What are the causes of splenomegaly?

Causes of Splenomegaly

Splenomegaly is almost always a sign of an underlying systemic condition, with the most common causes being liver disease, malignancy, and infection in the United States. 1 Understanding the various etiologies is essential for appropriate diagnosis and management.

Major Categories of Causes

1. Liver Disease and Portal Hypertension

• Cirrhosis - A leading cause of splenomegaly due to portal hypertension 2
• Wilson's disease - May present with isolated splenomegaly due to clinically inapparent cirrhosis with portal hypertension 3
• Alcoholic liver disease - Common cause of portal hypertension leading to splenomegaly 3
• Splanchnic vein thrombosis - Can cause splenomegaly and is often detected incidentally on abdominal imaging 4

2. Hematologic Disorders

• Myeloproliferative neoplasms - Including primary myelofibrosis, polycythemia vera, and essential thrombocythemia 3, 5
• Lymphoproliferative disorders - Such as lymphomas, chronic lymphocytic leukemia (CLL) 4
• Hemolytic anemias - Including autoimmune hemolytic anemia and hereditary spherocytosis 4
• Primary immune thrombocytopenia (ITP) - May occasionally present with mild splenomegaly, though moderate or massive splenomegaly suggests an alternative diagnosis 3

3. Infectious Causes

• Viral infections - Including infectious mononucleosis (EBV), HIV, and viral hepatitis 4, 1
• Bacterial infections - Such as endocarditis, tuberculosis, and brucellosis 1
• Parasitic infections - Particularly malaria and schistosomiasis in tropical regions, where up to 80% of people may have splenomegaly 1
• Fungal infections - Including histoplasmosis and coccidioidomycosis 1

4. Storage Disorders

• Gaucher disease - Most common lysosomal storage disorder causing splenomegaly 4
• Niemann-Pick disease - Including acid sphingomyelinase deficiency (ASMD) 4
• Mucopolysaccharidoses - Various types can cause hepatosplenomegaly 4

Diagnostic Approach

Initial Evaluation

1. Complete blood count - To assess for cytopenias suggesting hypersplenism 4
2. Liver function tests - To evaluate for liver disease 4
3. Abdominal ultrasound - To confirm splenomegaly and evaluate liver morphology 4

Further Workup Based on Clinical Suspicion

• Viral studies - Including hepatitis panel, EBV, CMV, and HIV testing 4
• Flow cytometry and bone marrow examination - For suspected hematologic malignancies 3
• CT or MRI - When malignancy is suspected or better characterization of lesions is needed 4
• PET-CT - Particularly useful for suspected lymphoma 4
• Specific enzyme assays - When storage disorders are suspected 4

Clinical Pearls and Pitfalls

Important Clinical Considerations

• Mild splenomegaly may be found in younger patients with ITP, but moderate or massive splenomegaly suggests an alternative diagnosis 3
• Patients with Wilson's disease may present with isolated splenomegaly due to clinically inapparent cirrhosis 3
• In tropical regions, malaria and schistosomiasis are common causes of splenomegaly 1

Potential Pitfalls

• Failing to recognize malignant infiltration in patients with massive hepatosplenomegaly 4
• Overlooking splenic sequestration as a life-threatening complication in sickle cell disease 4
• Underestimating the risks of splenectomy in patients with portal hypertension 4

Complications of Splenomegaly

• Hypersplenism leading to cytopenias, particularly thrombocytopenia 2
• Increased risk of splenic rupture, especially with contact sports 1
• Portal hypertension-related bleeding 2
• Acute infections due to impaired immune function 1

Understanding these various causes of splenomegaly allows for a systematic approach to diagnosis and appropriate management of the underlying condition.