“Hemolytic Uremic Syndrome (HUS): Pearls and Pitfalls” – Help From EMDocs

Hemolytic Uremic Syndrome (HUS): Pearls and Pitfalls Jan 8, 2016 from EMDocs is an excellent post. And as a bonus you can get CME for the post from FOAMbase. You can find a complete Table of Contents  of all the topics covered on FOAMbase (not all of the posts on FOAMbase feature CME but all are worth reviewing).

Here are the excerpts (but understand that there is much more in the EMDocs post then is covered in these excerpts. Since my posts are my study notes, this post is just a quick review for my study).

Before starting this post, quickly review Pediatric Diarrhea From Dr. Fox
Posted on November 14, 2017.

Here is, for me, the take home message of the post:

The main differential diagnoses to consider in the early stage, before the classic triad of anemia, thrombocytopenia, and acute kidney injury has developed, include other infectious causes of diarrhea.  These include Salmonella, Shigella, Campylobacter, Yersinia, Amebiasis, and Clostridium Difficile, all of which can cause abdominal pain, bloody diarrhea, leukocytosis, and fever.  The key differentiating factor is that infection with agents other than STEC should not develop anemia, thrombocytopenia, or acute renal failure.  Additionally other causes of severe abdominal pain and/or diarrhea/vomiting in the pediatric patient should be ruled out.  These conditions include appendicitis, intussusception, hernia, torsion (ovarian/testicular), obstruction, malrotation, inflammatory bowel disease, mesenteric adenitis, cholecystitis, pneumonia, strep pharyngitis, and nephrolithiasis.7,16

Here is the case presentation:

A three-year-old male presents with mom for seven days of fever, diarrhea, and decreased activity. When you walk into the room, you note a listless-appearing boy with pallor. His eyes appear sunken. He is tachycardic, tachypneic, and febrile, but with normal blood pressure and saturations for age. He was born at term with no prior medical history, and his immunizations are up to date.

Mom states he has not been acting like himself with decreased eating, decreased urine output, and decreased activity. He has also been irritable and not engaged when playing.  No one else has been sick in the family, but the patient and his four-year-old brother did go to a birthday party at a petting zoo over a week ago.

So the first question we ask on encountering a pediatric (or any) patient is – Sick Or Not Sick? – meaning unwell or not unwell.

If the child is unwell* (sick) as per the RCHM definition below Resource (1), then strongly consider immediate therapy. In this case, even before the labs were available this child appeared sick and initiation of therapy (Ceftriaxone and fluid bolus) is appropriate and was initiated.

You go through the pediatric assessment triangle (appearance, work of breathing, color/circulation). Your differential at this point is quite large, and with your concern for sepsis and hypovolemia, you provide a 20cc/kg bolus of NS. You obtain a CBC, renal function panel, lactate, urinalysis, and blood cultures and provide ceftriaxone. His labs return and you see the following:  WBC 18,000, hemoglobin/hematocrit 6.8/20.1, platelet count 18,000, creatinine 2.4, and BUN 63. When you return to the room, mom recalls that he had several days of bloody diarrhea, for which you obtain a stool specimen. This returns positive for blood.

HUS classically consists of the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury (AKI).  It is a relatively rare disorder, with an estimated incidence in the United States and Western Europe of two to three per 100,000 children less than 5 years old.  HUS can be broken down into two classifications: 1) Diarrhea (typical) vs. no-diarrhea (atypical) and 2) primary vs. secondary.  Primary refers to defects in the complement activation system, while secondary includes infection (E. coli, S. pneumonia, and HIV), drug toxicity, autoimmune disorders, and several other etiologies.  Most cases of HUS in pediatric patients are secondary (non-complement mediated) and occur after a prodrome of diarrhea (typical).1-3

HUS occurs most commonly during the summer in children under 3 years.4,5  The most common cause of HUS in pediatric patients is Shiga-toxin producing Escherichia coli (STEC), which accounts for 90% of cases in pediatric patients.6  The most common serotype leading to HUS is Enterohemorrhagic E. coli (EHEC) O157:H7, which produces Shiga toxin 1 and 2.7 Interestingly, while exposure to STEC results in 38-61% of patients developing hemorrhagic colitis, only 6-9% of patients infected with STEC experience HUS.8,9

