Neutropenic enterocolitis (typhlitis)
- Louis-Michel Wong Kee Song, MD, FRCP(C)
Louis-Michel Wong Kee Song, MD, FRCP(C)
- Associate Professor of Medicine
- Mayo Clinic College of Medicine
- Norman E Marcon, MD, FRCP(C)
Norman E Marcon, MD, FRCP(C)
- Professor of Medicine
- University of Toronto
Neutropenic enterocolitis is a life-threatening, necrotizing enterocolitis occurring primarily in neutropenic patients . Other terms that have been used to describe this syndrome include "necrotizing enterocolitis" and "ileocecal syndrome." Neutropenic enterocolitis occurs most commonly in individuals with hematologic malignancies who are neutropenic and have breakdown of gut mucosal integrity as a result of cytotoxic chemotherapy. "Typhlitis" (from the Greek word "typhlon," or cecum) describes neutropenic enterocolitis of the ileocecal region; we prefer the more inclusive term "neutropenic enterocolitis," since other parts of the small and/or large intestine are often involved.
The pathogenesis, clinical manifestations, diagnosis, management, and prognosis of neutropenic enterocolitis are reviewed here.
Other infectious complications of chemotherapy-induced neutropenia are discussed separately:
- Rolston KV, Bodey GP, Safdar A. Polymicrobial infection in patients with cancer: an underappreciated and underreported entity. Clin Infect Dis 2007; 45:228.
- Urbach DR, Rotstein OD. Typhlitis. Can J Surg 1999; 42:415.
- Katz JA, Wagner ML, Gresik MV, et al. Typhlitis. An 18-year experience and postmortem review. Cancer 1990; 65:1041.
- Nesher L, Rolston KV. Neutropenic enterocolitis, a growing concern in the era of widespread use of aggressive chemotherapy. Clin Infect Dis 2013; 56:711.
- Koransky JR, Stargel MD, Dowell VR Jr. Clostridium septicum bacteremia. Its clinical significance. Am J Med 1979; 66:63.
- Gorschlüter M, Mey U, Strehl J, et al. Invasive fungal infections in neutropenic enterocolitis: a systematic analysis of pathogens, incidence, treatment and mortality in adult patients. BMC Infect Dis 2006; 6:35.
- Wagner ML, Rosenberg HS, Fernbach DJ, Singleton EB. Typhlitis: a complication of leukemia in childhood. Am J Roentgenol Radium Ther Nucl Med 1970; 109:341.
- Pestalozzi BC, Sotos GA, Choyke PL, et al. Typhlitis resulting from treatment with taxol and doxorubicin in patients with metastatic breast cancer. Cancer 1993; 71:1797.
- Quigley MM, Bethel K, Nowacki M, et al. Neutropenic enterocolitis: a rare presenting complication of acute leukemia. Am J Hematol 2001; 66:213.
- Cunningham SC, Fakhry K, Bass BL, Napolitano LM. Neutropenic enterocolitis in adults: case series and review of the literature. Dig Dis Sci 2005; 50:215.
- Bremer CT, Monahan BP. Necrotizing enterocolitis in neutropenia and chemotherapy: a clinical update and old lessons relearned. Curr Gastroenterol Rep 2006; 8:333.
- Davila ML. Neutropenic enterocolitis. Curr Opin Gastroenterol 2006; 22:44.
- Moran H, Yaniv I, Ashkenazi S, et al. Risk factors for typhlitis in pediatric patients with cancer. J Pediatr Hematol Oncol 2009; 31:630.
- Sobel J, Mixter CG, Kolhe P, et al. Necrotizing enterocolitis associated with clostridium perfringens type A in previously healthy north american adults. J Am Coll Surg 2005; 201:48.
- Centers for Disease Control and Prevention (CDC). Fatal foodborne Clostridium perfringens illness at a state psychiatric hospital--Louisiana, 2010. MMWR Morb Mortal Wkly Rep 2012; 61:605.
- Wade DS, Nava HR, Douglass HO Jr. Neutropenic enterocolitis. Clinical diagnosis and treatment. Cancer 1992; 69:17.
