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  • 1. Necrotizing Gangrene of the Genitalia and Perineum from Infections in Urology ® Maxwell V. Meng, MD, Jack W. McAninch, MD, University of California School of Medicine, San Francisco. Abstract and Introduction Abstract Necrotizing gangrene of the genitalia and perineum is a fulminant, life-threatening infection. The infection may spread along subcutaneous planes and result in tissue necrosis. Infections are usually polymicrobial. The organisms most commonly isolated from wound cultures include Bacteroides, coliforms, Streptococcus, Staphylococcus, and Peptostreptococcus. Anorectal infections, genitourinary infections, and cutaneous injuries are the most frequent sources of infection in necrotizing genital gangrene. Despite increased experience in treating this condition, patients suffer significant morbidity and mortality. Early diagnosis and complete debridement of all necrotic tissue are essential for improved outcomes. Introduction Necrotizing soft-tissue infections of the genitalia and perineum present diagnostic and therapeutic challenges. Although uncommon, these infections can progress rapidly and cause significant morbidity and mortality. Therefore, they must be promptly diagnosed and aggressively treated to achieve an optimal outcome. The first reported case of such an infection was by Baurienne in 1764.[1] In 1883, the French venereologist Fournier described a syndrome of abrupt, idiopathic onset of genital gangrene in 5 young, previously healthy men.[2] Although the condition currently is recognized to afflict an older population of both genders and has identifiable risk factors, "Fournier's gangrene" still constitutes a urologic emergency. Because of a greater understanding of the etiology and pathogenesis of this disorder, improved therapy has resulted in improved outcomes. Etiology Fournier was unable to identify the cause of infection in his patients, but the etiology can be discerned in most cases today (Table). Anorectal infections, genitourinary infections, and cutaneous injuries are the most frequent sources of infection in necrotizing genital gangrene.[3] Among gastrointestinal causes (30% to 50%), ischiorectal, perianal, and intrasphincteric abscesses account for approximately 70%.[4] Nec-rotizing gangrene has also been reported to be secondary to minor anorectal procedures such as rectal mucosal biopsy, anal dilation, and hemorrhoidectomy as well as appendicitis, colorectal malignancy, and diverticulitis.[5-7] Genitourinary foci comprise the second major source of initial infection (20% to 40%); underlying urethral stricture and periurethral infection are most common.[8] Urologic conditions also associated include urethral trauma and instrumentation, indwelling urethral catheters, urethral calculi, epididymitis, prostate biopsy and massage, and bladder cancer extension.[8-10] Cutaneous injuries and infection account for 20% of cases.[4] Often the dermal source is minor, such as human and insect bites. Other reported etiologies involving trauma to the superficial soft tissues include vasectomy, circumcision, genital infections (balanoposthitis), and penile prosthesis insertion.[8,11]
  • 2. Necrotizing gangrene is less common in women. In 1 literature review of 449 cases, 14% involved women.[8] Typically, abscesses of the vulva or Bartholin's glands initiate the gangrene of the perineum. Episiotomy, septic abortion, pudendal nerve block, and coital injury are recognized factors in female necrotizing soft-tissue infections.[12,13] Additional host factors affect the development of necrotizing gangrene. Increased prevalence of comorbidities such as diabetes (30% to 60%) and alcoholism (40% to 50%) have been reported.[9,14] It is postulated that susceptibility to infection from decreased defense mechanisms and impaired active immune response contribute to the increased incidence. Malnutrition, AIDS, malignancy, renal failure, and immunosuppressive chemotherapy are other risk factors.[3,15,16] However, outcomes have not correlated with presence or absence of the comorbid states.[9,14] Anatomy The patterns of spread in genital and perineal necrotizing soft-tissue infection can be explained by the fascial anatomy of the perineum, external genitalia, and abdominal wall. The superficial perineal fascia (Colles' fascia) is attached laterally to the pubic rami and fascia lata of the thighs, and posteriorly to the urogenital diaphragm and perineal membrane. The anterior extensions of Colles' fascia include the tunica dartos of the penis and scrotum and Scarpa's fascia of the anterior abdominal wall. Buck's fascia of the penis, deep to the tunica dartos, is bound by adherence to the tunica albuginea distally at the coronal sulcus of the glans and proximally at the crus and suspensory ligament of the penis.[26] Infections originating in the ano-rectal region first penetrate the sphincteric musculature. Then, the infection spreads along the perianal region and may extend along Colles' fascia. While lateral spread is prevented by attachments of Colles' fascia, anterior and superior extension along dartos and Scarpa's fasciae is unhindered. Alternatively, anorectal infection may spread through the urogenital diaphragm to the perivesical space, then to the scrotum via the spermatic fascia. Urethral infections are initially limited by Buck's fascia, surrounding the corpora spongiosum and cavernosa. Once Buck's fascia is traversed, the infection spreads along the overlying tunica dartos and the contiguous layers of Scarpa and Colles. In general, necrotizing gangrene of urethral origin does not spread to the anal triangle, because Colles' fascia is attached to the peri-neal membrane posteriorly; however, if Colles' fascia or the urogenital diaphragm is violated, the infection can involve the ischiorectal and perivesical spaces. Clinical Features Most cases of necrotizing gangrene, regardless of location, begin insidiously. Patients initially complain of scrotal discomfort and associated malaise. As the infection worsens, fever and chills develop with genital skin changes. Scrotal swelling is usually present with erythema and increased pain (Fig. 1). However, the skin can appear relatively normal, which may account for the delay in presentation after the onset of symptoms, usually averaging 5 days. In addition, the pain may subside as pressure necrosis and infection of cutaneous nerves take place. Signs and symptoms frequently found at presentation include pain (100%), swelling (80% to 100%), fever (60% to 80%), and crepitus (60% to 70%).