Introduction
Background
Neutropenic enterocolitis is an acute life-threatening condition characterized by transmural inflammation of the small and large bowel in patients who are severely myelosuppressed and immunosuppressed.
The clinical presentation 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. Early recognition of the condition is paramount to a potentially good outcome.
Over the past 3 decades, this condition has increasingly been reported in adults with a variety of myeloproliferative disorders and solid malignant tumors and in adults who have had solid organ and bone marrow transplantation. Some cases in adults are due to the increasing use of myelotoxic chemotherapeutic regimens.
Pathophysiology
Although the exact etiology and progression are unknown, profound neutropenia appears to be the common denominator. Many factors have been described that may potentially play a role in the pathogenesis and include the following:
- Mucosal injury is 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, may compromise the blood supply, leading to further mucosal damage.
- The use of antibiotics and steroids may contribute to an altered enteric bacterial flora and overgrowth of fungi.
- Bacterial invasion of the impaired bowel wall may result in transmural inflammation, leading to perforation and peritonitis. Bacteremia, often recurrent, is a frequent complication.
The pathologic process appears to 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 are unknown because many patients survive and are never diagnosed. An autopsy study in children reported a prevalence rate of 24%, while a cohort study in children treated for acute myelogenous leukemia reported a frequency rate of 33%. Data regarding neutropenic enterocolitis in adults are sparse. In one systematic review, a 5.3% pooled incidence rate has been reported in adults.
International
An even greater paucity of information regarding the international incidence and prevalence rates of neutropenic enterocolitis exists in the published literature. A recent study from India performed by Jain et al (2000) has reported a frequency rate of 6.1% in 180 children undergoing chemotherapy for acute lymphocytic leukemia. A retrospective study from Turkey performed by Buyukasik et al (1997) reported an incidence rate of 6.5% for neutropenic enterocolitis in acute myeloid leukemia and 4.6% for neutropenic enterocolitis in acute lymphoblastic leukemia in adults.
Mortality/Morbidity
- Mortality rates of 5-100% have been reported during conservative management, with an average of about 40-50%.
- In a collective review of 178 published cases, the mortality rate 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.
Race
No predilection for any specific race is reported in the literature.
Sex
No sex predilection is reported in the literature.
Age
- No known frequency differences in age groups exist based on the published literature.
- Although neutropenic enterocolitis initially was described in children, it is increasingly reported in adults.
Clinical
History
Most patients who are affected with neutropenic enterocolitis are receiving antineoplastic drugs and are profoundly neutropenic (ie, <1000 cells/mm3).
- Symptoms 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 - May be cramping and intermittent or a continuous dull ache
- Fever
- Watery or bloody diarrhea - Occurs in about 25-45% of patients
- Nausea
- Vomiting
- Abdominal distention
- Oral and pharyngeal mucositis may manifest prior to the onset of colonic symptoms.
- The time course and severity of the clinical presentation is variable.
Physical
Physical findings vary depending on the severity of the disease and the presence or absence of complications.
- Abdominal distention, absence of 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 may suggest colonic perforation.
- Sepsis may elicit shock.
Causes
Although cytotoxic chemotherapeutic agents account for most cases, 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.
- Other predisposing conditions include the following:
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Further Reading
Keywords
necrotizing enterocolitis, ileocecal syndrome, typhlitis, acute ileocecal enterocolitis, transmural inflammation of the small bowel and large bowel in myelosuppression and immunosuppression, profound neutropenia, cecum, ileum, ascending colon, typhlitis, cecitis, right lower quadrant pain
Overview: Neutropenic Enterocolitis