and deep fascia is the finding that most commonly indicates Fournier disease. Widespread necrosis of the fascia with acute inflammatory cell infiltration and necrotic debris is frequently evident, as is the presence of causative microorganisms within the tissues.

This extensive inflammatory process is frequently present deep to intact skin. The skin itself is often minimally involved with the inflammatory process until late in the course of the disease.

Early recognition and high clinical suspicion are important in making a timely diagnosis, as early manifestations are often subtle. The most significant modifiable risk factor associated with NSTI mortality is delay to surgical intervention.

Treatment of Fournier gangrene involves several modalities. Surgery is necessary for definitive diagnosis and excision of necrotic tissue. High clinical suspicion is required for early diagnosis as the initial manifestations are often subtle. The most significant modifiable risk factor associated with mortality is delay to surgical intervention.[66] Earlier surgical intervention has been associated with reduced mortality.[67, 68]

In patients who present with systemic toxicity manifesting as hypoperfusion or organ failure, aggressive resuscitation to restore normal organ perfusion and function must take precedence over diagnostic maneuvers, especially if these diagnostic studies could compromise the resuscitative interventions.

Thus, the emergency department (ED) treatment of patients with Fournier gangrene includes aggressive resuscitation in anticipation of surgery. Provide airway management if indicated, give supplemental oxygen, and establish intravenous (IV) access and continuous cardiac monitoring. Crystalloid replacement is indicated for patients who are dehydrated or displaying signs of shock. A balanced crystalloid such as lactated Ringer’s solution is preferable.[66]

Early, broad-spectrum antibiotics are indicated. Tetanus prophylaxis is indicated if soft-tissue injury is present.

In addition, any underlying comorbid conditions (eg, diabetes, alcoholism) must ultimately be addressed. Such conditions are common in these patients, and potentially predispose to Fournier gangrene. Failure to adequately manage the comorbid conditions may threaten the success of even the most appropriate interventions to resolve the infectious disease.

Treatment of Fournier gangrene involves the institution of broad-spectrum antibiotic therapy. The antibiotic spectrum should cover staphylococci, streptococci, the Enterobacteriaceae family of organisms, coliforms and anaerobes.[66]  

A reasonable empiric regimen might consist of ciprofloxacin and clindamycin. Clindamycin is particularly useful in the treatment of necrotizing soft-tissue infections because of its gram-positive and anaerobic spectrum of activity. In animal models of streptococcal infection, clindamycin has been shown to yield response rates superior to those of penicillin or erythromycin, even in the context of delayed treatment.[69]

Other possible choices include ampicillin/sulbactam, ticarcillin/clavulanate, or piperacillin/tazobactam in combination with an aminoglycoside and metronidazole or clindamycin. Vancomycin can be used to provide coverage for methicillin-resistant Staphylococcus aureus (MRSA).[66]

In cases associated with sepsis syndrome, therapy with intravenous immunoglobulin (IVIG), which is thought to neutralize superantigens (eg, streptotoxins A and B) believed to mitigate the exaggerated cytokine response, has been shown to be a good adjuvant to appropriate antibiotic coverage and complete surgical debridement.[70]

If initial tissue stains (ie, potassium hydroxide [KOH] stain) show fungi, add an empiric antifungal agent such as amphotericin B or caspofungin.

In the event of a presumptive diagnosis based on a clinical examination or diagnostic study, the definitive diagnosis of Fournier gangrene is provided by examination with the patient under anesthesia followed by incision into the area of greatest clinical concern. If frankly gangrenous tissue is found or purulence is drained, the diagnosis of Fournier gangrene is established. See image below.

In a man with alcoholism and known cirrhosis who presented with exquisite pain limited to the scrotum, opening of the scrotum along the median raphe liberated foul-smelling brown purulence and exposed necrotic tissue throughout the mid scrotum. The testicles were not involved. Courtesy of Thomas A. Santora, MD.

Occasionally, early-stage Fournier disease manifests as severe cellulitis. If an incision is made, the fascia may appear edematous rather than exhibiting the gray-black appearance of well-established Fournier gangrene. In this instance, obtain an incisional biopsy sample of the deep fascia for frozen-section evaluation to exclude early necrotizing disease.

Excising necrotic tissue

Once a diagnosis of Fournier gangrene is established, all necrotic tissue must be excised. In a large retrospective review of 379 patients, Sugihara et al confirmed the opinion that early surgical intervention reduces mortality. Those who underwent earlier intervention had a lower fatality rate (odds ratio, 0.38) than those whose intervention was delayed to 3 days or later.[67]

The skin should be opened widely to expose the full extent of the underlying fascial and subcutaneous tissue necrosis. All fascial planes that separate easily with blunt dissection should be considered involved and therefore excised. The dissection should be carried out to include bleeding tissues (ie, tissue that is well vascularized).

