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Am Fam Physician. 2021;104(2):271-276

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Splenomegaly can be due to several mechanisms but is almost always a sign of a systemic condition. Patient habits, travel, and medical conditions can increase risk of splenomegaly and suggest etiology. Symptoms can suggest infectious, malignant, hepatic, or hematologic causes. Physical examination will typically reveal splenomegaly, but abdominal ultrasonography is recommended for confirmation. Physical examination should also assess for signs of systemic illness, liver disease, and anemia or other hematologic issues. The most common causes of splenomegaly in the United States are liver disease, malignancy, and infection. Except for apparent causes such as infectious mononucleosis, basic laboratory analysis and ultrasonography are the first-line steps in determining etiology. Malaria and schistosomiasis are common in tropical regions, where as many as 80% of people may have splenomegaly. Management of splenomegaly involves treating the underlying disease process. Splenectomies and spleen reduction therapies are sometimes performed. Any patient with limited splenic function requires increased vaccination and prophylactic antibiotics for procedures involving the respiratory tract. Acute infections, anemia, and splenic rupture are the most common complications of splenomegaly, and people with splenomegaly should refrain from participating in contact sports to decrease risk of rupture.

The spleen is part of the hepatoportal system and is the largest organ of the lymphatic system. Functions of the spleen include removing aging or abnormal blood cells, storing platelets and red blood cells, and producing and distributing immune cells and antibodies.1 The spleen is a major site of blood production outside of the bone marrow, especially during times of stress.13 Several general pathophysiologic mechanisms cause splenic enlargement. Hyperplasia and hypertrophy cause splenomegaly due to increased function of the spleen. Infiltrative processes can cause accumulation of abnormal cells in the spleen, which can be malignant, benign, or caused by glycogen storage disorders. Congestive processes result in blood pooling due to blockage of venous outflow.2,3 These mechanisms can lead to transient splenomegaly, such as with blood loss, infection, and during pregnancy, but in these cases the spleen returns to normal size after the condition resolves.2,4

Clinical recommendation Evidence rating Comments
History of liver disease and alcohol use should be assessed in patients presenting with splenomegaly in the United States.13,5 C Expert opinion based on cirrhosis being one of the most common causes of splenomegaly in the United States
Abdominal ultrasonography is the first-line imaging study suggested to confirm a suspected diagnosis of splenomegaly.3,5,6,8,14 C Blinded clinical trial and expert opinion based on low sensitivity and specificity of the abdominal examination for splenomegaly and cost of other imaging modalities
Vaccinations against encapsulated organisms are indicated in functionally asplenic patients to prevent infection.24,25 C Expert opinion based on clinical guidelines and a review article on management of functionally asplenic patients
Patients with infectious mononucleosis should restrict sports participation for at least 21 to 31 days after symptom onset.26,27 C Sports medicine guidelines based on expert opinion and a retrospective analysis on splenic rupture in patients with infectious mononucleosis and when they are likely to have a rupture

In the United States, the most common etiologies of splenomegaly are chronic liver disease, malignancies, and infections.3 Malignancies—usually leukemia or lymphoma—are common causes of splenomegaly, seen in close to one-third of affected patients.3 As many as one-third of patients with splenomegaly have cirrhosis, where abnormal liver parenchyma leads to congestive splenomegaly.3,5 Several infections can lead to splenomegaly. In the United States, infectious mononucleosis is a common etiology of splenomegaly in adolescents and young adults.3 Splenomegaly is common in patients with HIV, as a response to the virus or because of secondary infections.6 People who are born in tropical regions, global travelers, and military personnel deployed to tropical regions are at risk for parasitic infections that can lead to splenomegaly, most commonly schistosomiasis and chronic malaria.7 Common disorders associated with splenomegaly are shown in Table 1.2,3

CongestiveAny pathologic process that can cause advanced liver disease, congestive heart failure, portal hypertension, renal failure, splenic vein thrombosis
NeoplasticEssential thrombocytopenia, Hodgkin/non-Hodgkin lymphoma, leukemia (acute lymphoid leukemia, acute myeloid leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, hairy cell), metastatic disease, multiple myeloma, myelofibrosis, polycythemia vera, primary splenic tumors
InfectiousBabesiosis; Bartonella; Candida; endocarditis; hepatitis A, B, and C viruses; HIV; mononucleosis (Epstein-Barr virus, cytomegalovirus); splenic abscess; syphilis; tuberculosis
Tropical/parasitic considerationsActinomycosis, brucellosis, leishmaniasis (visceral), malaria, schistosomiasis, typhoid
Autoimmune/inflammatoryCollagen vascular disease, hemolytic anemia, immune thrombocytopenia, pernicious anemia, rheumatoid arthritis (Felty syndrome), systemic lupus erythematosus, thyrotoxicosis
Hematologic (nonmalignant)Beta thalassemia major, sickle cell anemia
Infiltrative (nonmalignant, noninfectious)Amyloidosis, glycogen storage disorders, sarcoidosis

Splenomegaly is a common finding in college freshman in North America, with rates of up to 3%, because of the high prevalence of infectious mononucleosis.3 Splenomegaly can affect up to 80% of people in tropical areas where malaria and schistosomiasis are endemic.7 People who have recently immigrated from overseas, children who are adopted from endemic areas, refugees, and travelers with splenomegaly often have chronic parasitic infections.7

Pertinent History

Personal and family history can suggest the etiology of splenomegaly (Table 23,817). Early satiety and fullness in the left upper quadrant can be due to an enlarged spleen.2,8 Family history of malignancies, liver disease, lipid storage disorders, or hematologic diseases can suggest an etiology for splenomegaly.2,8 Personal history may contain risk factors for splenomegaly, including alcohol consumption, intravenous drug use, and high-risk sexual behavior. Immigration from or travel to tropical areas increases the risk of infectious diseases such as malaria or schistosomiasis. Medical history of cancer, hematologic disorders, heart failure, or chronic liver disease increases the chance of splenomegaly (Table 12,3). Recent flulike symptoms, sore throat, abdominal pain, fever, weight loss, night sweats, and fatigue can suggest infection or malignancies, whereas bleeding, easy bruising, pallor, jaundice, and petechial rashes can be attributable to hematologic etiologies.

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