What causes splenomegaly (enlargement of the spleen)?

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From the Guidelines

Splenomegaly, or enlargement of the spleen, is caused by numerous conditions that fall into several categories, including infections, blood disorders, liver diseases, inflammatory and autoimmune conditions, and storage disorders, as supported by recent studies 1.

Causes of Splenomegaly

Some of the key causes of splenomegaly include:

  • Infections such as bacterial infections like endocarditis, viral infections such as mononucleosis (EBV), and parasitic diseases like malaria
  • Blood disorders like hemolytic anemias, leukemias, lymphomas, and myeloproliferative disorders
  • Liver diseases causing portal hypertension, such as cirrhosis, which can result in splenomegaly as blood backs up into the splenic vein
  • Inflammatory and autoimmune conditions like rheumatoid arthritis, lupus, and sarcoidosis
  • Storage disorders like Gaucher disease and Niemann-Pick disease, which cause splenomegaly due to accumulation of substances in splenic tissue

Underlying Mechanisms

The spleen enlarges in these conditions because it must work harder to filter abnormal blood cells, fight infections, or store excess cells. For instance, in the context of liver disease, portal hypertension leads to blood backing up into the splenic vein, causing the spleen to enlarge, as discussed in a recent study on liver transplantation 1.

Treatment Approach

Treatment depends entirely on addressing the underlying cause rather than the splenomegaly itself, which is a symptom rather than a primary disease. For example, in the case of symptomatic splenomegaly in myeloproliferative neoplasms, hydroxyurea is often used as the first-line treatment, with splenectomy considered for drug-refractory cases, as recommended in a study on the management of these conditions 1.

From the Research

Causes of Splenomegaly

  • Splenomegaly can be due to several mechanisms, but is almost always a sign of a systemic condition 2
  • Patient habits, travel, and medical conditions can increase the risk of splenomegaly and suggest etiology 2
  • The most common causes of splenomegaly in the United States are liver disease, malignancy, and infection 2
  • Malaria and schistosomiasis are common causes of splenomegaly in tropical regions, where as many as 80% of people may have splenomegaly 2
  • Infectious mononucleosis is also a common cause of splenomegaly, especially in the athletic population 3
  • Hyper-reactive malarial splenomegaly is a rare and severe form of chronic malaria that can cause splenomegaly 4

Pathophysiological Bases of Splenomegaly

  • The spleen is the largest immune organ in the human body and is also essential for red blood cell homeostasis and iron recycling 5
  • Pathological conditions can result in the spleen weighing in excess of 2000g and extending over 30 centimeters in length, a condition known as splenomegaly 5
  • The spleen plays a crucial role in filtering and destroying senescent red blood cells, infectious microorganisms, and Plasmodium-parasitized red blood cells 6

Risk Factors and Complications

  • Risk factors for splenomegaly include patient habits, travel, and medical conditions 2
  • Complications of splenomegaly include acute infections, anemia, and splenic rupture 2
  • People with splenomegaly should refrain from participating in contact sports to decrease the risk of rupture 2

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

Infectious mononucleosis and the spleen.

Current sports medicine reports, 2002

Research

[Hyper-reactive malarial splenomegaly].

La Revue de medecine interne, 2015

Research

Splenomegaly: Pathophysiological bases and therapeutic options.

The international journal of biochemistry & cell biology, 2018

Research

The role of the spleen in malaria.

Cellular microbiology, 2012

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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