Extensive empagliflozin-associated Fournier’s gangrene with complete functional recovery – A case report

INTRODUCTION

Fournier’s gangrene constitutes a rapidly progressive necrotizing fasciitis predominantly affecting the perineal, scrotal, and perianal regions.^[1] Originally described in association with diabetes mellitus, immunocompromised conditions, and local tissue trauma, recent pharmacovigilance data have revealed a disturbing connection with sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy.^[2] These antidiabetic agents have demonstrated remarkable efficacy in glycemic control and cardiovascular protection, yet post-marketing surveillance has uncovered alarming reports of severe necrotizing soft-tissue infections.^[3]

Current literature contains numerous case reports of SGLT2 inhibitor-associated Fournier’s gangrene, predominantly affecting older males (median age 58–65 years) with variable outcomes and limited long-term functional data.^[4] Most published cases lack comprehensive outcome assessment, surgical technique documentation, or validated functional evaluation tools, creating significant knowledge gaps in optimal management approaches. The pathophysiological mechanisms underlying this association remain poorly understood, with proposed hypotheses including enhanced glucose availability in the genitourinary tract promoting bacterial proliferation, potential immunosuppressive effects, and disruption of local microbial ecology.^[4]

This case report addresses critical literature gaps by presenting, to our knowledge, one of the youngest documented cases with a temporal association between empagliflozin use and Fournier’s gangrene with the most extensive scrotal involvement (80% surface area), yet achieving complete functional recovery. We introduce novel surgical management techniques and provide the first comprehensive functional outcome evaluation using validated instruments, offering new perspectives on prognosis and optimal care strategies for this devastating complication.

CASE REPORT

A previously healthy 35-year-old male with a 2-year history of type 2 diabetes mellitus sought emergency care following 3 days of progressively worsening perineal pain, high-grade fever (39.2°C), and constitutional symptoms. His medical background included well-controlled hypertension and dyslipidemia, with early-stage diabetic nephropathy. Current medications comprised empagliflozin 25 mg daily (commenced 8 months earlier), metformin 1000 mg twice daily, ramipril 2.5 mg daily, and atorvastatin 40 mg daily. He denied recent genitourinary procedures, trauma, or immunosuppressive therapy.

The patient first noticed symptoms ∼72 h before presentation. He presented to the emergency department at 14:30 h on day 3 of symptoms. Emergency department presentation revealed an acutely unwell patient with concerning vital signs: Tachycardia (112 bpm), hyperthermia (39.2°C), and borderline hypotension (102/66 mmHg). Physical examination demonstrated alarming findings of widespread erythema, significant tissue edema, and palpable crepitation throughout the perineal and scrotal regions. Extensive areas of black, gangrenous tissue were observed involving approximately 80% of the scrotal surface area, with posterior extension into the perineal region [Figure 1]. The necrotic process showed deep fascial involvement with substantial tissue destruction, creating large defects exposing underlying anatomical structures. Multiple confluent areas of tissue death were present, and the patient described excruciating pain that seemed disproportionate to visible changes.

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Figure 1: Clinical presentation of empagliflozin-induced Fournier’s gangrene in a 35-year-old male with type 2 diabetes mellitus. Extensive necrotizing fasciitis involving the scrotal region with multiple areas of black, necrotic tissue, and substantial tissue loss.

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Laboratory investigations revealed significant abnormalities: Marked leukocytosis (18,500/μL), severely elevated inflammatory markers (C-reactive protein 185 mg/L), profound hyperglycemia (24.8 mmol/L), and acute kidney injury (creatinine 180 μmol/L, baseline 120 μmol/L). Hemoglobin A1c (HbA1c) measured 8.2%, indicating suboptimal recent glycemic control. Blood cultures were obtained, and empirical broad-spectrum antimicrobial therapy with intravenous piperacillin–tazobactam 4.5 g every 6 h and clindamycin 600 mg every 8 h was initiated around 45 min after presentation.

Contrast-enhanced computed tomography of the pelvis revealed extensive soft-tissue gas collections and fluid accumulation consistent with necrotizing fasciitis involving the perineum, scrotum, and extending toward the lower anterior abdominal wall. The imaging findings confirmed the clinical suspicion of advanced necrotizing soft-tissue infection requiring immediate surgical intervention.

Emergency surgical exploration was performed at around 16:45 h, approximately 2 h and 15 min after initial presentation. Intraoperative findings revealed extensive necrotic fascial planes and subcutaneous tissue involving multiple anatomical layers: Dartos fascia, Colles’ fascia, and extension to Scarpa’s fascia. Remarkably, despite the massive scrotal wall destruction, both testes remained viable with intact vascular supply and normal-appearing tunica albuginea – an unusual finding given the extent of surrounding tissue necrosis.

A comprehensive debridement strategy was implemented, removing all necrotic and questionably viable tissue while carefully preserving testicular viability through meticulous microvascular assessment. The surgical team employed an innovative staged approach, utilizing negative pressure wound therapy between procedures to optimize tissue perfusion and promote healing. Real-time tissue viability was assessed using indocyanine green fluorescence imaging, a technique not previously described in SGLT2 inhibitor-associated cases. Tissue specimens yielded polymicrobial growth including Escherichia coli, Enterococcus faecalis, and Bacteroides fragilis. Culture sensitivities revealed E. coli resistant to ampicillin but sensitive to piperacillintazobactam, fluoroquinolones, and carbapenems; E. faecalis sensitive to ampicillin and vancomycin; and B. fragilis sensitive to metronidazole and clindamycin. The initial empirical antibiotic regimen provided adequate coverage for all identified organisms, and therapy was continued without modification based on these sensitivity results.

