Development of Fournier's gangrene after chemotherapy for the recurrence of testicular cancer despite the absence of anorectal lesions: A case report.

BACKGROUND: Fournier's gangrene usually occurs when a specific bacterium intrudes into soft tissue, causing a wound or tumor. We encountered a patient with Fournier's gangrene due to severe myelosuppression after chemotherapy, despite the absence of an initial lesion on the anus and rectum. CASE PRESENTATION: A 54-year-old man with a left testicular cancer recurrence had undergone chemotherapy. He had asymptomatic hepatitis and high hepatitis B virus DNA levels, which were normalized by administering tenofovir alafenamide fumarate. Twelve days after the start of chemotherapy, he complained of severe pain around the anus. The following day, he went into septic shock. Visual inspection showed dark purple skin discoloration on the left side of the anus. Laboratory data revealed severe neutropenia. Computed tomography showed a high density of soft tissue on the left side of the anus and gas bubbles in the left femoral ring. We diagnosed the patient with Fournier's gangrene due to a severe immunosuppressive state resulting from chemotherapy. We emergently removed necrotic tissue to the fullest extent possible. However, because the patient was in severe sepsis status, careful management in the intensive care unit was required for 32 days. After the first emergency operation, we performed several additional excisions. Finally, 391 days after the initial surgery, the patient was discharged from our hospital. The tumor has not recurred, and he is under outpatient observation in the urology department. CONCLUSION: Fournier's gangrene should be considered in patients who are in a severe myelosuppressive state due to chemotherapy, have normal hepatitis B virus DNA levels but high hepatitis B surface antigen after tenofovir administration, complain of severe pain in the perianal area, and have a dark purple skin discoloration around the anus, despite having no initial anorectal lesions.

Blastic plasmacytoid dendritic cell neoplasm in a young patient.

Blastic plasmacytoid dendritic cell neoplasm is a rare hematologic neoplasm originating from plasmacytoid dendritic cell precursors that has an aggressive disease course with typically poor prognosis. Herein, we report a man in his early twenties who presented with rapid onset of violaceous nodules and purpuric papules and macules that began on his chest before spreading to his arms, back, face, scalp, and legs. He also exhibited systemic symptoms including weight loss and night sweats. He was diagnosed with blastic plasmacytoid dendritic cell neoplasm and began treatment with aggressive multidrug therapy. Thus far his treatment has resulted in complete resolution of his cutaneous manifestations.

A Case of Fournier's Gangrene in a Patient Taking Canagliflozin for the Treatment of Type II Diabetes Mellitus.

BACKGROUND Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antihyperglycemic medications associated with an increased risk of urinary and genital infections due to their glycosuric effects. In 2018, the FDA issued a safety alert warning that multiple cases of Fournier's Gangrene (FG), a severe genital infection, had been reported in patients taking SGLT2 inhibitors. CASE REPORT We present a case of 72-year-old male with type II diabetes mellitus who developed FG while taking the SGLT2 inhibitor canagliflozin. Besides diabetes and canagliflozin use, his other risk factors were his age, gender, and remote history of radiotherapy for prostate cancer. He presented to the Emergency Department (ED) multiple times complaining of rectal pain and was admitted for a possible diagnosis of prostatitis. During his stay, he developed leukocytosis, his pain worsened, and examination of the perianal area was consistent with FG. He was treated with multiple surgical debridement procedures and broad-spectrum antibiotics; the source of infection was determined to be a perianal abscess. He stayed in the hospital for 1 month and was discharged home with outpatient wound care and vacuum dressing changes. Canagliflozin was discontinued during the hospital stay. CONCLUSIONS Due to the possible association of FG with SGLT2 inhibitors, patients who present with signs and symptoms consistent with FG should be examined for possible FG and treated promptly.

