Hemolytic Uremic Syndrome (HUS): Rebaked Morsel

Diarrhea is one of the most common complaints in the pediatric emergency department, especially in the summer and early fall. Bloody diarrhea makes up approximately 15% of these enteritis presentations and though many causes are benign, some may be harboring something more insidious… Shiga Toxin-producing E.coli (STEC) and this may be associated with a terrible problem – Hemolytic Uremic Syndrome (HUS)! Let’s take a minute to review (and rebake) a morsel on Hemolytic Syndrome in children:

Hemolytic Uremic Syndrome: Basics

• HUS is associated with Shiga Toxin-producing E.coli (STEC)
  • STEC is a bacteria not uncommonly isolated in bloody diarrhea, but very commonly associated with hemolytic uremic syndrome (HUS).
  • The most notable varietal of the STEC is E.coli 0157:H7 (do you remember that from medical school?).
  • E.coli 0157:H7 may lead to HUS in young children (~15%).
  • Though most children recover well after STEC is cultured from their stool, some will go on to display the findings that make up HUS.

• HUS findings:
  • Microangiopathic hemolytic anemia,
  • Renal failure, and
  • Thrombocytopenia
  • The most dreaded outcomes of HUS include need for renal replacement therapy both short and long term and unfortunately death. 

• HUS is often associated with bloody diarrhea… but…
  • There is a variant of HUS (D-) that is not associated with diarrhea;
  • HUS (D-) does not have seasonal variation and is relatively uncommon.

Hemolytic Uremic Syndrome: Presentation 

• The diarrhea associated with typical HUS may be bloody or watery.
• Timing is critical:
  • Early signs of HUS occur in the first several days after diarrhea begins.
  • Diagnostic criteria can still be met up to 13-14 days out.
  • It is critical to detect HUS early in its disease course to ensure the best outcomes. 
    • Studies show that good hydration early in the course of HUS have been associated with fewer poor outcomes (ie, dialysis).
    • Two recent studies found early intravascular repletion provided in the first 4 days after symptoms (diarrhea) set in was associated with a lower risk of HUS.
    • This of course, is made easier if you can get a stool sample to analyze in the first place.

• A thorough review of vital signs, physical exam findings and a complete blood count with differential, renal function panel and urinalysis offer valuable information in the patient being worked up for HUS. 
• Physical Exam Findings:
  • Hypertension
  • Lethargy
  • Decreased urine output
  • Darkening of the urine
  • Periorbital edema (that’s most prominent in the AM) 

• Early Lab Indicators:
  • Hyponatremia
  • Thrombocytopenia
  • Increased white count (>13,000)
  • Increased hematocrit
  • Creatinine above normal for the patient’s age/baseline 

• Utility of Ultrasound:
  • There are some key finding on ultrasound can help clue you in to HUS
  • These may prove useful in early identification of patients developing HUS in the setting of bloody diarrhea:
    • Marked thickening of the large bowel and interstitial wall
    • Increased echogenicity of the renal parenchyma (from immune complex deposition in the glomeruli).

Moral of the Morsel

• It’s not an anal fissure! Sure this may cause blood in stool, but consider Hemolytic Uremic Syndrome when evaluating pediatric patients with Bloody Diarrhea.
• Protect the Kidneys! Considering HUS and treating dehydration early has been shown to help keep the dialysis machine away!

References: 

Glatstein M, Miller E, Garcia-Bournissen F, Scolnik D. Timing and utility of ultrasound in diarrhea-associated hemolytic uremic syndrome: 7-year experience of a large tertiary care hospital. Clin Pediatr (Phila). 2010 May;49(5):418-21. doi: 10.1177/0009922809342582. Epub 2010 Jan 13. PMID: 20075028.

McKee,R., Schnadower, D., Tarr, P., Xie,J., Finkelstein, Y.,Desai, N., Lane, R., Bergmann, K., Kaplan, R., Hariharan, S., et al. 2020. HUS and RRT in STEC-infected Children. CID 2020:70 (15 April) 

Lin CY, Xie J, Freedman SB, McKee RS, Schnadower D, Tarr PI, Finkelstein Y, Desai NM, Lane RD, Bergmann KR, Kaplan RL, Hariharan S, Cruz AT, Cohen DM, Dixon A, Ramgopal S, Powell EC, Kilgar J, Michelson KA, Bitzan M, Yen K, Meckler GD, Plint AC, Balamuth F, Bradin S, Gouin S, Kam AJ, Meltzer JA, Hunley TE, Avva U, Porter R, Fein DM, Louie JP, Tarr GAM; Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Medicine Collaborative Research Committee (PEMCRC) STEC Study Group. Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments. J Pediatr. 2021 May;232:200-206.e4. doi: 10.1016/j.jpeds.2020.12.077. Epub 2021 Jan 5. PMID: 33417918; PMCID: PMC8084908.