- Aksoy DY, Tanriover MD, Uzun O, et al. Diarrhea in neutropenic patients: a prospective cohort study with emphasis on neutropenic enterocolitis. Ann Oncol 2007; 18:183.
- Bow EJ, Meddings JB. Intestinal mucosal dysfunction and infection during remission-induction therapy for acute myeloid leukaemia. Leukemia 2006; 20:2087.
- Sloas MM, Flynn PM, Kaste SC, Patrick CC. Typhlitis in children with cancer: a 30-year experience. Clin Infect Dis 1993; 17:484.
- Kirkpatrick ID, Greenberg HM. Gastrointestinal complications in the neutropenic patient: characterization and differentiation with abdominal CT. Radiology 2003; 226:668.
- Kaste SC, Flynn PM, Furman WL. Acute lymphoblastic leukemia presenting with typhlitis. Med Pediatr Oncol 1997; 28:209.
- Dworkin B, Winawer SJ, Lightdale CJ. Typhlitis. Report of a case with long-term survival and a review of the recent literature. Dig Dis Sci 1981; 26:1032.
- Musher DR, Amorosi EL, Gouge T, et al. Neutropenic typhlitis simulating carcinoma of the cecum. Gastrointest Endosc 1989; 35:449.
- Wallace J, Schwaitzberg S, Miller K. Sometimes it really is appendicitis: case of a CML patient with acute appendicitis. Ann Hematol 1998; 77:61.
- de Brito D, Barton E, Spears KL, et al. Acute right lower quadrant pain in a patient with leukemia. Ann Emerg Med 1998; 32:98.
- Cronin CG, O'Connor M, Lohan DG, et al. Imaging of the gastrointestinal complications of systemic chemotherapy. Clin Radiol 2009; 64:724.
- Mullassery D, Bader A, Battersby AJ, et al. Diagnosis, incidence, and outcomes of suspected typhlitis in oncology patients--experience in a tertiary pediatric surgical center in the United Kingdom. J Pediatr Surg 2009; 44:381.
- Cloutier RL. Neutropenic enterocolitis. Hematol Oncol Clin North Am 2010; 24:577.
- Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52:e56.
- American Academy of Pediatrics. Antimicrobial Agents and related therapy. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 30th ed, Pickering LK, Baker CJ, Kimberlin DW, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2012. p.800.
- Orenstein DM, Pattishall EN, Noyes BE, et al. Safety of ciprofloxacin in children with cystic fibrosis. Clin Pediatr (Phila) 1993; 32:504.
- Sendzik J, Lode H, Stahlmann R. Quinolone-induced arthropathy: an update focusing on new mechanistic and clinical data. Int J Antimicrob Agents 2009; 33:194.
- Pichichero ME, Arguedas A, Dagan R, et al. Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure. Clin Infect Dis 2005; 41:470.
- Jackson MA, Schutze GE, COMMITTEE ON INFECTIOUS DISEASES. The Use of Systemic and Topical Fluoroquinolones. Pediatrics 2016; 138.
- O'Brien S, Kantarjian HM, Anaissie E, et al. Successful medical management of neutropenic enterocolitis in adults with acute leukemia. South Med J 1987; 80:1233.
- Kouroussis C, Samonis G, Androulakis N, et al. Successful conservative treatment of neutropenic enterocolitis complicating taxane-based chemotherapy: a report of five cases. Am J Clin Oncol 2000; 23:309.
- Shamberger RC, Weinstein HJ, Delorey MJ, Levey RH. The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia. Cancer 1986; 57:603.
- Gorschlüter M, Mey U, Strehl J, et al. Neutropenic enterocolitis in adults: systematic analysis of evidence quality. Eur J Haematol 2005; 75:1.
- RISK FACTORS AND INCIDENCE
- CLINICAL MANIFESTATIONS
- Signs and symptoms
- DIFFERENTIAL DIAGNOSIS
- Antimicrobial therapy
- - Suggested regimens
- - Duration and transition to an oral regimen
- Supportive therapy
- - Granulocyte colony-stimulating factor
- Subsequent chemotherapy
- SUMMARY AND RECOMMENDATIONS