[7,9,14,27] Systemic manifestations, such as overt shock and altered mental status, do not often correlate with the physical findings and must be recognized early. (click image to zoom) Figure 1. Preoperative photograph of patient with ne gangrene of perineum demonstrating scrotal edema with minimal skin changes. Careful history can elucidate the etiology. Symptoms of urgency, frequency, decreased force of stream, and a history of perineal trauma, instrumentation, or urethral stricture point to a urologic diagnosis. Because of the increased frequency of gastrointestinal foci, a history of rectal pain and bleeding, hemorrhoids, and anal fissures can often be elicited. Acute and chronic skin infection of the scrotum or penis or a history of injection suggest a dermal source. Together with the risk factors discussed above, the presence of these signs, symptoms, and histories should raise a suspicion of necrotizing soft-tissue infections.
  • 3. Often nonspecific, abnormal laboratory values are present as the consequence of sepsis. Leukocytosis >15,000/µL is found at presentation in more than 80% of patients. Anemia frequently develops secondary to decreased production of RBCs and thrombosis. Hyponatremia, hyperglycemia, hypocalcemia, elevated creatinine, coagulopathy, and hypoalbuminemia can be present initially and may provide diagnostic clues to early necrotizing soft-tissue infections.[9,14,28,29] Due to the nonspecific symptoms, its indolent course, and often unremarkable cutaneous appearance, necrotizing gangrene of the perineum may be confused with other scrotal and intrascrotal pathology such as scrotal cellulitis or balanoposthitis. More serious conditions that mimic Fournier's gangrene include scrotal abscesses or incarcerated hernia. Finally, scrotal or penile gangrene may be primarily due to vessel occlusion from vasculitis, rather than infection. These conditions include IgE-positive hypersensitivity vasculitis, poly-arteritis nodosa, and pyoderma gangrenosum.[30,31] It is important to distinguish these conditions from Fournier's, because appropriate treatment in these patients may include corticosteroids and local wound care, not radical excision. Imaging Necrotizing gangrene of the genitalia and perineum is primarily a clinical diagnosis. Nevertheless, imaging modalities that have demonstrated utility in confirming the disease, evaluating extent, and determining the etiology include radiography, ultrasonography, and computed tomography (CT).[32] Plain radiographs of the abdomen and pelvis can demonstrate subcutaneous air before crepitus is palpable (Fig. 2). In addition, plain films may aid in defining an intra-abdominal source of the infection.[33,34] One retrospective review reported that plain films were more sensitive in detecting soft-tissue gas than physical examination; gas was visualized in all diabetics with necrotizing gangrene.[25] However, the absence of subcutaneous air in the perineum or scrotum should not exclude the diagnosis. (click image to zoom) Figure 2. Plain radiograph of pelvis at presentation, demo air within soft tissues. Ultrasonography has also proven useful in cases of necrotizing infections.[35,36] Gas can be detected even when not clinically evident, and the ultrasonographic appearance is striking -- the air appears as discrete, bright, hyperechoic areas with posterior acoustic shadowing (Fig. 3). Ultrasound can examine the scrotum, testes and epididymides, perirectal area, and abdomen, helping to differentiate necrotizing infections from other causes of scrotal pain. Typically, the testes and intrascrotal structures are normal in size and architecture within a thickened scrotal wall.[37] (click image to zoom) Figure 3. Ultrasound of scrotum, demonstrating char hyperechoic appearance of subcutaneous gas. CT of the abdomen and pelvis has not been well studied in necrotizing infections; however, it appears to have potential. One study described characteristic CT findings in necrotizing fasciitis associated with gangrene of the perineum.[38] The soft tissues are thickened with surrounding fat stranding and gas dissecting along fascial planes. Delineation of gas margins and identification of infected fluid collections by CT can suggest the extent of the gangrene. In addition, CT provides excellent anatomic detail of peri- neal, pelvic, and retroperitoneal structures and may diagnose the initial source of infection. MRI provides the same advantages as CT with improved soft-tissue resolution and multiplanar images.[39] Treatment Necrotizing infection of the genitalia and perineum is a surgical disease where medical therapy has a limited role. After diagnosis, initial management is aimed at preparation for surgery. Because sepsis may be present, hemodynamic stabilization via aggressive fluid resuscitation is necessary. In addition, transfusion of blood products may be required to correct anemia and coagulopathy. Need for invasive monitoring and ventilatory support should be addressed and promptly administered.
