Hemolytic Uremic Syndrome

Today, we talked about the case of a middle aged woman with recent diagnosis of metastatic breast cancer on palliative Paclitaxel who was admitted with acute onset of bloody diarrhea found to have Shiga toxin and progression to HUS!  She developed neurologic manifestations for which she underwent PLEX and is now recovering in rehab.


Clinical Pearls

  • TTP and HUS present very similarly and are difficult to distinguish clinically.  HUS typically has worse renal failure than TTP and rarely has neurologic manifestations.
  • Because they are tough to tease apart, start PLEX early if TTP is on your differential for HUS because TTP has a high mortality rate.
  • Acute diarrhea requires work up in those with severe illness, inflammatory features, risk factors, persistent symptoms, or work in fields that are of public health related concern (food handlers, daycare workers, etc.)
  • The most common cause of acute bloody diarrhea worldwide is shigella.
  • Bloody diarrhea with a normal fecal leukocyte/lactoferrin count is highly suggestive of E. histolytica.
  • Majority of shiga toxin produced in adults is by E coli.
  • Avoid antibiotics if possible in a patient with bloody diarrhea due to shiga toxin as it can precipitate HUS.

Indications for work up of acute diarrhea:

  • Age >65
  • Immunocompromised
  • Significant volume depletion
  • Blood in stool
  • Fever
  • Severe abdominal pain
  • Recent antibiotics
  • Known or suspected IBD
  • Food handler, daycare worker, healthcare worker
  • Recent travel

DDx for acute bloody diarrhea:

  • IBD
  • Ischemic colitis
  • Invasive infections
    • Shigella (most common)
    • EHEC and EIEC (most commonly associated with shiga toxin)
    • Campylobacter
    • Nontyphoidal salmonella
    • Entamoeba histolytica
    • Schistosoma (more common in resource limited settings)

Work up for acute bloody diarrhea:

  • Enteric pathogen panel (NAAT):
    • Campylobacter, salmonella, shigella species, vibrio, yersinia, shiga toxins, norovirus, and rotavirus
  • Stool culture
    • Grows campylobacter, Shigella, Salmonella, and E coli strains. If suspecting other organism, must specifically request that culture from lab
  • Stool leukocytes or lactoferrin
    • More helpful if negative to rule in amebiasis.

Shiga toxin mediated hemolytic uremic syndrome

  • Characterized by the triad of MAHA, thrombocytopenia, and acute renal failure. Rare neurologic manifestations can occur as in our patient.
    • Other clinical symptoms ⇒ bloody stools, absence of fever, WBC>10k, and abdominal pain.
    • 23-47% require hospitalization
  • 6-9% of people infected with EHEC (O157:H7 and O104:H4) can go on to developing HUS and it is much more common in children.
  • Pathophys
    • Ingestion of undercooked beef and E coli
    • Shiga toxin produced by E coli binds to vascular endothelial cell surface, thereby inhibiting protein synthesis, generating lots of cytokines and chemokines, and causing end organ damage and thrombosis.
  • Clinical course
    • HUS develops 5-10 days after onset of diarrhea
    • Up to 50% of patients require dialysis and 39% have long term renal injury.
    • Mortality is 3-5%
  • Treatment:
    • Supportive care is the mainstay
    • Some data from an outbreak in Germany suggests there may be benefit to plasma exchange (PLEX) via removal of shiga toxin and prothrombotic factors from the body
    • Eculizumab ⇒ beneficial in patients with complement-mediated HUS (not shiga-toxin mediated)

TTP: 

  • Main distinguishing features from HUS
    • Renal failure can often be mild
    • Neurologic impairment is more common
    • Mortality rates are much higher
    • Confirmatory test is ADAMTS13
    • Mainstay of treatment is PLEX!

Moral of this story: start PLEX while you’re waiting to decide if it’s HUS or TTP!

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