Multifocal bowel perforation from angioinvasive aspergillosis after bilateral lung transplantation: a case report and review of the literature
Highlight box
Key findings
• We present an extremely rare case of multifocal (jejunal and cecal) bowel perforation due to angio-invasive aspergillosis (angio-IA) in a patient who had undergone lung transplantation (LT).
• Multidisciplinary management and early surgical intervention are crucial for the management of these critically ill and complex patients.
What is known and what is new?
• LT patients are at high risk for opportunistic infections, including fungal infections like aspergillosis.
• This report highlights the first known case of angio-IA resulting in multifocal bowel perforation after LT and highlights importance of direct, aggressive surgical intervention.
What is the implication, and what should change now?
• Our report highlights that distal mycotic embolization to the bowel in the setting of IA after LT is possible.
• A high index of suspicion is warranted to assess for developing peritonitis in these complex patients in whom clinical presentation may be insidious, given the degree of post-transplant immunosuppression and often multiorgan system critical illness.
• Multidisciplinary management and early surgical intervention are crucial for the management of this life-threatening complication.
Introduction
Background
Lung transplantation (LT) is an accepted modality of treatment for end-stage lung disease. Due to the need for immunosuppression, impaired mucociliary clearance, and external allograft environmental exposure, LT patients are at particularly high risk of opportunistic infections (1,2). Fungal infections occur in up to a third of LT recipients, primarily caused by Aspergillus and Candida species (3). Invasive aspergillosis (IA) is an aggressive fungal infection, and disseminated disease (involvement of ≥2 noncontiguous organs) is associated with high mortality following LT (3,4). In rare cases, aspergillosis can become angioinvasive and shower emboli distally, which may compromise end-organ vasculature.
Rationale and knowledge gap
End-organ dysfunction from IA after LT is extremely rarely identified in pathologic analysis, as most patients who develop disseminated IA do not have pathology amenable to surgical interventions. Therefore, the extent of possible distal end-organ targets in the setting of IA after LT is poorly established and represents a key knowledge gap.
Objective
The present report addresses a patient with IA that led to bowel perforation after a bilateral LT. The unusual presentation and clinical course are discussed herein, followed by a review of the literature. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-221/rc).
Case presentation
A 62-year-old was admitted to the hospital for acute cellular rejection after he underwent bilateral LT 7 months prior. He was undergoing treatment with high-dose corticosteroid therapy and mycophenolate. The hospital course was further complicated by acute renal failure requiring renal replacement therapy and microangiopathic hemolytic anemia treated with eculizumab. On hospital day 15, he was intubated for acute hypoxemic respiratory failure. Bronchoalveolar lavage (BAL) revealed growth of Aspergillus fumigatus, blood cultures were negative for Aspergillus, and blood Galactomannan levels were significantly elevated. Computerized tomography (CT) of the chest showed multifocal consolidations concerning for pneumonia (Figure 1). He was subsequently started on triple antifungal treatment for presumed invasive pulmonary aspergillosis.
On hospital day 29, the patient developed worsening diffuse abdominal pain and increased vasopressor requirements. Physical examination demonstrated peritonitis. CT of abdomen and pelvis demonstrated small and large bowel wall thickening with scattered areas of pneumatosis intestinalis, small foci of pneumoperitoneum, and portal venous gas (Figures 2-4). An IVC filter (for history of a deep venous thrombus) and feeding tube are also noted on the CT abdomen/pelvis. After a brief interdisciplinary discussion with his family, he was taken for an exploratory laparotomy. Upon entry, there was a moderate volume of thin enteric appearing fluid but no feculent contamination. Necrotic cecal and proximal jejunal lesions on the antimesenteric bowel surfaces were identified. A proximal jejunal resection with primary anastomosis and a right hemicolectomy with end ileostomy and transverse colonic mucous fistula were performed. The patient returned to the intensive care unit. Ileostomy function was noted on postoperative day (POD) 2. He underwent percutaneous tracheostomy on POD 6, and tube feeds were initiated on POD 7. Despite this, he continued to have worsened respiratory failure, developed gram-negative bacteremia, and exhibited persistent hemodynamic instability. A CT scan to evaluate for intra-abdominal abscesses or leak had been recommended, but was unable to be completed due to his hemodynamic instability. Ultimately, the family decided to transition to comfort-focused measures, and he died on POD 12.
Pathologic analysis of the resected bowel segments demonstrated disseminated angioinvasive fungal infection with transmural ischemic necrosis. This confirmed the diagnosis of intestinal necrosis secondary to disseminated fungal invasion, likely secondary to angio-IA.
