m_sajr_v9_n3_a9.pdf 29 SA JOURNAL OF RADIOLOGY • October 2005 Abstract Neutropenic enterocolitis is a lethal, necro- tising inflammation of the caecum and contiguous bowel, found in immunocom- promised, neutropenic patients. A high index of clinical suspicion coupled with appropriate imaging modalities allows ear- lier diagnosis and can expedite the manage- ment of these severely ill patients. We describe the clinico-radiological features of this condition in the following case report, as well as a brief management approach to this rare, but increasingly recognised con- dition. Case report A 23-year-old female patient was referred from a peripheral hospital with a 1-week history of fever and frank rectal bleeding. On examination, the patient was pyrexial and pale. Numerous petechial haemorrhages were present on both fore- arms and shoulders. Shotty cervical and axillary lymph nodes, 4 cm hepatomegaly and 2 cm splenomegaly were palpated. The abdomen was mildly tender but there was no peritonism. Fundoscopy revealed bilat- eral retinal haemorrhages. Her neurological assessment was unremarkable. An initial chest radiograph was normal. Full blood count, on admission, revealed a haemoglobin level of 3.3 g/dl, a white cell count of 29.3 × 109/l with severe neutropenia (1%), predominance of blast cells (94%) and thrombocytopenia with a platelet count of 9 × 109/l. Blood cultures, on admission, were negative. Bone marrow aspirate and trephine biopsy confirmed the diagnosis of acute lymphoblastic leukaemia. On immunophe- notyping, the leukaemia cells were CD19+ (68.7%), CD10+ (83.8%) and CD34+ (86.5%) confirming cALLa+ acute lym- phoblastic leukaemia. The absolute CD4 count was 93 cells/µl. The patient was transfused with packed red cells and platelets, and intravenous antibiotics (amikacin and Tazocin) were commenced. The following day combined induction chemotherapy with vincristine, doxorubicin, cyclophosphamide, cytosine- arabinoside and prednisone was instituted. Following chemotherapy, there was persis- tent, severe pancytopenia. Two weeks later, despite continuous high-care treatment, the patient’s condition deteriorated. She developed acute, severe abdominal tenderness, pyrexia and hypotension, which necessitated immediate transfer to the intensive care unit (ICU). Abdominal radiograph (Fig. 1) revealed an abnormal bowel gas pattern with marked gastric and small bowel dilatation, and paucity of air in the right iliac fossa (RIF). Chest radiograph (Fig. 2) demonstrat- ed air-space opacification bilaterally with areas of confluence in the mid to lower zones, especially on the right in keeping with bronchopneumonia. Blood cultures confirmed septicaemia with a resistant strain of Escherichia coli, sensitive to meropenem only. The pancy- topenia deteriorated and the patient devel- oped acute renal failure with anuria. Her abdomen was moderately distended with generalised abdominal tenderness and rebound tenderness in the RIF. Bowel sounds were absent. Abdominal ultrasound demonstrated free intra-peritoneal fluid, acalculus chole- cystitis and bowel wall thickening in the RIF. Contrast-enhanced computed tomog- raphy (CT) scan confirmed presence of ascites and acalculus cholecystitis. There was also marked dilatation of the caecum with extensive bowel wall thickening involving the entire right colon, proximal transverse colon and terminal ileum. Stranding of the surrounding fat was pre- sent, indicative of the pericolic inflamma- tory process. (Figs 3 -7). CASE REPORT Neutropenic enterocolitis com- plicating acute lymphoblastic leukaemia S K Misser MB ChB P Corr MB ChB, MD, FFRad (D) SA, FRCR Department of Radiology Inkosi Albert Luthuli Central Hospital Nelson R. Mandela School of Medicine Durban V B Jogessar MB ChB, MRCP (UK), FRCPath(Lond), FCPath(SA) Department of Haematology Inkosi Albert Luthuli Central Hospital Nelson R Mandela School of Medicine Durban Fig. 1. Supine abdominal radiograph per- formed while in ICU. Fig. 2. Bed side unit supine chest radiograph. 