eMedicine Specialties > Pediatrics: General Medicine > Hematology

Splenomegaly

Author: Mundeep K Kainth, DO, Resident Physician, Department of Pediatrics, The Children's Hospital at Albany Medical Center
Coauthor(s): Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP, Associate Professor of Pediatric Hematology-Oncology, Department of Pediatrics, Albany Medical Center; Faculty, Alden March Bioethics Institute; Richard H Sills, MD, Professor of Pediatrics, Upstate Medical University
Contributor Information and Disclosures

Updated: Sep 4, 2008

Introduction

Background

Splenomegaly in childhood is generally first suspected upon physical examination. One third of newborns and 10% of children may normally have a palpable spleen. The tip of the normal, palpable spleen is soft, smooth, nontender and less than 1-2 cm below the left costal margin. A pathologically enlarged spleen is often firm, may have an abnormal surface, and is frequently associated with signs and symptoms of the underlying disease. When any of these features are noted, or if the tip of the spleen is enlarged more than 1-2 cm below the costal margin, further evaluation should be considered.¹

Pathophysiology

Anatomy

The spleen is the largest lymphoid organ in the body. The spleen and the lymph nodes are the major components of the mononuclear-phagocyte system (MPS). They serve as filters that remove damaged cells, microorganisms, and particulate matter and deliver antigens to the immune system. The MPS, originally called the reticuloendothelial system, consists of fixed phagocytic cells in different organs. These phagocytes locally interact with lymphocytes and play an essential role in the recognition of antigens and their interaction with immunocompetent cells.²

The splenic tissue consists of red and white pulp lying in a capsule. Blood enters the spleen through the splenic artery, a branch of the celiac artery. It then travels into the smaller arterioles and approaches the white pulp. The white pulp, rich in T and B lymphocytes, receives plasma for antigen processing. Splenic macrophages efficiently ingest these antigens and deliver them to the immunocompetent cells of the spleen for antibody production and stimulation of T-lymphocyte immune responses. The remaining hemoconcentrated blood continues into the contiguous red pulp, the sinuses and cords of which are also lined with macrophages.

The red pulp forms most of the splenic tissue and consists of splenic cords, the circulation of which is designated as open because no well-defined endothelial lining is present. To exit the cords, blood must pass through 1-µm to 5-µm slits in this fenestrated basement membrane to reach the venous sinusoids. The circulation through the cords is slow and congested. This delay provides prolonged exposure of blood cells, bacteria, and particulate matter to the dense mononuclear-phagocyte elements in the red pulp.

After reaching the sinuses, blood from the red pulp empties into the splenic vein, which joins the superior mesenteric vein to form the hepatic portal vein. Because no valves are present in the splenic venous system, the pressure in the splenic vein reflects the pressure in the portal vein.

Function

One of the primary functions of the spleen is the filtration of defective cells. Erythrocytes slowly pass through the hypoxic and acidotic environment of the splenic cords and then squeeze through narrow slits into the sinusoids. Although healthy erythrocytes readily accomplish this passage, aged and abnormal red cells, such as spherocytes and sickle cells, remain behind to be ingested by the macrophages lining the cords. Fc receptors on splenic macrophages also bind to IgG antibody-coated erythrocytes or platelets, which are mainly cleared by the spleen.

The spleen is also critical for clearing circulating, particularly encapsulated, bacteria. The amorphous polysaccharide coat of encapsulated bacteria greatly impairs their clearance in the absence of antibody, and only the spleen's highly efficient phagocytic cords can effectively clear them. The splenic white pulp processes these intravenous antigens and produces antibody that, during subsequent exposures, allows for efficient clearance by the rest of the MPS.

