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)

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.


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

 

Management

  • 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

 

Pearls:

  • Emergency clinicians need to consider this in immunocompromised population as mortality can range as high as 50%.
  • Many chemotherapeutics as well as immunosuppressives with off label use can induce typhlitis.
  • CT is gold standard though US can provide helpful information.
  • Initial management includes resuscitation, bowel rest, broad-spectrum antibiotics.
  • Surgical consultation should be reserved for severe cases.

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/

 

References

  1. Gray TL, Ooi CY, Tran D, Traubici J, Gerstle JT, Sung L. Gastrointestinal complications in children with acute myeloid leukemia. Leuk Lymphoma. 2010 May;51(5):768-77. doi: 10.3109/10428191003695652. PMID: 20350277.
  2. Urbach DR, Rotstein OD. Typhlitis. Can J Surg. 1999 Dec;42(6):415-9. PMID: 10593241; PMCID: PMC3795130.
  3. Shamberger RC, Weinstein HJ, Delorey MJ, Levey RH. The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia. Cancer. 1986 Feb 1;57(3):603-9. doi: 10.1002/1097-0142(19860201)57:3<603::aid-cncr2820570335>3.0.co;2-k. PMID: 3484659.
  4. Gorschlüter M, Mey U, Strehl J, Ziske C, Schepke M, Schmidt-Wolf IG, Sauerbruch T, Glasmacher A. Neutropenic enterocolitis in adults: systematic analysis of evidence quality. Eur J Haematol. 2005 Jul;75(1):1-13. doi: 10.1111/j.1600-0609.2005.00442.x. PMID: 15946304.
  5. Tamburrini S, Setola FR, Belfiore MP, et al. Ultrasound diagnosis of typhlitis. J Ultrasound. 2019;22(1):103-106. doi:10.1007/s40477-018-0333-2
  6. Rodrigues FG, Dasilva G, Wexner SD. Neutropenic enterocolitis. World J Gastroenterol. 2017 Jan 7;23(1):42-47. doi: 10.3748/wjg.v23.i1.42. PMID: 28104979; PMCID: PMC5221285.
  7. Cartoni C, Dragoni F, Micozzi A, Pescarmona E, Mecarocci S, Chirletti P, Petti MC, Meloni G, Mandelli F. Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography. J Clin Oncol. 2001 Feb 1;19(3):756-61. doi: 10.1200/JCO.2001.19.3.756. PMID: 11157028.
  8. Carter D, Eliakim R. Feasibility of Bedside Bowel Ultrasound Performed by a Gastroenterologist for Detection and Follow-Up of Inflammatory Bowel Disease. Isr Med Assoc J. 2017 Mar;19(3):139-142. PMID: 28457088.
  9. Anupindi SA, Halverson M, Khwaja A, Jeckovic M, Wang X, Bellah RD. Common and uncommon applications of bowel ultrasound with pathologic correlation in children. AJR Am J Roentgenol. 2014 May;202(5):946-59. doi: 10.2214/AJR.13.11661. PMID: 24758646.
  10. Li K, Zheng S, Dong K, Gao Y, Wang H, Liu G, Gao J, Xiao X. Diagnosis and outcome of neutropenic enterocolitis: experience in a single tertiary pediatric surgical center in China. Pediatr Surg Int. 2011 Nov;27(11):1191-5. doi: 10.1007/s00383-011-2938-9. Epub 2011 Jun 11. PMID: 21667116.
  11. Ullery BW, Pieracci FM, Rodney JR, Barie PS. Neutropenic enterocolitis. Surg Infect (Larchmt). 2009 Jun;10(3):307-14. doi: 10.1089/sur.2008.061. PMID: 19566419.
  12. Rodrigues FG, Dasilva G, Wexner SD. Neutropenic enterocolitis. World J Gastroenterol. 2017;23(1):42-47. doi:10.3748/wjg.v23.i1.42
  13. Chakravarty K, Scott DG, McCann BG. Fatal neutropenic enterocolitis associated with sulphasalazine therapy for rheumatoid arthritis. Br J Rheumatol. 1992 May;31(5):351-3. doi: 10.1093/rheumatology/31.5.351. PMID: 1349846.
  14. Bibbo C, Barbieri RA, Deitch EA, Brolin RE. Neutropenic enterocolitis in a trauma patient during antibiotic therapy for osteomyelitis. J Trauma. 2000 Oct;49(4):760-3. doi: 10.1097/00005373-200010000-00029. PMID: 11038099.
  15. Stentoft J. The toxicity of cytarabine. Drug Saf. 1990 Jan-Feb;5(1):7-27. doi: 10.2165/00002018-199005010-00003. PMID: 2178634.
  16. Cardona Zorrilla AF, Reveiz Herault L, Casasbuenas A, Aponte DM, Ramos PL. Systematic review of case reports concerning adults suffering from neutropenic enterocolitis. Clin Transl Oncol. 2006 Jan;8(1):31-8. doi: 10.1007/s12094-006-0092-y. PMID: 16632437.
  17. van Vliet M, van der Hoeven HJ, van der Velden WJ. Abdominal compartment syndrome in neutropenic enterocolitis. Br J Haematol. 2013 Feb;160(3):273. doi: 10.1111/bjh.12140. Epub 2012 Dec 4. PMID: 23206290.
  18. Wade DS, Douglass H Jr, Nava HR, Piedmonte M. Abdominal pain in neutropenic patients. Arch Surg. 1990 Sep;125(9):1119-27. doi: 10.1001/archsurg.1990.01410210045006. PMID: 2400304.
  19. Mullassery D, Bader A, Battersby AJ, Mohammad Z, Jones EL, Parmar C, Scott R, Pizer BL, Baillie CT. Diagnosis, incidence, and outcomes of suspected typhlitis in oncology patients–experience in a tertiary pediatric surgical center in the United Kingdom. J Pediatr Surg. 2009 Feb;44(2):381-5. doi: 10.1016/j.jpedsurg.2008.10.094. PMID: 19231539.
  20. Cloutier RL. Neutropenic enterocolitis. Emerg Med Clin North Am. 2009 Aug;27(3):415-22. doi: 10.1016/j.emc.2009.04.002. PMID: 19646645.
  21. Moran H, et al. Risk Factors for Typhlitis in Pediatric Patients with Cancer. J Pediatr Hematol Oncol 2009;31:630-634.

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