Introduction
Phlegmonous gastritis (PG) is a rare, rapidly progressive, and life-threatening bacterial infectious disease characterized by a thickened gastric wall ( 1 ). The disease typically presents with non-specific symptoms, such as fever, abdominal pain, nausea, and vomiting, making an early diagnosis challenging. Computed tomography (CT) and endoscopy play crucial roles in the accurate diagnosis of PG. Management of PG primarily involves antibiotic treatment, whereas surgical intervention may be required in cases with severe complications. A few sporadic cases have been reported in patients with hematologic diseases; however, there are no reports of the development of PG after transplantation. We herein report a case of PG that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Case Report
A 17-year-old male patient initially diagnosed with very severe aplastic anemia received immunosuppressive therapy with thymoglobulin, cyclosporine, and eltrombopag, but remained transfusion-dependent after 8 months. Therefore, the patient underwent allogeneic bone marrow transplantation from an human leukocyte antigen (HLA) 1 allele-mismatched unrelated donor with conditioning using fludarabine, cyclophosphamide, total body irradiation (2 Gy), and low-dose thymoglobulin (2.5 mg/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-term methotrexate, and the patient did not develop either acute or chronic GVHD. Two months after transplantation, the patient developed severe thrombotic microangiopathy, and tacrolimus was changed to cyclosporine (30 mg/day), mycophenolate mofetil (1,500 mg/day), and prednisone (20 mg/day).
Seven months after transplantation, the patient was admitted with sudden severe abdominal pain. At this time, his hematological recovery progressed sufficiently, and regular blood transfusions and granulocyte colony-stimulating factor were discontinued. The immunosuppressive regimen was unchanged. Regarding immune reconstitution, his immunoglobulin G level was supported by regular immunoglobulin infusions (approximately 400 mg/dL), and his CD4 count was 89 /μL. He was taking posaconazole and acyclovir as prophylaxis against infection. On admission, he developed fever, and a physical examination revealed significant upper abdominal tenderness. The patient had no history of raw food intake. Blood tests showed a normal white blood cell count (2,300 /μL) and C-reactive protein (CRP) level (0.02 mg/dL) but elevated procalcitonin (PCT) level (＞100 ng/mL). In addition, blood PCR tests for varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus were negative. Contrast-enhanced abdominal CT revealed a diffusely thickened gastric wall with mucosal enhancement ( Figure ), leading to a diagnosis of PG. Abscesses or perforations were not detected.
The patient's clinical course is shown in Figure . He was continued on a regular proton pump inhibitor and infection prophylaxis with posaconazole and acyclovir. Immunosuppressive therapy, as previously mentioned, included mycophenolate mofetil and prednisone, whereas cyclosporine was discontinued because of elevated creatinine levels. Piperacillin/tazobactam (PIPC/TAZ) and clindamycin were immediately initiated with bowel rest. Despite these treatments, the patient developed septic shock with respiratory and renal failure, requiring multiple vasopressors, intubation, ventilation management, and extracorporeal ultrafiltration (ECUM). The day after admission, PIPC/TAZ was switched to meropenem, and daptomycin was added. On day 3 of admission, esophagogastroduodenoscopy (EGD) revealed significant edema with exudate without ulceration or abscess, consistent with PG ( Figure ). The gastric biopsy specimen showed non-specific inflammatory findings, including erosion, with no evidence of cytomegalovirus.
The patient's general condition gradually improved, leading to extubation on day 5. Subsequently, vasopressors and ECUM were discontinued on day 6, and feeding resumed on day 9. After 2 weeks of antibiotic treatment, a CT scan showed improvement of the diffuse gastric wall edema ( Figure ), and he was successfully discharged. The causative organism could not be identified by blood culture, including those obtained before and during antibiotic treatment, gastric fluid culture, or gastric biopsy specimen culture obtained during EGD.
Discussion
To the best of our knowledge, based on a comprehensive literature review, this is the first case of PG following allo-HSCT. We report a case of PG that developed seven months after allo-HSCT for severe aplastic anemia, which improved with antibiotic treatment.
