eMedicine Specialties > Gastroenterology > Colon

Neutropenic Enterocolitis

Author: Keith Sultan, MD, Faculty Practice, Division of Gastroenterology, Hepatology and Nutrition, North Shore University Hospital, Manhasset, New York
Coauthor(s): Rajeev Vasudeva, MD, FACG, Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine
Contributor Information and Disclosures

Updated: Jul 9, 2009

Introduction

Background

Neutropenic enterocolitis, also known as typhlitis (from the greek "typhlon" for cecum) is an acute life-threatening condition classically characterized by transmural inflammation of the cecum, often with involvement of the ascending colon and ileum, in patients who are severely myelosuppressed.1,2,3,4,5,6,7,8

The clinical presentation of neutropenic enterocolitis (typhlitis) can be dramatic, and the outcome may be devastating. Mortality rates are high, and treatment is controversial, with options varying from conservative medical management to surgical intervention.1,2,3,4,5,6,7,8 Early recognition of neutropenic enterocolitis (typhlitis) is paramount to a potentially good outcome.

Although initially described in children undergoing chemotherapy for leukemia9 over the past 3 decades, neutropenic enterocolitis (typhlitis) has increasingly been reported in adults with a variety of myeloproliferative disorders, solid malignant tumors, and in the setting of immunosuppression with solid organ and bone marrow transplantation. Some cases in adults are due to the increasing use of myelotoxic chemotherapeutic regimens.

For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Colitis, Abdominal Pain in Adults, and Complete Blood Count.

Pathophysiology

Although the exact etiology and progression of neutropenic enterocolitis (typhlitis) are unknown, profound neutropenia appears to be the common denominator. Many factors have been described that may potentially play a role in the pathogenesis of neutropenic enterocolitis (typhlitis), and they include the following:

  • Mucosal injury caused by cytotoxic drugs – However, mucosal injury can occur in the absence of cytotoxic drug therapy, and neutropenia itself can cause mucosal ulcerations.
  • Cecal distention – Whether primary or secondary to vinca alkaloids, cecal distention may compromise the blood supply, leading to further mucosal damage.
  • The use of antibiotics and steroids – These agents may contribute to an altered enteric bacterial flora and overgrowth of fungi.
  • Bacterial, and sometimes fungal invasion of the impaired bowel wall – These may result in transmural inflammation, leading to perforation and peritonitis. Bacteremia is a frequent complication, with less frequent fungemia.10

The pathologic process of neutropenic enterocolitis (typhlitis) may involve the cecum alone, or it may extend to the ileum, ascending colon, or both. It is felt that cecal distensibility and limited blood supply may predispose the cecum to injury more often than other areas.

Frequency

United States

The exact incidence and prevalence rates of neutropenic enterocolitis (typhlitis) are unknown, because many patients survive and are never diagnosed with this condition. Also, because there is no gold standard of diagnosis for neutropenic enterocolitis (typhlitis), the inclusion criteria differ among studies.

An autopsy study in children reported a prevalence rate of 24%,11 whereas a cohort study in children treated for acute myelogenous leukemia (AML) reported a frequency rate of 33%.12 Data regarding neutropenic enterocolitis (typhlitis) in adults are sparse. In one systematic review, a 5.3% pooled incidence rate was been reported in adults.10  

International

An even greater paucity of information regarding the international incidence and prevalence rates of neutropenic enterocolitis (typhlitis) exists in the published literature. A study from India performed by Jain et al reported a frequency rate of 6.1% in 180 children undergoing chemotherapy for acute lymphocytic leukemia (ALL).13 A retrospective study from Turkey performed by Buyukasik et al reported an incidence rate of 6.5% for neutropenic enterocolitis (typhlitis) in acute myeloid leukemia and 4.6% for neutropenic enterocolitis (typhlitis) in acute lymphoblastic leukemia.14  Another Turkish study, a large prospective cohort study of adults, showed an incidence rate of 3.5%, which was significantly associated with acute leukemias and anthracycline administration in adults.15  

Mortality/Morbidity

  • Mortality rates of 5-100% have been reported during conservative management of neutropenic enterocolitis (typhlitis), with an average mortality rate of about 40-50%.
  • In a collective review of 178 published cases, the mortality rate of neutropenic enterocolitis (typhlitis) was reported at 48% for conservative management and 21% for surgical management; however, these numbers cannot be compared with each other because of selection bias. No prospective randomized trials comparing surgery to medical management have been performed.

Race

No predilection for neutropenic enterocolitis (typhlitis) in any specific race is reported in the literature.

