What are the causes of fever with hepatosplenomegaly in children aged 0-2 years?

Causes of Fever with Hepatosplenomegaly in Children Aged 0-2 Years

In infants and young children aged 0-2 years presenting with fever and hepatosplenomegaly, you must immediately consider serious bacterial infections (particularly urinary tract infection, pneumonia, and meningitis), hemophagocytic lymphohistiocytosis (HLH), and congenital infections as the most critical diagnoses that require urgent evaluation and treatment. 1, 2, 3

Immediate Life-Threatening Causes to Rule Out First

Hemophagocytic Lymphohistiocytosis (HLH)

• HLH presents with unremitting fever, hepatosplenomegaly, and cytopenias and is rapidly fatal without treatment 3
• Look for: bleeding manifestations, lymphadenopathy, skin rash, shock, jaundice, CNS symptoms, or renal failure 3
• Laboratory findings include: cytopenia affecting two or three cell lines, elevated ferritin, elevated LDH, hypertriglyceridemia, and hypofibrinogenemia 3
• Familial HLH typically presents in the first 2 years of life, though atypical presentations can occur 4
• Bone marrow biopsy showing hemophagocytosis confirms diagnosis in most cases 3

Serious Bacterial Infections (SBI)

• Only 58% of infants with bacteremia or bacterial meningitis appear clinically ill, so you cannot rely on appearance alone 1, 5
• Urinary tract infection (UTI) has a prevalence of 3-7% in febrile children aged 2 months to 2 years without obvious source, higher in girls (6.5-8.1%) and uncircumcised boys 1
• Pneumonia occurs in 7% of febrile children under 2 years and can present with minimal respiratory symptoms initially 1, 5
• For infants 1-3 months old, bacterial meningitis remains a critical consideration requiring cerebrospinal fluid evaluation 1, 5

Common Infectious Causes

Viral Infections

• Epstein-Barr virus (EBV) can cause fever, hepatosplenomegaly, lymphadenopathy, and lymphocytosis, and may trigger secondary HLH 2
• Cytomegalovirus (CMV) and other congenital infections present with hepatosplenomegaly in this age group 1
• Measles with complications can cause secondary HLH with hepatosplenomegaly 3

Bacterial Infections Beyond SBI

• Disseminated tuberculosis presents with fever, hepatosplenomegaly, and can trigger secondary HLH 3
• Sepsis with shock may present with hepatosplenomegaly and multi-organ involvement 3

Metabolic and Storage Disorders

Acid Sphingomyelinase Deficiency (ASMD/Niemann-Pick Disease)

• Infantile neurovisceral ASMD presents at 6 months with marked abdominal distension, severe hepatosplenomegaly, failure to thrive, and chronic diarrhea 1
• Look for: hypotrophic muscles, dyslipidemia, elevated liver transaminases, thrombocytopenia, leukopenia, and interstitial lung disease 1
• Chronic visceral ASMD may present with isolated splenomegaly at routine visits in the first 2 years 1
• Diagnosis requires enzyme assay for acid sphingomyelinase activity and genetic testing of SMPD1 gene 1

Parasitic Infections (Less Common in This Age Group)

Visceral Larva Migrans (Toxocariasis)

• Usually seen in children under 5 years through ingestion of contaminated soil 1
• Presents with fever, eosinophilia, dyspnea, wheeze, cough, hepatosplenomegaly, and urticarial rash 1
• Most infections are asymptomatic; symptomatic cases require high index of suspicion 1

Diagnostic Approach Algorithm

Step 1: Assess Severity and Obtain Vital Signs

• Document rectal temperature ≥38.0°C (100.4°F) 1, 5
• Assess for toxic appearance, respiratory distress, altered consciousness, or signs of shock 1, 5
• Note that antipyretic use in previous 4 hours may mask fever severity 1, 5

Step 2: Immediate Laboratory Evaluation

• Complete blood count with differential looking for cytopenias (suggests HLH), lymphocytosis (suggests viral infection or HLH), or leukocytosis 2, 3
• Urine testing with leukocyte esterase, nitrites, leukocyte count, or Gram stain for UTI 1
• Blood culture before starting antibiotics 1
• Liver function tests and coagulation studies 3
• Ferritin, LDH, triglycerides, and fibrinogen if HLH suspected 3

Step 3: Imaging Based on Clinical Findings

• Chest radiograph if cough, hypoxia, rales, fever ≥39°C, fever duration >48 hours, or tachypnea/tachycardia out of proportion to fever 1, 5
• Avoid chest radiograph if wheezing or high likelihood of bronchiolitis 1
• Abdominal ultrasound to characterize hepatosplenomegaly and assess for masses or lymphadenopathy 1

Step 4: Age-Specific Considerations

• For infants 1-3 months: strongly consider lumbar puncture as there are no reliable predictors to exclude meningitis in well-appearing febrile infants 1, 5
• For children approaching 2 years: lumbar puncture only if specific meningeal signs present 5

Step 5: Specialized Testing When Initial Workup Non-Diagnostic

• Bone marrow biopsy if persistent fever with hepatosplenomegaly and cytopenias 3
• Enzyme assays and genetic testing for lysosomal storage disorders if chronic progressive hepatosplenomegaly 1
• EBV serology and viral PCR if lymphocytosis and lymphadenopathy present 2
• Stool ova and parasites with eosinophilia 1

Critical Pitfalls to Avoid

• Never assume a well-appearing child cannot have serious bacterial infection or HLH 1, 5, 3
• Do not delay treatment for HLH while awaiting confirmatory tests; initiate HLH-2004 protocol if clinical suspicion is high 3
• Obtain urine culture even with negative dipstick if UTI still suspected 1
• Consider factitious disorder imposed on another (FDIA) if symptoms persist despite appropriate treatment and resolve when caregiver is separated from child 6
• Do not overlook metabolic storage disorders in infants with chronic progressive hepatosplenomegaly and developmental concerns 1
• Remember that viral infections can coexist with bacterial infections 5