Real-world evidence on sodium-glucose cotransporter-2 inhibitor use and risk of Fournier's gangrene.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with increased occurrence of Fournier's gangrene (FG), a rare but serious form of necrotizing fasciitis, leading to a warning from the Food and Drug Administration. Real-world evidence on FG is needed to validate this warning. METHODS: We used data from IBM MarketScan (2013-2017) to compare the incidence of FG among adult patients who initiated either SGLT2i, a dipeptidyl peptidase-4 inhibitor (DPP4i), or any non-SGLT2i antihyperglycemic medication. FG was defined using inpatient International Classification of Diseases, Ninth Edition and Tenth Edition diagnosis codes 608.83 and N49.3, respectively, combined with procedure codes for debridement, surgery, or systemic antibiotics. We estimated crude incidence rates (IRs) using Poisson regression, and crude and adjusted HRs (aHR) and 95% CIs using standardized mortality ratio-weighted Cox proportional hazards models. Sensitivity analyses examined the impact of alternative outcome definitions. RESULTS: We identified 211 671 initiators of SGLT2i (n=93 197) and DPP4i (n=118 474), and 305 329 initiators of SGLT2i (n=32 868) and non-SGLT2i (n=272 461). Crude FG IR ranged from 3.2 to 3.8 cases per 100 000 person-years during a median follow-up of 0.51-0.58 years. Compared with DPP4i, SGLT2i initiation was not associated with increased risk of FG for any outcome definition, with aHR estimates ranging from 0.25 (0.04-1.74) to 1.14 (0.86-1.51). In the non-SGLT2i comparison, we observed an increased risk of FG for SGLT2i initiators when using FG diagnosis codes alone, using all diagnosis settings (aHR 1.80; 0.53-6.11) and inpatient diagnoses only (aHR 4.58; 0.99-21.21). CONCLUSIONS: No evidence of increased risk of FG associated with SGLT2i was observed compared with DPP4i, arguably the most relevant clinical comparison. However, uncertainty remains based on potentially higher risk in the broader comparison with all non-SGLT2i antihyperglycemic agents and the rarity of FG. TRIAL REGISTRATION NUMBER: EUPAS Register Number 30018.

Safety of Sodium-Glucose Co-Transporter 2 Inhibitors.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have a well-defined safety profile based on data obtained from numerous clinical trials, including cardiovascular outcomes trials (CVOTs) and postmarketing pharmacovigilance reporting. Adverse events including risk of genital mycotic infection and volume depletion-related events are consistent with the mechanism of action of this drug class. However, several emergent (albeit infrequent) serious safety issues have also been reported. In their respective CVOTs, the proportion of patients with reported diabetic ketoacidosis was similar in empagliflozin or canagliflozin compared with their placebo groups, but it was higher for dapagliflozin. Canagliflozin may be associated with an increased risk of bone fracture and lower limb amputation; however, data are inconclusive. There is no evidence linking SGLT2 inhibitors with an increased risk of cancer, but these agents, particularly dapagliflozin, should be used with caution in patients with hematuria or a history of bladder cancer. Postmarketing reports of acute kidney injury have occurred in patients receiving SGLT2 inhibitors, and cases identified in recent CVOTs occurred with similar frequency in SGLT2 inhibitor and placebo groups. Common adverse events associated with SGLT2 inhibitors (such as genital infections or volume depletion) are generally mild and manageable by patients or by primary care physicians, and the risk of rare events (such as ketoacidosis) can be minimized by appropriate patient selection and early recognition of symptoms. When selecting treatment, it is important that clinicians weigh the known risks of SGLT2 inhibitors against their proven benefits, including the reduction of adverse cardiovascular and renal outcomes.

Fournier Gangrene Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases.

