Pediatric Splenomegaly

Anatomy

The spleen is the largest lymphoid organ in the body. Although these data are controversial, Rosenberg et al proposed that normal splenic lengths should be no greater than the following[24] :

• 6.0 cm at age 3 months
• 6.5 cm at age 6 months
• 7.0 cm at age 12 months
• 8.0 cm at age 2 years
• 9.0 at age 4 years
• 9.5 cm at age 6 years
• 10.0 cm at age 8 years
• 11.0 cm at age 10 years
• 11.5 cm at age 12 years
• 12.0 cm at age 15 years or older (females);13.0 cm at age 15 years or older (males)

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. The MPS delivers antigens to the immune system; originally called the reticuloendothelial system, the MPS 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.[25]

The splenic tissue consists of red and white pulp contained in a capsule. Blood enters the spleen through the splenic artery, a branch of the celiac artery, and then travels into the smaller arterioles, approaching 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 hemo-concentrated 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 the spleen 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, with this delay providing 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. This is clinically significant in patients with portal hypertension.

Function

One of the primary functions of the spleen is the filtration of defective blood cells. Erythrocytes slowly pass through the hypoxic and acidotic environment of the splenic cords and squeeze through narrow slits into the sinusoids. Although normal erythrocytes readily accomplish this passage, aged or abnormal red cells, such as spherocytes and sickle cells, remain in the spleen to be ingested by the macrophages lining the cords.[26]

In addition, Fc receptors on splenic macrophages bind to immunoglobulin G (IgG) antibody–coated erythrocytes or IgG antibody–coated platelets, which are subsequently 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 if the bone marrow is unable to meet demands. The production of blood cells by the spleen is referred to as extramedullary hematopoiesis.[27]

In addition, the spleen is critical for removing circulating bacteria. The amorphous polysaccharide coat of encapsulated bacteria greatly impairs their clearance in the absence of antibody, and only the spleen's phagocytic cords can effectively clear encapsulated organisms.

The splenic white pulp processes intravenous antigens and produces antibody that, during subsequent exposures, permits efficient bacterial clearance by the rest of the MPS.[27]

Frequency

United States

A 1- to 2-cm splenic tip is palpable in approximately 30% of full-term neonates and in as many as 10% of healthy children overall.[4] A 1967 study found that approximately 3% of healthy college freshmen had palpable spleens, with initial and follow-up research confirming that the students within this subgroup were not at increased risk for subsequent serious disease.[28, 29]

International

Due to the varying incidence of infections that cause splenomegaly, the prevalence of the condition in children differs by geographical region.

Malaria, schistosomiasis, and other infections in endemic areas are frequent causes of splenomegaly.[30, 1]

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%.[31] Such hyperendemic areas may have a prevalence of massive splenomegaly (hyper-reactive malarial splenomegaly) of 1-2% in children.[32]

Mortality/Morbidity

Splenic rupture

Splenic rupture may occur in acute splenomegaly associated with infectious mononucleosis. The incidence is approximately 1:1000, and it usually occurs in the first 3 weeks of illness.[33] The American Academy of Pediatrics Council on Sports Medicine and Fitness has recommended that children with acute splenomegaly restrict their participation in sports.[34] Disorders associated with chronic splenomegaly do not result in the same level of splenic friability and risk of rupture as disorders that cause acute splenomegaly.[35, 36] Spleens are also prone to rupture if they contain infected tissue, malignant cells, hematomas, or other space-occupying lesions.[37, 38]

Hypersplenism

Hypersplenism is the occurrence of (most commonly) thrombocytopenia, and occasionally leukopenia and anemia, in the context of significant splenomegaly. The thrombocytopenia is usually mild but is variable. In liver cirrhosis, the underlying mechanism may involve mechanical pooling and cytokine effects changes.

A clinical syndrome resulting from excess splenic function, hypersplenism occurs as the spleen’s MPS tissues hypertrophy. The reduction of circulating blood elements has been attributed to several possible mechanisms: excessive splenic phagocytic activity, splenic antibody formation that causes hematopoietic cell destruction, increased activity of normal splenic function, and sequestration of blood cells.