PG is an acute pyogenic infection of the stomach, which can arise from localized or disseminated infections. The pathophysiological process is mainly caused by bacterial invasion of the submucosa, where the infection spreads and diffuses into the mucosa and serous membranes ( 2 ). This invasion leads to a severe inflammatory response, resulting in rapid progression. PG is classified into two types based on the extent of the lesion: the localized type, where the infection is confined to a specific part of the stomach, and the diffuse type, where the entire stomach is affected ( 2 ).
The mortality rate of PG ranges from 42 to 92%, and is particularly high in cases with diffuse gastric infiltration ( 2 , 3 ). The initial symptoms of PG include non-specific abdominal pain, nausea, vomiting, and fever. Known causative major risk factors include mucosal injury such as chronic gastritis, ulcer disease, and an immunocompromised state. Other reported risk factors include malnutrition and malignancy ( 2 , 4 ). A few sporadic cases have been reported in patients with hematologic malignancies, including acute myeloid or lymphoblastic leukemia, and multiple myeloma. Chemotherapy, including cytotoxic agents, the use of corticosteroids, and a neutropenic state, may contribute to the development of PG. In this case, the patient had no gastrointestinal abnormalities on EGD before allo-HSCT and no history of gastrointestinal problems. The patient was treated with multiple immunosuppressive drugs and had delayed immune recovery, which could have contributed to the risk of PG.
Regarding the diagnosis, CT is useful and typically reveals a significantly thickened hypodense gastric wall. EGD or endoscopic ultrasound may be more useful in visualizing the extent of gastric wall thickening, detecting fibrinopurulent exudates and edematous mucosa, and identifying the causative organism using culture tests or biopsy ( 4 ). However, their use may be limited by the patient's overall condition. In addition, in this case, the patient's PCT levels increased significantly earlier than his CRP levels, which may reflect the more rapid elevation of PCT levels in response to bacterial infection.
The most common pathogen is Streptococcus spp., which accounts for approximately 70% of PG cases ( 2 - 4 ). Other bacteria include Staphylococcus spp., Entereobacter spp., Eschericbia coli , and Bacillus cereus ( 1 , 2 , 9 ). However, a single causative organism is not always identified, and up to one-third of PG cases are caused by multiple organisms ( 2 ). Therefore, broad-spectrum antibiotics are essential for the initial treatment. In addition, surgical resection decreases the mortality rate, particularly in cases with diffuse infiltration ( 2 ); however, it requires careful consideration because of the highly invasive nature of the procedure, and it is mainly reserved for cases with local complications such as perforation ( 7 ). Several patients with hematologic malignancies have recovered with antibiotics alone ( 1 , 5 , 6 , 8 ); therefore, prompt comprehensive treatment, including hemodynamic management and nutritional support, may help overcome the poor prognosis of PG. In this case, total gastrectomy was considered at the time of the diagnosis but was not performed because of its invasiveness and potential impact on the quality of life. Because EGD showed no significant necrosis or ischemia, and his condition improved with supportive care, conservative management was continued.
The optimal duration of antibiotic treatment for PG has not been established, and there is no consensus regarding the need for prolonged treatment after clinical improvement ( 4 ). Several reports have suggested that a 10-14 day course is sufficient, with no documented recurrences ( 4 - 6 ). Symptom resolution and imaging improvements are important considerations in determining the duration of treatment.
Bacterial infections after allo-HSCT can occasionally be fatal even long after engraftment. In our case, the patient was continuously treated with immunosuppressive drugs, including corticosteroids, and an inadequate immune recovery after allo-HSCT may have contributed to the severity of the condition. Given the high mortality rate, when a patient presents with severe abdominal pain and characteristic gastric wall thickening on CT, physicians should consider PG as a differential diagnosis and initiate immediate antibiotic intervention.
Informed consent was obtained from the patient for publication of this case report or from their legal guardians or wards.
The authors state that they have no Conflict of Interest (COI).
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