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Hemolytic Uremic Syndrome Clinical Presentation

  • Author: Robert Stanley Rust, Jr, MD, MA; Chief Editor: Amy Kao, MD  more...
 
Updated: Dec 17, 2013
 

History

See the list below:

  • Hemolytic uremic syndrome (HUS) may arise as a familial or an idiopathic illness, and it may or may not be associated with an identifiable prodrome or provocation.
  • Postinfectious HUS is more common than heritable forms of HUS. Postinfectious HUS may occur after infections by viruses or bacteria, and the prodromal manifestation often includes diarrhea.
  • Viruses isolated in cases of HUS include echoviruses, adenoviruses, and coxsackieviruses. Identified bacterial organisms include Salmonella, Shigella, Streptococcus, and Yersinia species.
  • In some instances, the presence of an exanthem or enanthem may assist in identifying a particular infectious agent. An example is a coxsackie rash associated with fever and diarrhea before the onset of renal failure.
  • Diarrhea-associated postinfectious HUS is most likely to occur in children younger than 5 years. It represents what Drummond called "classic infantile" cases. Children uncommonly have a nondiarrheal prodrome, usually as a respiratory infection or sepsis.
  • In industrialized nations, verotoxigenic E coli O157:H7 appears to be the most important cause of postinfectious HUS. This is usually heralded by the development of hemorrhagic colitis. In one study, this particular serotype of E coli was identified in 46% of children with classic infantile postinfectious HUS.
    • HUS due to this agent has a distinct midsummer seasonal predilection.
    • A history of consuming undercooked cooked ground beef is the most important risk factor with E coli O157:H7 infection; this finding suggests an epizootic reservoir.
    • Relatively uncommon routes of acquisition include exposure to contaminated water or milk and fecal-oral routes from human or animal sources.
  • Various degrees of cramping abdominal pain precede the onset of diarrhea by days to weeks.
  • Vomiting occurs in 30-60% of patients.
  • Diarrhea is usually non bloody at the outset. However, in approximately 38-70% of cases involving E coli O157:H7, the diarrhea becomes hemorrhagic within 1-2 days. Approximately 3-9% (up to 20% in some epidemics) of children who have this course develop overt HUS.
  • A history of using antibiotics, such as trimethoprim sulfa or antimotility agents, increases the risk of HUS with verotoxigenic colitis.
  • Abdominal pain and fever may be severe. Severe abdominal tenderness or prolonged vomiting may suggest pancreatitis, and a surgical abdomen suggests the possibility of bowel infarction.
  • In nonindustrialized nations, the most important cause of hemorrhagic enterocolitis is Shigella dysentery type 1.
  • Patients may have a history of residing in or traveling to areas where S dysenteriae or Yersinia infections is endemic.
  • Patients may have a history of having contact with another person, particularly a child, who traveled from an endemic area and who developed dysentery.
  • Dysentery due to S dysenteriae or Yersinia organisms may be severe.
  • Children without diarrhea may have had a prodromal respiratory illness or sepsis; these children have a prognosis distinctly worse than that of patients with a diarrheal prodrome.
  • Patients may have a history of severe fever.
  • A variety of noninfectious processes may precede sporadic cases of HUS. Many of these processes arise more commonly in adults than in children. Patients may have a history of the following:
    • Henoch-Schönlein purpura
    • HIV infection or AIDS
    • Systemic lupus erythematosus (SLE)
    • Antiphospholipid antibody syndrome
    • Scleroderma
    • Polyarteritis nodosa
    • Wegener granulomatosis
    • Malignant hypertension
    • Kidney radiation
    • Bone marrow or stem cell transplantation
    • Various organ allograft kidney transplantations, usually more than 7 months before HUS
    • Immunosuppression with cyclosporin, tacrolimus, or methylprednisolone (Tacrolimus-associated disease is usually seen in individuals older than 40 years, more commonly in men than in women.)
    • Pancreatic cancer treated with gemcitabine
    • Cancer treated with mitomycin or other chemotherapy drugs
    • Snake envenomation
    • Diethylene glycol exposure
    • Pregnancy or use of oral contraceptives
  • Familial and sporadic forms of HUS need not be preceded by diarrhea or another definable illness (other than fatigue, irritability, and lethargy).
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Physical

Physical findings depend on the nature of the prodromal illness and the degree to which various organ systems are involved in the HUS phase.