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 often the result of portal hypertension. Extrahepatic venous obstruction from portal vein thrombosis is the most frequently identified cause of increased portal pressures. Hepatic function will be normal in extrahepatic venous obstruction. Intrahepatic obstruction is typically due to cirrhosis. In addition to splenomegaly on examination, patients with portal hypertension may have caput medusae (dilated veins surrounding the umbilicus), edema, and/or gynecomastia.[39, 40, 41, 10]

Cytopenias in hypersplenism contribute to overall morbidity. The cytopenias are usually mild but may be severe and symptomatic. Thrombocytopenia is the most common abnormality. In hepatic cirrhosis, the underlying mechanism may include mechanical pooling and cytokine effect.

Race

There is an indirect relationship between splenomegaly and ethnic origin. Specific causes of splenomegaly have differing frequency in various racial groups. Examples include splenic sequestration as a complication of sickle cell disease in patients of African, West Asian, Southeast Asian, or Mediterranean ancestry and non-cirrhotic portal fibrosis in patients of Iranian, South Asian, or Japanese ancestry.[42] Pyruvate kinase deficiency is seen with increased frequency in some Amish communities and in several European regions.[43]  

Age

The etiology of splenomegaly varies with age due to auxologic factors and as a result of differing infection rates in relation to age group.

The prognosis of splenic enlargement depends on the etiology and severity and the risks of side effects from therapy.

For non-pathologic enlargement of the spleen, reassurance of the family is sufficient. However, disease-specific education should be provided to patients who have pathologic splenomegaly. Some patients must be advised to avoid splenic trauma. Selected individuals will need to undergo self-examination (or parental examination) of the spleen to monitor for changes in size that may suggest sequestration or other complications. All patients with an absent spleen or with reduced splenic function should be carefully educated about the risks of infection and the need for vaccination. They must also understand the indications for clinical evaluation and must be prepared to obtain urgent medical attention when there are concerning signs or symptoms.

Risks of traumatic rupture of a large and/or fragile spleen must also be discussed. Other education depends on the specific etiology of the splenomegaly and the potential side effects of the prescribed treatment.

Despite the extensive differential diagnosis of splenomegaly, careful history taking and physical examination, along with a CBC count and manual differential, often help to narrow down the list of likely causes.

The history should include attention to the following important areas[44] :

• Duration of known enlargement of the spleen
• Exposure to hepatotoxic agents or microorganisms resulting in hepatitis or portal hypertension
• Abdominal trauma that may cause splenic hematoma
• Signs of infection or known infections such as hepatitis, mononucleosis, malaria, or salmonellosis
• Inflammatory bowel disease
• Bone pain, fever, malaise, lethargy, pallor, bruising, weight loss, night sweats, or other findings that may indicate malignancy
• Jaundice suggestive of hepatobiliary disease

The patient should also be assessed for the following:

• Complicated neonatal course - Eg, sepsis, hypotension
• Umbilical catheter thrombosis
• Hyperbilirubinemia, anemia - Eg, due to hereditary hemolysis
• Heart disease - Eg, congestive heart failure
• Past surgeries - Eg, leading to infection, thrombosis, portal hypertension and cholecystectomy due to cholelithiasis
• Anemia or transfusions - Eg, due to hematologic abnormalities and/or resulting in hepatitis
• Abdominal trauma - Possibly resulting in splenic pseudocyst or hematoma
• Travel - Possible exposure to malaria, leishmaniasis, schistosomiasis, trypanosomiasis, or other microorganisms
• Sexual behavior - Possible presence of sexually transmitted infections, including human immunodeficiency virus (HIV), cytomegalovirus (CMV), and hepatitis

With regard to family history, carefully document the presence or absence of the following:

• Anemia
• Cholecystectomy
• Splenectomy - Eg, due to hemolytic anemia

The patient’s ethnicity should also be determined:

• 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
• European or American-Amish ancestry - Associated with pyruvate kinase deficiency and hereditary spherocytosis
• Ashkenazi Jewish ethnicity - Increased incidence of Gaucher disease and Niemann-Pick disease ^[45]
• Asian ethnicity - Increased incidence of portal hypertension secondary to noncirrhotic portal fibrosis and increased incidence of G6PD deficiency

The patient should be examined in the supine or right lateral decubitus position. Palpation should start at the pubis and move toward the left upper quadrant to identify the medial and inferior border of the spleen. If the enlarged tip of the spleen is below the examiner's hands, he or she may not detect it. Likewise, light pressure should be used because the spleen can easily be displaced without the clinician identifying the organ’s edge. At times, the superior medial edge of the spleen is more readily palpated than the inferior margin. 

The characteristic downward movement of the spleen with inspiration can help in differentiating the spleen from other masses of the left upper quadrant.

