Neutropenic Enterocolitis

Neutropenic Enterocolitis

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Neutropenic enterocolitis, also known as typhlitis (from Greek typhlon [“blind”], referring to the 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, 9]

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

Although initially described in children undergoing chemotherapy for leukemia over the past three decades, [10]  neutropenic enterocolitis has increasingly been reported in adults with a variety of myeloproliferative disorders or solid malignant tumors, as well as 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 that have a high potential to induce mucosal damage. [11]

For patient education resources, see the Digestive Disorders Center, as well as Colitis, Abdominal Pain in Adults, and Complete Blood Count (CBC).

Although the exact pathogenesis and progression of neutropenic enterocolitis are unknown, profound neutropenia appears to be the common denominator, in conjunction with intestinal mucosal injury and immune compromise. [9] Many factors have been described that may potentially play a role in the pathogenesis of neutropenic enterocolitis, including the following:

The pathologic process of neutropenic enterocolitis may involve the cecum alone, or it may extend to the ileum, the 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.

Although cytotoxic chemotherapeutic agents account for most cases of neutropenic enterocolitis, other conditions may also predispose some patients to develop this condition.

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, leucovorin, and pemetrexed. [13]

There have been described cases of neutropenic enterocolitis associated with the monoclonal antibody alemtuzumab, [14] as well as with pegylated interferon (PEG-INF) in combination with ribavirin. [15, 16]

Other predisposing conditions for neutropenic enterocolitis include the following:

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

An autopsy study in children reported a prevalence of 24%, [17] whereas a cohort study in children treated for acute myelogenous leukemia (AML) reported a frequency of 33%. [18] A retrospective review of 1224 children treated for malignancy showed an incidence of only 1.4%, 53% of whom were treated for leukemia. [19] Data regarding neutropenic enterocolitis in adults are sparse. In one systematic review, a 5.3% pooled incidence was reported in adults. [12]

An even greater paucity of information regarding the international incidence and prevalence rates of neutropenic enterocolitis exists in the published literature.

A study from India performed by Jain et al reported a frequency of 6.1% in 180 children undergoing chemotherapy for acute lymphocytic leukemia (ALL). [20]

A retrospective study of data from 20 patients in Turkey reported an incidence of 6.5% for neutropenic enterocolitis in acute myeloid leukemia and 4.6% for neutropenic enterocolitis in acute lymphoblastic leukemia. [21] Another Turkish study, involving prospective data from 215 adults, showed an incidence of 3.5%, which was significantly associated with acute leukemias and anthracycline administration in adults. [22]

Polish investigators of a prospective study that examined 297 adult patients following hematopoietic stem cell transplantation diagnosed neutropenic enterocolitis in 12% of patients using the criteria of abdominal pain, diarrhea, and bowel-wall thickening larger than 4 mm on abdominal ultrasonography. [23]

A lower incidence, 0.22%, was reported in another study in the treatment of malignancy, not specifically leukemia. [24]

No predilection for neutropenic enterocolitis in any specific race or in either sex has been reported in the literature.

On the basis of the published literature, no frequency differences in age groups are known to exist for neutropenic enterocolitis. It has been noted, however, that although neutropenic enterocolitis was initially described in children, it is increasingly reported in adults.

The prognosis of neutropenic enterocolitis is generally poor and is highly dependent on the rapidity of restoration of the white blood cell (WBC) count. The potential for recovery from neutropenic enterocolitis may be improved by early, accurate diagnosis along with aggressive and meticulous medical and supportive therapy. [25]

Mortality figures in the range of 5-100% have been reported during conservative management of neutropenic enterocolitis; average mortality is about 40-50%.

In a collective review of 178 published cases, mortality for neutropenic enterocolitis was reported as 48% with conservative management and 21% with surgical management [26] ; however, these numbers cannot be compared with each other because of selection bias. No known prospective randomized trials comparing surgery with medical management have been performed.

Complications of neutropenic enterocolitis include the following:

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Keith Sultan, MD, FACG Assistant Professor of Medicine, Division of Gastroenterology, Hofstra North Shore-LIJ School of Medicine

Keith Sultan, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association

Disclosure: Nothing to disclose.

Rajeev Vasudeva, MD Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Rajeev Vasudeva, MD is a member of the following medical societies: American College of Gastroenterology, Columbia Medical Society, South Carolina Gastroenterology Association, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, South Carolina Medical Association

Disclosure: Received honoraria from Pricara for speaking and teaching; Received consulting fee from UCB for consulting.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Robert J Fingerote, MD, MSc, FRCPC Consultant, Clinical Evaluation Division, Biologic and Gene Therapies, Directorate Health Canada; Consulting Staff, Department of Medicine, Division of Gastroenterology, York Central Hospital, Ontario

Robert J Fingerote, MD, MSc, FRCPC is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada, Canadian Medical Association

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ 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: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

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