What causes splenomegaly (enlargement of the spleen)?

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From the Guidelines

Splenomegaly is caused by various conditions that lead to increased workload, congestion, or infiltration of the spleen, including infections, liver diseases, blood disorders, inflammatory conditions, and storage disorders. The spleen enlarges because it's working harder to filter blood, fighting infection, or becoming congested with abnormal cells or substances. According to the most recent and highest quality study 1, the treatment of splenomegaly focuses on addressing the primary condition rather than the splenomegaly itself.

Some of the common causes of splenomegaly include:

  • Infections like mononucleosis, malaria, bacterial endocarditis
  • Liver diseases such as cirrhosis, portal hypertension
  • Blood disorders like hemolytic anemia, leukemia, lymphoma
  • Inflammatory conditions like rheumatoid arthritis, lupus
  • Storage disorders like Gaucher's disease

Diagnosis of splenomegaly typically requires imaging studies like ultrasound or CT scan, along with blood tests to identify the underlying cause. In severe cases where the spleen becomes extremely enlarged or dysfunctional, surgical removal (splenectomy) may be necessary, though this is avoided when possible due to the spleen's important immune functions 1. The use of JAK inhibitors has also been suggested as a treatment option for symptomatic splenomegaly, with splenectomy being considered in patients with large and painful splenomegaly where JAK inhibitors are not available or prove ineffective 1.

It's worth noting that the management of splenic trauma has changed considerably in the last few decades, with a focus on non-operative management (NOM) and the use of angiography/angioembolization (AG/AE) to preserve the spleen and its function 1. Additionally, splenic abscess is a rare complication of infective endocarditis, and definitive treatment is splenectomy with appropriate antibiotics 1.

Overall, the treatment of splenomegaly should be individualized and based on the underlying cause, with a focus on addressing the primary condition and preserving the spleen's important immune functions whenever possible.

From the Research

Causes of Splenomegaly

  • Splenomegaly can be due to several mechanisms, but is almost always a sign of a systemic condition 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
  • Hyper-reactive malarial splenomegaly is a rare and severe form of chronic malaria that can cause splenomegaly 3
  • Chronic malaria can evolve to hyper-reactive malarial splenomegaly, a life-threatening complication 4

Pathophysiology of Splenomegaly

  • The pathophysiology of hyper-reactive malarial splenomegaly involves an intense immune reaction (predominantly B cell-driven) to repeated/chronic infections with Plasmodium sp. 3
  • 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 centimetres in length, a condition termed splenomegaly 5

Risk Factors for Splenomegaly

  • Patient habits, travel, and medical conditions can increase the risk of splenomegaly and suggest etiology 2
  • Infection by malaria is the most common cause of spleen rupture and splenomegaly, albeit variably, a landmark of malaria infection 6
  • Residence in a malaria-endemic area is a risk factor for hyper-reactive malarial splenomegaly 3

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

[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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