Percussion over the left lateral areas of the lower ribs may reveal splenomegaly that is not evident upon palpation. Percussion is particularly helpful in obese or crying patients.[46, 47, 48]

Document weight and height with percentiles for age to identify growth abnormalities, and obtain vital signs, including heart rate and blood pressure. Identify tachycardia, which may be seen in anemia, and fever, which may be present in inflammatory and infectious conditions.

Examine the patient supine with the hips and knees flexed.  Place a pillow underneath the neck. Ensure relaxation of the abdominal musculature.  Begin palpation at the iliac bone and palpate both lower quadrants. Percuss the lowest intercostal space in the left anterior axillary line; evaluate the space that is bound superiorly by the sixth rib, laterally by the axillary line, and inferiorly by the costal margin. Dullness to percussion in this area may indicate splenomegaly.

Assess the patient’s general appearance to document ill appearance. This will guide evaluation but is nonspecific and may be seen in various conditions, including malignancy, chronic hemolysis, chronic infection, metabolic disease, liver disease, and inflammatory disease.

Dermal findings

These include the following:

• 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
• Exanthems - Eg, due to acute and chronic infections, systemic lupus erythematosus, rheumatoid arthritis, infective endocarditis, hemangiomata, histiocytosis, or immunodeficiency

Head, eye, ear, nose, and throat findings

These include the following:

• 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

These include the following:

• Dyspnea, fatigue - Eg, due to anemia or congestive heart failure
• Cardiac murmur - Eg, due to anemia or endocarditis

Gastrointestinal findings

These include the following:

• Abdominal tenderness - Eg, due to gallstones, hepatitis, trauma, or acute splenomegaly
• Distention, prominent abdominal veins, ascites - Eg, due to liver disease
• Abnormal size or texture of the liver

Musculoskeletal findings

These include the following:

• Joint abnormalities - Eg, due to systemic lupus erythematosus, rheumatoid arthritis, or autoimmune inflammatory disease
• Bone abnormalities - Eg, due to storage diseases or osteopetrosis

Neurologic abnormalities

These include the following:

• Poor vision - Eg, due to osteopetrosis
• Uveitis, iritis - Eg, due to sarcoidosis or rheumatoid arthritis
• Inappropriate developmental milestones - Eg, due to storage diseases or other chronic illness

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

Splenomegaly is often categorized into the following groupings:

• Sequestration of blood cells - Such as in hemolytic conditions
• Proliferation due to infection or inflammation
• Deposition - Such as in Niemann-Pick and Gaucher disease and in some infections
• Infiltration due to granulomatous, histiocytic, lymphoproliferative, or malignant conditions
• Endowment - As caused by space-occupying lesions

Splenic masses

Hematomas of the spleen may develop after trauma, including birth trauma, and may occur in accessory spleens, as well as in the main spleen. Some splenic hematomas arise as complications of medical procedures, and they may also appear spontaneously as part of disease processes. Splenic hematomas can be associated with symptomatic bleeding and other complications and require evaluation and monitoring. Some cases may be managed medically, but resection is frequently required for splenic hematomas.[49, 18, 50]

Splenic cysts are rare and are often discovered incidentally. Some patients with splenic cysts may report gastrointestinal complaints such as pain, nausea, altered bowel habits, flatulence, fullness, or emesis. 

Primary splenic cysts are the most common type of splenic cyst in children.[51] The lesions are broadly categorized based on whether they are parasitic or non-parasitic in origin and by histology and etiology.   Size, symptoms, and cause will determine the nature of any required treatment. There is a risk that a splenic cyst may become complicated by thrombocytopenia, bleeding, infection, or rupture. Splenectomy or partial splenectomy is sometimes performed.[51]

Hyperplasia

The most common mechanism of pathologic splenomegaly in children is hyperplasia of the MPS. This is due to a variety of conditions that result in excessive antigenic stimulation, including infection and immune dysfunction, as well as hemolysis.[25, 52]

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, other, more common viral illnesses of childhood are the most frequent causes of pediatric infectious splenomegaly.

Other common infectious etiologies include bacterial, protozoal, and fungal infections. In endemic areas, malaria and schistosomiasis are frequent causes of splenomegaly. Concomitant, generalized lymphadenopathy is common in many of these infectious conditions.

Inflammation and hyperplasia due to collagen vascular diseases such as juvenile rheumatoid arthritis are relatively uncommon, but clinically significant, causes of splenomegaly.