Background: Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors has been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region. Objective: To describe and compare reported cases of FG in diabetic adults receiving treatment with SGLT2 inhibitors or other antiglycemic agents. Design: Descriptive case series. Setting: U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and published case reports. Patients: Adults receiving SGLT2 inhibitors or other antiglycemic agents. Measurements: Clinical and laboratory data. Results: The FDA identified 55 unique cases of FG in patients receiving SGLT2 inhibitors between 1 March 2013 and 31 January 2019. The patients ranged in age from 33 to 87 years; 39 were men, and 16 were women. Time to onset after initiation of SGLT2-inhibitor therapy ranged from 5 days to 49 months. All patients had surgical debridement and were severely ill. Reported complications included diabetic ketoacidosis (n = 8), sepsis or septic shock (n = 9), and acute kidney injury (n = 4). Eight patients had fecal diversion surgery, 2 patients developed necrotizing fasciitis of a lower extremity that required amputation, and 1 patient required a lower-extremity bypass procedure because of gangrenous toes. Three patients died. For comparison, the FDA identified 19 FG cases associated with other antiglycemic agents between 1984 and 31 January 2019: metformin (n = 8), insulin glargine (n = 6), short-acting insulin (n = 2), sitagliptin plus metformin (n = 2), and dulaglutide (n = 1). These patients ranged in age from 42 to 79 years; 12 were men, and 7 were women. Two patients died. Limitation: Inability to establish causality or incidence, variable quality of reports, possible underreporting, and confounding by indication. Conclusion: FG is a newly identified safety concern in patients receiving SGLT2 inhibitors. Physicians prescribing these agents should be aware of this possible complication and have a high index of suspicion to recognize it in its early stages. Primary Funding Source: None.

Fournier's gangrene in a man on empagliflozin for treatment of Type 2 diabetes.

BACKGROUND: Sodium-glucose cotransporter 2 (SLGT2) inhibitors has been associated with an increased risk of genital infections secondary to increased glycosuria. CASE REPORT: We report a case of a 41-year-old man with type 2 diabetes treated with empagliflozin and metformin who presented with scrotal swelling. He described multiple preceding episodes of genital thrush for which he self-administered over-the-counter anti-fungal treatment. On examination, he was afebrile and hemodynamically stable. Perineal examination revealed grossly swollen and indurated scrotum with bilateral inguinal lymphadenopathy. Investigations showed elevated inflammatory markers and HbA1c of 99 mmol/mol (11.2%). Computed tomography revealed features consistent with Fournier's gangrene. He underwent emergency exploration and debridement under anaesthetic with a later return to theatre for further exploration, washout and application of a vacuum dressing. He then received a split skin graft to his perineum. He required a 2-week course of intravenous antibiotics and was discharged home on oral antibiotics. Empagliflozin was ceased on admission and he was commenced on a basal bolus insulin regimen for glycaemic optimisation. CONCLUSION: There is a wide clinical spectrum of genital infections associated with SGLT2 inhibitors with most being generally mild and easily treated. However, risk factors such as diabetes, obesity, immunosuppressed states, smoking, alcohol abuse and end-stage renal or liver failure may increase the risk of potentially more severe infections such as Fournier's gangrene. Timely cessation of SGLT2 inhibitors in individuals with multiple risk factors may help prevent progression to more severe genital infections.

Urological complications of illicit drug use.

Illicit drug use is prevalent worldwide; over 24 million people are estimated to have used recreational drugs during the past month in the UK and USA alone. Illicit drug use can result in a wide spectrum of potential medical complications that include many urological manifestations. To ensure optimal care and treatment, urologists need to be cognizant of these complications in their patients, particularly among youths. Ketamine uropathy is thought to affect over one-quarter of ketamine users and can lead to severe lower urinary tract symptoms, as well as upper tract obstruction. Cannabis use has been associated with an increased risk of bladder cancer, prostate cancer and nonseminomatous germ cell tumours in case-control studies. Fournier's gangrene has been reported following injection of heroin and cocaine into the penis. Excessive use of cough medicines can lead to the development of radiolucent stones composed of ephedrine, pseudoephedrine and guaifenesin. As the current evidence is mostly limited to case reports and case series, future epidemiological studies are needed to fully address this issue.

