Sugita, Mayumi*; Mori, Tetsuya*; Shimada, Hiroyuki*; Shimasaki, Noriko*; Morikawa, Yasuhide†; Takahashi, Takao*
Departments of *Pediatrics and †Surgery, Keio University School of Medicine, Tokyo, Japan
Address correspondence and reprint requests to Dr. Tetsuya Mori, Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160–8582, Japan (e-mail: firstname.lastname@example.org).
Pneumatosis cystoides intestinalis (PCI) is a rare complication after hematopoietic stem cell transplantation that is characterized by multiple intramural gas collections in the bowel wall (1,2). PCI also has been associated with chronic obstructive lung disease, collagen diseases, necrotizing enterocolitis in premature infants, intestinal infections, ischemic bowel disorders, and immunosuppressive drug therapy (3). The pathogenesis of PCI is unknown. Mechanical, bacterial, and mucosal damage of the bowel wall are the most commonly accepted causes. Patients with PCI either have no symptoms or present with pain, tenderness, diarrhea, vomiting, and flatulence. PCI often resolves spontaneously with conservative therapy such as bowel rest, oxygen supplement, or antibodies. However, in some cases complications such as intestinal perforation, cecal volvulus, ileus, or intussusception may occur and may require surgery (3). A few reports have described PCI in cases of childhood intussusception (4–6). We report a 6-year-old Japanese girl with colocolic intussusception and PCI which occurred 10 months after cord blood stem cell transplantation.
A 5-year-old girl with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in the blastic phase received a cord blood stem cell transplantation (CBSCT) from a 5/6 HLA-antigen matched unrelated donor. Cytarabine (3,000 mg/m2 twice a day intravenously for 4 days) and total body irradiation (12 Gy) were used for conditioning, and a short-course methotrexate and cyclosporine therapy was given for graft-versus-host disease (GVHD) prophylaxis. Her post-transplant course was initially complicated by acute GVHD involving the skin, but her gastrointestinal system was unaffected. Although prednisolone and tacrolimus seemed to be effective for treating the GVHD, skin GVHD progressed to grade IV disease on day 53, prompting the use of pulse therapy with methylprednisolone and rabbit antithymocyte globulin. Acute GVHD improved 2 months after onset. The treatment was subsequently modified and the child was maintained on lower dose oral prednisolone and cyclosporine. Three months after the CBSCT, the patient developed extensive chronic GVHD affecting the skin and lungs. The prednisolone dose was increased to treat her respiratory distress. Lung GVHD was stabilized by this treatment, but the patient's oxygen saturation dropped to 90% without oxygen supplementation. She also experienced recurrent respiratory infections caused by Pseudomonas aeruginosa. The patient's CML was in complete remission 2 months after the CBSCT.
Four months after the transplantation, a routine plain abdominal x-ray disclosed multiple pockets of air suggesting the presence of PCI (Fig. 1A). The patient had no serious abdominal symptoms at the time, and no additional diagnostic examinations to confirm the diagnosis of PCI or treatments were performed. Five months after transplantation, the patient developed abdominal pain and distension. PCI was noted on a computed tomography (CT) scan of the abdomen showing air cysts in the wall of the colon. The daily dose of prednisolone was reduced by one half and oxygen supplementation and antibiotics were started to treat the PCI. Symptoms resolved within 10 days, although a few pockets of air remained visible on an abdominal plain film. Ten months after transplantation, the patient developed severe and intermittent abdominal pain after defecation. No history of bloody stool was present. She had no fever or vomiting. An abdominal examination revealed a soft and mobile mass in the right lower quadrant. A plain film abdominal x-ray revealed an “onion-like” gas lesion on the right side (Fig. 1B). An ultrasound examination did not show any signs of intussusception. However, a contrast CT scan optimized to air revealed a colo-colonic intussusception of the ascending colon with air in the bowel wall (Fig. 2). The intussusception was reduced by a barium enema. The patient's abdominal symptoms disappeared after reduction of the intussusception. The multiple air pockets visible on the abdominal film slowly regressed and were no longer detectable 5 months later. The patient had no subsequent problems related to PCI despite the continued use of immunosuppressive therapy for chronic GVHD.
We report here a case of intussusception associated with PCI after CBSCT. Although the causes of most childhood intussusceptions are unknown, lead points for intussusception such as an inverted appendiceal stump, Meckel diverticulum, intestinal polyp, duplication, or lymphosarcoma, are found in 10% to 15% of patients (7). A few reports have described childhood intussusceptions associated with PCI. One report described an intussusception associated with idiopathic PCI (4). Another described a patient with Crohn disease (5). A third report described an infant with Peters' anomaly who had been treated with oral steroid therapy (6). To our knowledge, this is the first description of intussusception associated with PCI after hematopoietic stem cell transplantation.
PCI is rarely noted in the reports of fatalities in patients receiving hematopoietic stem cell transplantation and immunosuppression (8,9). PCI has been reported to occur during immunosuppression for GVHD, and during infections in stem cell transplant patients (8–10). In the current case, the patient had severe acute GVHD of the skin and subsequent chronic GVHD of the skin and lungs. Although the gastrointestinal system seemed intact, no evaluation was performed at the time; thus, we cannot be sure that there may not have been some asymptomatic GVHD of the gastrointestinal system. No organisms associated with intestinal infection were detected by stool culture, serologic tests, or polymerase chain reaction methods. The prolonged use of immunosuppressive drugs, including prednisolone, and the chronic lung disease caused by chronic GVHD of lungs were obvious risk factors for PCI in the current case. However, the pathogenesis of PCI in this patient remains a matter of speculation.
The patient experienced intussusception 6 months after the first obvservation of PCI. Although the initial abdominal pain associated with PCI resolved with conservative treatment, multiple air pockets in the bowel wall were visible on plain films of the abdomen until the onset of intussusception. The risk factors for PCI, such as the use of immunosuppressive drugs and the existence of the chronic lung disease, also remained. Because pneumatosis can act as the lead point for an intussusception, any patient who experiences PCI secondary to a primary complication or disease should be considered to be at risk for intussusception.
Ultrasonography is a useful and noninvasive procedure for the diagnosis and treatment of intussusception (7). Ultrasound examinations, as well as the clinical history and physical findings, provide useful diagnostic information. In addition, intussusceptions can be reduced under ultrasonographic guidance in some cases. In the current case, the patient's clinical history and physical findings, the sudden onset and intermittent abdominal pain, and the abdominal mass were compatible with a diagnosis of intussusception. The ultrasound examination did not reveal the typical findings of an intussusception. The CT scan revealed the colo-colonic intussusception. The air in the bowel wall from the PCI might have prevented detection of the intussusception by ultrasonography. Whether sufficient information can be obtained from abdominal ultrasound examinations in patients with PCI remains unknown. In the current case, a CT scan was useful for diagnosing the intussusception associated with PCI. Our experience suggests that if a patient with PCI has a clinical history and physical findings suggestive of intussusception a CT scan should be considered as a potentially useful diagnostic procedure.
The authors thank the medical and nursing staff of the 3-N ward at Keio University Hospital for their dedicated care of this patient.
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