Malignancy

Splenomegaly can be a presenting sign of neoplasia, being a key such feature in leukemia and lymphoma. Histiocytic disorders may also present with infiltration of the spleen.[53]

Metastasis to the spleen, which is uncommon in children, has been reported in neuroblastoma.

Portal venous system abnormalities

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. In an Italian multicenter, national study by Di Giorgio et al, children with noncirrhotic portal vein thrombosis were evaluated, and the condition was noted to be diagnosed subsequent to the detection of splenomegaly in 40% of patients.[54]

Deposition causing splenomegaly

Storage diseases may result in splenomegaly, and in Gaucher and Niemann-Pick disease, it is often the first clinical manifestation.[55] Splenomegaly arises from the accumulation of abnormal lipids in splenic macrophages.

A study by McGovern et al of adults and children with Niemann-Pick disease indicated that over the report’s follow-up period, the risk of death for patients with a history of severe splenomegaly or prior splenectomy was 10-fold that of individuals with moderate splenomegaly or intact spleens. With regard to a history of severe splenomegaly alone, the odds ratio for mortality was 6.0.[56]

Masses

After trauma, palpable subcapsular hematomas may form in the spleen, which may eventually develop into clinically palpable pseudocysts. Patients with congenital true splenic cysts usually present with asymptomatic splenomegaly.

Extramedullary hematopoiesis

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

Hypersplenism is a clinical syndrome in which cytopenias result from excessive splenic function and splenic hypertrophy. The pathologic action of the spleen, that is, the reduction of circulating blood elements, has been attributed to four possible mechanisms: excessive splenic phagocytic activity, splenic antibody formation that causes hematopoietic cell destruction, overactivity of splenic function, and sequestration.[57] In patients with cirrhosis, abnormalities of cytokine production may contribute to the cytopenias noted.[40]

As the spleen enlarges, it can sequester erythrocytes, leukocytes, and platelets, resulting in cytopenias. 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

Splenic sequestration crisis is a specific form of acute hypersplenism in young children with sickle cell anemia.[57]

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, making sequestration no longer possible.

Splenomegaly is usually the result of a systemic disorder rather than primary splenic disease. Therefore, diagnostic studies are not directed solely towards the spleen. Instead, the goal of testing should be to evaluate any abnormal findings detected during the history or physical examination. 

The most useful initial laboratory test is the complete blood count (CBC) with manual differential and peripheral blood smear. This test should be performed on all patients with an enlarged spleen.

Assessment of transaminase levels and other examinations of hepatobiliary function may be indicated. Additional diagnostic studies will depend on the patient presentation and should be tailored to each individual.

Imaging is not required for all children who are being evaluated for splenomegaly. If imaging is performed, ultrasonography is recommended; this modality can be used to measure splenic dimensions and show splenic architecture. Ultrasonography will also rule out the presence of space-occupying lesions and will provide information about other intra-abdominal organs. 

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) of the left upper quadrant can help in further evaluating splenic parenchymal architecture, and can be used in defining splenic size and shape.[7, 8] These imaging modalities are, however, rarely indicated. Ultrasonography alone is the most appropriate means of imaging the spleen in pediatric patients, since it is noninvasive and does not employ ionizing radiation; moreover, it lacks radiographic magnification, and patients are not subject to the osmotic side effects of iodinated contrast. In addition to being safe, ultrasonography displays real-time images and is easily repeated, with no anesthesia required.[1]

CT scanning or MRI should be used only if there is a clear need for additional imaging detail that cannot be provided by ultrasonography. Emitting gamma radiation, technetium-99m (99mTc) sulfur colloid can be used to examine the reticuloendothelial system via scintillation scanning; moreover, it is the only test that provides functional information about the spleen. It is not indicated in routine evaluation of splenomegaly.[9]

The most useful initial laboratory tests include a complete blood count (CBC) with differential, peripheral blood smears, and liver function tests.[52]

The CBC may be revealing, as follows:

• Pancytopenia may be present because of bone marrow infiltration and hypersplenism.

• The WBC count may reveal atypical lymphocytes (eg, neutropenia, or neutrophilia (eg, due to infection or leukemia).

• Hemoglobin concentrations, RBC smears, and reticulocyte counts may reveal anemia, abnormal erythrocyte morphology, reticulocytosis (eg, due to hemolysis), or malarial parasites.

