ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Approach to the child with an enlarged spleen

Approach to the child with an enlarged spleen
Author:
Kenneth L McClain, MD, PhD
Section Editor:
Sarah O'Brien, MD, MSc
Deputy Editor:
Carrie Armsby, MD, MPH
Literature review current through: Jul 2022. | This topic last updated: Jul 20, 2022.

INTRODUCTION — This topic reviews the approach to the child whose spleen is enlarged on physical examination and/or is more than minimally enlarged on abdominal imaging. The clinical or diagnostic significance of a spleen that is not palpable on physical examination and is only minimally enlarged on imaging is uncertain.

The approach to the adult patient with splenomegaly and other splenic disorders is discussed separately. (See "Evaluation of splenomegaly and other splenic disorders in adults".)

DEFINITIONS — The following terms are used in this topic:

Splenomegaly – The term splenomegaly can refer to a finding on physical examination or on imaging (or both):

On physical examination, splenomegaly is generally defined as a palpable splenic edge felt >2 cm below the left costal margin. A palpable spleen tip may be a normal finding in up to 30 percent of neonates; the frequency drops to approximately 10 percent in healthy school-age children and <3 percent in young adults. (See 'Examination of the spleen' below.)

On imaging studies, splenomegaly is defined as splenic length or volume that is above the upper limits of normal for age. (See 'Imaging' below.)

Massive splenomegaly – A spleen is massively enlarged if its lower pole is within the pelvis or if it crosses the midline.

OVERVIEW OF SPLENIC FUNCTION — The spleen has immune and hematopoietic functions. It also serves to remove senescent or abnormal red blood cells (RBCs) from the circulation.

The spleen as a hematopoietic organ – At various times during gestation and/or extrauterine life, the spleen is capable of supporting elements of the erythroid, myeloid, megakaryocytic, lymphoid, and monocyte-macrophage (ie, reticuloendothelial) systems. In certain disease states (eg, beta thalassemia major, primary myelofibrosis), it may become the site of extramedullary hematopoiesis and contain developing erythroid, myeloid, and megakaryocytic precursors. (See "Diagnosis of thalassemia (adults and children)".)

White pulp – The white pulp of the spleen is a major part (up to 25 percent) of the lymphoid tissue in the body. Like lymph nodes, it has germinal centers where early B-lymphocytes predominate, along with plasma cells. T-lymphocytes are the major population around periarteriolar sheaths. When foreign antigens are present in the circulation, the spleen plays a key role in providing a milieu for the immunologic response. Thus, in the absence of the spleen, antibody production may be significantly diminished. As an example, when pneumococcal vaccine is given intramuscularly to asplenic individuals, the immunoglobulin G and M (IgG and IgM) antibody titers are lower than noted in normal individuals [1]. Likewise, the titers of pneumococcal antibodies decline more rapidly in asplenic patients [2].

Red pulp – The largest component of the spleen is the red pulp. It consists of the RBCs surrounding endothelial cords of Billroth and interdigitating splenic sinusoids, which are lined with macrophages. Because of the anatomic arrangement of blood vessels, RBCs are relatively concentrated in the terminal splenic arteries, as plasma with potentially antigenic material is shunted to the white pulp. In patients with sickle cell disease (SCD), a consequence of the high RBC concentration in these arterioles and sinusoids is that relatively mild degrees of hypoxia can cause the irreversible RBC sickling, leading to splenic infarction (autosplenectomy). (See "Overview of the clinical manifestations of sickle cell disease".)

Sinusoids – In the splenic sinusoids, which course through white and red pulp, macrophages line the vascular spaces. These macrophages are important parts of the immune system in presenting antigens to lymphocytes in the white pulp, as well as in destroying antibody-coated bacteria or hematopoietic cells. When red cells squeeze through these sinusoids, the surrounding macrophages are able to remove senescent red cells, destroy or reform erythrocytes with abnormal membranes, and remove red cell inclusions such as nuclear remnants, like Howell-Jolly bodies. As a result, when the spleen is absent, many of these abnormal red cells may circulate, along with red cells containing nuclear remnants (ie, Howell-Jolly bodies) (picture 1 and picture 2). (See "Evaluation of splenomegaly and other splenic disorders in adults", section on 'Properties of the normal spleen'.)

