Fournier’s Gangrene in an HIV-Positive Patient Using a Sodium-Glucose Cotransporter-2 Inhibitor: A Case Report

Woohyuk Yoon; Joon Ho Lee

doi:10.22467/jwmr.2025.03202

Abstract

Fournier’s gangrene (FG) is a rapidly progressive necrotizing fasciitis affecting the perineal, genital, or perianal regions. It is a rare but potentially life-threatening condition that predominantly affects immunocompromised individuals, including those infected with the human immunodeficiency virus (HIV). Recent findings have highlighted the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) for patients with diabetes mellitus, such as prevention and treatment of cardiovascular disease, heart failure, and kidney disease. This supports both the expansion of their indications and the development of drug combinations with first-line medications. However, the increased risk of genitourinary infections is a well-known side effect of SGLT2i. This report describes the case of a 62-year-old man with well-controlled HIV infection, hypertension, and diabetes mellitus, who was using an SGLT2i and presented with FG. The patient underwent prompt surgical debridement, antibiotic therapy, and discontinued the SGLT2i, followed by wound reconstruction using a local transposition flap. This resulted in a successful outcome, with no further wounds observed for 3 months. This case underscores the potential synergistic risk factors of SGLT2i use and HIV infection in the development of FG and highlights the critical importance of prompt surgical intervention.

Key Words: Fournier gangrene; Sodium-glucose transporter 2 inhibitors; HIV; Immunocompromised host; Case reports

Introduction

Fournier’s gangrene (FG) is a rare but potentially life-threatening condition characterized by rapidly progressive necrotizing fasciitis that affects the perineal, genital, or perianal regions. The pathophysiology of FG involves synergistic infection by both aerobic and anaerobic microorganisms. Known risk factors include diabetes mellitus (DM), chronic alcoholism, compromised immune system such as human immunodeficiency virus (HIV) infection, advanced age, cardiovascular disease, chronic kidney disease, malnutrition, recent trauma or surgery in the genital area, and obesity; with most cases occurring in males with pre-existing health conditions that weaken their immune response.

Advances in anti-retroviral therapy has led to increased survival of patients with HIV. As the HIV-infected population ages and more HIV-infected individuals live with DM, drug selection for patients with HIV infection and DM needs more critical attention, as this group has two compounding risk factors for developing FG. The management of DM for patients with HIV infection typically follows the same protocols as for immunocompetent individuals. Recent findings have highlighted the advantages of using sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with diabetes [1]. SGLT2i have shown promise in preventing and treating cardiovascular disease, heart failure, and kidney disease, leading to the expansion of their indications and the development of combination drug tablets with first-line medications [2]. However, a well-known side effect of SGLT2i is an increased risk of genitourinary infections. Concerns are growing about the potential contributory role of glycosuria induced by use of SGLT2i in creating a favorable environment for microbial proliferation, leading to potential development of FG, particularly in patients with HIV infection [3].

Herein, we report the case of a 62-year-old man with well-controlled HIV infection, hypertension, and DM, who developed FG while using an SGLT2i. This case underscores the potential synergistic risk factors of SGLT2i use and HIV infection in FG development and emphasizes the critical importance of early surgical intervention in managing this condition. The report was approved by the Institutional Review Board of Dongguk University Hospital (IRB approval No. 110757-202501-HR-01-02) and the patient provided written informed consent for the publication and use of his images.

Case

A 62-year-old man presented to the emergency department with persistent left scrotal pain, swelling, and eschar formation that was refractory to 1 week of antibiotic therapy (Fig. 1). The patient had a 13-year history of HIV infection and was being treated with a bictegravir/emtricitabine/tenofovir-alafenamide combination regimen. HIV viral load results showed less than 30 copies/mL indicating undetectable level, and a CD4 count of >750 cells/μL. His medical history also included hypertension, DM, dyslipidemia, and a prior cerebral infarction. Initial laboratory investigations revealed a C-reactive protein level of 22.85 mg/dL and a white blood cell count of 19,700/μL. Abdominal computed tomography showed emphysema in the left scrotal wall (Fig. 2). A review of his medical history and medications revealed that the patient had been taking dapagliflozin, an SGLT2 inhibitor. Following an endocrinology consultation, dapagliflozin was discontinued and replaced with linagliptin, a dipeptidyl peptidase-4 inhibitor.

The patient was admitted for prompt surgical debridement and antibiotic therapy. Empirical intravenous third-generation cephalosporins were administered immediately. Surgical debridement was performed in cooperation with the department of urology. The necrotic scrotal skin and underlying soft tissue were excised, and necrosis of the left epididymis was identified and resected (Fig. 3). Tissue samples and wound swabs were sent for microbiological analysis, identifying Actinomyces turicensis and Corynebacterium jeikeium. Antibiotics were replaced with intravenous vancomycin based on the culture and antibiotic susceptibility results. Daily Betadine-soaked gauze dressings were applied for 3 weeks following the initial debridement. The wound progressed favorably, with sufficient granulation tissue formation and resolution of signs of infection, providing favorable conditions for reconstruction (Fig. 4).

