Acute lymphoblastic leukemia with pneumatosis cystoides intestinalis after hematopoietic stem cell transplantation: a case report

Abstract

Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by air accumulation within the subserosa or submucosa of the gastrointestinal wall. We herein report a case involving a woman in her early 30s who developed PCI after undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. The patient had a history of multiple COVID-19 infections. Imaging revealed extensive pneumoperitoneum and mesenteric emphysema; nevertheless, the patient remained clinically stable with a benign abdominal examination. She eventually recovered after 1 month of conservative treatment. We believe the PCI in this case had a multifactorial etiology, potentially involving both HSCT and COVID-19. Raising awareness of PCI may help avoid unnecessary surgical interventions and associated morbidity.

Introduction

Pneumatosis cystoides intestinalis (PCI) is a relatively rare condition characterized by multiple gas-filled cysts in the subserosa or submucosa of the intestinal wall, typically involving the colon and small intestine. ¹ PCI often lacks specific clinical manifestations and is usually asymptomatic, making it prone to misdiagnosis or underdiagnosis, particularly when detected incidentally during imaging examinations. Although PCI is generally benign with a favorable prognosis, severe cases can lead to complications such as intestinal obstruction, bleeding, perforation, and septic shock. ² These complications may be fatal if not treated aggressively.

We recently treated a patient who had undergone allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia and had repeatedly tested positive for COVID-19. PCI was diagnosed based on computed tomography (CT) findings and confirmed through multidisciplinary discussions. Following conservative treatment, the patient’s intestinal gas resolved, and she was discharged in an improved condition.

Case presentation

A woman in her early 30s presented with a 3-day history of fever. She had been diagnosed with acute lymphoblastic leukemia more than 1 year previously and had received various chemotherapy regimens combined with immunotherapy agents. She subsequently underwent allogeneic HSCT followed by the administration of immunosuppressive drugs to prevent graft-versus-host disease (GVHD). After discharge, the patient repeatedly tested positive for COVID-19 and underwent several courses of antiviral medications.

On this occasion, the patient had developed a fever and sought treatment at another hospital, where she again tested positive for COVID-19. A chest CT scan revealed new nodules with cavity formation in the upper lobes of both lungs, indicating potential infectious lesions. Additionally, a CT scan revealed multiple gas shadows in the mesentery and retroperitoneum, as well as gas accumulations in the colon wall, possibly due to ischemic infection. She was then referred to our hospital for further management.

Upon admission, enhanced CT angiography of the small intestinal arteries showed multiple gas accumulations around the colorectal wall and retroperitoneum (Figure 1), along with thickening and strengthening of the distal ileum wall and dilation of the intestinal cavity. Physical examination revealed a soft abdomen with mild tenderness but no rebound pain or muscle tension. Given the possibility of intestinal perforation, an urgent multidisciplinary consultation was held to discuss a potential diagnosis of PCI. With the patient’s consent, we implemented various conservative measures, including fasting, gastrointestinal decompression, antibiotics, and component blood transfusion.

Figure 1.

Computed tomography angiography scan at admission. The red arrows show scattered gas accumulation around the colorectal wall and retroperitoneum.

A follow-up CT scan 1 week later showed a significant reduction in abdominal gas absorption compared with the previous imaging findings (Figure 2). A further total abdominal CT scan 2 weeks later revealed no free gas in the abdominal cavity. The patient’s condition continued to steadily improve, and she was discharged from the hospital 1 month later.

Figure 2.

Computed tomography scan showing less scattered gas compared with the previous results.

Discussion

PCI is a rare disease with an incidence of approximately 0.03%. ³ It is highly suspected in patients with intestinal pneumoperitoneum but without acute abdominal manifestations. PCI can be classified as primary or secondary, accounting for approximately 15% and 85% of cases, respectively. ⁴

The exact etiology and pathogenesis of PCI are unknown. Various clinical factors have been implicated, ⁵ including gastrointestinal disorders, chronic obstructive pulmonary disease, infection by gas-producing bacteria, and the use of α-glucosidase inhibitors. However, no single explanation can account for all cases of PCI.