Platelet reservoir – The spleen acts as a reservoir for platelets; one-third of the circulating platelet mass is temporarily sequestered within a normal-sized spleen, and up to 90 percent may be found within a markedly enlarged spleen. When the spleen is removed, this reservoir function is also removed. Following splenectomy, it is common for the platelet count to temporarily exceed 1 × 106/microL in a normal child, without an apparent increased risk for thrombosis [3].

Splenomegaly may be caused by a process that increases normal splenic function (eg, hemolysis) or may be due to infiltrative, infectious, or vascular disorders. Similarly, removal of a spleen may alleviate disease by more than one mechanism. As an example, thrombocytopenia may be alleviated in immune thrombocytopenia through the loss of a large number of antiplatelet antibody-producing lymphocytes, as well as through the removal of splenic macrophages capable of destroying antibody-coated platelets. (See "Immune thrombocytopenia (ITP) in children: Management of chronic disease", section on 'Splenectomy'.)

CAUSES OF SPLENOMEGALY — The most common causes of splenomegaly in children include infection (eg, Epstein-Barr virus [EBV] or cytomegalovirus [CMV], though many infectious agents can cause splenomegaly), malignancy, disorders of immune regulation (eg, systemic lupus erythematosus, rheumatoid arthritis, common variable immunodeficiency), and hemolytic anemia (eg, sickle cell disease [SCD] and other hereditary and acquired hemolytic anemias) [4,5]. Other important considerations include portal hypertension, storage diseases, and space-occupying lesions (eg, hemangioma, cyst, hamartoma) (table 1).

In a case series of >1400 hospitalized patients with splenomegaly, one-quarter of whom were <18 years old, the most common disease categories were hematologic (67 percent, including leukemia, lymphoma, and hemolytic anemia), infectious (8 percent), hepatic (11 percent), and congestive or inflammatory (9 percent) [6]. In otherwise healthy individuals seen in the outpatient setting, the most common etiology of splenomegaly is infectious mononucleosis [5].

Infection — Infectious etiologies of splenomegaly include:

Viral infections, particularly EBV and CMV, which are among the most common causes of splenomegaly in children (see "Infectious mononucleosis" and "Overview of cytomegalovirus infections in children")

Tuberculosis (see "Tuberculosis disease in children")

Infective endocarditis (see "Infective endocarditis in children")

Malaria (see "Laboratory tools for diagnosis of malaria", section on 'General principles')

HIV (see "Pediatric HIV infection: Classification, clinical manifestations, and outcome")

Cat scratch disease (see "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease")

Babesiosis (see "Babesiosis: Clinical manifestations and diagnosis")

Fungal infections (see "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis")

Leishmaniasis (see "Visceral leishmaniasis: Clinical manifestations and diagnosis")

Toxoplasmosis (see "Toxoplasmosis: Acute systemic disease")

Hematologic malignancy — Childhood leukemias and lymphomas are important causes of splenomegaly. These include:

Acute lymphoblastic leukemia (ALL), including precursor B cell ALL and precursor T cell ALL/lymphoma (see "Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children" and "Clinical manifestations, pathologic features, and diagnosis of B cell acute lymphoblastic leukemia/lymphoma" and "Clinical manifestations, pathologic features, and diagnosis of precursor T cell acute lymphoblastic leukemia/lymphoma")

Acute myeloid leukemia (see "Acute myeloid leukemia in children and adolescents")

Hodgkin lymphoma (see "Overview of Hodgkin lymphoma in children and adolescents")

Non-Hodgkin lymphoma (see "Overview of non-Hodgkin lymphoma in children and adolescents")

Other lymphoproliferative disorders — In addition to lymphoma, other lymphoproliferative disorders that may present with splenomegaly include:

