Pediatric Hemolytic Uremic Syndrome Clinical Presentation

  • Author: Robert S Gillespie, MD, MPH; Chief Editor: Craig B Langman, MD   more...
 
Updated: Sep 26, 2011
 

History

Patients with diarrhea-associated hemolytic-uremic syndrome (D+ HUS) experience several days of diarrhea, with or without vomiting, followed by sudden onset of symptoms such as irritability and pallor. In more than 80% of patients, the diarrhea is evidently bloody. Other symptoms include restlessness, oliguria, edema, and macroscopic hematuria. In some patients, the prodrome may improve as hemolytic-uremic syndrome symptoms begin. The clinical picture may mimic that of an acute abdomen. In patients infected with a Shiga toxin (Stx)–producing strain of E coli, hemolytic-uremic syndrome occurs in 5-15%. The risk of progression to hemolytic-uremic syndrome is increased in very young or elderly persons, in patients who have been treated with antimotility drugs or antibiotics, and in patients with a fever or a high leukocyte count.

The history should include inquiry about possible recent exposure to E coli, such as consuming undercooked meat, encounters with livestock or petting zoos, contacts with other persons with diarrhea, and attendance at daycare or school. However, most cases of D+ hemolytic-uremic syndrome are sporadic, with no clearly identifiable source of infection, even when stool culture yields a toxigenic organism. Outbreaks involving multiple persons more commonly lead to a source.

Non–diarrhea-associated hemolytic-uremic syndrome (D- HUS) may follow a respiratory illness, especially when caused by S pneumoniae.

Features of all forms of hemolytic-uremic syndrome include the following:

  • Hematology
    • Hemolysis occurs in all patients with hemolytic-uremic syndrome. It can proceed rapidly, resulting in a rapid fall of the hematocrit.
    • Platelet counts usually fall below 40,000/mcL. However, the degree of thrombocytopenia does not correlate with the severity of hemolytic-uremic syndrome, and some children can maintain relatively normal kidney function despite severe hematologic abnormalities.
    • Many patients have petechiae, purpura, and oozing from venipuncture sites.
    • Overt bleeding is less common.
  • CNS
    • Patients often present with sudden onset of lethargy and irritability.
    • Other findings may include ataxia, coma, seizures, cerebral swelling, hemiparesis, and other focal neurologic signs.
    • CNS changes may be caused by cerebral ischemia from microthrombi, effects of hypertension, hyponatremia, or uremia.
    • D- hemolytic-uremic syndrome tends to be associated with a greater number of neurologic symptoms than D+ hemolytic-uremic syndrome.
  • Renal system
    • Acute renal insufficiency usually begins with the onset of hemolysis. Although patients have decreased urine output, frequent diffuse watery stools may mask this sign.
    • If renal insufficiency is not recognized and treated, hyponatremia, hyperkalemia, severe acidosis, ascites, edema, pulmonary edema, and hypertension ensue.
  • GI tract: D+ hemolytic-uremic syndrome is usually preceded by 3-12 days of watery or bloody diarrhea. Vomiting and crampy abdominal pain are also common. Note that diarrhea may improve as the other hemolytic-uremic syndrome symptoms begin (eg, thrombocytopenia, renal insufficiency). Life-threatening complications include intestinal perforation or necrosis. Even without these complications, the colitis of hemolytic-uremic syndrome may cause severe abdominal pain which may persist for several days into the illness.
  • Infectious signs: Fever is present in 5-20% of patients. The presence of fever, leukocytosis, or both is a prognostic indicator of the risk of developing more severe hemolytic-uremic syndrome.
  • Pancreas: Mild pancreatic involvement is common but can be severe on occasion, with necrosis, pseudocysts, or both, which can leave the patient with insulin-dependent diabetes and, on rare occasion, exocrine dysfunction.
  • Cardiovascular: Congestive heart failure may occur.
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Physical

  • Blood pressure may be elevated unless the patient is volume depleted (eg, from diarrhea.)
  • Child appears ill and pale.
  • Abdominal pain and tenderness may be present, possibly severe.
  • Peripheral edema may be present.
  • Petechiae, purpura, or oozing from venipuncture sites may be present.
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Causes

The causes of D+ hemolytic-uremic syndrome and D- hemolytic-uremic syndrome differ.

  • D+ hemolytic-uremic syndrome
    • GI tract infection with Stx–producing E coli (STEC) precedes most cases of typical D+ hemolytic-uremic syndrome. Stx1 is identical to the Stx produced by Shigella dysenteriae. Stx2 has a 55-60% amino acid homology with Stx. They injure the gut and lead to hemorrhagic colitis. Most cases worldwide are associated with STEC 0157:H7 infection. This organism is very resilient; viable bacteria has been reported in environments up to 10 months following initial contamination. Aside from Stx production, this bacteria produces virulence factors that mediate tight adherence to the host cell, facilitating transluminal transport of the toxins into the systemic circulation. Cattle are the major reservoir for human infection. The use of antimotility agents, antidiarrheal agents, and antibiotics has been reported to increase the risk of developing hemolytic-uremic syndrome.
    • Other causes of hemolytic-uremic syndrome include infection by the following:
      • S dysenteriae (established as an etiologic agent)
      • Salmonella typhi (established as an etiologic agent)
      • Campylobacter jejuni (established as an etiologic agent)
      • Yersinia species
      • Pseudomonas species
      • Bacteroides species
      • Entamoeba histolytica
      • Aeromonas hydrophilia
      • Organisms of the class Microtatobiotes
  • D- hemolytic-uremic syndrome
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Contributor Information and Disclosures
Author

Robert S Gillespie, MD, MPH  Department of Pediatrics, Cook Children's Medical Center

Robert S Gillespie, MD, MPH is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology, and Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Craig S Wong, MD, MPH  Assistant Professor, Division of Pediatric Nephrology, Department of Pediatrics, University of New Mexico School of Medicine; Director of Pediatric Kidney Transplantation, Division of Pediatric Nephrology, Department of Pediatrics, University of New Mexico Transplant Services, Children's Hospital of New Mexico

Craig S Wong, MD, MPH is a member of the following medical societies: American Society of Nephrology and American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Ronald D Prauner  MD, Assistant Professor of Pediatrics, F Edward Herbert School of Medicine, Uniformed Services of the Health Sciences; Assistant Deputy Commander for Medicine; Fort Belvoir Community Hospital, Fort Belvoir, VA; Consultant to the Army Surgeon General for Pediatric Subspecialties; Staff Pediatric Hematologist-Oncologist, Fort Belvoir Community Hospital

Ronald D Prauner is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Christian Medical & Dental Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard Neiberger, MD, PhD  Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical & Dental Society, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, and Southwest Pediatric Nephrology Study Group

Disclosure: The Osler Institute Honoraria Speaking and teaching

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Luther Travis, MD  Professor Emeritus, Departments of Pediatrics, Nephrology and Diabetes, University of Texas Medical Branch School of Medicine

Luther Travis, MD is a member of the following medical societies: Alpha Omega Alpha, American Federation for Medical Research, International Society of Nephrology, and Texas Pediatric Society

Disclosure: Nothing to disclose.

Howard Trachtman, MD  Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine

Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD  The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, Children's Memorial Hospital

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology

Disclosure: Merck Grant/research funds None; NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Tamara Biega, MD, to the original writing and development of this article.

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Peripheral blood smear in hemolytic-uremic syndrome (HUS) showing many schistocytes and RBC fragments due to hemolysis, and relatively few platelets reflective of thrombocytopenia.
 
 
 
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