Introduction:
Neutropenic enterocolitis (NEC) or typhlitis is a rare medical condition that causes inflammation (swelling) of the cecum and sometimes involves ascending colon or the terminal ileum. It is often associated with neutropenia (decreased white blood cell [WBC] count). Neutropenic enterocolitis is also referred to as necrotizing enterocolitis or ileocecal syndrome. The causes of neutropenic enterocolitis are mostly polymicrobial, including gram-negative bacilli, anaerobes, gram-positive cocci, and fungi. It is most commonly caused by Pseudomonas aeruginosa, Bacteroides spp, Viridian group streptococci, Escherichia coli, Klebsiella spp, Enterococci, Clostridium spp, and Candida spp. Of which Clostridium septicum and Stenotrophomonas maltophilia cause severe sepsis.
What Are the Symptoms of Neutropenic Enterocolitis?
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The most common symptoms include abdominal pain, fever, and diarrhea. In severe cases, there might be chances of bloody diarrhea.
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Abdominal distension and paralytic ileus are also seen.
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Fever might be absent in severe neutropenia.
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Abdominal pain usually occurs in the right lower quadrant and may be diffuse or localized. Mucositis of oral or anal mucosa helps confirm the diagnosis of neutropenic enterocolitis. Rigid abdomen refers to abdominal perforation.
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Patients with complicated NEC appear ill, febrile, and dehydrated, with unstable vital signs.
What Is the Pathophysiology of Neutropenic Enterocolitis?
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The pathology of neutropenic enterocolitis is not yet clearly identified as it is secondary to many other causes. However, one of the mechanisms is that the body’s exposure to cytotoxic medications disrupts the mucosal barrier, and it allows the translocation of bacteria from the gut. This bacterial invasion into the colonic wall causes necrosis and perforation.
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Further, neutropenic enterocolitis (NEC) is also associated with malignant patients under chemotherapeutic agents (anti-cancer drugs). The most commonly associated chemotherapeutic drugs are Etoposide, Cytosine Arabinoside, Taxane-based agents, and Etoposide corticosteroids. The chemotherapeutic agents cause mucosal injuries such as mucositis, necrosis of the cecal wall, and cecal wall distension and alter the intestinal peristalsis.
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Sometimes radiotherapy can cause intestinal mucositis, which coexists with leukemic infiltrate or intramural hemorrhage due to thrombocytopenia (abnormally low platelet count).
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The histopathological findings show intestinal wall edema, disruption of the mucosal surface, and engorged blood vessels. Surgical evaluation of neutropenic enterocolitis shows thickened and swollen bowels with areas of ulceration and hemorrhage.
What Are the Radiological Findings of Neutropenic Enterocolitis?
Ultrasonography:
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In ultrasonography, neutropenic enterocolitis appears as thickened hypoechoic bowel wall, thickened echogenic mucosa, and decreased or absent bowel peristalsis in the right lower quadrant of the abdomen (RLQ).
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Color Doppler ultrasound reveals hypervascularity of the bowel wall and mucosa.
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Sometimes, the patient complains of pain while pressing the transducer.
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Ultrasonography cannot differentiate perforation or abscess with NEC and requires additional imaging techniques.
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Small bowel distension with air produces a ring-down artifact on ultrasonography, thus heightening the visualization of the right colon.
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In severe neutropenic enterocolitis cecal wall usually measures above 1 cm.
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Localized hypokinesis of affected bowel loops preserves motility.
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Pericecal fat appears as increased echogenicity.
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Haustral folds in the affected colonic area are often preserved.
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In some pediatric patients, echogenic thickening of mucosa has been reported.
Computed Tomography (CT) Scan:
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In a computed tomography scan, neutropenic enterocolitis appears as circumferential, eccentric low attenuation thickening of the colon wall and cecal distention.
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High attenuation colonic wall thickening represents hemorrhage.
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CT scan easily identifies the complications of neutropenic enterocolitis, such as pneumoperitoneum, pneumatosis coli, pericolonic fluid collection, and abscess. These complications require immediate surgical management.
What Are the Diagnostic Criteria Used in Neutropenic Enterocolitis?
NEC diagnosis should be based on a combination of radiological and clinical findings.
Gorschluter et al. provided diagnostic criteria for NEC, which include fever, bowel wall thickening, and abdominal pain, along with the exclusion of Clostridium difficile as a cause of the swelling of the colon (colitis).
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Fever (axillary temperature above 38.0 degrees Celsius or rectal temperature over 38.5 degrees Celsius).
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Abdominal pain (in an analogous visual scale with the pain score of degree 1 to 10, the patient should determine at least degree 3).
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In computed tomography or ultrasonography, the bowel wall thickening is demonstrated as more than 4 mm in the transverse scan and more than 30 mm in the longitudinal scan.
How Is Neutropenic Enterocolitis Treated?
Supportive Therapy-
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Bowel rest with nasogastric suction.
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Parenteral nutrition.
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Intravenous (IV) fluids.
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In severe thrombocytopenia, platelet replacement is done.
Antimicrobial Therapy-
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Broad-spectrum antimicrobial therapy is required in neutropenic enterocolitis.
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Monotherapy with a Carbapenem, Piperacillin-Tazobactam, or Cephalosporin such as Cefepime with Metronidazole.
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If mucositis is present, treatment is given against gram-positive bacteria. In such a case, Vancomycin is considered.
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A combination of anti-microbial therapy with Tigecycline increases the survival rate in NEC.
Surgery-
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The surgery is recommended for complicated neutropenic enterocolitis (NEC), including bowel perforation, pneumoperitoneum (abnormal collection of gas or air in the abdominal cavity), or gastrointestinal bleeding.
What Are the Differential Diagnosis of Neutropenic Enterocolitis?
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Clostridium difficile infection - Infection of the large intestine causes inflammation (swelling) of the colon.
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Acute appendicitis - Inflammation of the finger-shaped projection from the colon causes sudden pain in the lower right side of the abdomen.
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Cytomegalovirus colitis - Inflammation of the colon due to Cytomegalovirus causes abdominal pain, diarrhea, rectal bleeding, and fever.
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Norovirus infection - A highly contagious viral infection that causes severe diarrhea and vomiting.
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Ischemic colitis - Inflammation of the large intestine or colon due to blood flow restriction.
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Graft versus host disease in transplant patients - A complication of the stem cell or bone marrow transplant in which the graft (donor cells) attacks the host cells (body's cells) by considering them as foreign bodies.
Conclusion:
An uncommon medical disorder called neutropenic enterocolitis (NEC), also known as typhlitis, causes inflammation (swelling) of the cecum and may also affect the ascending colon or the terminal ileum. It frequently goes hand in hand with neutropenia (decreased white blood cell [WBC] count). Necrotizing enterocolitis and ileocecal syndrome are other names for neutropenic enterocolitis. Patients with neutropenia (neutrophil count less than 500 per microliter) are at increased risk for neutropenic enterocolitis. Angiography is not a routine examination tool in neutropenic enterocolitis. If the entire cecum is hypervascular, it may be shown as intense staining of cecal folds and mucosa in angiography. The ileocecal part of the intestine becomes more vulnerable to neutropenic enterocolitis because of abundant lymphoid tissue, decreased vascularity (blood supply), increased stasis, and their ability to distend (expand). The mortality rate of neutropenic enterocolitis is higher in post-chemotherapy patients.