The splenic cords are uniquely capable of removing erythrocytic inclusions, such as nuclear remnants (ie, Howell-Jolly bodies) or precipitated globin (ie, Heinz bodies), without destroying the cell. The spleen also serves as a reservoir for platelets and produces blood components (extramedullary hematopoiesis) if the bone marrow is unable to meet demands.³

Frequency

United States

A 1-cm to 2-cm splenic tip is palpable in 30% of full-term neonates and in as many as 10% of healthy children. Approximately 3% of healthy college freshmen have palpable spleens. Initial and follow-up studies confirm that these college freshmen are not at high risk for subsequent serious disease.^4,5,1

International

Malaria, schistosomiasis, and other infections in endemic areas are frequent causes of splenomegaly.⁶

In malaria-endemic areas, the prevalence of splenomegaly (ie, spleen rate) is a measure of malaria exposure. In hyperendemic areas (eg, Papua New Guinea), the spleen rate in children exceeds 50%.⁷ Such hyperendemic areas have a prevalence of massive splenomegaly (hyperreactive malarial splenomegaly) of 1-2% in children.⁸

Mortality/Morbidity

Splenic rupture may occur in acute splenomegaly associated with infectious mononucleosis. The incidence is 1:1000, and it usually occurs in the first 3 weeks of illness.⁹

Splenectomy is uncommonly performed in children with splenomegaly. Nevertheless, should it be clinically indicated, the overall risk of postsplenectomy sepsis is approximately 2%, with increased incidence and mortality in young children.^10,11

Hypersplenism is the occurrence of thrombocytopenia, and occasionally leukopenia and anemia, in the context of significant splenomegaly.¹² The cytopenias are usually mild but may contribute to overall morbidity.¹³

Race

Specific causes of splenomegaly are most common in certain racial groups. Examples include splenic sequestration as a complication of sickle cell disease in patients of African or Mediterranean ancestry and noncirrhotic portal fibrosis in patients of Iranian, South Asian, or Japanese ancestry.¹⁴

Age

The etiology of splenomegaly varies with age. For example, splenic sequestration in sickle cell disease occurs early in life, before the splenic involution that ultimately occurs in most patients with sickle cell disease.

Clinical

History

Despite the extensive differential diagnoses of splenomegaly, careful history taking and physical examination, along with a CBC count and liver function tests, often help in narrowing the list of possible causes. The history should include attention to the following important areas, as listed below.¹⁵

• Chief symptoms
  • Acute or chronic nature
  • Painful or asymptomatic manifestation
  • Ingestion of hepatotoxic agents resulting in hepatitis or portal hypertension
  • Abdominal trauma that may cause splenic hematoma
  • Acute illness such as hepatitis, mononucleosis, or malaria
  • Diarrhea (eg, salmonellosis, inflammatory bowel disease)
  • Bone pain, fever, malaise, lethargy, or bruising (eg, associated with leukemia)
  • Weight loss, fevers, night sweats (eg, associated with Hodgkin disease)
  • Jaundice
• Medical history
  • Complicated neonatal period (eg, sepsis, hypotension)
  • Umbilical catheter thrombosis
  • Hyperbilirubinemia, anemia (eg, due to hereditary spherocytosis or hemolysis)
  • Heart disease (eg, congestive heart failure)
  • Past surgeries (eg, leading to infection, thrombosis, portal hypertension)
  • Transfusions (eg, resulting in hepatitis)
  • Hepatitis
  • Abdominal trauma (possibly resulting in splenic pseudocyst)
  • Travel (possible presence of malaria, leishmaniasis, schistosomiasis, or trypanosomiasis)
  • Sexual behavior (possible presence of hepatitis, cytomegalovirus [CMV], or human immunodeficiency virus [HIV])
  • Known blood disorder (eg, sickle cell disease, hereditary spherocytosis)
• Family history
  • Anemia, cholecystectomy (eg, due to hemolytic anemia–associated gallstones)
  • Splenectomy (eg, due to hemolytic anemia)
  • Mediterranean ethnicity (increased incidence of thalassemia and glucose-6-phosphate dehydrogenase [G6PD] deficiency)
  • African ethnicity (increased incidence of sickle cell anemia, G6PD deficiency, and hereditary pyropoikilocytosis)
  • Ashkenazi Jewish ethnicity (increased incidence of Gaucher disease and Niemann-Pick disease)
  • Northern European ethnicity (increased incidence of pyruvate kinase deficiency and hereditary spherocytosis)
  • Asian ethnicity (increased incidence of G6PD)
  • South Asian ethnicity (increased incidence of portal hypertension secondary to noncirrhotic portal fibrosis)

Physical

The patient should be examined in the supine or right lateral decubitus position. The spleen is best palpated with the clinician kneeling on the patient's right side and by palpating the left upper quadrant of the abdomen with the right hand.

