What are the causes of splenomegaly?

Causes of Splenomegaly

The most common causes of splenomegaly are liver disease, hematologic disorders, and infections, with specific etiologies varying by geographic region and patient population. 1

Major Categories of Splenomegaly

Hematologic Disorders (30-57% of cases)

• Leukemias (acute and chronic) - most frequently associated with massive splenomegaly 2
• Lymphomas 3
• Myeloproliferative disorders - myelofibrosis has the highest incidence (78%) of massive splenomegaly 2
• Hemolytic anemias 1

Hepatic Diseases (11-41% of cases)

• Cirrhosis with portal hypertension 4
• Chronic liver diseases of various etiologies 3
• Wilson's disease - may present with isolated splenomegaly due to clinically inapparent cirrhosis 4
• Non-cirrhotic portal hypertension - can cause significant splenomegaly 4

Infectious Diseases (16-36% of cases)

• Viral infections - including infectious mononucleosis 1
• Bacterial infections - endocarditis, tuberculosis 2
• Parasitic infections - malaria, schistosomiasis (common in tropical regions) 4, 1
• HIV/AIDS - particularly when complicated by opportunistic infections like Mycobacterium avium complex 3

Lysosomal Storage Disorders

• Acid sphingomyelinase deficiency (ASMD/Niemann-Pick disease) - can cause massive splenomegaly (>10x normal size) 4, 5
• Gaucher disease - common cause of significant splenomegaly 4
• Niemann-Pick disease type C 4
• Lysosomal acid lipase deficiency (LALD) 4

Congestive/Inflammatory Disorders (4-10% of cases)

• Congestive heart failure 2, 3
• Autoimmune disorders - including rheumatoid arthritis with Felty syndrome 4
• Thyrotoxicosis 2
• Sarcoidosis 4

Primary Splenic Disorders (1-6% of cases)

• Splenic vein thrombosis 3
• Primary splenic cysts 6
• Splenic hemangiomas 6

Drug-Induced Splenomegaly

• Medications causing hemolysis 7
• Drugs causing liver damage with subsequent portal hypertension 7
• Drug effects typically resolve when medication is discontinued 7

Clinical Patterns and Associations

Massive Splenomegaly

• Most commonly associated with hematologic disorders (81% of cases) 2
• Chronic leukemias and myelofibrosis are the most frequent causes 2
• In patients with AIDS and massive splenomegaly, Mycobacterium avium complex is found in 73% of cases 3
• ASMD can cause massive splenomegaly (>10x normal) 4

Splenomegaly with Portal Hypertension

• Often associated with liver cirrhosis 4
• Can present with:
  • Thrombocytopenia 4
  • Esophageal varices 4
  • Ascites 4
  • Decreased portal blood flow velocity on Doppler ultrasound 4

Splenomegaly with Cytopenia

• Suggests hypersplenism, which can occur in many conditions causing splenomegaly 2
• Particularly common in portal hypertension and hematologic disorders 4
• Thrombocytopenia correlates with increasing portal pressure 4

Diagnostic Approach

Initial Evaluation

• Complete blood count - to assess for cytopenias 5
• Liver function tests - abnormal in hepatic causes 2
• Abdominal ultrasound - confirms splenomegaly and evaluates liver morphology 5
• Lipid profile - may reveal mixed dyslipidemia in storage disorders 5

Further Diagnostic Testing Based on Initial Findings

• For hematologic associations - bone marrow biopsy 3
• For hepatic associations - liver biopsy and/or elastography 3, 5
• For infectious disease associations - lymph node biopsy, serologies 3
• For suspected storage disorders - genetic testing (e.g., SMPD1 gene for ASMD) 5

Important Clinical Considerations

• Splenomegaly is almost always a sign of an underlying systemic condition rather than a primary splenic disorder 1
• The differential diagnosis varies significantly by geographic region - malaria and schistosomiasis are common causes in tropical regions 1
• Patients with splenomegaly should avoid contact sports due to risk of splenic rupture 1
• In young adults with unexplained hepatosplenomegaly, rare disorders like ASMD are often diagnosed with significant delay 5