Human infection is due to ingestion of contaminated meat that is not properly cooked, unpasteurized dairy, and fruits or vegetables.  Fecal oral transmission may also occur, resulting in outbreaks in daycares or nursing homes.10

The second most common cause of HUS in children is infection with Streptococcus pneumoniae.  Pneumococcal-associated HUS occurs mainly in young infants and adults, accounting for 5-15% of childhood cases of HUS and 40% of non-STEC HUS.11,12Patients with pneumococcal associated HUS typically present with pneumonia (70%) or meningitis (20-30%) and is associated with a higher morbidity and mortality.12-14

Primary HUS is more rare.  Inherited forms of HUS account for fewer than 3% of all cases (children and adults) of HUS.1 The two main causes of the complement dysregulation seen in primary HUS are complement gene mutations and antibodies to complement factor H.15  This form is more common in adults and has a poorer prognosis.1

Presentation

The classic course of HUS is a prodromal period of diarrhea followed by acute renal failure.  Diarrhea typically begins around 3 days following ingestion of STEC.1  Patients with HUS will present with diarrhea in 91% of cases and with bloody diarrhea in 57% of cases.16  Patients usually have abdominal pain, vomiting, and non-bloody diarrhea, followed by bloody diarrhea approximately 5 days after first symptom onset.  Fever occurs in about 30% of cases, and neurologic symptoms are present in about 25% of cases.1 Pain and vomiting/diarrhea can be severe and mimic conditions such as inflammatory bowel disease, appendicitis, and nephrolithiasis.1, 9

The most common complication of HUS is acute kidney injury (AKI).   HUS is the one of the main causes of AKI in children under the age of three.7 Renal involvement varies from hematuria and proteinuria to severe renal failure and oliguria.  Acute renal failure with anuria occurs in 40% of cases, with 61% of those requiring dialysis.1,18

In addition to the kidneys, HUS can affect many organ systems including the central nervous system, the gastrointestinal tract, the heart, the pancreas, and the liver.19-21

Differential Diagnosis

In a pediatric patient presenting with abdominal pain and diarrhea, HUS is not often considered at the top of the initial differential diagnosis.  The diagnosis can be further complicated as the patient may present without bloody diarrhea and may not even develop bloody diarrhea.  The main differential diagnoses to consider in the early stage, before the classic triad of anemia, thrombocytopenia, and acute kidney injury has developed, include other infectious causes of diarrhea.  These include Salmonella, Shigella, Campylobacter, Yersinia, Amebiasis, and Clostridium Difficile, all of which can cause abdominal pain, bloody diarrhea, leukocytosis, and fever.  The key differentiating factor is that infection with agents other than STEC should not develop anemia, thrombocytopenia, or acute renal failure.  Additionally other causes of severe abdominal pain and/or diarrhea/vomiting in the pediatric patient should be ruled out.  These conditions include appendicitis, intussusception, hernia, torsion (ovarian/testicular), obstruction, malrotation, inflammatory bowel disease, mesenteric adenitis, cholecystitis, pneumonia, strep pharyngitis, and nephrolithiasis.7,16

Lab abnormalities

Ordering the correct laboratory studies is essential in correctly diagnosing HUS and differentiating other conditions with similar presentations.  Any patient with a history of diarrhea, particularly if bloody, with multisystem involvement warrants a CBC with peripheral smear, renal function panel, urinalysis, liver function enzymes, and LDH.  Additionally, stool samples should be collected to test for occult blood.

Treatment

As soon as HUS is suspected, consultation with the pediatric intensivist and nephrologist is warranted.   The mainstay of treatment is supportive with resuscitation and constant monitoring.   Major aspects of HUS that must be managed acutely include fluid status, anemia, thrombocytopenia, acute kidney injury, hypertension, and neurologic abnormalities.27

 

Resources:

(1) *The following definition of unwell is from the RCHM Guideline on petechiae and purpura(but the definition can be used in every infant or child you are evaluating for any complaint):

Children should be considered unwell when they have the following features:

Abnormal vital signs

  • Tachycardia
  • Tachypnoea and or desaturation in air
  • Increasing systolic to diastolic difference in blood pressure (ie widened pulse pressure)

Poor peripheral perfusion

  • Cold extremities
  • Prolonged capillary refill

Altered conscious state

  • Irritability (inconsolable crying or screaming)
  • Lethargy (including as reported by family or other staff)
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