30 SA JOURNAL OF RADIOLOGY • October 2005 CASE REPORT The radiological features were consis- tent with a diagnosis of neutropenic ente- rocolitis (NE). The patient’s condition pro- gressively worsened despite supportive therapy, which included inotropic agents, assisted ventilation and broad-spectrum antimicrobials. The patient died in ICU. Discussion NE, also referred to as typhlitis, is a life- threatening infectious disease with the epi- centre located at the caecum and ascending colon. The term NE partly describes the aetiology and pathology of this condition, which is being reported with increasing fre- quency. Patients who are profoundly neu- tropenic due to underlying medical condi- tions such as leukaemia or AIDS,1 or who are rendered neutropenic following chemotherapy for an underlying malignan- cy, are at special risk of developing NE. The chemotherapeutic agents commonly incriminated are Taxol, doxorubicin, cyto- sine-arabinoside and vinca alkaloids, which are administered in various combinations. Many mechanisms leading to the devel- opment of NE have been proposed. Some authors have provided evidence to suggest that NE is a toxin-mediated disease and prior chemotherapy is unnecessary for its pathogenesis. Others have reported the condition only following combined regi- mens of chemotherapy. It is postulated that a combination of factors in most patients (as in the patient reported here) precipi- tates NE. Autopsy studies identified multiple clostridial species in necrotic bowel wall of patients with NE.2,3 Clostridia, which are a normal component of the alimentary flora are thought to secrete a necrotising β-toxin. Ordinarily this toxin is inactivated by neu- trophil proteases. In severely neutropenic patients, the absence of neutrophil proteas- es permits clostridial toxin-mediated bowel wall injury.4 The appendix has the highest carriage rate of clostridia. This is the reason that the inflammatory process and ensuing necrosis are concentrated in the terminal ileum, caecum and right colon.5 Following clostridial toxin-mediated mucosal necrosis, secondary bacterial translocation leads to acute septicaemia (Fig. 8). The commonest organisms cul- tured include E. coli, Klebsiella, Pseudomonas, Enterococcus, Candida and Clostridia.6 Pathologically, NE is characterised by inflammation and oedema that progresses to ulceration, necrosis and bowel wall per- foration.7 The differential diagnosis for NE includes acute appendicitis, appendix mass, intussusception, ischaemic colitis or other inflammatory processes, e.g. bacterial gas- tro-enteritis, viral colitis, inflammatory bowel disease or pseudomembranous coli- tis. Blood cultures are an important labo- ratory investigation that should be per- formed as early as possible, such that organism isolation and sensitivity can be known early on. This allows rapid, directed antimicrobial therapy. The findings of plain abdominal radi- ographs are usually nonspecific and they rarely help in the diagnosis of NE. Occasionally, right colonic and small bowel dilatation, thumb printing, paucity of air in the right colon and soft tissue mass displac- Fig. 3. Contrast-enhanced CT scan at the level of the mid-upper poles of the kidneys demonstrates pericolic inflammatory strand- ing (black arrows) surrounding the colon, proximal to hepatic flexure, in the anterior pararenal space. Note the distended stomach anteriorly (white arrow). Fig. 4. Contrast-enhanced CT scan at the level of the inferior poles of the kidneys demonstrates marked mural thickening (black arrow) of the ascending colon with pericolic inflammation. Fig. 5. Contrast-enhanced CT scan demon- strating the thick-walled right colon (black arrows) and mesenteric stranding. Note free fluid in the left paracolic gutter (white arrow). Fig. 6. Contrast enhanced CT scan at the pelvic inlet demonstrating marked caecal wall thickening (black arrows) and inflammatory reaction at the ileocaecal valve (white arrow). Fig. 