  • 4. Empiric, broad-spectrum antibiotic therapy should be instituted.[27] Typical regimens include penicillin for streptococci, clostridia, and certain anaerobes, gentamicin for gram-negative rods, and clindamycin for bacteroides and other anaerobes. More recently, semisynthetic penicillins and third-generation cephalosporins have emerged as alternatives to aminoglycosides. Surgical debridement should not be delayed by uncertainty in diagnosis or radiologic studies. Examination under anesthesia and exploration can be performed easily if any doubt exists. One study reported the utility of intraoperative frozen section in confirming the early diagnosis of necrotizing gangrene.[18] These biopsies, although rarely required, also can demonstrate evidence of the vascular immune disorders that can be misdiagnosed as necrotizing infections. Operative management consists of radical debridement of all areas with overt necrosis. Recent reports indicate that incision and drainage are insufficient.[21,40] We have found outcomes to be correlated with adequacy of initial debridement. Mortality was 100% in 4 patients treated with incision and drainage, but only 8% in 12 patients undergoing complete debridement.[21] Intraoperative findings include edema, liquefactive necrosis of the subcutaneous tissues, and watery pus. Skin changes greatly underestimate the severity of the underlying tissue damage. Thus, extensive unroofing of the involved areas is needed (Fig. 4). If the fascia separates easily from the skin and subcutaneous tissues above, necrosis is generally present and debridement is continued. Deep fascia and muscle are seldom involved. The challenge is to determine tissue viability and the extent of necessary debridement, maintaining a balance between inadequate excision and preservation of threatened but nonischemic tissue. Drains can be placed in areas of questionable viability to prevent fluid collections and early skin closure. (click image to zoom) Figure 4. Intraoperative photograph after debridement of al tissue, with extensive skin loss but preservation of testes. Even after satisfactory initial debridement, subsequent procedures are likely to be necessary; reports have documented a mean of 2 to 4 procedures per patient.[9,29,41] Reexamination of the wound in the operating room is helpful to completely evaluate wound progress, comfortably change extensive dressings, and determine need for further debridement. If the patient does not improve clinically after initial surgery, with resolving fever and leukocytosis, then inadequate debridement should be suspected. Diversion, either fecal or urinary, is occasionally required. Controversy exists regarding the need for colostomy. While some advocate diverting colostomy in most cases of perineal necrotizing gangrene, others believe this to be unnecessary, even with significant gangrene of perirectal tissues. Generally, colostomy is indicated if the sphincter is grossly infected, rectal or colonic perforation has occurred, incontinence is present, or if the rectal wound is large.[42,43] Criteria for urinary drainage are likewise unclear. Many patients are safely managed with an indwelling catheter, although some recommend routine suprapubic diversion in all patients. Indications for supra- pubic catheterizations include stricture disease and urinary extravasation or phlegmon.[7] Intraoperative cystourethroscopy and retrograde urethrography can be performed to evaluate urethral integrity. Despite extensive tissue involvement and radical debridement, the testicles are routinely spared. This is presumed to be due to the copious and independent blood supply. Orchiectomy is performed when conditions such as scrotal abscesses or severe epididymo-orchitis affect testicular viability. Coverage of the testes is important to prevent dessication. Initially, moist dressings and gauze impregnated with petroleum jelly provide sufficient protection. Delayed closure of the scrotum is often an option because of the redundant nature of scrotal skin. If this is not possible, the testes can be placed in temporary subcutaneous pouches of the medial thighs or lower abdominal wall for later scrotal reconstruction.[9,44] The large defects in the scrotum, perineum, and abdominal wall after debridement often necessitate later reconstruction. We have a significant experience in treatment of genital skin defects and have found excellent results using skin grafts.[9,44,45] Once the patient has improved and local wound healing is