Send samples of excised tissue for aerobic and anaerobic cultures and a histologic assessment.

Given the characteristic thrombosis of the nutrient vessels, the overlying skin has impaired blood supply and should be excised if significantly undermined. The authors strongly recommend radical excisional debridement (see below image) with electrocautery in order to reduce the considerable operative blood loss if the area of involvement is extensive.

Patient with Fournier gangrene following radical debridement. A dorsal slit was made in the prepuce to expose the glans penis. Urethral catheterization was performed. Incision into the point of maximal tenderness on the right side of the perineum revealed gangrenous necrosis that involved the anterior and posterior aspects of the perineum, the entirety of the right hemiscrotum, and the posterior medial aspect of the right thigh. The skin and involved fascia were excised from these areas. Reconstruction of this defect was performed in a staged approach. A gracilis rotational muscle flap taken from the right thigh was used to fill the cavity in the posterior right perineum as the first step. The remainder of the defect was covered with split-thickness skin grafts. This patient made a full recovery.

The testicles are often spared in the necrotizing process. If they are uninvolved, place the exposed testicles in a subcutaneous pocket to prevent desiccation. If a testicle is involved in the necrotic process or its viability is questioned, perform orchiectomy.

Once the infection is eradicated, healthy granulation tissue develops; this signifies the time to proceed to reconstruction.

Options for reconstruction include the following:

• Primary closure of the skin, if possible
• Local skin flap coverage
• Split-thickness skin grafts
• Muscular flaps, which are used to fill a cavity (eg, ischiorectal space)

On the basis of a systematic review of 16 studies, Karian et al concluded that, "most reconstructive techniques provide reliable coverage and protection of testicular function with an acceptable cosmetic result. There is no conclusive evidence to support flap coverage of exposed testes rather than skin graft." However, these authors recommended skin grafting or flap reconstruction for defects larger than 50% of the scrotum or extending beyond the scrotum; for defects confined involving less than 50% of the scrotum that cannot be closed primarily without tension, they recommended reconstruction with a scrotal advancement flap or healing by secondary intention.[71]

Konofaos and Hickerson have reported a two-step technique for treating scrotal defects with total skin loss involving exposed testes. The first step consists of primary closure with a wrap-around skin grafting. The second step comprises reapproximating the testes and shaping the neoscrotum to optimize cosmesis.[72]

Hyperbaric oxygen therapy (HBO) has been used as an adjuvant to surgical and antimicrobial therapy. Indications include failure of conventional treatment, documented clostridial involvement, or myonecrosis or deep tissue involvement. HBO is postulated to reduce systemic toxicity, prevent extension of necrotizing infection, and inhibit growth of anaerobic bacteria.

HBO has shown some promising results.[73, 74, 75]  A retrospective single-center study by Mladenov et al found that the survival rate for 192 patients with necrotizing fasciitis or Fournier gangrene who underwent HBO was higher than that for individuals who were ineligible for HBO treatment owing to contraindications (73.5% vs 36.4%, respectively). The survival rate of the patients who received HBO was comparable to that of patients who did not require HBO (75.5%).[76]

However, in one series, there was actually a trend toward increased mortality in patients undergoing HBO, although this trend may have been related to selection bias (ie, HBO may have been used in patients who were more ill).[77] The role of HBO in the treatment of Fournier disease needs to be clarified with a prospective controlled trial.[77]

Decisions regarding HBO must be made on an individual basis, taking into consideration the stability of the patient. Use of HBO must not delay surgical debridement.

The role of topical agents in wound care requires further investigation. Unprocessed honey, applied directly to the surface of the wounds, has been reported by some authors to enzymatically debride, sterilize, and dehydrate wounds and to improve local tissue oxygenation and re-epithelialization. However, the salutatory effect of honey is likely related to its physical property of hyperosmolarity.[78] Therefore, honey holds little advantage over other hygroscopic agents.[79]

The application of growth hormones and other trophic agents holds the potential to promote faster wound healing.

One published case report advocates irrigation of the perineum with superoxidized water as well as application of gauze soaked in zinc peroxide and hydrogen peroxide.

In patients who require cutaneous reconstruction for tissue loss secondary to necrotizing soft tissue infections, including Fournier gangrene, Hersant et al reported significantly improved clinical outcomes and shortened wound healing time when split-thickness skin grafting (STSG) is followed by spraying autologous platelet-rich plasma (A-PRP) and thrombin gel on the wound bed and on the graft after stable fixation. In their prospective, controlled, open-label randomized study, the mean complete healing time was almost 50% shorter in patients (n=14) who received STSG plus A-PRP/thrombin gel than in those (n=13) receiving STSG alone (37.9 vs. 73.7 days, respectively; P=0.01).[80]

Use of intravenous immunoglobulins (IVIG) and therapeutic plasma exchange (TPE) have been reported, although evidence is limited.[66]

Fournier gangrene is a true surgical emergency. At minimum, immediate urologic or general surgical consultation is mandatory, and management often requires a multidisciplinary team, including a urologist, a general surgeon, and an intensive care specialist.