Gangrena de Fournier en asociación con el uso de anti-inflamatorios no esteroideos: Reporte de un caso pediátrico / An unusual presentation of Fournier's gangrene: ¿Is there a relationship with NSAID use? Pediatric case report

La gangrena de Fournier es una enfermedad amenazante para la vida, que se caracteriza por fascitis necrosante del área perineal. Afecta con mayor frecuencia a pacientes adultos con inmunosupresión y son pocos los casos reportados en la población pediátrica. El uso de fármacos anti-inflamatorios no esteroideos (AINEs) se ha asociado con fascitis necrosante, probablemente por supresión de la inmunidad durante la infección. Describimos el caso de un paciente con 6 meses de edad sin factores inmu-nosupresores, con gangrena de Fournier, probablemente asociada a la ingesta de AINEs.

Founier's gangrene is a rare but life-threatening disease characterized by necrotizing fasciitis of the perineal area. It mostly affects adult patients with an immunosuppressant factor and there are only a few cases reported in children. Use of nonsteroidal anti-inflammatory drugs has been associated with necrotizing fasciitis probably because of suppressing host immunity during infection. We describe a case of a six month old infant without im-munosuppressant factors, with Founier´s gangrene probably associated with nonsteroidal anti-inflammatory intake.

Fournier's gangrene as a possible side effect of bevacizumab therapy for resected colorectal cancer.

Bevacizumab is a humanized monoclonal antibody approved by the US Food and Drug Administration for use in combination with fluorouracil (FU)-based chemotherapy for first-line treatment of patients with metastatic colorectal carcinoma (CRC). Its mechanism of action is inhibition of tumor angiogenesis by neutralizing vascular endothelial growth factor. Adverse events resulting from its use include gastrointestinal perforation, wound-healing complications, hemorrhage, and arterial thromboembolism. We present a case of a 67-year-old man who developed Fournier's gangrene during treatment with bevacizumab 4 months after completing mFOLFOX6 (5-FU/leucovorin/oxaliplatin) for CRC. Other than bevacizumab, the patient had no medications and had no medical conditions that would predispose to Fournier's gangrene.

Fournier's gangrene and scrotal ulcerations during all-trans-retinoic acid therapy for acute promyelocytic leukemia.

Scrotal ulcers are a rare manifestation in patients with acute promyelocytic leukemia. Fournier's gangrene (FG) is even rarer. We describe three adolescents and young adults who developed scrotal ulcerations during induction with all-trans-retinoic acid. One patient developed FG. These lesions are predominantly seen in Asian population. A good outcome with supportive management occurred in all the cases.

Penoscrotal reconstruction using groin and bilateral superomedial thigh flaps: a case of penile vaselinoma causing Fournier's gangrene.

Penile augmentation by the injection of mineral oil provokes many serious, undesirable effects. Although there are reports of complications such as deformity, ulceration, necrosis, and erectile dysfunction, Fournier's gangrene resulting from the injection of petroleum jelly into the penis has not been reported. Here, we present a 42-year-old man with penile vaselinoma causing Fournier's gangrene which was treated successfully with aggressive surgical debridement, followed by penoscrotal reconstruction using groin and bilateral superomedial thigh flaps.

Fournier's gangrene following penile self-injection with cocaine.

To date, there have been no reports of Fournier's gangrene following penile self-injection of cocaine. We report a case of cocaine-induced Fournier's gangrene requiring parenteral antibiotics followed by primary surgical debridement and delayed reconstructive procedure of penile skin.

Fournier's gangrene during induction treatment of acute promyelocytic leukemia, a case report.

Fournier's gangrene is described as a fulminant necrotizing fasciitis of the scrotum and penis. Few cases have been reported in the context of acute leukemia. We describe a case, complicating the induction treatment of an acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. The evolution was favorable, following surgical excision and broad-spectrum antibiotic therapy. The respective roles of all-trans-retinoic acid and granulocytopenia are discussed. This devastating and life-threatening infection must be kept in mind for early clinical, bacteriological, and radiological diagnosis and surgical management.