Langerhans cell histiocytosis (see "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis")

Hemophagocytic lymphohistiocytosis (see "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis")

Autoimmune lymphoproliferative syndrome (see "Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis")

Castleman disease and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) (see "HHV-8/KSHV-associated multicentric Castleman disease" and "POEMS syndrome")

Hemolytic anemia — Congenital and acquired hemolytic anemias represent a major cause of splenomegaly (table 2). In these conditions, splenomegaly results from sequestration of destroyed red blood cells (RBCs). SCD is included in this category. Splenomegaly is a clinical feature of SCD in early childhood, but, by late childhood or adulthood, the spleen is typically small and atrophic due to repeated splenic infarction. The natural history of splenic involvement depends to some degree on the type of SCD. This is discussed in greater detail separately. (See "Overview of hemolytic anemias in children" and "Overview of the clinical manifestations of sickle cell disease", section on 'Splenic sequestration crisis'.)

Liver disease/portal hypertension — Splenomegaly is a feature of liver disease, particularly end-stage liver failure (cirrhosis). Cirrhosis-related splenomegaly results from congestion due to portal hypertension. Other sequelae of portal hypertension (eg, esophageal varices, gastroesophageal bleeding, ascites) may also be present. Causes of cirrhosis in children include (see "Causes of cholestasis in neonates and young infants"):

Biliary atresia (see "Biliary atresia")

Choledochal cysts (see "Biliary cysts")

Primary sclerosing cholangitis (see "Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis")

Viral hepatitis (see "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents" and "Hepatitis C virus infection in children")

Autoimmune hepatitis (see "Overview of autoimmune hepatitis")

Alpha-1 antitrypsin deficiency (see "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency")

Metabolic disease (eg, galactosemia) (see "Galactosemia: Clinical features and diagnosis")

Cystic fibrosis (see "Cystic fibrosis: Hepatobiliary disease")

Alagille syndrome (see "Causes of cholestasis in neonates and young infants", section on 'Alagille syndrome')

Wilson disease (see "Wilson disease: Clinical manifestations, diagnosis, and natural history")

Intestinal failure (see "Intestinal failure-associated liver disease in infants")

Portal vein thrombosis — Portal vein thrombosis (PVT) is another cause of portal hypertension and splenomegaly. In neonates, PVT is most commonly associated with umbilical venous catheters. In older children, PVT may be a complication of liver transplant or may occur in children with underlying risk factors (eg, malignancy, inherited thrombophilia, antiphospholipid antibodies). (See "Neonatal thrombosis: Clinical features and diagnosis", section on 'Portal vein thrombosis' and "Venous thrombosis and thromboembolism (VTE) in children: Risk factors, clinical manifestations, and diagnosis", section on 'Other venous thrombosis'.)

Heart failure — Hepatosplenomegaly is a common finding in patients with volume overload and systemic venous congestion due to heart failure. Causes of heart failure in children are summarized in the table (table 3) and discussed in detail separately. (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis".)

Disorders of immune regulation — Splenomegaly may be noted in children with autoimmune diseases (eg, systemic lupus erythematosus, rheumatoid arthritis) and in some primary immunodeficiencies (eg, common variable immunodeficiency). (See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis" and "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications" and "Common variable immunodeficiency in children".)

Storage disease — Splenomegaly is a prominent feature of many lysosomal storage disorders, including Gaucher disease, Niemann-Pick disease, and the mucopolysaccharidoses. These disorders are reviewed in greater detail separately. (See "Inborn errors of metabolism: Classification", section on 'Lysosomal storage disorders' and "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis" and "Overview of Niemann-Pick disease" and "Mucopolysaccharidoses: Clinical features and diagnosis".)

Space-occupying lesions — Discrete space-occupying lesions that may present with splenomegaly include splenic hemangioma, hamartoma, and cysts. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications" and "Evaluation of splenomegaly and other splenic disorders in adults", section on 'Cystic lesions'.)

