What are the causes of splenomegaly?

Causes of Splenomegaly

The most common causes of splenomegaly include liver disease (particularly cirrhosis with portal hypertension), hematologic disorders, infections, and malignancies. A systematic approach to diagnosis is essential for proper management of the underlying condition.

Major Categories of Splenomegaly

Liver Disease and Portal Hypertension

• Cirrhosis - most common cause of splenomegaly in developed countries 1
• Portal vein thrombosis - leading to portal hypertension 1
• Wilson's disease - can present with hepatomegaly and splenomegaly 2
• Hepatosplenic schistosomiasis - with portal hypertension 2

Infectious Causes

• Leishmaniasis (Visceral/Kala-azar) - common in endemic regions 2
• Malaria - particularly with tropical splenomegaly syndrome 2
• Infectious mononucleosis - common cause in young adults 3
• Bacterial infections - including typhoid fever, brucellosis, and subacute bacterial endocarditis 2
• HIV/AIDS - often with opportunistic infections 2

Hematologic Disorders

• Myeloproliferative disorders - polycythemia vera, essential thrombocythemia, primary myelofibrosis 1
• Lymphoproliferative disorders - lymphomas, chronic lymphocytic leukemia 2, 1
• Hemolytic anemias - hereditary spherocytosis, thalassemia 1
• Primary immune thrombocytopenia (ITP) - may present with mild splenomegaly 2
• Hemophagocytic lymphohistiocytic syndrome 2

Malignancies

• Leukemias - acute and chronic forms 2, 1
• Lymphomas - Hodgkin and non-Hodgkin 1
• Metastatic cancer - particularly from GI malignancies 4

Autoimmune/Inflammatory Disorders

• Systemic lupus erythematosus 2
• Rheumatoid arthritis with Felty syndrome 2
• Sarcoidosis 4

Other Causes

• Storage diseases - Gaucher disease, Niemann-Pick disease 4
• Amyloidosis 4
• Congestive heart failure - leading to passive congestion 4

Diagnostic Approach

Initial Evaluation

1. Complete blood count with differential - to identify cytopenias (particularly thrombocytopenia, which is the most common manifestation of hypersplenism) 1
2. Peripheral blood smear - to detect abnormal cells, parasites, or morphologic changes 2
3. Liver function tests - including AST, ALT, alkaline phosphatase, bilirubin, and albumin 1
4. Abdominal ultrasound - first-line imaging modality to confirm splenomegaly and assess for liver disease or portal hypertension 1

Additional Testing Based on Clinical Suspicion

• Infectious workup - blood cultures, viral studies (EBV, CMV, HIV, hepatitis), malaria smears in endemic areas 2
• Flow cytometry and bone marrow examination - for suspected hematologic malignancies 2
• CT or MRI - for detailed assessment of spleen size and focal lesions 1
• Liver biopsy - when liver disease is suspected 2

Important Clinical Considerations

Complications of Splenomegaly

• Hypersplenism - sequestration and destruction of blood cells leading to cytopenias 5
• Splenic rupture - risk increases with size; patients should avoid contact sports 3
• Increased risk of infections - particularly if functional hyposplenism develops 1

When to Consider Splenectomy

• Refractory symptoms despite medical therapy
• Massive splenomegaly causing mechanical symptoms
• Severe hypersplenism with significant cytopenias
• Splenic infarction or rupture 1

Key Points to Remember

• Splenomegaly is almost always a sign of an underlying systemic condition rather than a primary disorder 3
• Thrombocytopenia is the most common hematologic abnormality associated with splenomegaly 1
• In tropical regions, infectious causes like malaria and schistosomiasis predominate, while in developed countries, liver disease and malignancy are more common 3
• Management focuses on treating the underlying cause rather than the splenomegaly itself 3

By systematically evaluating patients with splenomegaly using this approach, clinicians can efficiently identify the underlying cause and initiate appropriate treatment to improve outcomes.