Sex

No sex predilection for neutropenic enterocolitis (typhlitis) is reported in the literature.

Age

  • No known frequency differences in age groups exist for neutropenic enterocolitis (typhlitis) based on the published literature.
  • Although neutropenic enterocolitis (typhlitis) was initially described in children, it is increasingly reported in adults.

Clinical

History

Most patients who are affected with neutropenic enterocolitis (typhlitis) are receiving antineoplastic drugs and are profoundly neutropenic (ie, <1000 cells/mm3).

  • Symptoms of neutropenic enterocolitis (typhlitis) usually occur within 10-14 days after initiation of cytotoxic chemotherapy.
  • The typical presentation mimics acute appendicitis.
  • Symptoms include the following:
    • Right lower quadrant abdominal pain, which may be cramping and intermittent or a continuous dull ache
    • Fever
    • Watery or bloody diarrhea,15 which occurs in about 25-45% of patients
    • Nausea
    • Vomiting
    • Abdominal distention
  • Oral and pharyngeal mucositis, which may manifest before the onset of colonic symptoms
    Ulcerative oral mucositis lesion on the lateral a...

    Ulcerative oral mucositis lesion on the lateral and ventral surfaces of the tongue.

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    Ulcerative oral mucositis lesion on the lateral a...

    Ulcerative oral mucositis lesion on the lateral and ventral surfaces of the tongue.

  • The time course and severity of the clinical presentation of neutropenic enterocolitis (typhlitis) is variable.

Physical

Physical findings in patients with neutropenic enterocolitis (typhlitis) vary depending on the severity of the disease and the presence or absence of complications.

  • Abdominal distention, hypoactive bowel sounds, and a tympanitic abdomen may suggest an ileus.
  • The abdomen may be markedly tender, especially in the right lower quadrant.
  • The cecum may be palpated as a boggy mass.
  • Rebound tenderness and rigidity may suggest colonic perforation.
  • Shock may be present due to sepsis.

Causes

Although cytotoxic chemotherapeutic agents account for most cases of neutropenic enterocolitis (typhlitis), other conditions that may predispose some patients to develop this condition exist.

  • The cytotoxic chemotherapeutic agents include cytosine arabinoside, vinca alkaloids, and doxorubicin.
  • Other drugs that have been implicated anecdotally include paclitaxel, docetaxel, procainamide, sulfasalazine, 5-fluorouracil, vinorelbine, carboplatin, cisplatin, gemcitabine, and leucovorin. 
  • There have been newly described cases of neutropenic enterocolitis (typhlitis) associated with the monoclonal antibody alemtuzumab16 as well as with pegylated interferon (PEG-INF) with ribavirin.17
  • Other predisposing conditions for neutropenic enterocolitis (typhlitis) include the following:

More on Neutropenic Enterocolitis

Overview: Neutropenic Enterocolitis
Differential Diagnoses & Workup: Neutropenic Enterocolitis
Treatment & Medication: Neutropenic Enterocolitis
Follow-up: Neutropenic Enterocolitis
Multimedia: Neutropenic Enterocolitis
References
Further Reading
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References

  1. Keidan RD, Fanning J, Gatenby RA, Weese JL. Recurrent typhlitis. A disease resulting from aggressive chemotherapy. Dis Colon Rectum. Mar 1989;32(3):206-9. [Medline].

  2. Wade DS, Nava HR, Douglass HO Jr. Neutropenic enterocolitis. Clinical diagnosis and treatment. Cancer. Jan 1 1992;69(1):17-23. [Medline].

  3. Davila AD, Willenbucher RF. Neutropenic typhlitis. In: Feldman M, Sleisenger MH, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia, Pa: Saunders; 1998:1998-2000.

  4. Gorbach SL. Neutropenic enterocolitis. Clin Infect Dis. Oct 1998;27(4):700-1. [Medline].

  5. Urbach DR, Rotstein OD. Typhlitis. Can J Surg. Dec 1999;42(6):415-9. [Medline].

  6. Gorschluter M, Mey U, Strehl J, et al. Neutropenic enterocolitis in adults: systematic analysis of evidence quality. Eur J Haematol. Jul 2005;75(1):1-13. [Medline].

  7. Davila ML. Neutropenic enterocolitis. Curr Opin Gastroenterol. Jan 2006;22(1):44-7. [Medline].

  8. Ullery BW, Pieracci FM, Rodney JR, Barie PS. Neutropenic enterocolitis. Surg Infect (Larchmt). Jun 2009;10(3):307-14. [Medline].