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives. However, verbal consent with a witness was obtained.
Discussion
Key findings
We present a rare case of perforated bowel secondary to angio-IA in a patient who underwent bilateral LT.
Strengths and limitations
This case meaningfully contributes to the understanding of angio-IA and demonstrates that bowel perforation is an extremely serious complication of this disease. We report for the first time the manifestation of bowel perforation secondary to IA in the setting of LT. As a case report, the major limitation of this study is an inherently small sample size. Furthermore, as the patient died secondary to persistent respiratory failure despite early, aggressive surgical intervention, we cannot comment on long-term gastrointestinal recovery after angioinvasive disease or the risk of other sites of perforation due to multifocal vasa recta embolization. Both issues may significantly impact the clinical course of other patients who develop bowel perforation after IA.
Comparison with similar research
Most reported cases of angio-IA are in immunocompromised patients with hematologic malignancies or after solid-organ transplantation (4). Bowel perforation secondary to angioinvasive disease is extremely uncommon and thus far has only been identified in the setting of hematologic malignancies and ongoing chemotherapy. To our knowledge, bowel perforation due to angioinvasive IA after LT has not been previously reported (5,6).
Explanations of findings
Infections are common after any solid-organ transplant and are a leading cause of post-LT morbidity and mortality within the first year after transplantation (7-9). While most opportunistic infections are viral or bacterial, fungal infections are prevalent in 15–35% of patients after LT (1,2). Aspergillus and Candida species are most frequently implicated and manifest within the first 6 to 12 months after transplant (4). Those who develop IA infection rarely have extrapulmonary sites of infection (10). In a review of 78 cases of post-LT IA cases, only 5% had extrapulmonary dissemination (limited to osteomyelitis, endophthalmitis, and a retroperitoneal abscess) (10). Expectedly, IA was associated with a high mortality rate (52%), and late-onset infection and single-LT recipients were at significantly higher risk (10).
Implications and actions needed
Early diagnosis and treatment of IA are critical to survival (11). Clinical presentation includes persistent fever, cough, hemoptysis, and pleuritic chest pain. CT scans may reveal nodules, cavitary lesions, or halo signs indicative of IA. Galactomannan levels in the serum and BAL-obtained specimens, sputum and blood cultures, and histopathology of infected tissues aid in expedient diagnosis (4). When suspected, voriconazole is the first-line treatment for IA along with reduction of immunosuppression (3,12). In cases of severe IA, echinocandins are often used in combination with voriconazole (3,4). In the setting of localized pulmonary angioinvasive disease, surgical resection of necrotic lung tissue may be necessary to control the infection (6). Pulmonary failure due to overwhelming infection is not uncommon, and patients are at high risk for multiorgan system failure (3,12).
A rare, devastating complication of IA is angioinvasive disease (13). Classical manifestations of intestinal perforation include peritonitis and leukocytosis, which may be absent or depressed in immunocompromised LT patients (14,15). A high index of suspicion to expedite workup for new-onset abdominal pain in immunocompromised patients is vital (8). When ischemia and/or bowel perforation are diagnosed or strongly suspected, early laparotomy is the mainstay of treatment (8,9,14,15). As patients with disseminated fungal infections are often in septic shock with high vasopressor requirements, we recommend early resection and delayed reconstruction whenever possible to mitigate the downstream complications of anastomotic leak or breakdown. In this case, we faced multifocal perforations. We assessed that he would not tolerate a high-output proximal jejunostomy (40 cm from the ligament of Treitz) and would likely not tolerate repeat operative intervention. We elected to resect the necrotic jejunal segment and perform a primary jejunojejunal anastomosis. We did not reconstruct after performing a right hemicolectomy, and instead fashioned an end ileostomy with transverse colon mucus fistula.
Conclusions
IA with dissemination to the intestines, causing focal necrosis, is extremely rare. It is important to diagnose and treat IA early to help prevent further progression. Immunosuppressed patients who develop new-onset abdominal pain need to be worked up promptly to rule out significant intraperitoneal pathology. Early operative intervention is crucial, and inclusive consideration for patient factors, technical factors, and anticipated postoperative recovery should guide intraoperative management.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-221/rc
Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-221/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-221/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives. However, verbal consent with a witness was obtained.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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Cite this article as: Kerlee K, Ehab J, Watson J, Weill P, Chandra R, Keshavamurthy S, Mehta A, Shoultz TH. Multifocal bowel perforation from angioinvasive aspergillosis after bilateral lung transplantation: a case report and review of the literature. AME Case Rep 2025;9:91.