7. Contrast-enhanced CT scan at mid to lower pelvis revealed ascites. ing small bowel loops may be noted.8 Free intra-abdominal air is an ominous sign. Contrast enema, uncommonly per- formed in NE, may demonstrate rigidity and thickening of the caecum. Barium enema is usually contraindicated as there is a potential risk of perforation. Ultrasound (US) is a useful additional tool. Bowel wall thickening that produces a target or halo, with echogenic walls is sug- gestive of colitis, but is nonspecific.9 It may be used as a follow-up tool to assess gradual decline in bowel wall thickening during treatment. The diagnostic procedure of choice is contrast-enhanced abdominal CT scan10 with the lowest false-negative rate of 15%. Severe transmural inflammation, symmet- rical circumferential bowel wall thickening of the caecum and pericaecal inflammation can all be accurately depicted.11,12 High attenuation within the thickened colonic wall may represent haemorrhage. Inflammatory pericolonic stranding of mesenteric fat is common. In addition, CT readily demonstrates complications of NE, viz. pneumatosis coli, pneumoperitoneum, pericolonic collections and abscess forma- tion. These complications may require urgent surgical management.13 Endoscopic procedures including colonoscopy and flexible sigmoidoscopy are rarely performed, as they are relatively contraindicated in the setting of neutrope- nia and thrombocytopenia. Management is necessarily empiric because there is no diagnostic test that is entirely sensitive and specific for NE. Medical care includes: • Admission to ICU with close monitoring, especially abdominal US examinations, full blood counts and biochemistry. • Intravenous fluids, blood and platelet transfusions as required. • Nil by mouth with nasogastric tube suc- tion. • Parenteral broad-spectrum antibiotics that cover enteric gram-negative and anaerobic organisms (including Clostridia). Some centres add metronida- zole, if pseudomembranous colitis can- not be immediately excluded.14 • Postpone all chemotherapy (for leukaemia) until symptoms have com- pletely resolved.15 • Discontinuation of medications, which may worsen the condition or confuse the clinical picture, e.g. drugs with anti- cholinergic side-effects, anti-diarrhoeal agents and narcotics. • If the patient remains febrile after 72 hours of antibiotic therapy, fungal cul- tures should be taken and an antifungal agent16 should be added. • In addition, viral studies especially for cytomegalovirus (CMV) are advised as CMV colitis may closely mimic NE. Ganciclovir may then be instituted. • Additional medical support with recom- binant Granulocyte Colony Stimulating Factor has been advocated.17 Surgical intervention is clearly limited to specific indications, in light of the inherent risks of surgery in the pancy- topenic, immunocompromised individual. Shamberger et al 13 proposed these indica- tions for surgery: • Persistent gastro-intestinal bleeding after resolution of neutropenia, thrombocy- 31 SA JOURNAL OF RADIOLOGY • October 2005 CASE REPORT Fig. 8. Algorithm of the pathophysiological processes in NE. 32 SA JOURNAL OF RADIOLOGY • October 2005 CASE REPORT topenia or other clotting abnormality. • Free intra-abdominal perforation. • Unrelenting intra-abdominal sepsis ± septicaemia (suggested by clinical deteri- oration requiring vasopressors or large volumes of fluid). • Clinical signs or radiological evidence for intra-abdominal abscess. Surgical procedures performed include: • Caecostomy and drainage • Two-stage right hemi-colectomy or total colectomy • Defunctioning of the colon with a loop ileostomy. Extensive resection is deemed necessary as necrotic mucosa in the bowel may be concealed by relatively normal appearing serosal surface at operation. NE carries a poor prognosis with an average mortality rate of 40 - 50%. Earlier detection with better imaging modalities and high index of suspicion has resulted in much lower mortality rates. Joint med- ical/surgical consultation