• The platelet count may indicate thrombocytopenia due to decreased production (eg, due to bone marrow infiltration), increased destruction (eg, due to immunologic causes, drug reactions, or viral infections), or sequestration or hypersplenism.

Hepatobiliary function tests may identify abnormalities, as follows: 

• Hypoalbuminemia, prolonged prothrombin time, indirect and direct hyperbilirubinemia (eg, due to liver dysfunction) (see Albumin, Prothrombin Time, and Bilirubin)
• Isolated indirect hyperbilirubinemia (eg, due to hemolysis) or direct hyperbilirubinemia due to obstruction.
• Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (eg, due to liver damage)
• Elevated gamma glutamyltransferase (GGT) and alkaline phosphatase levels (eg, due to biliary obstruction)

Obtain an antinuclear antibody titer to screen for systemic lupus erythematosus if there are signs or symptoms that indicate a rheumatologic etiology for splenomegaly.

Measure immunoglobulin levels, neutrophil function, and T-cell subclasses (eg, due to immunodeficiency).

Viral testing may be appropriate for some patients. Consider testing for EBV, CMV, Toxoplasma gondii, parvovirus, and HIV, as indicated. Perform appropriate testing to detect malaria in high-risk populations.

Cultures may reveal bacterial, fungal, or other infections.

Examine the bone marrow to screen for leukemia, lymphoma, storage diseases, and disseminated fungal or mycobacteria infections, if indicated based on other findings on history and physical examination.

Ultrasonography can confirm the presence of the enlarged spleen or space-occupying lesions (eg, cyst, abscess), provide accurate dimensions, and help in distinguishing between splenic enlargement and other causes of a left subchondral mass (eg, kidney). Confirming or excluding splenomegaly in patients with obesity, in whom palpation can be very challenging, is useful. Often, a single craniocaudal measurement is used to report spleen size; awareness of the normal values for age is important.[58] Collateral blood vessels develop secondary to portal hypertension, and reversal of portal vein blood flow direction may be visualized with Doppler ultrasonography.

CT scanning and MRI of the left upper quadrant can help in further clarifying abnormalities in size and shape and in defining parenchymal pathology. The "splenic index" is the product of the length, width, and thickness of the spleen and has limited value.[7, 8]

Radioisotopic scanning with a 99mTc sulfur colloid (spleen scan) can provide functional information about the spleen that other radiologic studies do not provide.[30]

Biopsy of the spleen may be performed. The results are of limited value in common diagnoses, and the procedure is associated with a notable risk, particularly bleeding.

The diagnosis is occasionally recognized after splenectomy.

Examples of disease that might be examined with biopsy include infiltrative diseases, such as Gaucher disease, Niemann-Pick disease, amyloidosis, Tangier disease, and glycogen-storage diseases. Other diseases that may be diagnosed with splenic tissue include Langerhans cell histiocytosis, sarcoidosis, systemic lupus erythematosus, and Hodgkin disease. In Hodgkin disease, biopsy samples were often obtained in the past with staging laparotomy, but this is no longer performed because of improved imaging and systemic therapy.

Because splenomegaly is usually the result of a systemic disease, the primary goal is treatment of the underlying process.  

Splenectomy

If the patient meets the appropriate criteria, splenectomy may be offered. Careful evaluation and planning are required prior to surgical removal of a child’s spleen. 

Hemolytic conditions and space-occupying lesions are the most common diagnoses behind splenectomy in children.

Splenectomy for hemolytic conditions

Some hemolytic conditions with severe manifestations will require splenectomy. Appropriate evaluation of the patient’s history and laboratory findings is key.

In general, patients should be offered splenectomy only if there is severe transfusion-dependent anemia  or symptomatic splenomegaly. Consult a hematologist to determine disease-specific guidelines for splenectomy. Stomatocytosis is a definitive contraindication for splenectomy due to the risk of thromboembolic complications.[10]

Sickle hemoglobinopathies may result in splenectomy if the patient meets specific criteria such as repeated or severe sequestration episodes. Conservative management is sometimes effective, however, so the decision to remove the spleen should be based on the individual child’s risk. Some children with hematologic conditions that are being treated with splenectomy should also undergo cholecystectomy at the same time as spleen removal.[11, 12]

Splenectomy for splenic lesions

Because the definition and grading of splenomegaly in children is not standardized, surgical management is not standardized either. Accurate evaluation of the spleen size and configuration is key to planning the surgical procedure. Furthermore, the benefit-to-risk ratio must be carefully determined if splenectomy is considered. Partial spleen removal may be an option.[13, 14, 15, 16] Minimally invasive techniques are preferred in splenectomy in children but require pediatric-specific instruments and protocols.[4, 17]

