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Case Report Pneumocystis Cystoides Intestinalis with Pneumoperitoneum and Pneumoretroperitoneum in a Patient with Extensive Chronic Graft- Versus-Host Disease

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Case Report Pneumocystis Cystoides Intestinalis with Pneumoperitoneum and Pneumoretroperitoneum in a Patient with Extensive Chronic Graft- Versus-Host Disease Bone Marrow Transplantation, (1999) 24, 331–333 1999 Stockton Press All rights reserved 0268–3369/99 $12.00 http://www.stockton-press.co.uk/bmt Case report Pneumocystis cystoides intestinalis with pneumoperitoneum and pneumoretroperitoneum in a patient with extensive chronic graft- versus-host disease A Schulenburg1, C Herold2, E Eisenhuber2, G Oberhuber3, B Volc-Platzer4, HT Greinix1, E Reiter1, F Keil1 and P Kalhs1 1Department of Medicine I, Bone Marrow Transplantation Unit; Departments of 2Radiology, 3Pathology, and 4Dermatology, University of Vienna, Austria Summary: Case report Pneumatosis cystoides intestinalis is a rare finding of A 50-year-old Caucasian male who was diagnosed with intramural gasfilled cysts in the bowel wall and some- myelodysplasia, subtype chronic myelomonocytic leuke- times free air in the abdomen. A few conditions are mia, underwent BMT after conditioning with cyclophos- reported to cause this disease, one of them being phamide and fractionated total body irradiation (12 Gy) at immunosuppression. We describe a 50-year-old Cauca- our institution. He received 3.2 × 108 nucleated bone mar- sian male with extensive chronic graft-versus-host dis- row cells/kg body weight from his HLA-identical sibling. ease (GVHD) of the gut and skin who developed PCI GVHD prophylaxis consisted of cyclosporin A and a short with pneumoperitoneum and pneumoretroperitoneum. course of methotrexate according to the Seattle protocol.5 To our knowledge, this is the first report of PCI occur- During aplasia, he experienced fever and Staphylococcus ring in a patient with active chronic GVHD which aureus bacteremia. On day +16 the patient developed acute resolved spontaneously. GVHD grade II of the skin that resolved with corticostero- Keywords: Pneumatosis cystoides intestinalis; chronic ids (2 mg/kg/day). Two months after transplantation, he graft-versus-host disease received pre-emptive gancyclovir therapy because of cyto- megalovirus (CMV) reactivation. Five weeks later exten- sive GVHD of skin required treatment with steroids. Seven months after BMT, herpes encephalitis was diagnosed Pneumatosis cystoides intestinalis (PCI) is a rare disorder which resolved with acyclovir therapy. Another course of consisting of multiple intramural gas collections in the pre-emptive gancyclovir for CMV reactivation was also bowel wall. Patients are either asymptomatic or present administered. with diarrhea, pain, tenderness, vomiting and flatulence. One month later the patient presented with diarrhea, The pathogenesis of this abnormality is still unknown. It slight diffuse abdominal pain and flatulence. Parenteral is associated with chronic obstructive pulmonary disease, nutrition and electrolyte and fluid infusions were started. necrotizing enterocolitis in premature infants, intestinal Colonoscopy showed signs of diffuse mucosal irritation. On obstruction, ischemic bowel disorders, bacterial and viral histological examination biopsy specimens from two 1 2 infections and drug therapy. In contrast to other gastro- regions of the colon showed individual crypt cell necrosis, intestinal diseases PCI is a benign finding and usually crypt abscesses with cell flattening and degeneration con- resolves spontaneously. It responds well to conservative sistent with GVHD grade II.6 CMV infection was ruled out therapy. Rarely, PCI is observed after allogeneic bone mar- by in situ hybridization. Stool cultures revealed no bac- row transplantation (BMT) where fatalities have been terial, viral or fungal infection. Steroids were added to the 3,4 reported in patients receiving immunosuppression. We continuous immunosuppressive treatment with cyclosporin. describe a patient with myelodysplastic syndrome given an The latter was replaced by FK506 since no clinical allogeneic marrow graft. He experienced extensive chronic improvement with cyclosporin was seen after 2 weeks. A graft-versus-host disease (GVHD) and developed PCI 8 few days later the patient experienced relief of pain and a months after BMT. normalization of bowel habit. On routine chest X-ray on day +292, a large amount of free air between the liver and the right hemidiaphragm was seen (Figure 1). A contrast enhanced computed tomography scan of the abdomen dem- ¨ onstrated intramural gas collections, free intra- and retro- Correspondence: Dr A Schulenburg, AKH Vienna, Universitaetsklinik fur Innere Medizin I, Knochenmarktransplantation, Waehringer Guertel 18– peritoneal air and abdominal distension (Figures 2 and 3). 