  • 5. complete, reconstruction can be considered. The testes are covered with meshed, split-thickness skin grafts, creating a neoscrotum, and the penile shaft is covered with unmeshed split-thickness skin grafts (Fig. 5). Alternative methods of skin coverage include rotational or free myocutaneous flaps and omental flaps.[44] (click image to zoom)Figure 5. (A) Appearance of genitalia after reconstruction of scrotum with split-thickness skin graft. (B) The penis has been covered with unmeshed, split-thickness skin gra Other issues in treating patients with perineal necrotizing gangrene include nutritional support and the potential utility of hyperbaric oxygen and topical agents. Calorie balance is important in critically ill patients with large open wounds and preexisting malnutrition. Enteral or parenteral supplementation when the patient has insufficient intake, prolonged intubation, or compromised gastrointestinal function is beneficial. Because of the importance of anaerobic organisms in necrotizing infections, hyperbaric oxygen has been proposed as an adjunctive therapy.[46,47] Although experimental studies have demonstrated increased leukocyte phagocytic function, fibroblast proliferation, and decreased endotoxin with the use of hyperbaric oxygen, the clinical evidence supporting its utility is inconclusive. Routine wound care, consisting of saline or Dakin's soaked dressings, is important after debridement. However, some investigators have proposed the use of unprocessed honey not only as part of postoperative wound care, but as initial, definitive therapy.[48,49] The studies, although encouraging, involve small numbers of patients and do not provide sufficient evidence to pursue nonoperative management of necrotizing infections. Outcomes Reported mortality rates from genital and perineal necrotizing soft-tissue infections range from 0% to 80%.[3,7] In 2 series with 57 and 29 patients, mortality was 18% and 21%, respectively.[8,9] One review of 449 cases (1979-1988) reported overall mortality of 22%.[14] Patients were typically hospitalized 40 days. Determinants of outcome have not been clearly defined. In numerous studies, factors such as age, source of infection, delay in diagnosis, comorbidities, and extent of infection and debridement are not consistently associated with prognosis. It is clear, however, that delay in adequate surgical intervention leads to increased mortality. An objective index has been developed in order to quantify "deviations from homeostasis," the parameter that best predicts outcome.[29] Variables in the classification system include signs of sepsis (temperature, heart rate, respiratory rate) and laboratory values (sodium, potassium, creatinine, hematocrit, WBC count, bicarbonate). Morbidity from necrotizing infections is significant. Early complications include sepsis, respiratory and renal failure, and coagulopathy; delayed complications that have been reported include fistulae, infertility, and urethral strictures.[9,14] Summary Necrotizing soft-tissue infections of the genitalia and perineum represent a diverse collection of rapidly progressive, potentially lethal diseases. Patients at risk include those with increased susceptibility to infections from gastrointestinal, genitourinary, and cutaneous sources. The clinical picture is not always clear; therefore, a high index of suspicion must be maintained in order to make an early diagnosis. Radiologic clues may provide additional information. Prompt surgical excision of necrotic tissue, along with broad-spectrum antibiotics and aggressive supportive care, is paramount to improved survival. Despite advances in understanding the disease, imaging techniques, and modern medicine, necrotizing gangrene of the genitalia and perineum carries significant morbidity and mortality. Teamwork Is the Key
  • 6. This is an excellent review of a disease entity that continues to perplex and frustrate managing physicians. Aggressive teamwork is the key to the successful treatment of these patients with complex problems. The use of a multidisciplinary approach using the expertise of the urologist, the reconstructive surgeon, and either a general surgeon or colon/rectal surgeon as an operative team is critical to the successful management. Furthermore, general support through nutrition, intensive care, hyperbaric oxygen, and infectious disease specialists have all helped lower the mortality rate. The cosmetic appearance of most of these men is dramatically better today through some of the reconstructive techniques currently used. S. Lee Guice III, MD Department of Urology Nalle Clinic Charlotte, N.C.
