EM@3AM: Typhlitis

Author: Rachel Bridwell, MD (@rebridwell, EM Resident Physician, San Antonio, TX) // Reviewed by: Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX); Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 62-year-old male is brought to the ED by his wife for abdominal pain and fever for 2 days. He has recently completed induction chemotherapy for AML with cytarabine and daunorubicin a few days prior. Review of systems is remarkable for vomiting and anorexia. He denies previous abdominal surgeries or tobacco history.

Exam reveals BP 96/69 mm Hg, HR 122, T 101.9 oral, RR 28, SpO2 97% on room air. He is ill appearing and has dry mucous membranes but no mucositis. Abdominal exam reveals guarding and tenderness in the right lower quadrant.

What is the diagnosis, and what’s the next step in your evaluation and treatment?

Epidemiology:

• Typhlitis or neutropenic enterocolitis is a life-threatening process involving the cecum which can spread to the ascending colon or terminal ileum
• Commonly associated with acute myeloid leukemia and acute lymphoblastic leukemia
• Etiology is multifactorial to include:
  • Profound neutropenia and immunocompromised status
  • Increased invasion of micro-organisms
  • Injury of the gastric mucosa secondary to cytotoxic drugs with possible ulceration
  • Engorged vessels
• Drugs most responsible include taxane drugs, cytosine arabinoside (Cytarabine), gemcitabine, vincristine, cyclophosphamide, 5-fluorouracil, leucovorin, and daunorubicin, though a variety of chemotherapeutics have been implicated
  • Cytosine arabinoside has an association with typhlitis due to its adverse effects, specifically ileus and gastrointestinal toxicity especially in mucosal surfaces
  • Additionally, immunosuppressive agents for organ transplant and sulfasalazine have contributed to typhlitis
• Associated with chemotherapy within 2 weeks of symptom onset and stem cell transplant
• Incidence of pediatric typhlitis in acute leukemia ranges from 0.35- 33%
• In adults, frequency is estimated at 5.6%
• Diagnosis delay carries a high mortality rate ranging from 21-50%

Microbiology

• Implicated organisms include gram-negative rods, gram-positive cocci, enterococci, viruses, and fungi
  • Contributions from translocation and bacteremia
  • Associations with:
    • Clostridium septicum
    • E. coli
    • S. pneumoniae
    • Enterobacter spp.
    • Morganella morganii
    • S. viridans spp.
    • Fungi

Clinical Presentation:

• Fever, abdominal pain, nausea, diarrhea
  • Trifecta of abdominal pain, neutropenia, and fever occur in 78% of pediatric patients
    • In contrast, abdominal pain absent in 9%, fever absent in 16%
    • Neutropenia absent in 12%
  • Distension also common
  • Localized RLQ pain or diffuse
  • If late presentation, abdominal compartment syndrome may occur, presenting with distension and ascites
  • Melena and hematochezia are more rare presentations
  • If bowel necrosis and perforation have occurred, patient may present with peritonitis and profound decompensation

Evaluation:

• Assess ABCs
  • Fever, hypotension, tachycardia
• Perform a complete physical examination
  • Abdominal exam to assess for tenderness, peritonitis, guarding, rebound
  • Diligent integumentary exam in the setting of immunocompromised state
  • Check for mucositis in oropharynx
• Imaging:
  • Abdominal radiography may show a dilated cecum, small bowel dilation, as well as an ascending colon with liquid or gaseous contents, though sensitivity and specificity are lacking
  • Computed tomography is optimal for diagnosis, can evaluate severity of disease, and assess for etiologies and other complications
    • Findings include:
      • Cecal wall thickening circumferentially—suggests need for surgical treatment and finding affects prognosis
        • Colonic wall thickness of greater than 1 cm carries a mortality rate of 60%
      • Pericolonic inflammation
      • Pneumatosis
      • Perforation

• • Ultrasound may provide rapid point of care assessment in clinically unstable patients
  • Findings include:
    • Wall thickening
    • Fluid collection
    • Increased bowel layer echogenicity
    • Lymphadenopathy
    • Hyperemic bowels

• Laboratory evaluation:
  • CBC with differential
    • Absolute neutrophil count <500/uL are at greatest risk of developing typhlitis
    • ANC of 1000/uL has been reported in typhlitis cases
    • Recovery of leukocyte counter after typhlitis has been associated with survival
    • Concomitant thrombocytopenia common
  • Blood culture to include 2 peripherals and any indwelling lines as well as stool culture

• ABCs—Assess for degree of septic shock and aggressive resuscitate
• Antimicrobials:
  • Piperacillin-tazobactam +/- aminoglycoside
  • Cefepime or ceftazidime plus metronidazole
  • Imipenem-cilastatin/meropenem
  • In those with high risk for C. difficile, add oral vancomycin or fidaxomicin
• Bowel rest
  • Possible villous atrophy and integrity breaching
  • Consider parenteral nutrition in patients at risk for malnutrition
• Consult hematology-oncology
• Consider surgical consult in severe disease:
  • Bowel perforation
  • Uncontrolled bleeding status post pancytopenia correction
  • Abscess
  • Bowel necrosis
  • No primary anastomosis recommended
• Disposition: admit with oncology and possible surgical consultation

Further Reading:

FOAM Resources

1. https://pedemmorsels.com/typhlitis/
2. https://foamcast.org/tag/foam/
3. https://emergencymedicinecases.com/episode-33-oncologic-emergencies/
4. http://www.emdocs.net/ed-management-bone-marrow-transplant-patient-pearls-pitfalls/
5. https://litfl.com/neutropaenic-sepsis/

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