20, A-1090 Vienna, Austria The patient was switched to oral nutrition and steroids were Received 7 December 1998; accepted 11 March 1999 reduced. His symptoms resolved within 10 days and he was PCI in a patient with GVHD A Schulenburg et al 332 Figure 3 Contrast-enhanced CT of the abdomen performed on day +293 after transplantation at the level of the pelvis demonstrates extensive intra- mural gas collections in the wall of the sigmoid colon (arrows). Figure 1 Plain abdominal radiograph performed on day +292 after trans- plantation showing intramural gas collections (arrows) suggestive for dif- Figure 4 CT of the abdomen performed on day +410 after transplan- fuse Pneumatosis cystoides intestinalis; in addition, free retroperitoneal tation at the level of the renal hilum shows no evidence of Pneumatosis gas is present. intestinalis, pneumoperitoneum or pneumoretroperitoneum. discharged. Periodic X-rays of the abdomen in the out- patient department showed continuing resorption of free air. A computed tomography scan of the abdomen showed no more free air or intramural gas cysts 4 months after the diagnosis of PCI (Figure 4). At present the patient is in complete hematological remission with clinical signs of chronic limited GVHD 18 months after BMT. Discussion PCI is characterized by multiple mucosal, submucosal or subserosal gas collections in the bowel wall, with or with- out free air in the abdomen.7,8 PCI has been reported in several clinical settings including necrotizing enterocolitis in premature infants, obstructive pulmonary disease, + Figure 2 Contrast-enhanced CT of the abdomen performed on day 293 immunosuppression9–12 or infections, and has a benign after transplantation at the level of the renal hila reveals multiple gas- 3,4,14 filled cysts and streaky air collections (arrows) in the bowel wall of the course. After BMT, the occurrence of PCI has been transverse colon (image displays window settings optimized to demon- repeatedly associated with acute GVHD, infections or strate air). Additionally, small amounts of free intra- and retroperitoneal immunosuppressive medication. In these patients fatal out- gas are present, notably behind the liver (open arrows). comes have been observed. We report a severely immuno- PCI in a patient with GVHD A Schulenburg et al 333 compromised patient with extensive chronic GVHD who intestinalis with free air mimicking intestinal perforation in a experienced multiple viral infections and episodes of graft- bone marrow transplant patient. Bone Marrow Transplant versus-host disease after BMT and had PCI with an 1994; 14: 323–326. uneventful course. In this patient neither bacterial nor viral 4 Day DL, Ramsay NKC, Letourneau JG. Pneumatosis intesti- infection could be detected at the onset of gastrointestinal nalis after bone marrow transplantation. Am J Roentgenol 1998; 151: 85–87. symptoms. Gastrointestinal perforation was excluded. PCI 5 Storb R, Deeg HJ, Pepe M et al. Methotrexate and cyclospor- was asymptomatic and resolved spontaneously over time. ine versus cyclosporine alone for prophylaxis of graft-versus- To our knowledge this is the first report of the occurrence host disease in patients given HLA-identical marrow grafts for of PCI in association with active chronic GVHD. The leukemia: long-term follow-up of a controlled trial. Blood pathogenesis of PCI in this case remains speculative. 1989; 73: 1729–1734. Patients with chronic GVHD of the gut have mucosal dam- 6 Bombi JA, Palou J, Bruguera M et al. Pathology of bone mar- age in the bowel allowing intraluminal air under pressure row transplantation. Semin Diagn Pathol 1992; 9: 220–231. to diffuse into the bowel wall. Peyer’s patches could also 7 Boerner M, Fried B, Warshauer DM, Isaacs K. Pneumatosis be a locus of minor resistance due to decreased cellularity, intestinalis. Dig Dis Sci 1996; 41: 2272–2285. and allow the entry of air into the bowel wall.5 It has also 8 Heng Y, Schuffler MD, Haggitt RC, Rohrmann CA. Pneuma- tosis intestinalis: a review. Am J Gastroenterol 1995; 90: been suggested that gas-producing bacteria could be the 1747–1758. cause of PCI. 9 Kopp AF, Gronewaller AE, Laniado M. Pneumatosis cys- After intestinal perforation has been radiologically toides intestinalis with pneumoperitoneum and pneumoretro- excluded, conservative treatment13 of PCI is advisable peritoneum following chemotherapy. Abdom Imaging 1997; including parenteral nutrition and a diet of low-flatulence- 22: 395–397. producing carbohydrates. In cases of concomitant infection 10 Gagliardi G, Thompson IW, Hershman MJ et al. Pneumatosis appropriate antimicrobial therapy is beneficial in these coli: a proposed pathogenesis and review of the literature. Int patients. J Colorectal Dis 1996; 11: 111–118. 11 Takanashi M, Hibi S, Todo S et al. Pneumatosis cystoides intestinalis with abdominal free air. Pediatr Hematol Oncol 1998; 15: 81–84. References 12 Zuber M. Freie Luft im Abdomen nach Zytostatikatherapie. Med Klin 1997; 92: 654. 1 Mannes GP, de Boor WJ, van der Jagt EJ et al. Pneumatosis 13 Scheidler J, Stabler A, Kleber G, Neidhardt D. Computed tom- intestinalis and active cytomegaloviral infection after lung ography in Pneumatosis intestinalis: differential diagnosis and transplantation. Chest 1994; 105: 929–930. therapeutic consequences. Abdo-Imaging 1995; 20: 523–528. 2 Williams NM, Watkin DF. Spontaneous pneumoperitoneum 14 de Magelhaes-Silverman M, Simpson J, Ball E. Pneumoperi- and other nonsurgical causes of intraperitoneal free gas. Post- toneum without peritonitis after allogeneic peripheral blood grad Med J 1997; 73: 531–537. stem cell transplantation. Bone Marrow Transplant 1998; 21: 3 Lipton J, Patterson B, Mustard R, Tejpar I et al. Pneumatosis 1153–1154..
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