Splenic lesions such as cysts, abscesses, and hematomas are a common indication for splenectomy.[18]

Postsurgical complications of splenectomy

Splenectomy has been found to result in increased risk for several conditions, including stroke, pulmonary hypertension, arrhythmia, and myocardial infarction.[19, 20]

The most closely correlated adverse effect of pediatric splenectomy is infection, with all persons without normal splenic function being at increased risk for infections and children being at higher risk than adults. Infection risk is greatest during the first few years after spleen removal.[21, 22]

The risk of infection from the gram-negative organisms Capnocytophagacanimorsus and Bordetellaholmesii is particularly increased. Asplenic patients also have greater susceptibility to infection from intra-erythrocytic parasites and encapsulated bacteria. 

Overwhelming post-splenectomy infection (OPSI) syndrome is rare but may be fatal. A syndrome of fulminant sepsis occurring in asplenic or hyposplenic individuals, the condition is associated with high mortality and morbidity. Poorly opsonized bacteria such as encapsulated bacteria are the most common infectious organisms causing OPSI. Early signs of OPSI may be mild and nonspecific.

Because patients without functional spleens are immunocompromised, appropriately timed vaccination must be performed to reduce the risk of post-splenectomy infection.

Asplenic patients must also undergo urgent clinical evaluation whenever they have any signs or symptoms that are suggestive of infection. The nature and duration of any antimicrobial prophylaxis should be individually determined for each post-splenectomy patient based on diagnosis, age, exposures, and other factors that modify risk.[23, 21]

Because splenomegaly is usually the result of a systemic disease, the primary goal is treatment of the underlying process. In certain circumstances, splenectomy may be the therapy of choice for symptoms or complications caused by the enlarged organ. However, because of the risk of overwhelming sepsis in children who are asplenic, the risks and benefits must be carefully weighed when splenectomy is being considered.[59, 60]

• The new PCV7 conjugated pneumococcal vaccine and the older PPV23 polyvalent pneumococcal vaccines, as well as the Haemophilus influenzae vaccine, should be administered to all children who are asplenic and to those about to undergo splenectomy. The polyvalent pneumococcal vaccine is effective only if the patient is aged 2 years or older. Meningococcal vaccine, MCV4, is often administered to these patients in this age group as well. To maximize antibody formation, patients should be vaccinated at least 14 days before elective splenectomy.[34]

• Daily penicillin is recommended to prevent pneumococcal septicemia in asplenic children younger than 5 years. Antibiotic prophylaxis is often administered for several years after splenectomy in patients older than 5 years, but the role of prophylaxis in these children is less well documented than it is in others.

• In patients with homozygous sickle cell anemia or sickle beta-zero thalassemia, oral penicillin prophylaxis should be started when the diagnosis is established. This therapy should be administered until at least age 5 years. The role of penicillin prophylaxis in patients with hemoglobin sickle cell disease is controversial. Patients with sickle beta+ thalassemia do not appear to need penicillin prophylaxis.

• Febrile illnesses in asplenic children should be approached as potentially life-threatening events and evaluated thoroughly, with a low threshold for treatment with intravenous antibiotics that cover Streptococcus pneumoniae and H influenzae. The increasing prevalence of drug-resistant S pneumoniae and the decreasing incidence of H influenzae infections are complicating factors in determining the optimal choice of antibiotics.

Formal vaccine recommendations in anatomic or functional asplenia from the US Centers for Disease Control and Prevention (CDC)

An increased infection risk from encapsulated bacteria, particularly S pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and H influenzae type b (Hib), exists in persons with anatomic asplenia (that is, those whose spleen has been surgically removed or is congenitally absent) or functional asplenia (such as develops in cases of sickle cell disease). Thus, an age-appropriate series of PCV13 inoculations should be administered to children. This includes two doses of PCV13 to unvaccinated children aged 2-5 years, and a dose of PCV13 to children aged 6 years or older who have not previously been inoculated with the vaccine. Two doses of PPSV23 should be administered to patients aged 2 years or older, with each dose given 5 years apart and starting at least 8 weeks after all recommended doses of PCV13 have been completed. When both PCV13 and PPSV23 administration are indicated, inoculation should begin with doses of PCV13, with PPSV23 given 8 weeks after the last PCV13 dose.[61]