A deep external pudendal artery-based transposition flap was planned. The second surgical debridement resulted in a defect measuring 7 cm in length and 7 cm in width (Fig. 5). Doppler ultrasonography revealed a single perforator located 1 cm from the wound margin. The fasciocutaneous flap was elevated and transposed to cover the defect. Subcutaneous sutures and drain were placed beneath the inguinal crease to eliminate potential dead space and minimize the risk of complications (Fig. 6). The patient was closely monitored, and no further wound issues were observed over the following 3 months (Fig. 7).

Discussion

We report a case of successful treatment of FG in a patient with HIV and a history of SGLT2i administration. FG is a severe, life-threatening condition characterized by fascial breakdown and tissue necrosis, often presenting with painful, red, and swollen genitalia, accompanied by necrotic patches or palpable crepitus caused by gas-producing bacteria. In severe cases, FG can spread to the fascial layers of the perineum and thighs, potentially causing systemic symptoms ranging from mild fever to severe septic shock [4].

SGLT2i, also known as gliflozins, are a groundbreaking class of medications that have revolutionized the treatment of type 2 diabetes and cardiovascular diseases. SGLT2i work by blocking the action of the SGLT2 protein in the kidneys, which is responsible for reabsorbing glucose from the glomerular filtrate into the bloodstream [1]. By inhibiting this process, these medications promote the excretion of excess glucose through the urine, effectively lowering blood sugar levels. Furthermore, they go beyond glycemic control, with numerous studies revealing their potential to improve cardiovascular and renal outcomes [2]. Despite these benefits, the U.S. Food and Drug Administration (FDA) has issued warnings regarding the rare occurrence of FG in patients taking SGLT2i [5]. Meta-analysis of multiple randomized controlled trials was performed to verify the FDA warnings. However, it has failed to detect any effect of SGLT2i upon the risk of FG [6]. Nevertheless, considering the small number of recorded cases included in the meta-analysis and continuing reports of FG occurrence in patients treated with SGLT2i, further research is required to discover its possible correlation [7].

HIV infection is also a risk factor for FG due to its immunosuppressive effects. The first documented case of FG associated with HIV infection was reported in 1991, with subsequent cases reported in Western literature [8]. An epidemiological study in Nairobi, Kenya suggested that DM is the main comorbidity of FG in Western literature, whereas HIV infection was the main associated illness followed by alcoholism in African clinical settings [9]. A few studies suggest that FG mortality has a linear correlation with the HIV viral load, although others suggest that delayed recognition or suboptimal treatment is linked to higher mortality [10]. However, aggressive interventions for FG have yielded comparable recovery rates in HIV-positive and HIV-negative patients [11].

Our patient had a low viral load and high CD4 count with good compliance on a single-tablet anti-retroviral therapy, indicating well-controlled HIV infection status [12]. Although the mere presence of HIV infection does not establish a direct link to FG, pro-inflammatory states in chronic HIV infection have been associated in the development of peripheral gangrene due to increase in complement activation, endothelial cell dysfunction, hypercoagulable state, and vasculitis [13,14]. We hypothesize that the combination of HIV infection and SGLT2i use in DM management may potentiate the risk of FG. To the best of our knowledge, a single case has been published highlighting the occurrence of FG in an HIV-positive patient taking empagliflozin, an SGLT2i [15]. This case underscores the importance of recognizing the compounding risks of FG as a complication of SGLT2i use, especially in patients with HIV infection.

While the presence of HIV does not alter the fundamental treatment strategy for FG early detection is crucial to reduce the mortality rate. Attentive monitoring and patient education are essential to ensure timely interventions. Clinicians should maintain vigilance for FG in such patients and instruct them to seek immediate medical attention if symptoms develop. If FG is suspected, immediate discontinuation of the SGLT2i, initiation of broad-spectrum antibiotics, and prompt surgical debridement are critical to improving outcomes and preventing complications.

In conclusion, patients with HIV infection treated with SGLT2i for DM require close monitoring for potential FG development. Further research is warranted to assess the benefit-risk profile of SGLT2i use in patients with DM and HIV infection.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Fig. 1.

Patient photograph upon arrival to the emergency room. A 62-year-old man presented with persistent left scrotal pain, swelling, and eschar formation, unresponsive to a week of antibiotic therapy.

Fig. 2.

Abdominal computed tomography findings. Computed tomography scan showing emphysema within the left scrotal wall (red circle).

Fig. 3.

Intraoperative photograph of scrotal wound during first debridement. Necrotic scrotal skin and underlying soft tissue have been excised, and necrosis of the left epididymis is identified and resected.

Fig. 4.

Wound healing. After 3 weeks of Betadine-soaked dressing application, sufficient granulation tissue formation and resolution of infection signs are observed.

Fig. 5.

Intraoperative photograph of second debridement. The defect measures 7 cm in length and 7 cm in width. Doppler ultrasonography identifies a single perforator located 1 cm from the wound margin.

Fig. 6.

Intraoperative photographs of flap reconstruction. (A) A fasciocutaneous flap is elevated and transposed to cover the defect. (B) Subcutaneous sutures and a drain are placed beneath the inguinal crease to eliminate potential dead space and minimize the risk of complications. Skin staples are applied on the wound margin.

Fig. 7.

Three months postoperative follow-up photograph. The patient’s wound recovered without complication and no further wound issues were observed.

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