Causes of Splenomegaly
Splenomegaly is most commonly caused by liver disease, malignancy, and infection, with specific etiologies determined by targeted diagnostic testing and appropriate disease-specific treatment. 1
Major Categories of Splenomegaly
1. Hematologic Disorders
- Malignancies:
- Leukemias (chronic lymphocytic leukemia, chronic myeloid leukemia)
- Lymphomas (Hodgkin and non-Hodgkin)
- Myeloproliferative neoplasms (primary myelofibrosis, polycythemia vera) 2
- Non-malignant:
- Hemolytic anemias
- Immune thrombocytopenia 2
- Hereditary conditions (thalassemias, sickle cell disease)
2. Infectious Causes
- Bacterial: Endocarditis, tuberculosis, brucellosis
- Viral: Infectious mononucleosis (EBV), HIV, viral hepatitis
- Parasitic: Malaria, schistosomiasis (particularly common in tropical regions) 1
- Fungal: Histoplasmosis
3. Liver Disease and Portal Hypertension
- Cirrhosis (alcoholic, viral, non-alcoholic steatohepatitis)
- Portal or splenic vein thrombosis
- Budd-Chiari syndrome
- Portal hypertension (defined as hepatic venous pressure gradient >6 mmHg) 1
4. Inflammatory and Autoimmune Disorders
- Systemic lupus erythematosus 2
- Rheumatoid arthritis (especially with Felty's syndrome)
- Sarcoidosis
- Amyloidosis
5. Infiltrative Disorders
- Gaucher disease
- Niemann-Pick disease
- Glycogen storage diseases
- Amyloidosis
6. Other Causes
- Splenic cysts or tumors
- Congestive heart failure
- Splenic artery aneurysm
- Splenic sequestration crisis in sickle cell disease
Diagnostic Approach
Initial Evaluation
- Complete blood count with differential to evaluate for cytopenias or elevated cell counts 1
- Liver function tests to assess for liver disease 1
- Abdominal ultrasound to confirm splenomegaly (>13 cm is considered enlarged) 2, 1
Further Investigations Based on Initial Findings
- Bone marrow examination for suspected hematologic malignancies 1
- Testing for infectious causes based on risk factors and exposure history
- Genetic testing for suspected hereditary conditions 1
Important Clinical Considerations
Physical Examination Findings
- Mild splenomegaly may be found in younger patients with ITP 2
- Moderate or massive splenomegaly suggests alternative causes like lymphoproliferative disorders 2
- Constitutional symptoms (fever, weight loss), hepatomegaly, or lymphadenopathy might indicate underlying disorders such as HIV, SLE, or lymphoproliferative disease 2
Complications of Splenomegaly
- Hypersplenism leading to cytopenias, particularly thrombocytopenia
- Increased risk of splenic rupture (patients should avoid contact sports) 1
- Portal hypertension and its sequelae
- Splenic infarction
Pitfalls to Avoid
- Failing to recognize malignant infiltration in patients with massive hepatosplenomegaly 1
- Overlooking splenic sequestration as a life-threatening complication in sickle cell disease 1
- Underestimating the risks of splenectomy in patients with portal hypertension 1
- Performing splenectomy in patients with severe thrombocytopenia, which may be a marker of impending leukemic transformation 1
Management Considerations
- Treatment is directed at the underlying cause of splenomegaly 1
- For symptomatic splenomegaly in myeloproliferative disorders, hydroxyurea is the first-line treatment 2, 1
- Splenectomy may be considered for:
- Perioperative mortality of splenectomy is 5-10%, with complications in approximately 50% of patients 2, 1
By systematically evaluating patients with splenomegaly using this approach, clinicians can identify the underlying cause and implement appropriate disease-specific treatment to improve outcomes.