This document provides an overview of the potential causes of splenomegaly (enlarged spleen). It discusses various infectious, hematologic, infiltrative, congestive, inflammatory, and primary splenic disorders that can result in splenomegaly. Common causes include viral infections like mononucleosis, bacterial infections, parasitic infections, hematologic conditions involving the bone marrow like thalassemia, infiltrative disorders from cancer metastasis or lipid/mucopolysaccharide accumulation, congestive disorders from portal vein obstruction, and inflammatory diseases like lupus.

1. Differential Diagnosis of Splenomegaly
Infection
• Viral infection
o The most common cause of splenomegaly in children
o Splenic enlargement is usually transient and mild to moderate in severity.
o Common viral infections include:
 Epstein-Barr virus (infectious mononucleosis)
o Splenomegaly occurs in 50–75% of cases of infectious
mononucleosis.
 Cytomegalovirus
 HIV
 Bacterial infection
o Acute bacterial infections
o Subacute bacterial endocarditis
o Congenital syphilis
o Tuberculosis
o Other chronic bacterial infections
o Septicemia from meningococcus or pneumococcus may also be associated
with splenomegaly.
 Parasitic infection
o Toxoplasmosis
o Malaria
o Leishmaniasis
 Fungal infection
o Candidiasis
o Histoplasmosis
 Progressive disseminated histoplasmosis can occur in healthy
children < 2 years.
 Results from exposure to the fungus in endemic areas of the U.S.
(Mississippi, Ohio, and Missouri River valleys)
 Early symptoms are fever, failure to thrive, and
hepatosplenomegaly.
o Coccidioidomycosis
Hematologic disorders
• Splenic enlargement as a result of extramedullary hematopoiesis
o Occurs in diseases associated with increased demand on the bone marrow
for cell production, eg, thalassemia major
• Acute splenic sequestration crisis is a medical emergency that requires prompt
recognition and treatment.
o It is a leading cause of death in children with sickle cell anemia.
o A rapidly enlarging spleen with:
 Falling hematocrit
 Pallor
 Dyspnea
 Weakness
 Left-sided abdominal pain
• Hemolytic anemias—congenital and acquired
o Red cell membrane defects
 Hereditary spherocytosis
 Hereditary elliptocytosis
o Red cell hemoglobin defects
 Sickle cell disease and related syndromes
 Thalassemia

2. o Red cell enzyme defects
 Pyruvate kinase deficiency
 Glucose-6-phospate dehydrogenase deficiency
 Others
o Autoimmune hemolytic anemia
• Extramedullary hematopoiesis
o Occurs in diseases associated with increased demand on the bone marrow
for cell production.
 Thalassemia major
 Osteopetrosis
 Myelofibrosis
Infiltrative disorders
• In malignant infiltration, the spleen is firm, massively enlarged, and crosses the
midline of the body.
• The spleen is commonly infiltrated in:
o Leukemias and lymphomas
o Lipidoses
o Mucopolysaccharidosis
 Phagocytic reticuloendothelial elements of the spleen accumulate
large amounts of lipid and mucopolysaccharide, respectively.
o Langerhans cell histiocytosis
o Metastatic neoplasia of the spleen is rare and is usually caused by
neuroblastoma.
Congestive splenomegaly (Banti syndrome)
• Splenomegaly may occur from obstruction of the hepatic, portal, or splenic veins.
• Common causes include:
o Portal vein thrombosis
o Cirrhosis
o Congestive heart failure
o Umbilical vein catheterization or septic omphalitis in neonates may also
result in obliteration of the portal, hepatic, or splenic veins.
• Congestive splenomegaly is the most common cause of hypersplenism
(splenomegaly), peripheral blood cytopenias from excessive splenic function, and
increased bone marrow production of the affected blood cells.
Inflammatory diseases
• Splenomegaly is the result of increased numbers of reticuloendothelial cells that
remove antibody-coated cells and proteins in inflammatory diseases, such as:
o Systemic lupus erythematosus
o Rheumatoid arthritis (Still disease)
o Serum sickness
o Sarcoidosis
o Immune thrombocytopenias and neutropenias
• Lymphoid hyperplasia may occur as a result of accelerated antibody production in
the spleen.
Primary splenic disorders
• Splenoptosis (wandering spleen)
o Splenoptosis, or wandering spleen, is a congenital fusion anomaly of dorsal
mesogastrium.

3. o Results in a spleen of normal size that moves freely within the peritoneal
cavity
o A patient with splenoptosis usually has an asymptomatic abdominal mass.
• Cysts
o Splenic cysts may mimic splenomegaly.
o 2 types of splenic cysts have been identified:
 Congenital (epidermoid)
 Acquired (pseudocyst) from trauma or infarction
o Cysts are generally asymptomatic, and their presence is usually confirmed
by radiologic studies.
• Hemangiomas and lymphangiomas
• Subcapsular hemorrhage
o Abdominal trauma may cause subcapsular hemorrhage of the spleen.
o Abdominal pain
• Accessory spleen may also mimic splenomegaly.
o Found in 10–15% of individuals