  • 7. Case Report Fungal Fournier Gangrene from Infections in Urology® Posted 08/12/2003 Scott Rutchik, MD, Melinda Sanders, MD Abstract and Introduction Abstract A diagnosis of Fournier gangrene always calls for prompt medical and often surgical action. The addition of a fungal infection can only enhance the possibility of increased morbidity. Treatment options for patients with this rare combination are discussed. Introduction Fournier gangrene, a necrotizing fasciitis that originates in the perineum, represents one of the few true emergencies in urology practice. Typically, the infection involves anaerobic bacteria. Fungal infection, however, has only been implicated in a single case report in the medical literature.[1] We describe here perhaps only the second case of Fournier gangrene with a fungal organism. Fungal Fournier Gangrene from Infections in Urology® Case Report A 74-year-old man presented to the urology clinic with a 10-day history of fever accompanied by scrotal swelling and pain. He had been undergoing treatment from his primary care physician with an oral fluoroquinolone for presumed epididymo-orchitis. His medical history was significant for poorly controlled diabetes and severe peripheral vascular disease that had necessitated bilateral above-knee amputations. Physical examination revealed a hemodynamically stable patient with a tender discolored scrotum and swelling extending into the suprapubic area with palpable crepitus throughout. A clinical diagnosis of Fournier gangrene was made, and emergent debridement was undertaken. The initial incision into the scrotum yielded watery pus with a fungal odor. Approximately 350 mL of pus was aspirated from the wound. Extensive debridement of the scrotum and base of the penis was performed, exposing necrosis of the scrotum that tracked into the inguinal and suprapubic area. The right testicle was absent; the left testicle did not appear to be grossly infected and was spared. The skin over the suprapubic area appeared viable and was not excised. A suprapubic tube was placed, and the wound was packed with a sterile dressing. Gram stain of the wound fluid demonstrated yeast, and intravenous therapy with a third-generation cephalosporin and fluconazole was begun pending results of final wound cultures. A second debridement procedure was performed 48 hours later. Aerobic and anaerobic cultures of material obtained from the primary debridement demonstrated only Candida albicans; blood cultures were negative. Pathologic examination of the debrided tissue showed acute suppurative inflammation (Figure). Daily whirlpool therapy was initiated, as were wet-to-dry dressing changes. The patient was discharged from the hospital on postoperative day 4, with arrangements made for outpatient wound care.
  • 8. Figure. (click image to zoom) Photomicrograph demonstrates an area of intact striking underlying edema and inflammation (hematoxylin-eosin, ×200). (Photogra Walz.) Discussion Fournier gangrene is somewhat of a misnomer for this disease, because true myonecrosis is uncommon. Nonetheless, this does not detract from the seriousness of the illness, because the infection tends to follow the distribution of Scarpa fascia, thereby allowing for extension as far cephalad as the clavicles and as far caudad as the fascia lata. Although the disease was classically described in patients with periurethral abscess, more contemporary presentations occur in the diabetic or immunocompromised host.[2,3] Modern interventions have greatly improved the prognosis for patients with Fournier gangrene, but the disease still is capable of producing grave morbidity, because large areas of tissue debridement may be required for disease control. Dahm and associates[4] reported a 20% mortality rate in their contemporary case series, with depth of invasion, extent of infection, and treatment with hyperbaric oxygen observed as the most important prognostic variables. It should be noted, however, that the use of hyperbaric oxygen is a controversial treatment for patients with Fournier gangrene, although it may be a useful adjunct to debridement and antibiotic therapy in severe circumstances. The extensive tissue infarction and destruction seen in Fournier gangrene is usually the result of anaerobic bacterial infection. In many cases, this infection may begin as a primary infection with less virulent organisms, with anaerobic infection occurring as a secondary phenomenon. Thus, initial antibiotic therapy should consist of broad-spectrum coverage that includes agents active against anaerobes. Because of the rarity of fungal infection in this scenario, antifungal agents are probably not required in most cases. Because our patient's solitary testicle appeared viable at surgery, we believe that the most likely scenario to explain his clinical course was a misdiagnosed scrotal abscess that was managed with a broad- spectrum antibiotic, resulting in selection for yeast. Thus, we cannot rule out the possibility that a bacterial infection had been the initial inciting event. Nevertheless, in this patient, fungal sepsis did not develop, and he did not require extensive hospitalization, perhaps emphasizing the importance of early recognition and intervention in the management of all types of Fournier gangrene.