The patient required three additional surgical debridements over the subsequent 7 days, performed on post-operative days 2 (∼48 h after initial surgery), 4 ( ∼96 h after initial surgery), and 7 (∼168 h after initial surgery), with each procedure guided by fluorescence imaging and clinical assessment. Empagliflozin was immediately discontinued upon diagnosis establishment. Antimicrobial therapy consisted of intravenous piperacillin–tazobactam and clindamycin for 14 days, followed by oral antibiotic continuation with amoxicillin–clavulanate (875/125 mg twice daily) for an additional 7 days. Glycemic management transitioned to intensive insulin therapy. Following comprehensive wound care protocols and rehabilitation, hospital discharge occurred after 28 days with specialized home nursing support.

Three-month follow-up evaluation demonstrated remarkable recovery with complete wound healing and no evidence of recurrent infection. Comprehensive functional assessment revealed several noteworthy findings rarely documented in existing literature. Testicular function remained intact with normal testosterone levels (18.2 nmol/L, reference range 12–30 nmol/L), and complete preservation of erectile function was observed. Diabetes management successfully transitioned to combination metformin and insulin therapy, achieving significantly improved glycemic control (HbA1c 7.1%).

Six-month evaluation confirmed sustained excellent recovery with full return to normal daily activities and occupational responsibilities. Formal sexual function assessment using the International Index of Erectile Function-5 questionnaire demonstrated a score of 22/25, indicating normal erectile function (scores >21 suggest absence of erectile dysfunction).^[5] Psychological evaluation using the post-traumatic stress disorder checklist for DSM-5 (PCL-5) revealed a score of 8/80, indicating the absence of significant psychological trauma (scores <31 suggest no clinically meaningful post traumatic stress disorder [PTSD] symptoms).^[6] The patient expressed high satisfaction with both functional and cosmetic outcomes. Scrotal reconstruction was deemed unnecessary due to excellent spontaneous tissue regeneration and acceptable esthetic appearance.

DISCUSSION

This case presents several distinctive features that differentiate it from previously published SGLT2 inhibitor-associated Fournier’s gangrene reports and provide valuable insights for clinical practice. At 35 years of age, the patient represents, to our knowledge, one of the youngest documented cases of temporal association between empagliflozin use and Fournier’s gangrene in the literature, with most reported cases occurring in patients aged 51–75 years.^[7-10] This finding challenges prevailing assumptions about age-related risk stratification and emphasizes the need for vigilance across all age demographics.

While this case report demonstrates a temporal association between empagliflozin use and Fournier’s gangrene development, it is important to acknowledge that case reports cannot establish causality. The patient had multiple risk factors for Fournier’s gangrene, including diabetes mellitus with suboptimal glycemic control (HbA1c 8.2%) and diabetic nephropathy, both of which are independently associated with increased infection risk. The temporal relationship – with gangrene developing 8 months after empagliflozin initiation – is consistent with patterns observed in pharmacovigilance data but does not prove that empagliflozin directly caused this condition.

The extensive scrotal involvement (80% surface area) with complete functional preservation represents an unprecedented outcome in the existing literature. Previous cases with comparable tissue destruction typically resulted in sexual dysfunction, testicular loss, or requirement for complex reconstructive procedures.^[7,8] Our patient’s exceptional recovery provides important prognostic insights and offers hope for similar cases.

The rapid disease progression observed (72 h from symptom onset to extensive involvement) paradoxically resulted in the most favorable functional outcome reported to date. This finding suggests that the rapidity of progression may not necessarily predict poor outcomes when managed with aggressive early intervention, challenging traditional prognostic assumptions.

The innovative surgical approach utilized in this case, incorporating staged debridement with negative pressure wound therapy and real-time indocyanine green fluorescence imaging, has not been previously described in SGLT2 inhibitor-associated Fournier’s gangrene management. These techniques may have contributed to the remarkable functional preservation observed and could inform future management protocols.

This case provides the first comprehensive functional outcome assessment using validated instruments in SGLT2 inhibitor-associated Fournier’s gangrene literature. Previous reports lack detailed functional evaluation, limiting their utility for patient counseling and prognosis determination. The documented preservation of sexual function and absence of psychological trauma provide crucial information for clinical decision-making.

The pathophysiological mechanisms underlying the association between SGLT2 inhibitors and Fournier’s gangrene remain incompletely understood. These medications enhance urinary glucose excretion, potentially creating favorable conditions for bacterial proliferation within the genitourinary tract.^[3] In addition, SGLT2 inhibitors may possess immunomodulatory properties that could predispose to severe infectious complications.^[7]

Epidemiological studies demonstrate significantly increased Fournier’s gangrene risk among SGLT2 inhibitor users compared to other antidiabetic therapies.^[7-10] The condition typically develops within months of treatment initiation, consistent with our patient’s timeline.

The exceptional recovery achieved in this case, despite extensive tissue involvement, suggests that specific factors, including younger age, absence of significant comorbidities, rapid medical intervention, and innovative surgical techniques, may significantly impact outcomes. These findings provide evidence-based prognostic factors for patient counseling and treatment planning.

Healthcare providers prescribing SGLT2 inhibitors should provide comprehensive patient education regarding Fournier’s gangrene recognition, emphasizing immediate medical evaluation for suspicious symptoms. This case demonstrates that even extensive disease can achieve excellent functional outcomes with appropriate management – crucial information for shared decision-making and patient counseling.

CONCLUSION

This case demonstrates that extensive SGLT2 inhibitor-associated Fournier’s gangrene can achieve complete functional recovery through aggressive early intervention and innovative surgical techniques. Despite affecting one of the youngest patients with the most extensive scrotal involvement documented, excellent outcomes were achieved, challenging traditional prognostic assumptions and providing hope for similar cases requiring optimal management strategies.