Palpation should start just above the pubis and move toward the left upper quadrant to find the medial border of the spleen. The examiner usually palpates the spleen by feeling its inferolateral margins. If the enlarged tip of the spleen is below the examiner's hands, he or she often misses it. Likewise, light pressure should be used with small children, because the spleen can easily be pushed out of the way without the clinician feeling its edge. At times, the superior medial edge of the spleen is more readily palpated than the inferior margin.

Percussion over the left lateral areas of the lower ribs may reveal splenomegaly that is not evident upon palpation.^16,17,18 This procedure is particularly helpful in a crying child in whom splenic palpation is difficult. It is similarly helpful in children and adolescents who are obese. A normal-sized liver and spleen may also become palpable if pulmonary pathology is causing hyperinflation of the lungs (pseudosplenomegaly). The spleen is occasionally confused with the left lobe of the liver or with a tumor in the left upper quadrant (eg, Wilms tumor, neuroblastoma). The characteristic downward movement of the spleen with inspiration and its relatively flat surface and shape can help in differentiating it from other masses of the left upper quadrant. Important features on physical examination are as follows:¹⁵

• General findings - Failure to thrive, ill-appearing (eg, in the presence of malignancy, chronic hemolysis, chronic infection, metabolic disease, liver disease, or inflammatory disease)
• Dermal findings
  • Pallor (eg, due to anemia, which may indicate hemolysis, bone marrow infiltration, or hypersplenism)
  • Petechiae, purpura (eg, due to thrombocytopenia, which may indicate bone marrow failure, autoimmune disorder, or hypersplenism)
  • Jaundice (eg, due to hemolytic anemia or liver disease)
  • Itching, pruritus (eg, due to liver dysfunction, Hodgkin lymphoma)
  • Rashes (eg, due to acute and chronic infections, systemic lupus erythematosus, rheumatoid arthritis, infective endocarditis, histiocytoses, or hemangiomata)
  • Eczematous rash (eg, due to Langerhans cell histiocytosis or immunodeficiency)
• Head, eyes, ears, nose, and throat findings
  • Icterus (eg, due to hemolytic anemia or liver dysfunction)
  • Cherry red retinal spots, cloudy corneas (eg, due to lipid storage diseases)
• Respiratory and cardiovascular findings
  • Dyspnea, fatigue (eg, due to anemia or congestive heart failure)
  • New murmur (eg, due to infective endocarditis)
• GI findings
  • Abdominal tenderness (eg, due to gallstones, hepatitis, trauma, or acute splenomegaly)
  • Distention, prominent abdominal veins, ascites (eg, due to liver disease)
  • Enlarged liver with a firm, knobby texture
• Musculoskeletal findings
  • Joint pain (eg, due to systemic lupus erythematosus, rheumatoid arthritis, or autoimmune inflammatory diseases)
  • Poor bone growth (eg, due to storage diseases or osteopetrosis)
  • Bone pain (eg, due to leukemia or Gaucher disease)
• Neurologic findings
  • Poor vision (eg, due to osteopetrosis)
  • Uveitis, iritis (eg, due to sarcoidosis or rheumatoid arthritis)
  • Loss of developmental milestones (eg, due to storage diseases, chronic infection, or immunodeficiency)

Causes

Despite the numerous causes of splenomegaly (see Differentials), the spleen is rarely the primary site of disease.