  9. Wagner ML, Rosenberg HS, Fernbach DJ, Singleton EB. Typhlitis: a complication of leukemia in childhood. Am J Roentgenol Radium Ther Nucl Med. Jun 1970;109(2):341-50. [Medline].

  10. Gorschluter 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. Feb 26 2006;6:35. [Medline]. [Full Text].

  11. Katz JA, Wagner ML, Gresik MV, Mahoney DH Jr, Fernbach DJ. Typhlitis. An 18-year experience and postmortem review. Cancer. Feb 15 1990;65(4):1041-7. [Medline].

  12. Shamberger RC, Weinstein HJ, Delorey MJ, Levey RH. The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia. Cancer. Feb 1 1986;57(3):603-9. [Medline].

  13. Jain Y, Arya LS, Kataria R. Neutropenic enterocolitis in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol. Jan-Feb 2000;17(1):99-103. [Medline].

  14. Buyukasik Y, Ozcebe OI, Haznedaroglu IC, et al. Neutropenic enterocolitis in adult leukemias. Int J Hematol. Jul 1997;66(1):47-55. [Medline].

  15. Aksoy DY, Tanriover MD, Uzun O, et al. Diarrhea in neutropenic patients: a prospective cohort study with emphasis on neutropenic enterocolitis. Ann Oncol. Jan 2007;18(1):183-9. [Medline].

  16. Marie I, Robaday S, Kerleau JM, Jardin F, Levesque H. Typhlitis as a complication of alemtuzumab therapy. Haematologica. May 2007;92(5):e62-3. [Medline].

  17. Kasturi KS, Mummadi RR, Sood GK. Neutropenic enterocolitis: An unusual complication of HCV combination therapy with PEG-IFN and ribavirin. Eur J Intern Med. Jul 2008;19(5):372-3. [Medline].

  18. Cartoni C, Dragoni F, Micozzi A, et al. Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography. J Clin Oncol. Feb 1 2001;19(3):756-61. [Medline].

  19. McCarville MB, Adelman CS, Li C, et al. Typhlitis in childhood cancer. Cancer. Jul 15 2005;104(2):380-7. [Medline]. [Full Text].

  20. Kirkpatrick ID, Greenberg HM. Gastrointestinal complications in the neutropenic patient: characterization and differentiation with abdominal CT. Radiology. Mar 2003;226(3):668-74. [Medline]. [Full Text].

  21. Horton KM, Corl FM, Fishman EK. CT evaluation of the colon: inflammatory disease. Radiographics. Mar-Apr 2000;20(2):399-418. [Medline]. [Full Text].

  22. Cardona Zorrilla AF, Reveiz Herault L, Casasbuenas A, Aponte DM, Ramos PL. Systematic review of case reports concerning adults suffering from neutropenic enterocolitis. Clin Transl Oncol. Jan 2006;8(1):31-8. [Medline].

  23. Gafter-Gvili A, Fraser A, Paul M, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med. Jun 21 2005;142(12 pt 1):979-95. [Medline].

  24. Kuderer NM, Dale DC, Crawford J, Lyman GH. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol. Jul 20 2007;25(21):3158-67. [Medline].

  25. 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. Feb 2009;44(2):381-5. [Medline].

  26. Alt B, Glass NR, Sollinger H. Neutropenic enterocolitis in adults. Review of the literature and assessment of surgical intervention. Am J Surg. Mar 1985;149(3):405-8. [Medline].

  27. Avigan D, Richardson P, Elias A, et al. Neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors: a case series with a review of the literature. Cancer. Aug 1 1998;83(3):409-14. [Medline]. [Full Text].

  28. Badgwell BD, Cormier JN, Wray CJ, et al. Challenges in surgical management of abdominal pain in the neutropenic cancer patient. Ann Surg. Jul 2008;248(1):104-9. [Medline].

  29. Crosby WH, Haubrich WS. The death of Walter Reed. JAMA. Sep 17 1982;248(11):1342-5. [Medline].

  30. Cunningham SC, Fakhry K, Bass BL, Napolitano LM. Neutropenic enterocolitis in adults: case series and review of the literature. Dig Dis Sci. Feb 2005;50(2):215-20. [Medline].

  31. Ettinghausen SE. Collagenous colitis, eosinophilic colitis, and neutropenic colitis. Surg Clin North Am. Oct 1993;73(5):993-1016. [Medline].

  32. Gomez L, Martino R, Rolston KV. Neutropenic enterocolitis: spectrum of the disease and comparison of definite and possible cases. Clin Infect Dis. Oct 1998;27(4):695-9. [Medline].

