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The significance of splenomegaly depends on the underlying disease. Splenomegaly can be caused by diseases that result in hyperplasia of the lymphoid and reticuloendothelial systems (e.g., infections, connective tissue disorders), infiltrative disorders (e.g., Gaucher disease, leukemia, lymphoma), hematologic disorders (e.g., thalassemia, hereditary spherocytosis), and conditions that cause distention of the sinusoids whenever there is increased pressure in the portal or splenic veins (portal hypertension). Table 12-3 lists the various causes of splenomegaly.

Table 12-3. Causes of Splenomegaly

I. Infectious splenomegaly (due to antigenic stimulation with hyperplasia of the reticuloendothelial and lymphoid systems)

A. Bacterial: acute and chronic systemic infection, subacute bacterial endocarditis, abscesses, typhoid fever, miliary tuberculosis, tularemia, plague

B. Viral: infectious mononucleosis (Epstein-Barr virus), cytomegalovirus, HIV, hepatitis A, B, C

C. Spirochetal: syphilis, lyme disease, leptospirosis

D. Rickettsial: Rocky Mountain spotted fever, Q fever, typhus

E. Protozoal: malaria, babesiosis, toxoplasmosis, toxocara canis, toxocara cati, leishmaniasis, schistosomiasis, trypanosomiasis

F. Fungal: disseminated candidiasis, histoplasmosis, coccidioidomycosis, South American blastomycosis

II. Hematologic disorders

A. Hemolytic anemias, such as thalassemia, splenic sequestration crisis in sickle cell disease, hereditary spherocytosis

B. Extramedullary hematopoiesis as in osteopetrosis and myelofibrosis

C. Myeloproliferative disorders (e.g., polycythemia vera, essential thrombocythemia)

III. Infiltrative splenomegaly

A. Nonmalignant

1. Langerhans cell histiocytosis

2. Storage diseases such as Gaucher disease, Niemann-Pick disease, GM-1 gangliosidosis, glycogen storage disease type IV, Tangier disease, Wolman disease, mucopolysaccharidoses, hyperchylomicronemia types I and IV, amyloidosis, and sarcoidosis

B. Malignant

1. Leukemia

2. Lymphoma: Hodgkin and non-Hodgkin

IV. Congestive splenomegaly

A. Intrahepatic (portal hypertension): cirrhosis of the liver (e.g., neonatal hepatitis, a1-antitrypsin deficiency, Wilson disease, cystic fibrosis)

B. Prehepatic or portal vein obstruction (e.g., thrombosis, vascular malformations)

V. Immunologic diseases

A. Serum sickness, graft-versus-host disease

B. Connective tissue disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis—Felty syndrome, mixed connective tissue disorder, Sjögren syndrome, macrophage activation syndrome, systemic mastocytosis)

C. Common variable immunodeficiency

D. Autoimmune lymphoproliferative syndrome (ALPS) (Canale-Smith syndrome)

VI. Primary splenic disorders

A. Cysts

B. Benign tumors (e.g., hemangioma, lymphangioma)

C. Hemorrhage in spleen (e.g., subcapsular hematoma)

D. Partial torsion of splenic pedicle leading to congestive splenomegaly, cyst, and abscess formation

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