From the Guidelines
Hepatosplenomegaly is most commonly caused by infections, hematologic disorders, storage diseases, infiltrative diseases, autoimmune conditions, portal hypertension, and certain cancers. The causes of hepatosplenomegaly can be diverse, spanning several disease categories. According to a consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency 1, hepatosplenomegaly is a common clinical presentation for patients with acid sphingomyelinase deficiency (ASMD), with the liver being the primary affected organ. Other potential causes of hepatosplenomegaly include:
- Infections such as viral hepatitis, malaria, leishmaniasis, schistosomiasis, and infectious mononucleosis
- Hematologic disorders like leukemias, lymphomas, hemolytic anemias, and myeloproliferative disorders
- Storage diseases, including Gaucher disease, Niemann-Pick disease, and lysosomal acid lipase deficiency (LALD) 1
- Infiltrative diseases such as amyloidosis and sarcoidosis
- Autoimmune conditions like systemic lupus erythematosus and rheumatoid arthritis
- Portal hypertension from liver cirrhosis
- Certain cancers with metastasis to these organs
The underlying mechanism typically involves inflammation, cellular infiltration, congestion from blood flow obstruction, or abnormal substance accumulation within these organs. Diagnosis requires a thorough history, physical examination, laboratory tests, and imaging studies. Treatment targets the underlying cause rather than the hepatosplenomegaly itself, such as antimicrobials for infections, chemotherapy for malignancies, or enzyme replacement therapy for certain storage diseases, as seen in ASMD patients 1.
From the Research
Causes of Hepatosplenomegaly
The causes of hepatosplenomegaly, which is the abnormal enlargement of the liver and spleen, can be attributed to various conditions. These include:
- Metabolic diseases, such as lysosomal storage diseases (LSDs) 2, 3
- Congestive conditions, which may lead to increased pressure in the liver and spleen
- Neoplastic conditions, such as cancer, which can cause enlargement of the liver and spleen
- Infectious diseases, such as disseminated nontuberculous mycobacteriosis in patients with acquired immunodeficiency syndrome (AIDS) 4
- Toxic conditions, which may be caused by exposure to certain substances
- Inflammatory conditions, which can cause swelling and enlargement of the liver and spleen
Specific Conditions Associated with Hepatosplenomegaly
Some specific conditions that have been associated with hepatosplenomegaly include:
- Lysosomal storage diseases, such as Gaucher disease, cholesterol ester storage disease (CESD), and Niemann-Pick diseases 2, 3
- Hemophilia, which can lead to abnormalities of the spleen and liver due to intensive replacement therapy 5
- Hemophagocytic syndrome, which is characterized by a proliferation of cytologically benign, actively phagocytic macrophages in bone marrow, spleen, or lymph nodes, and can cause hepatic dysfunction 6
- Disseminated Mycobacterium avium complex (MAC) infection, which can cause massive and progressive hepatosplenomegaly in patients with AIDS 4
Diagnostic Approaches
To diagnose the underlying cause of hepatosplenomegaly, various diagnostic approaches can be used, including:
- Laboratory tests, such as liver function tests and complete blood counts
- Imaging studies, such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI)
- Biopsy of the liver or spleen to examine for histological abnormalities
- Molecular testing, such as genetic testing for LSDs 2