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E n t e ro c o l i t i s
Robert L. Cloutier, MD, FAAEM
KEYWORDS
Neutropenia Enterocolitis Typhlitis Fever
Chemotherapy Cancer
Necrotizing enterocolitis has long been acknowledged in the pediatric literature but
has been relatively rare in adult patients. Over time, the term neutropenic enterocolitis
has evolved to better appreciate the role that neutropenia plays in the pathogenesis of
this condition. Early reports date back to 1933, when Cooke observed submucosal
hemorrhage and appendiceal perforation in leukemic children (cited in Cunningham
and colleagues1). More contemporary reports date to 1962, with a case series by
A version of this article was previously published in the Emergency Medicine Clinics of North
America, 27:3.
Department of Emergency Medicine, Doernbecher Children’s Hospital, Oregon Health &
Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, USA
E-mail address: cloutier@ohsu.edu
Amromin and Salomon (cited in Cunningham and colleagues1). They reported a large
series of 69 adults with NE and acute leukemia or lymphoma over a 5-year period.
These patients, characteristically, developed necrotizing enteric lesions shortly after
intensive chemotherapy. Development of these enteric lesions was generally indepen-
dent of patient response to chemotherapy. Interestingly, most patients experienced
excellent therapeutic responses to their chemotherapy before the onset of NE.1 The
patients almost uniformly experienced abdominal pain, distension, leukopenia, and
intestinal necrosis with histologic evidence of bacterial invasion of the mucosa and
submucosa of the bowel wall.1,5 All patients in this series succumbed to their disease
after the development of NE.5 NE has also been termed ileocecal syndrome or
typhlitis.
The literature discussing NE is varied and characterized by numerous case reports
and case series, illustrating cases of NE across a spectrum of patients, both with and
without cancer. There is, however, only a single analysis of the current state of
evidence regarding NE by Gorschlüter and colleagues.6 In that review, no clinical trials
or case control studies were cited in the NE literature. Overall, prospective studies
were rare and did not tend to reflect the highest levels of scientific evidence. There
are many unanswered questions, and our understanding of the pathophysiology of
NE is sparse at best. Official diagnostic criteria are also difficult to find, as are firm
guidelines for treatment. Thus, the overall grade assigned to evidence in this article
is low, given the virtual absence of any meaningful prospective research or clinical
trials. In an editorial response by Sherwood L. Gorbach, summing up the state of
our poor understanding of NE, he aptly describes the challenges of fully grasping
NE thus: ‘‘the diversity of the pathology is matched by the difficulty in establishing
the diagnosis on the basis of only clinical findings.’’2 What can be said, however, is
that any progress made to date, to improve outcomes in NE, has been the result of
rapid identification and aggressive intervention, frequently by frontline providers
such as ED physicians.
Neutropenic patients presenting for care in the ED, after the administration of chemo-
therapy, represent a particularly high-acuity patient population, requiring a thoughtful
and thorough evaluation for all potential sources of infection. Patients are routinely
evaluated for potential sources of infection by chest radiography, complete blood
counts, blood cultures, and urine analysis. Neutropenic patients, presenting with
either generalized or focal abdominal pain, along with fever, should uniformly be
considered at risk for NE.
Several specific chemotherapeutic agents have been implicated in the development
of NE. These include, among others, taxane-based therapies (ie, paclitaxel and doce-
taxel), gemcitabine, cytosine arabinoside, vincristine, doxorubicin, cyclophospha-
mide, 5-fluorouracil, leucovorin, and daunorubicin3–5,7,8 (Box 1). The types of
malignancies involved are also varied. Initial reports almost exclusively cited NE as
a complication of pediatric leukemias. Although leukemias and many forms of
lymphoma comprise a large number of the cases of NE, a wide variety of solid tumors,
including breast, lung, colorectal, and ovarian cancer, have also been implicated.3,4,7,8
Although most patients present with NE after chemotherapeutic treatment for
cancer, there are a small number of reported cases presenting in leukemic patients
before the initiation of chemotherapy or as their presenting event leading to diag-
nosis.9–11 There is also a case report of a trauma patient who developed NE after
receiving antibiotics for osteomyelitis.12 The underlying cause in this case was
Neutropenic Enterocolitis 579
Box 1
Chemotherapeutic agents implicated in neutropenic enterocolitis
Paclitaxel
Docetaxel
Gemcitabine
Cytosine
Arabinoside
Vincristine
Doxorubicin
Cyclophosphamide
5 -Fluorouracil
Leucovorin
Daunorubicin
Box 2
Reported nononcologic causes of neutropenic enterocolitis
AIDS
Nafcillin in the treatment of osteomyelitis
Aplastic anemia
Cyclic neutropenia
Bone marrow suppression for bone marrow or renal transplantation
580 Cloutier
Box 3
Common signs and symptoms of neutropenic enterocolitis
the differences between NE, C difficile colitis and potential graft-versus-host disease
(GVHD) in the bone marrow transplant patient. A study by Kirkpatrick and Greenberg
retrospectively characterized the CT features of neutropenic patients with radio-
graphic bowel abnormalities.18 Their findings note numerous differences between
the 3 entities described earlier, in terms of their CT appearance. NE was best charac-
terized by its predilection for the right colon and cecum, with episodic appearances in
the small bowel. It was also noted to exhibit the greatest degree of pneumatosis and
mesenteric stranding as compared with GVHD or C difficile colitis.18
For the ED physician, the hemodynamic stability of the patient is of paramount
importance in determining which imaging modality to use. Patients able to safely
tolerate transport to the CT scanner will benefit from a more detailed imaging modality
compared with ultrasound. CT may also help narrow the differential diagnosis by char-
acterizing the extent and nature of the BWT (Fig. 1).
Patients who are hemodynamically unstable may benefit from the rapid detection of
BWT using ultrasound, which can be performed at the bedside. For patients who are
critically ill, the ED physician should request emergent surgical consultation for poten-
tial operative resection of necrotic bowel.
Early case series of NE demonstrated a preference for surgical intervention.5 Early and
definitive resection of the ischemic bowel was associated with significant reductions in
overall mortality from NE. Heterogeneity of the disease process and its myriad presen-
tations, coupled with its incredibly high mortality rate, led many to believe in early
surgical therapy for all patients with NE. As experience with the disease has increased,
a greater proportion of the cases have been successfully managed medically, using
aggressive hemodynamic support, bowel rest, and broad-spectrum antibiotic therapy
with surgery reserved for the more severe cases.5,6,14
Antibiotic recommendations for patients with NE are numerous and varied. The
Infectious Disease Society of America published a lengthy series of guidelines for anti-
biotic use in neutropenic patients with cancer in 2002.19–23 Unfortunately, these guide-
lines only offer vague recommendations regarding abdominal infections. Overall, the
Fig. 1. Computed tomography of the abdomen illustrating bowel wall thickening associ-
ated with neutropenic enterocolitis. This is most notable in the upper portions of the image
surrounded by intraluminal contrast (arrows).
582 Cloutier
Table 1
Antibiotics for empiric treatment of adult and pediatric neutropenic enterocolitis
desired. Lastly, a vigilant eye must be kept on any acute changes in the abdominal
examination and the hemodynamic profile of the patient, pending transfer to an inten-
sive care unit or operative setting.
SUMMARY
REFERENCES