Another example of a space-occupying lesion is intracapsular hematoma due to traumatic injury. In most cases, there is a clear preceding history of substantial blunt abdominal trauma. However, relatively minor trauma can cause splenic rupture in children with underlying splenomegaly due to another etiology (eg, mononucleosis). (See "Liver, spleen, and pancreas injury in children with blunt abdominal trauma" and "Infectious mononucleosis", section on 'Avoiding splenic rupture'.)

Other — Other less common causes of splenomegaly in children include sarcoidosis and metastatic tumors (eg, neuroblastoma). (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis" and "Extrapulmonary manifestations of sarcoidosis" and "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma".)

CAUSES OF MASSIVE SPLENOMEGALY — A spleen is considered to be massively enlarged if its lower pole is within the pelvis or if it crosses the midline. Only a few diseases cause this degree of splenic enlargement. These include the following disorders, each of which is discussed separately:

Leukemia (lymphoid or myeloid) (see "Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children" and "Acute myeloid leukemia in children and adolescents")

Lymphoma, usually the more indolent variants (see "Overview of Hodgkin lymphoma in children and adolescents" and "Clinical manifestations, pathologic features, and diagnosis of precursor T cell acute lymphoblastic leukemia/lymphoma")

Thalassemia major (see "Diagnosis of thalassemia (adults and children)")

Acute splenic sequestration in sickle cell disease (SCD) (see "Overview of the clinical manifestations of sickle cell disease", section on 'Splenic sequestration crisis')

Langerhans cell histiocytosis (see "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis")

Hemophagocytic lymphohistiocytosis (see "Treatment and prognosis of hemophagocytic lymphohistiocytosis")

Autoimmune lymphoproliferative syndrome (see "Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis")

Castleman disease (see "HHV-8/KSHV-associated multicentric Castleman disease")

Gaucher disease (see "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis")

HIV infection with Mycobacterium avium complex (see "Mycobacterium avium complex (MAC) infections in persons with HIV")

Kala-azar (see "Visceral leishmaniasis: Clinical manifestations and diagnosis")

Hyperreactive malarial splenomegaly syndrome, also called tropical splenomegaly syndrome (see "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children")

EVALUATION

History — The history may provide valuable clues as to the possible cause of splenomegaly (table 1).

A history of recent febrile illness, pharyngitis, and fatigue suggests a viral etiology (eg, Epstein-Barr virus [EBV], cytomegalovirus [CMV], viral hepatitis). (See "Infectious mononucleosis" and "Overview of cytomegalovirus infections in children".)

If more pronounced constitutional symptoms are noted (eg, persistent fevers, night sweats, weight loss, decreased activity level), systemic diseases such as leukemia, lymphoma, systemic lupus erythematosus, malaria, or tuberculosis should be considered.

In some cases, the presence of an underlying condition is already known and the spleen may revert to normal size when the underlying disease is brought under control with appropriate therapy.

Physical examination

Examination of the spleen

Palpation method – Proper examination of the spleen requires relaxation of both the abdominal musculature of the patient and the examiner's hand(s). The examiner should begin palpating low in the abdomen/pelvis and advance upward. Effectiveness in palpating the spleen can be maximized by the following:

With the child supine, allow the child to feel the examining hand on the abdomen and to become adjusted to its presence before pressing down. Do not suddenly increase pressure during palpation, as an enlarged spleen may be quite tender (particularly if it has enlarged quickly) and the child may be reluctant to allow the examination to continue.

The examiner should be seated comfortably in a chair alongside the patient's bed or examining table, with the examiner on the patient's right side, the right hand doing the palpation and the left hand underneath and supporting the patient's left lower rib cage.

Make sure that the child is relaxed, with arms at the sides of the abdomen. If the arms are raised, this may stiffen the abdominal musculature and make examination more difficult. Having the child slightly flex his/her the legs and neck may also help relax the abdominal musculature.