It is also recommended that persons with anatomic or functional asplenia receive meningococcal conjugate (MenACWY) and serogroup B (MenB) vaccines, while it is routinely advised that all children through age 59 months be inoculated with Hib vaccine. One dose of Hib vaccine should be administered to unimmunized asplenic patients older than 59 months.[61]

Splenic trauma is the most common indication for splenectomy, although attempts at splenic preservation are important. Nonsurgical management for splenic trauma has success rates of 52-98%, with failure usually occurring in the first 96 hours. Splenic cysts, tumors, and vascular lesions may also require surgical removal. Whenever possible, splenic tissue is preserved to decrease the risk of septicemia, but total splenectomy is occasionally necessary.[62, 63]

Splenectomy can cure hypersplenism but is not usually indicated because the secondary cytopenias rarely cause serious problems. However, in patients with portal hypertension, vascular shunts may be necessary to prevent esophageal variceal bleeding.

Splenectomy may be helpful in improving cytopenias in several medical conditions, including congenital anemias (eg, hereditary spherocytosis,[64] elliptocytosis) and autoimmune disorders (eg, immune thrombocytopenic purpura, autoimmune hemolytic anemia,[23] hypersplenism). In thalassemia major, splenectomy may initially decrease the transfusion requirements caused by hypersplenism. However, the benefit must be carefully weighed against the risk of sepsis.

In Gaucher disease, splenectomy may be necessary when the mechanical strain of the enlarged spleen requires intervention.

Splenectomy may be indicated in children with sickle cell anemia and a history of splenic sequestration crisis in order to prevent recurrences of the crisis.

As part of exploratory laparotomy, splenectomy was once an important component of staging of Hodgkin disease. This procedure is rarely used because of improvements in imaging modalities, the high risk of postsplenectomy sepsis, and the increased use of chemotherapy in patients, which allows treatment decisions to be made on the basis of radiologic evaluation alone. Furthermore, data suggest that splenectomy increases the risk of second malignancy in patients treated for Hodgkin disease.

Li et al described the successful use of suture suspension in the performance of single-incision laparoscopic splenectomy. In the study, which involved nine children with splenomegaly due to hereditary spherocytosis, suture suspension reportedly improved splenic hilum exposure.[65]

For elective surgery, laparoscopic splenectomy is preferable to open splenectomy, except in patients with massive splenomegaly.[66] Even so, a retrospective study by Hassan and Al Ali on 32 children with massive splenomegaly suggested that laparoscopic splenectomy for this condition is safe and effective, with patients experiencing reductions in pain and blood loss, improved recovery, and a shorter hospital stay; operative time, though, was significantly longer than with open splenectomy.[67]

A review of the American College of Surgeons National Surgical Quality Improvement Program Pediatric (NSQIP-P) data set showed that out of 673 patients who underwent elective splenectomy from 2012-2016, 613 (91%) did so laparoscopically with minimal morbidity, suggesting this has become the new standard as surgeons become more familiar with the technique.[68]

A prospective study by Van Der Veken et al indicated that laparoscopic splenectomy in children, for either simple or massive splenomegaly, can be more safely performed if patients undergo perioperative spleen embolization, as carried out by an interventional radiologist in the operating room.[69]

Pelizzo et al advised careful evaluation of spleen size, suggesting that laparoscopic splenectomy is unsafe with a splenic long axis of 12-15 cm, and completely unfeasible in preadolescents with a splenic long axis of more than 15 cm.[4]

A pediatric hematologist and/or oncologist may assist in the assessment of the spleen and in guiding the evaluation process when the cause of splenomegaly is not obvious or when a primary hematologic or oncologic disorder is suspected.

According to the American Academy of Pediatrics and the Council of Sports Medicine and Fitness, children with acutely enlarged spleens should avoid contact, collision, or limited-contact sports.[34] Viral-related splenomegaly rarely lasts longer than 2 months.

The duration for which contact restriction should persist after acute infectious mononucleosis remains uncertain. In the absence of trauma, the incidence of splenic rupture is approximately 1:1000, usually occurring in the first 3 weeks of illness. No evidence-based guidelines are available. More conservative suggestions recommend that children with infectious mononucleosis and resolution of splenomegaly noted on examination have 3 weeks of rest, with a 4-week graded return to activity. Recommendations should be individualized for each patient.

