Typhilitis

• Polymicrobial infiltration of the colonic wall in severely neutropenic patients.
• Luminal narrowing and wall thickening of the cecum and ascending colon

Description

Typhilitis, also known as neutropenic enterocolitis, is a life-threatening acute inflammatory and necrotising colitis predominantly seen in patients with profound neutropenia. It typically involves the cecum and occasionally the terminal ileum/appendix. The term “typhlitis” is derived from the Greek “typhlon,” meaning cecum. The condition is particularly associated with patients undergoing chemotherapy, thereby suffering from compromised immune systems. It is the most common severe gastrointestinal complication in neutropenic patients.

Pathogenesis

Typhilitis results from a combination of mucosal barrier injury, local immunosuppression, and dysregulation of intestinal flora, primarily due to cytotoxic chemotherapy. The damaged mucosa and reduced immune response allow for bacterial translocation, which, in the context of neutropenia, can lead to rapid progression to necrosis and perforation.

Epidemiology, Risk Factors & Associations

• Chemotherapy (greatest risk factor, especially those with high mucotoxic profiles)
• Haematological malignancies (most common association, due to frequent induction of profound neutropenia)
• Bone marrow transplant recipients
• Severe, prolonged neutropenia (>10 days, with neutrophil counts typically below 0.5 x 10^9/L)

Clinical Features

• Acute abdominal pain, typically localised to the right lower quadrant
• Fever
• Diarrhoea or constipation
• Signs of sepsis in severe cases
• Pathognomonic signs include severe tenderness over the cecum, absent bowel sounds in advanced cases.

Complications

• Bowel perforation (can occur in severe cases, necessitating surgical intervention). Risk is included by performing barium enema, hence it is contraindicated.
• Sepsis (common progression from local infection, especially without prompt treatment)
• Gastrointestinal bleeding (less common, but significant when occurs)

Pathological Features

Histopathology

• Macroscopic: Bowel wall thickening, often localised to the cecum and terminal ileum.
• Microscopic: Transmural inflammation, mucosal necrosis, and evidence of bacterial infiltration in severe cases.

Radiological Features

General Features

• Typical appearance includes bowel wall thickening, particularly of the cecum, ascending colon and adjacent ileum, causing luminal narrowing.
• Pneumatosis intestinalis and portomesenteric venous gas are critical radiological signs indicating severe disease and potential for perforation.
• Associated findings in severe cases include free fluid and signs of perforation.

CT

• Portal Venous Phase
  • CT is the most sensitive modality for diagnosis and complication detection.
  • Bowel wall thickening
    • >4 mm considered abnormal; usually involves caecum ± ascending colon ± terminal ileum
    • Thickening is circumferential, symmetric, and homogeneous in early disease
    • May be up to 2–3 cm thick in severe cases
    • Mucosal enhancement pattern:
      • Mucosal hyperenhancement in early inflammatory stages
      • Hypoenhancement or non-enhancing segments may indicate necrosis or impending perforation
  • Pericolonic fat stranding
    • Often disproportionate to degree of wall thickening
    • Indicates transmural inflammation and early serosal extension
    • Fat stranding may extend to adjacent mesentery or retroperitoneum
  • Pneumatosis intestinalis
    • Intramural gas is a critical red flag indicating transmural necrosis
    • Appears as linear or bubbly hypodense areas within the bowel wall
  • Portal venous gas or pneumoperitoneum
    • Late or ominous signs
    • Indicate bowel necrosis, gangrene, or perforation
    • May precede clinical signs of peritonitis in neutropenic patients
  • Caecal dilatation
    • In some cases, a ballooned caecum may be seen due to localised ileus
    • Should raise suspicion even in absence of overt mural thickening
  • Fluid-filled bowel loops
    • Suggestive of impaired motility or evolving necrosis
    • Not specific but often seen in the inflamed caecum or adjacent colon
  • Adjacent fluid collections or abscesses
    • Low-density collections with or without rim enhancement
    • Rare but significant when present; increase likelihood of surgical intervention

FL

• Barium Enema: Contraindicated due to high risk of perforation

Grading and Staging

Not applicable for typhilitis as it does not have a formal grading or staging system.

Diagnosis

Diagnosis is primarily based on clinical presentation in conjunction with radiological findings, especially in the setting of neutropenia.

Differential Diagnosis

Clinically-based

• Appendicitis: typically presents with similar right lower quadrant pain but usually occurs in immunocompetent patients.

Imaging-based

• Inflammatory bowel disease: can cause similar symptoms; however, does not typically present acutely in neutropenic patients.
• Infectious colitis: may mimic typhilitis but often has a different clinical context.
• Pseudomembranous colitis: Usually pancolonic but can be segmental
• Ischemic colitis: Rarely limited to the ascending colon.

Management

• Immediate cessation of the offending chemotherapeutic agent.
• Broad-spectrum antibiotics.
• Supportive care, including fluids and, if necessary, surgical intervention for complications like perforation.
• Referral to a gastroenterologist and a surgeon, especially in severe cases.