What are the symptoms of childhood Hemolytic Uremic Syndrome (HUS)?

Symptoms of Childhood Hemolytic Uremic Syndrome

Childhood HUS presents with a classic triad of symptoms: microangiopathic hemolytic anemia (causing pallor and fatigue), thrombocytopenia (causing bleeding manifestations), and acute renal injury (causing decreased urine output and fluid retention), typically preceded by bloody diarrhea 4-5 days before HUS symptoms develop. 1, 2, 3

Core Clinical Manifestations

Hematologic Symptoms

• Anemia-related symptoms: Pallor, fatigue, and weakness due to microangiopathic hemolytic anemia 4, 5
• Bleeding manifestations: Purpura (skin bruising), melena (bloody stools), and other bleeding due to thrombocytopenia (platelet count <150,000/mm³) 6, 1
• These symptoms result from red blood cell destruction and platelet consumption 3, 7

Gastrointestinal Prodrome

• Diarrhea: Most children (in typical STEC-HUS) present with a prodromal diarrheal illness lasting approximately one week before HUS develops 4, 6
• Bloody diarrhea: Characteristic of STEC infection, appearing 4-5 days before HUS symptoms manifest 1, 2
• Important timing distinction: If diarrhea and HUS appear simultaneously or with a very short interval, suspect atypical HUS rather than typical STEC-HUS 1, 3

Renal Manifestations

• Oliguria: Decreased urine output is a primary presenting feature 6, 4
• Hematuria: Blood in the urine 1, 6
• Edema: Fluid retention and swelling 6
• Hypertension: Elevated blood pressure occurs frequently 6
• Approximately two-thirds of children with HUS require dialysis therapy 4

Neurological Symptoms (10-20% of cases)

• Altered mental status: Confusion, irritability, or altered sensorium 6, 1
• Seizures: Convulsions may occur 1, 6
• Encephalopathy: Including hypertensive encephalopathy 6, 1
• Motor symptoms: Generalized weakness and focal motor deficits 1
• Vision changes: Visual disturbances 1
• Coma: In severe cases 6

Critical Diagnostic Considerations

Incomplete Presentations

• Up to 50% of children may not present with all three classic features (anemia, thrombocytopenia, renal involvement) at disease onset, making early diagnosis challenging 3, 8
• Providers must maintain high suspicion even when some symptoms are missing 8
• Near-normal hemoglobin may indicate dehydration masking anemia rather than absence of disease 2

Age-Specific Considerations

• Most common in infants and children under 1 year of age 6
• In infants presenting in the first year of life, consider complement-unrelated genetic causes (DGKE, WT1 mutations) or metabolic disorders like methylmalonic acidemia with homocystinuria 1, 3

Severity Indicators

• Factors associated with worse outcomes: Prolonged oliguria, elevated blood urea levels, presence of encephalopathy, and evidence of disseminated intravascular coagulation (DIC) 6
• Mortality ranges from 3-5%, nearly always associated with severe extrarenal disease, particularly severe CNS involvement 4

Common Pitfalls to Avoid

• Do not dismiss HUS diagnosis if renal dysfunction appears mild initially—some children present with prominent hematologic features but less apparent renal involvement 8
• Do not wait for all three classic features to be present before considering HUS, as incomplete presentations are common at onset 3, 8
• Recognize the timing pattern: STEC-HUS typically develops 4-5 days after diarrhea onset; shorter intervals or simultaneous onset suggests atypical HUS requiring different management 1, 3