If examining the child in the supine position is difficult, placing the child in the right lateral decubitus position with knees and neck flexed can improve the ability to palpate the spleen. This maneuver helps relax the abdominal musculature and rotates the spleen from its usual posterior position to a more anterior position.

With greater degrees of enlargement, the spleen rotates to a more anterior and rightward position and may extend downward into the pelvis. Under these circumstances, the lower pole of the spleen may not be felt easily, because it is well below the left costal margin. In such cases, splenomegaly is appreciated either by palpating at successively lower levels on the left side of the abdomen or by palpating the medial edge of the spleen. The presence of a notch or indentation on the medial splenic edge is a further indication that the mass is spleen and not the left kidney or a pancreatic pseudocyst.

Interpretation – A palpable spleen may represent a normal finding, splenomegaly, or massive splenomegaly:

Normal finding – The spleen is palpable in nearly one-third of healthy neonates, 10 percent of healthy children, and approximately 3 percent of healthy adolescents and young adults [4]. A nontender spleen that is normal or only minimally enlarged will be quite movable with respiration and may be palpable only at the end of inspiration. Using a light touch, with the skin depressed under the left costal margin, one can feel a minimally enlarged spleen as a rounded edge with the consistency of normal liver, which slips under the examiner's fingers at the end of inspiration and back on expiration. A normal spleen is soft and nontender.

Splenomegaly – A splenic edge felt >2 cm below the left costal margin is an abnormal finding. An abnormal spleen often feels hard, unlike the soft sensation of palpating a minimally enlarged spleen in a healthy child. Tenderness to palpation also suggests an abnormal finding.

Massive splenomegaly – A spleen is considered to be massively enlarged if its lower pole is within the pelvis or if it crosses the midline. In extreme cases, the enlarged spleen may even be palpable in the right upper quadrant. Exquisite splenic tenderness suggests infarction or perisplenitis in such massively enlarged spleens.

Numerous studies have shown wide interobserver variability in the ability to detect an enlarged spleen on physical examination, which generally is not associated with the level of clinical experience [7].

Other examination findings — Other physical examination findings that are important to note when evaluating a child with splenomegaly include:

Lymphadenopathy – Lymphadenopathy may be a sign of infection (eg, EBV or HIV-1) or malignancy (table 4A-B). (See "Peripheral lymphadenopathy in children: Evaluation and diagnostic approach" and "Clinical manifestations and treatment of Epstein-Barr virus infection" and "Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children".)

Jaundice – Jaundice may indicate underlying hemolytic anemia or liver disease. (See "Overview of hemolytic anemias in children" and "Acute liver failure in children: Etiology and evaluation".)

Hepatomegaly and other signs of liver disease – Hepatomegaly, firm liver edge, ascites, and/or spider angiomata suggest underlying liver disease. (See "Acute liver failure in children: Etiology and evaluation".)

Rashes and/or joint swelling – Rashes and/or joint swelling suggest a systemic autoimmune disorder such as systemic lupus erythematosus or rheumatoid arthritis. (See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis" and "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications".)

Petechiae and ecchymoses – Petechiae and ecchymoses may be present in patients with thrombocytopenia resulting from splenic enlargement. They may also be a sign of underlying malignant hematologic disease. (See "Causes of thrombocytopenia in children".)

Initial diagnostic testing — Initial testing for children with unexplained splenomegaly includes imaging (chest radiograph and abdominal ultrasound) and laboratory testing.

Imaging

Imaging modalities – Ultrasonography is usually the initial imaging test for evaluation of a child with unexplained splenomegaly because it is readily available, noninvasive, does not expose the child to radiation, and does not require sedation. Ultrasound is an important adjunct to the physical examination in that it more accurately determines spleen size and identifies focal or diffuse pathologic changes. The spleen normally appears homogeneous on ultrasound; it is slightly more echogenic than the kidney and iso- to slightly more echogenic than the liver (image 1) [8]. Doppler imaging is useful for evaluating splenic and portal blood flow. A finding of slow or reversed portal blood flow is suggestive of portal hypertension. (See "Portal hypertension in adults", section on 'Ultrasonography'.)