is vital in the management of the NE patient. An increase in the neutrophil count is an important indicator of recovery and prognosis. It is essential that the physician consid- er the possibility of this potentially fatal condition in any neutropenic patient with the appropriate clinical presentation. Modern imaging modalities have changed NE from being diagnosed as a late-stage disease, best managed with immediate surgery and poor outcome, to a condition recognisable in its early stage and amenable to conservative, active medical manage- ment. References 1. Cutrona AF, Blinkhorn RJ, Crass J, Spagnuolo PJ. Probable neutropenic enterocolitis in patients with AIDS. Rev Infect Dis 1991; 113: 828-831. 2. Moir DH, Bale PM. Necropsy findings in child- hood leukaemia, emphasising neutropenic entero- colitis and cerebral calcification. Pathology 1976; 88: 247-258. 3. King A, Rampling A, Wight DG, Warren RE. Neutropenic enterocolitis due to Clostridium sep- ticum infection. J Clin Pathol 1984; 337: 335-343. 4. Newbold KM, Lord MG, Baglin TP. Role of clostridial organisms in neutropenic enterocolitis. J Clin Pathol 1987; 440: 471. 5. Blenkinsopp WK, Dupont PA. Bacteria in necrotis- ing enterocolitis. Lancet 1977; 22: 617. 6. Gomez L, Martino R, Rolston KV. Neutropenic enterocolitis: Spectrum of the disease and compar- ison of definite and possible cases. Clin Infect Dis 1998; 227: 695-699. 7. Katz JA, Wagner ML, Gresik MV, Mahoney DH, Fernbach DJ. Typhlitis: an 18-year experience and post-mortem review. Cancer 1990; 665: 1041- 1047. 8. Mcnamara MJ, Chalmers AG, Morgan M, Smith SEW. Typhlitis in acute childhood leukaemia: radi- ological features. Clin Radiol 1986; 337: 83-86. 9. Gootenberg JE, Abbondanzo SL. Rapid diagnosis of neutropenic enterocolitis (typhlitis) by ultra- sonography. American Journal of Paediatric Haematology/Oncology 1987; 99: 222. 10. Frick MP, Maile CW, Crass JR. Computed tomog- raphy of neutropenic colitis. Am J Roentgenol 1984; 1143: 763. 11. Vas WG, Seelig R, Mahanta B. Neutropenic colitis: evaluation with computed tomography. Journal of Computed Tomography 1988; 112: 211-215. 12. Gayer G, Zissin R. Typhlitis: a computed tomogra- phy diagnosis. Israel Medical Association Journal 2002; 44: 146-147. 13. Shamberger RC, Weinstein HJ, Delorey MJ, Levey RH. The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukaemia. Cancer 1986; 557: 603. 14. Wade DS, Nava HR, Douglass HO. Neutropenic enterocolitis. Clinical diagnosis and treatment. Cancer 1992; 669(1): 17-23. 15. Keidan RD, Fanning J, Gattenby RA, Weese JL. Recurrent typhlitis: a disease resulting from aggressive chemotherapy. Dis Colon Rectum 1989; 332: 206-209. 16. Marr KA. Empirical antifungal therapy - new options, new tradeoffs. N Engl J Med 2002; 3346: 278-280. 17. Hanada T, Ono I, Hirano C. Successful treatment of neutropenic enterocolitis with recombinant granulocyte colony stimulating factor in a child with acute lymphocytic leukaemia. Eur J Paediatr 1990; 1149: 811-812. www.aucklandhealthcareers.co.nz Look here first...Look here first... Staff Nuclear Medicine Technologist / MRT Do you like variety? Here is a chance for you to work 20 hours per week as an MRT and 20 hours per week as a Staff Nuclear Medicine Technologist. The Nuclear Medicine Department provides the sole public Radionuclide imaging service and most of the specialised paediatric Nuclear Medicine examinations to the upper North Island of New Zealand. The Department is well equipped with modern imaging equipment. Your responsibilities will include working in all aspects of Diagnostic Nuclear Medicine, performing examinations on both Outpatients and Inpatients. Applicants must hold a qualifi cation recognised for registration by the New Zealand Medical Radiation Technologists Board. Ref No: 006144 To apply online please go to www.aucklandhealthcareers.co.nz if you’re looking to work in an up to if you’re looking to work in an up to the minute healthcare environmentthe minute healthcare environment