  33. Hanada T, Ono I, Hirano C, Kurosaki Y. Successful treatment of neutropenic enterocolitis with recombinant granulocyte colony stimulating factor in a child with acute lymphocytic leukaemia. Eur J Pediatr. Aug 1990;149(11):811-2. [Medline].

  34. Hoelzer D. Hematopoietic growth factors--not whether, but when and where. N Engl J Med. Jun 19 1997;336(25):1822-4. [Medline].

  35. Kulaylat M, Doerr R, Ambrus J. A case presentation and review of neutropenic enterocolitis. J Med. 1997;28(1-2):1-19. [Medline].

  36. Lev R, Sweeney KG. Neutropenic enterocolitis. Two unusual cases with review of the literature. Arch Pathol Lab Med. May 1993;117(5):524-7. [Medline].

  37. Mulholland MW, Delaney JP. Neutropenic colitis and aplastic anemia: a new association. Ann Surg. Jan 1983;197(1):84-90. [Medline]. [Full Text].

  38. Nagler A, Pavel L, Naparstek E, Muggia-Sullam M, Slavin S. Typhlitis occurring in autologous bone marrow transplantation. Bone Marrow Transplant. Jan 1992;9(1):63-4. [Medline].

  39. Or R, Mehta J, Nagler A, Craciun I. Neutropenic enterocolitis associated with autologous bone marrow transplantation. Bone Marrow Transplant. May 1992;9(5):383-5. [Medline].

  40. Park YB, Lee JW, Cho BS, et al. Incidence and etiology of overt gastrointestinal bleeding in adult patients with aplastic anemia. Dig Dis Sci. Jan 23 2009;epub ahead of print. [Medline].

  41. Shaked A, Shinar E, Freund H. Neutropenic typhlitis. A plea for conservatism. Dis Colon Rectum. May 1983;26(5):351-2. [Medline].

  42. Sloas MM, Flynn PM, Kaste SC, Patrick CC. Typhlitis in children with cancer: a 30-year experience. Clin Infect Dis. Sep 1993;17(3):484-90. [Medline].

  43. Spencer SP, Power N, Reznek RH. Multidetector computed tomography of the acute abdomen in the immunocompromised host: a pictorial review. Curr Probl Diagn Radiol. Jul-Aug 2009;38(4):145-55. [Medline].

  44. Tiseo M, Gelsomino F, Bartolotti M, Barili MP, Ardizzoni A. Typhlitis during second-line chemotherapy with pemetrexed in non-small cell lung cancer (NSCLC): A case report. Lung Cancer. Aug 2009;65(2):251-3. [Medline].

  45. Weinberger M, Hollingsworth H, Feuerstein IM, Young NS, Pizzo PA. Successful surgical management of neutropenic enterocolitis in two patients with severe aplastic anemia. Case reports and review of the literature. Arch Intern Med. Jan 11 1993;153(1):107-13. [Medline].

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Further Reading

Related eMedicine Topics

National Guideline Clearinghouse

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Keywords

neutropenic enterocolitis, typhlitis, necrotizing enterocolitis, ileocecal syndrome, pseudomembranous colitis, typhlitis, acute ileocecal enterocolitis, transmural inflammation of the small bowel and large bowel in myelosuppression and immunosuppression, profound neutropenia, cecum, ileum, ascending colon, cecitis, right lower quadrant pain

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Contributor Information and Disclosures

Author

Keith Sultan, MD, Faculty Practice, Division of Gastroenterology, Hepatology and Nutrition, North Shore University Hospital, Manhasset, New York
Keith Sultan, MD is a member of the following medical societies: American College of Gastroenterology and American Gastroenterological Association
Disclosure: Nothing to disclose.

Coauthor(s)

Rajeev Vasudeva, MD, FACG, Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine
Rajeev Vasudeva, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Columbia Medical Society, South Carolina Gastroenterology Association, and South Carolina Medical Association
Disclosure: Pricara Honoraria Speaking and teaching; UCB Consulting fee Consulting

Medical Editor

Robert J Fingerote, MD, MSc, BSc, FRCPC, Consultant, Clinical Evaluation Division, Biologic and Gene Therapies, Directorate Health Canada; Consulting Staff, Department of Medicine, Division of Gastroenterology, York Central Hospital, Richmond Hill, Ontario
Robert J Fingerote, MD, MSc, BSc, FRCPC is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, Canadian Medical Association, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Douglas M Heuman, MD, FACP, FACG, AGAF, Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine
Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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