• The most common mechanism of splenomegaly in children is hyperplasia of the MPS, which can be categorized as excessive antigenic stimulation (ie, infection), disorders of immunoregulation (ie, autoimmune disorders), or excessive destruction of abnormal blood cells (ie, hemolysis).^2,19
  • Excessive antigenic stimulation due to infection is the cause of most cases of splenomegaly in children. Viral infections are the most frequent culprits, and the associated splenomegaly is usually transient and only mild to moderate in severity. Although Epstein-Barr virus (EBV) and CMV are well known causes of splenomegaly, the most typical viral illnesses of childhood are the most frequent causes.
  • Other common infectious etiologies include bacterial, protozoal, and fungal infections. In endemic areas, malaria and schistosomiasis are routine causes of splenomegaly. Concomitant generalized lymphadenopathy is common in many of these infectious etiologies.
  • Inflammation due to collagen vascular diseases, such as juvenile rheumatoid arthritis, and increased destruction of blood cells from hemolytic anemias are relatively uncommon, but clinically significant, causes of splenomegaly.
  • Splenomegaly can be a presenting sign of neoplasia. One half of children with acute lymphoblastic leukemia have splenomegaly. Splenomegaly is also a frequent finding in non-Hodgkin lymphoma, Hodgkin disease, and acute or chronic myeloblastic leukemia. Metastatic involvement of the spleen, which is uncommon in children, is most often caused by neuroblastoma. Histiocytes can infiltrate the spleen; Langerhans cell histiocytosis and other rare histiocytic disorders are usually the cause of this condition.
  • Obstructed venous blood flow of intrahepatic or extrahepatic etiology can cause splenomegaly. The most common causes include portal vein thrombosis, hepatic cirrhosis, and congestive heart failure. Children with extrahepatic portal venous obstruction, such as cavernous transformation, often present with splenomegaly as the primary manifestation of their disease.
  • Many storage diseases result in splenomegaly. In Gaucher or Niemann-Pick disease, splenomegaly is often the first clinical manifestation. Splenomegaly is the result of the accumulation of abnormal lipids in splenic macrophages.
  • After trauma, palpable subcapsular hematomas may develop in the spleen, which may eventually develop into clinically palpable pseudocysts. Patients with congenital splenic cysts usually present with asymptomatic splenomegaly.
  • Although normally found only during the first 6 months of life, extramedullary hematopoiesis may occur in diseases associated with intense demand on the bone marrow for cell production. Thalassemia major, osteopetrosis, and idiopathic myelofibrosis are examples of this rare cause of splenomegaly.
• Hypersplenism is a clinical syndrome in which cytopenias result from excessive splenic function, which occurs as the spleen and its MPS tissues hypertrophy. The pathologic action of the spleen, ie, the reduction of circulating blood elements, has been attributed to 4 possible mechanisms: excessive splenic phagocytic activity, splenic production of an antibody that results in the destruction of hematopoietic cells, overactivity of splenic function, and sequestration.²⁰ In patients with cirrhosis, abnormalities of cytokine production may contribute to the cytopenias noted.¹³
  • As the spleen enlarges, it can sequester erythrocytes, leukocytes, and platelets, resulting in mild-to-moderate decreases in some or all of these cell lines. Severe reductions in cell counts are unusual and should prompt a search for alternative etiologies.
  • Venous obstruction is the most common cause of hypersplenism. Any increase in portal pressure is reflected in the splenic venous sinuses. This impairs blood flow out of the cords and results in the sequestration of blood cells and hypersplenism. Hypersplenism in children is most frequently caused by portal hypertension. Extrahepatic venous obstruction from portal vein thrombosis is the most common cause of increased portal pressures. In extrahepatic venous obstruction, hepatic function is normal. Intrahepatic venous obstruction is usually due to cirrhosis.
  • Portal hypertension usually increases flow through minor collateral vessels between the portal circulation and the systemic circulation. Portal hypertension can result in recognizable dilatation of the superficial abdominal veins and esophageal varices. Patients with these varices may present with sudden and catastrophic GI hemorrhage.
• Splenic sequestration crisis is a specific form of acute hypersplenism in young children with sickle cell anemia.²⁰
  • Children less than 6 years old can develop rapid splenic sequestration and splenomegaly with the consumption of large volumes of erythrocytes. They present with sudden weakness, dyspnea, and left-sided abdominal pain in addition to splenomegaly.
  • Splenic sequestration is an emergency. Rapid death from hypovolemic shock can result.
  • Treatment consists of fluids and erythrocyte transfusions. To prevent recurrences, splenectomy may be indicated. In most patients with sickle cell disease, the spleen eventually involutes, and sequestration is no longer possible.

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