Transfer to a tertiary facility may be required if these resources are not available at the initial facility. Initial debridement may be performed if required in anticipation of transfer. Arrange for transfer once the patient has been stabilized and resuscitative efforts have begun.

Results of a retrospective review of 1801 cases of necrotizing soft tissue infections in the 2010-2015 American College of Surgeons National Surgical Quality Improvement Program Participant Use Data Files suggest that interhospital transfer status is not an independent risk factor for mortality or morbidity after surgical management. Of the 1801 patients with necrotizing soft tissue infections, gas gangrene, or Fournier gangrene, 1243 (69.0%) were in the non-transfer group and 558 (31.0%) were in the transfer group. Although the transfer group experienced higher rates of 30-day mortality (14.5% versus 13.0%) and major morbidity (64.5% versus 60.1%) than the non-transfer group, the differences were not significant after risk adjustment.[81]

The goals of pharmacotherapy in Fournier gangrene are to reduce morbidity and to control the infection. Broad-spectrum antibiotics should be given early in treatment. Tetanus prophylaxis is indicated if soft-tissue injury is present.

Class Summary

Initiate early broad-spectrum antibiotics as soon as possible. Providing coverage for gram-positive, gram-negative, aerobic, and anaerobic bacteria is essential. Penicillins and beta-lactamase inhibitors or triple antibiotics are potential choices.

Vancomycin (Vancocin)

Vancomycin is a potent antibiotic directed against gram-positive organisms and active against enterococcal species. It is useful for the treatment of septicemia and skin structure infections.

Vancomycin is indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or for those who have infections with resistant staphylococci. For abdominal penetrating injuries, combine with an agent active against enteric flora and/or anaerobes.

To avoid toxicity, assay of vancomycin trough levels after the third dose drawn 0.5 h prior to next dosing currently is recommended. Dose adjustment may be necessary in patients with renal impairment; follow creatinine clearance (CrCl).

Ampicillin-sulbactam sodium (Unasyn)

This is a drug combination that uses a beta-lactamase inhibitor with ampicillin; covers skin, enteric flora, and anaerobes; not ideal for nosocomial pathogens.

Ticarcillin and clavulanate potassium (Timentin)

This antipseudomonal penicillin plus beta-lactamase inhibitor provides coverage against most gram-positive and gram-negative organisms and most anaerobes. It contains 4.7-5 mEq of sodium per gram. Ticarcillin inhibits biosynthesis of bacterial cell wall mucopeptide and is effective during the active growth stage.

Piperacillin and tazobactam (Zosyn)

This combination of an antipseudomonal penicillin and a beta-lactamase inhibitor inhibits biosynthesis of bacterial cell wall mucopeptide and is effective during the stage of active multiplication.

Gentamicin

An aminoglycoside antibiotic used for gram-negative bacterial coverage, gentamicin is commonly used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Consider using gentamicin when penicillins or other less toxic drugs are contraindicated, when bacterial susceptibility tests and clinical judgment indicate use, and in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms.

Dosing regimens are numerous and are adjusted on the basis of CrCl and changes in the volume of distribution. Gentamicin may be administered IV or IM.

Metronidazole (Flagyl)

Metronidazole is an imidazole ring-based antibiotic that is active against anaerobes. It is usually given in combination with other antimicrobial agents, except when used for Clostridium difficile enterocolitis, in which case monotherapy is appropriate.

Metronidazole is active against various anaerobic bacteria and protozoa. It appears to be absorbed into cells of microorganisms that contain nitroreductase; then, unstable intermediate compounds are formed that bind DNA and inhibit synthesis, causing cell death.

Clindamycin (Cleocin)

Clindamycin is a lincosamide useful in treatment against serious skin and soft-tissue infections caused by most staphylococci strains; it is also effective against aerobic and anaerobic streptococci, except enterococci. This agent inhibits bacterial protein synthesis by inhibiting peptide chain initiation at the bacterial ribosome, where it preferentially binds to the 50S ribosomal subunit, causing bacterial growth inhibition.

Class Summary

Fatal tetanus associated with Fournier gangrene has been documented in the literature. Patients with noncurrent tetanus status require immunization in the emergency department.

Diphtheria and tetanus toxoid (Decavac)

Tetanus toxoid is manufactured by first culturing Clostridium tetani and then detoxifying the toxin with formaldehyde. This toxoid commonly is combined with diphtheria toxoid, and both serve to induce production of serum antibodies to toxins produced by the bacteria.