  • Fever may be present.
  • Skin changes include the common finding of pallor. The patient's skin may be dry or doughy if they are dehydrated, and mucous membranes may be dry in such patients. [61]
  • Pulmonary findings may reflect a respiratory prodromal illness to postinfectious HUS, or it may be the consequence of renal failure or CNS, cardiac, or pulmonary involvement in HUS.
  • Postinfectious HUS with diarrheal prodrome may produce abdominal tenderness.
  • Colonic ischemia may be severe enough to represent a surgical emergency.
  • Abdominal tenderness is occasionally due to the development of pancreatitis.
  • Patients develop acute renal failure and enter a catabolic state with acidemic uremia and hypertension.
  • Neurologic manifestations, most commonly behavioral changes, motor seizures, and encephalopathy, are seen in 30-40% of children with classic postinfectious HUS with a diarrheal prodrome. Such manifestations are more common in familial cases.
  • Blindness, ataxia, hemiparesis, coma, and decerebrate rigidity are reported. Neurologic findings such as these indicate a poorer prognosis.
  • Whether neurologic changes are the result of cerebral microangiopathy or secondary to metabolic disturbances and hypertension is not always clear.
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Causes

The various known causes of HUS are also discussed in the Pathophysiology and Clinical sections.

In brief, postinfectious HUS is due to viruses (eg, echoviruses, adenoviruses, coxsackieviruses) and bacteria (eg, Salmonella, Shigella, Streptococcus, and Yersinia species, as well as verotoxigenic E coli O157:H7).

In one study, the O157:H7 serotype of E coli was identified in 46% of patients. Undercooked hamburger appears to be a major vehicle for food-borne E coli O157:H7 outbreaks in children, suggesting an epizootic reservoir. Several adult cases of TTP have been associated with the same pathogen, though this association is less common in adults than in children. Use of an antimotility agent or trimethoprim-sulfamethoxazole (TMP-SMX) appears to increase the risk for HUS. Data from preliminary studies suggest that the use of SYNSORB-pk may be effective in absorbing verotoxin in the intestine, preventing HUS.

  • The immunologic form of HUS is associated with a decrease in serum concentrations of C'3, an event that can be detected only after presentation. Other secondary forms of HUS include those occurring in association with SLE, scleroderma, malignant hypertension, kidney radiation, immunosuppression, snake-venom intoxication, diethylene glycol intoxication, or chemotherapy with mitomycin or cyclosporin.
  • Endocrine causes include pregnancy and use of oral contraceptives.
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Contributor Information and Disclosures
Author

Robert Stanley Rust, Jr, MD, MA Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia School of Medicine; Chair-Elect, Child Neurology Section, American Academy of Neurology

Robert Stanley Rust, Jr, MD, MA is a member of the following medical societies: Child Neurology Society, Society for Pediatric Research, American Headache Society, International Child Neurology Association, American Academy of Neurology, American Epilepsy Society, American Neurological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nestor Galvez-Jimenez, MD, MSc, MHA The Pauline M Braathen Endowed Chair in Neurology, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Additional Contributors

David A Griesemer, MD Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina

David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, Society for Neuroscience, American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Nothing to disclose.

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Peripheral smear in hemolytic uremic syndrome, with findings of microangiopathic hemolytic anemia. Note schistocytes/helmet cells, as well as decrease in platelets. Image courtesy of Emma Z Du, MD.
 
 
 
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