Neutropenic enterocolitis, also known as Typhilitis is a medical emergency seen in neutropenic patients especially cancer patients who receive myelosuppressive therapy.

1. Neutropenic
Enterocolitis
Prepared by:
Tarek Ahmed
Pediatric Oncology Resident
National Cancer Institute-Cairo University

2. Introduction
• life-threatening, necrotizing enterocolitis occurring primarily in neutropenic
patients.
• 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” describes neutropenic enterocolitis of the ileocecal region; the
more inclusive term, “neutropenic enterocolitis,” is appropriate when other
parts of the small and/or large intestine are involved.

3. PATHOGENESIS
• Incompletely understood.
• It probably involves a combination of factors, including mucosal injury by
cytotoxic drugs or other means, profound neutropenia, and impaired host
defense to invasion by microorganisms.
• The microbial infection leads to necrosis of various layers of the bowel wall.
The cecum is almost always affected.
• The predilection for the cecum is possibly related to its distensibility and its
diminished vascularization relative to the rest of the colon.

4. • Gross and histologic examinations may reveal bowel wall thickening, discrete
or confluent ulcers, mucosal loss, intramural edema, hemorrhage, and
necrosis.

5. RISK FACTORS AND INCIDENCE
• Originally reported in children who underwent induction chemotherapy for
acute leukemia.
• It has subsequently been described in children and adults with acute myeloid
leukemia, multiple myeloma, myelodysplastic syndromes, aplastic anemia,
acquired immunodeficiency syndrome, cyclic or drug-induced neutropenia,
and after immunosuppressive therapy for solid malignancies and transplants.
• The true incidence of Neutropenic Enterocolitis is unknown.

6. CLINICAL MANIFESTATIONS
• Neutropenic Enterocolitis must be considered in the differential diagnosis of any
profoundly neutropenic patient (absolute neutrophil count <500 cells/microL), who
presents with fever and abdominal pain, usually in the right lower quadrant.
• Symptoms often appear 10 to 14 days after cytotoxic chemotherapy, at a time when
neutropenia is most profound and the patient is febrile.
• Additional symptoms may include abdominal distension, nausea, vomiting, and
watery or bloody diarrhea.
• Peritoneal signs and shock suggest the possibility of bowel wall perforation.
Stomatitis and pharyngitis, suggesting the presence of widespread mucositis.

7. DIAGNOSIS
• Neutropenic Enterocolitis is usually diagnosed by characteristic computed
tomography (CT) or ultrasound findings in high-risk patients.
• CT is the preferred diagnostic modality since it appears to have a lower false-
negative rate of diagnosis (15 percent) than does ultrasound (23 percent) or plain x-
rays of the abdomen (48 percent).
• Findings include the presence of a fluid-filled, dilated and distended cecum.
• Findings on CT may include diffuse cecal wall thickening; presence of intramural
edema, air or hemorrhage; localized perforation with free air; or soft tissue mass
suggesting abscess formation.

9. • CT is usually helpful in the differentiation of typhlitis from appendicitis,
appendiceal abscess, or even pseudomembranous colitis.
• Blood and stool cultures and C. difficile toxin assays should be performed.
• Plain films of the abdomen are nonspecific but, occasionally, a fluid-filled, distended
cecum with dilated adjacent small bowel loops, thumbprinting, or localized
pneumatosis intestinalis is seen.
• In a stable patient with possible typhlitis without an indication for an emergency
laparotomy, a diagnostic laparoscopy can be considered when the diagnosis remains
in doubt despite cross-sectional CT imaging

10. • Barium enema is hazardous in the presence of potentially necrotic bowel, since it
can cause perforation.
• Similarly, colonoscopy is relatively contraindicated in the presence of neutropenia
and thrombocytopenia, and air insufflation may precipitate cecal perforation.
• However, it may be reasonable to perform a flexible sigmoidoscopy with gentle
manipulation and air insufflation if pseudomembranous colitis is suspected,
although a sigmoidoscopy may be negative despite the presence of infection since
pseudomembranes confined to the cecum have been described in neutropenic
cancer patients with C. difficile infection.

11. • In those very few patients who underwent colonoscopic examination,
mucosal irregularity with nodularity, ulcerations, and hemorrhagic friability, as
well as a mass-like lesion mimicking carcinoma have been described.

12. MANAGEMENT
• In patients without complicated Neutropenic Enterocolitis (ie, peritonitis,
perforation, or severe bleeding), nonsurgical management with bowel rest,
nasogastric suction, intravenous fluids, nutritional support, blood product support
(packed red blood cells and fresh frozen plasma as needed), and broad-spectrum
antibiotics is a reasonable initial approach.
• Examples of appropriate antimicrobial regimens include piperacillin-tazobactam as
monotherapy or combination therapy
with cefepime or ceftazidime plus metronidazole.
• Antibiotic coverage for C. difficile should be added if pseudomembranous colitis
has not been excluded.

13. • Fungemia and fungal invasion of the bowel can occur. As a result, an
antifungal agent should be started in neutropenic patients with protracted
fever (>72 hours) despite broad-spectrum antibiotics.
• An antifungal agent with activity against fluconazole-resistant Candida spp as
well as Aspergillus spp is favorable. Examples of appropriate antifungal
agents include voriconazole and amphotericin B formulations.
• Anticholinergic, antidiarrheal, and opioid agents should be avoided since they
may aggravate ileus.

14. • Surgical intervention is recommended for those with peritonitis, free perforation,
persistent gastrointestinal bleeding despite correction of coagulopathy and
cytopenias, or clinical deterioration during close observation and serial
examinations.
• If surgery is performed, a two-stage right hemicolectomy is the preferred approach,
and further chemotherapy should be delayed until recovery. A surgeon may be
tempted not to resect edematous bowel without apparent severe inflammation or
gangrene. The caveat is that diffuse mucosal necrosis may be present underneath
unimpressive serosal inflammation; incomplete removal of all necrotic tissue
uniformly results in death.

16. • Patients developing Neutropenic Enterocolitis during chemotherapy are
prone to develop this complication again during subsequent treatments.
Sufficient time should be allowed for complete healing. In addition, bowel
decontamination has been suggested before resumption of chemotherapy.

17. PROGNOSIS
• Initial reports of patients with Neutropenic Enterocolitis described
mortality rates between 40 to 50 percent, with most deaths attributed to
transmural bowel necrosis, perforation, and sepsis. More recently, early
recognition and progress in management have probably reduced mortality.