Even with large spleens, most disorders associated with chronic splenomegaly are characterized by reduced splenic friability with minimal risk of rupture. In children with chronically enlarged spleens, decision to restrict activity should be made on a case-by-case basis.[35]

Rarely, the condition underlying splenomegaly may require dietary modifications. There are no dietary changes that must be recommended due to splenic enlargement itself.

The choice of therapy depends on the specific etiology of the splenomegaly.

Class Summary

Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components, which act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties. Patients with decreased or absent splenic function are at increased risk for several vaccine-preventable infections.

Preferred sites for IM injection are the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in toddlers and young children. Do not inject in the gluteal area or areas with a major nerve trunk or blood vessel.

Minor illnesses (eg, mild upper respiratory tract infection with or without low-grade fever) are not generally contraindications.

If possible, administration of pneumococcal, meningococcal, and Hib vaccines should be performed at least 14 days prior to elective splenectomy. In the absence of preoperative vaccinations, inoculations should be given postprocedurally immediately after the patient’s condition stabilizes.

The CDC ACIP recommends that all children receive one of the conjugate vaccines licensed for use in infants beginning routinely at age 2 mo.

Pneumococcal 7-valent conjugate vaccine (Prevnar)

Sterile solution of saccharides of capsular antigens of S pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 protein. These 7 serotypes responsible for >80% of invasive pneumococcal disease in children < 6 y in the United States and account for 74% of penicillin-nonsusceptible S pneumoniae (PNSP) and 100% of pneumococci with high-level penicillin resistance.

Customary age for first dose is 2 mo, but can be administered as young as 6 wk. Preferred sites for IM injection are anterolateral aspect of thigh in infants or deltoid muscle of upper arm in toddlers and young children. Do not inject in gluteal area or areas with a major nerve trunk or blood vessel.

Number of 0.5-mL doses is 3 for infants aged 7-11 mo (4 wk apart; third dose after first birthday), 2 for those aged 12-23 mo (2 mo apart), and 1 for those aged 2-5 y.

Minor illnesses (eg, mild upper respiratory tract infection with or without low-grade fever) are not generally contraindications.

Pneumococcal vaccine polyvalent (Pneumovax-23)

Polyvalent vaccine used for prophylaxis against infection from S pneumoniae. Used in populations at increased risk of pneumococcal pneumonia (ie, >55 y, chronic infection, asplenia, immunocompromise).

Meningococcal vaccine (Menomune A/C/Y/W-135, Menactra)

Capsular polysaccharide antigens (groups A, C, Y, and W-135) of Neisseria meningitidis. For active immunization against invasive meningococcal disease caused by inclusive serogroups. May be used to prevent and control outbreaks of serogroup C meningococcal disease according to Centers for Disease Control and Prevention (CDC) guidelines.

Routine vaccination recommended for high-risk groups (eg, patients with deficiencies in late complement components [C3, C5-C-9], functional or actual asplenia, or laboratory or industrial exposure to N meningitidis aerosols; travelers or residents of hyperendemic areas).

Vaccine induces antibody response for serogroup A in individuals as young as 3 mo, but poorly immunogenic for serogroup C in recipients < 18-24 mo.

Haemophilus influenza type b vaccine (PedvaxHIB, HibTITER, ActHIB)

For routine immunization of children against invasive diseases caused by H influenzae type B by decreasing nasopharyngeal colonization. The CDC ACIP recommends that all children receive one of the conjugate vaccines licensed for use in infants beginning routinely at age 2 mo.

Class Summary

Daily antibiotic prophylaxis with penicillin is recommended to prevent pneumococcal septicemia in selected populations of anatomically or functionally asplenic children.

Penicillin VK (V-Cillin K, Veetids, Pen-Vee K)

Inhibits biosynthesis of cell-wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations reached. Most effective during stage of active multiplication. Low concentrations produce bacteriostatic effects.

For patients who require follow-up, family education should be provided at each outpatient visit. Tailor follow-up and education to the underlying disease and the potential side effects of therapy.

The development of hypersplenism with resulting anemia, leukopenia, and/or thrombocytopenia may be mild or severe and depends on the underlying condition and disease course.

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.[33] Therefore, the American Academy of Pediatrics, through its Council on Sports Medicine and Fitness, has recommended that children with acute splenomegaly restrict their participation in sports.[34, 35] Disorders associated with chronic splenomegaly do not have the same splenic friability and risk of rupture.[35, 36]  

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.[59, 60]