Causes of Splenomegaly
Splenomegaly is almost always a sign of an underlying systemic condition, with the most common causes being liver disease, hematologic disorders, infections, and infiltrative diseases. 1
Hepatic Causes
- Cirrhosis with portal hypertension is a common cause of splenomegaly, often associated with thrombocytopenia and other signs of portal hypertension 2
- Wilson's disease may present with isolated splenomegaly due to clinically inapparent cirrhosis 2, 3
- Non-cirrhotic portal hypertension can cause significant splenomegaly 2
- Chronic liver disease is frequently associated with splenomegaly and hypersplenism 4
Hematologic Disorders
- Myeloproliferative disorders, particularly myelofibrosis, are associated with massive splenomegaly (>10cm below costal margin) 5, 6
- Leukemias (both acute and chronic) are common causes of splenomegaly 6
- Lymphomas frequently cause splenomegaly and are often accompanied by lymphadenopathy 7
- Chronic hemolytic anemias can lead to splenomegaly 8
Infectious Causes
- Malaria and schistosomiasis are common causes of splenomegaly in tropical regions 9, 1
- Endocarditis can lead to splenic abscess and splenomegaly 5
- Tuberculosis is associated with splenomegaly 6
- HIV/AIDS, particularly with opportunistic infections like Mycobacterium avium complex, can cause massive splenomegaly 7
Infiltrative and Storage Disorders
- Acid sphingomyelinase deficiency (ASMD/Niemann-Pick disease) commonly presents with hepatosplenomegaly, which can be massive (>10x normal size) 2, 5
- Gaucher disease is a common cause of significant splenomegaly 2
- Niemann-Pick disease type C and lysosomal acid lipase deficiency (LALD) are also associated with splenomegaly 2, 3
- Glycogen storage diseases can present with hepatosplenomegaly 3
Autoimmune and Inflammatory Disorders
- Rheumatoid arthritis with Felty syndrome can cause splenomegaly 2, 8
- Systemic lupus erythematosus (SLE) may present with splenomegaly 9
- Thyrotoxicosis can be associated with splenomegaly through inflammatory mechanisms 6
Congestive Disorders
- Congestive heart failure can lead to splenomegaly 6, 7
- Splenic vein thrombosis can cause isolated splenomegaly 3
Clinical Patterns and Associations
- Massive splenomegaly (>10cm below costal margin) is most commonly associated with hematologic disorders, particularly chronic leukemias and myelofibrosis 6
- Splenomegaly with portal hypertension is often associated with thrombocytopenia 2
- Splenomegaly with fever suggests infectious etiology 5
- Splenomegaly with lymphadenopathy strongly suggests hematologic malignancy 6
- Splenomegaly with abnormal liver function tests suggests hepatic etiology 6
Diagnostic Approach
- Physical examination may reveal splenomegaly, but abdominal ultrasonography is recommended for confirmation 1
- Complete blood count to assess for cytopenias (anemia, thrombocytopenia, leukopenia) is essential 5
- Liver function tests are important, especially when hepatic causes are suspected 2
- Bone marrow examination may be informative in patients older than 60 years or those with systemic symptoms 9
- In patients with suspected ITP, mild splenomegaly may be found in younger patients, but moderate or massive splenomegaly suggests an alternative cause 9