What are the causes of splenomegaly (enlargement of the spleen)?

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From the Guidelines

Splenomegaly is primarily caused by infections, hematologic disorders, liver diseases, inflammatory and autoimmune conditions, storage diseases, and other factors that lead to increased workload, immune activation, congestion, or infiltration of the spleen. The causes of splenomegaly can be categorized into several groups, including:

  • Infections such as bacterial infections like endocarditis and tuberculosis, viral infections such as mononucleosis (EBV), HIV, and CMV, and parasitic infections like malaria and leishmaniasis 1
  • Hematologic disorders like hemolytic anemias, leukemias, lymphomas, myeloproliferative disorders, and hemoglobinopathies like sickle cell disease and thalassemia 1
  • Liver diseases causing portal hypertension, such as cirrhosis and portal vein thrombosis, which can result in congestive splenomegaly 1
  • Inflammatory and autoimmune conditions like rheumatoid arthritis, systemic lupus erythematosus, and sarcoidosis 1
  • Storage diseases including Gaucher's disease and Niemann-Pick disease, which lead to splenomegaly due to accumulation of substances in the spleen 1
  • Other causes such as amyloidosis, splenic cysts or tumors, and certain medications 1

The spleen enlarges in these conditions due to increased workload, immune activation, congestion from portal hypertension, or infiltration by abnormal cells or substances. Diagnosis typically requires identifying the underlying cause through history, physical examination, laboratory tests, and imaging studies 1.

It is essential to note that splenectomy, which is sometimes considered as a treatment option for certain conditions like immune thrombocytopenia, is an invasive and irreversible process that leads to a loss of multiple hematological and immunological functions 1. Therefore, unless there is an urgent need to raise the platelet count and the patient does not respond to or cannot tolerate second-line medical therapies, splenectomy should generally be reserved for patients in whom other treatment options have been exhausted.

In terms of diagnosis, noninvasive tests like ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) can provide evidence of morphological abnormalities associated with cirrhosis and portal hypertension, and the presence of portocollateral circulation on these imaging modalities is 100% specific for clinically significant portal hypertension (CSPH) 1. The combination of platelet count with other unrelated noninvasive tests (NITs) improves the noninvasive diagnosis of CSPH, and liver stiffness (LS) by transient elastography (TE; FibroScan) has proved very accurate for discriminating patients with and without CSPH 1.

Overall, the diagnosis and management of splenomegaly require a comprehensive approach that takes into account the underlying cause, the patient's clinical presentation, and the potential risks and benefits of different treatment options.

From the Research

Causes of Splenomegaly

The causes of splenomegaly can be diverse and are often related to systemic conditions. Some of the key causes include:

  • Liver disease, which is one of the most common causes of splenomegaly in the United States 2
  • Malignancy, which can lead to splenomegaly due to various mechanisms 2
  • Infection, such as infectious mononucleosis, malaria, and schistosomiasis, which are common in tropical regions 2, 3
  • Hematologic disorders, such as blood diseases that affect the spleen's function 4, 3
  • Vascular abnormalities and hemolysis, which can also cause splenomegaly 3

Pathophysiological Bases of Splenomegaly

Splenomegaly can occur as a physiological response to stress or as a chronic process that is often detrimental to the individual's wellbeing 5. The spleen's ability to expand is termed splenomegaly, and it can weigh in excess of 2000g and extend over 30 centimeters in length in pathological conditions 5.

Diagnostic Approach

A logical approach to diagnosing splenomegaly involves considering the patient's history, physical examination, and laboratory routine test results 4, 6. Abdominal ultrasonography is recommended for confirmation of splenomegaly, and basic laboratory analysis is often the first-line step in determining the etiology 2. In some cases, extensive radiological and laboratory investigations may fail to yield a diagnosis, resulting in "isolated" splenomegaly, which can be challenging to manage 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Splenomegaly: Diagnosis and Management in Adults.

American family physician, 2021

Research

Why does my patient have lymphadenopathy or splenomegaly?

Hematology/oncology clinics of North America, 2012

Research

Splenomegaly: Pathophysiological bases and therapeutic options.

The international journal of biochemistry & cell biology, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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