PCI can occur in patients with hematological diseases after HSCT, especially in patients with cutaneous or gastrointestinal GVHD.^6,7 Previous studies^8,9 have demonstrated a significantly higher incidence of PCI in children treated with allogeneic HSCT and in children with GVHD. A study by Wallace et al. ¹⁰ involving 990 children with HSCT showed that the systemic use of steroid hormones was associated with an elevated incidence of PCI. The most likely reason for this is the development of neutropenia following cytotoxic chemotherapy. The gas released by the proliferation of intestinal bacteria increases the intestinal pressure and breaks down the intestinal mucosal barrier, allowing the gases to gradually accumulate in the submucosal area. Myeloablative chemotherapy regimens for HSCT and immunosuppressive prophylaxis for GVHD result in prolonged neutropenia, which is considered a risk factor for the development of PCI.

A few patients have developed PCI after receiving molecularly targeted therapies, including adult patients treated with bevacizumab, sunitinib, and gefitinib. ¹¹ Kim et al. ¹² reported a case of an 11-year-old patient with relapsed precursor B-cell acute lymphoblastic leukemia who developed PCI after treatment with blinatumomab.

In the current case, the patient had undergone chemotherapy and immunotherapy within the past 6 months and had received immunosuppressive agents for GVHD prophylaxis following allogeneic HSCT. These factors are important contributors to the development of PCI. Furthermore, the patient had repeatedly tested positive for COVID-19 after transplantation. However, reports of PCI occurring in combination with HSCT or COVID-19 are limited.

Wong et al. ¹³ revealed a mortality rate of up to 77.8% among nine patients with COVID-19 infection combined with PCI. Following a diagnosis of PCI, most patients experienced worsening of their condition, such as increased vasopressin requirements and acute kidney injury. The mean time to death after PCI diagnosis was only 6.4 days, suggesting that PCI may be an unfavorable prognostic indicator in patients with COVID-19. Previous studies have indicated that COVID-19 may invade gastrointestinal cells, disrupt the integrity of the intestinal wall, and disturb normal gut flora, resulting in increased mucosal permeability and gas dissection into the bowel wall. ¹⁴

The clinical manifestations and laboratory tests associated with PCI are nonspecific. ¹⁵ CT scans are considered particularly valuable for diagnosing PCI, ¹⁶ but laparoscopy or surgical exploration may be necessary when noninvasive tests fail to confirm the diagnosis.

To date, there are no clear guidelines or expert consensus on the management of PCI, and its prognosis depends on the severity of the condition and associated comorbidities. Asymptomatic or mildly symptomatic patients generally do not require specific treatment, with 50% improving spontaneously and up to 70% experiencing symptom relief with nonsurgical interventions. ⁴ Conservative treatment options include hyperbaric oxygen therapy to increase oxygen partial pressure and facilitate gas diffusion from cysts into the bloodstream as well as gastrointestinal decompression to relieve symptoms. Antibiotics may also be used to inhibit the growth of gas-producing bacteria in the intestines. However, surgical resection of the affected bowel segments is necessary in patients with significant abdominal symptoms or acute complications such as severe recurrent bloody stools, intestinal obstruction, torsion, or necrosis. ⁴ Previous research has shown that low pH levels (<7.3), reduced bicarbonate levels (<20 mEq/L), elevated lactate levels (>2 mmol/L), increased amylase levels (>200 U/L), and the presence of portal gas are insufficient predictors of intestinal necrosis or mortality in patients with PCI. ¹⁷

Conclusion

PCI is a rare disease with an unknown etiology and pathogenesis. Treatment should be tailored to the patient’s clinical symptoms and diagnostic test results. This case highlights the importance of raising awareness about PCI and provides valuable information regarding its potential etiology and more rational therapeutic approaches. In patients with hematologic diseases, PCI may be associated with prolonged immunodeficiency due to chemotherapy and other treatments, possibly in combination with various pathogenic microbial infections. Clinical awareness of PCI is crucial to avoid unnecessary surgical interventions. Case reports play an essential role in sharing unique clinical experiences, and further research is needed to develop better diagnostic techniques and treatment regimens.

The reporting of this study conforms to CARE guidelines. ¹⁸