However, ultrasonography lacks specificity in characterizing spleen pathology and, therefore, focal lesions on ultrasound should generally be further evaluated with computed tomography or magnetic resonance imaging [8]. Other imaging modalities include nuclear medicine liver-spleen colloid study and positron emission tomography. These imaging techniques may reveal accessory spleens (found in 30 percent of autopsies) and polysplenia associated with congenital heart disease, biliary atresia, or situs inversus. A "wandering spleen" resulting from a lack of ligamentous attachment can be found anywhere in the abdomen. (See "Causes of acute abdominal pain in children and adolescents", section on 'Gastrointestinal' and "Heterotaxy (isomerism of the atrial appendages): Anatomy, clinical features, and diagnosis", section on 'Spleen'.)

Causes of splenomegaly that may be elucidated by imaging techniques include portal hypertension (eg, due to cirrhosis or portal vein thrombosis [PVT]), isolated cysts, hemangioma, lymphangioma, or hamartomas. Focal abnormalities can result from trauma to the spleen (eg, subcapsular hematoma, splenic rupture), abscess, granulomas, lymphoproliferative disease, Langerhans cell histiocytosis, Gaucher disease, Niemann-Pick disease, or sarcoidosis.

Spleen size – Splenomegaly on ultrasound is defined as splenic length or volume that is above the upper limits of normal for age [9,10]. Normal values for splenic length (from the dome to the tip) measured by ultrasound were defined in a study of 230 children undergoing abdominal ultrasound for reasons unrelated to the spleen [9]. The upper limits of normal for splenic length based upon age were as follows:

Age 3 months – 6 cm

Age 12 months – 7 cm

Age 6 years – 9.5 cm

Age 12 years – 11.5 cm

Age ≥15 years – 12 cm for girls and 13 cm for boys

In this study, all patients with palpable splenomegaly on physical examination had ultrasonographic splenic length measurements that exceeded these normal limits.

Laboratory evaluation — The initial laboratory evaluation of the child with unexplained splenomegaly includes (algorithm 1):

Complete blood count including platelet count and differential

Reticulocyte count

Review of the peripheral blood smear

Liver function tests

Lactate dehydrogenase

C-reactive protein and/or erythrocyte sedimentation rate

EBV and CMV serologies

Additional tests may be warranted based on the clinical history (eg, tuberculin skin testing for children with relevant exposure and antinuclear antibody as a screen for autoimmune diseases for children with suggestive symptoms).

The complete blood count should be interpreted in the context of other clinical findings. Cytopenias (neutropenia, anemia, and/or thrombocytopenia) are common in children with splenomegaly and represent a nonspecific finding. Cytopenias may be due to trapping of blood cells in the enlarged spleen (termed "hypersplenism") or may be due to other causes (eg, infection, malignancy).

The cytopenias seen with hypersplenism are not associated with morphologically abnormal circulating white or red blood cell (RBC) forms. Only a minimally predictable relationship exists between the degree of splenomegaly and the presence or degree of these cytopenias [11]. (See "Evaluation of splenomegaly and other splenic disorders in adults", section on 'Hypersplenism'.)

DIAGNOSTIC APPROACH — For most children who present with unexplained splenomegaly, a likely diagnosis (or diagnostic category) can be arrived at based upon the history, physical examination, and initial imaging and laboratory findings. In most cases, additional testing is needed to establish the specific diagnosis (table 1 and algorithm 1).

Suspected infectious mononucleosis – A diagnosis of infectious mononucleosis is suggested by fever, pharyngitis, fatigue, and lymphadenopathy. Laboratory abnormalities include lymphocytosis and atypical lymphocytes on peripheral blood smear (picture 3). The diagnosis is confirmed with heterophile antibody testing and/or serologic testing for Epstein-Barr virus (EBV) and cytomegalovirus (CMV). (See "Infectious mononucleosis", section on 'Diagnosis'.)

Suspected systemic infection – Systemic infection may be suggested by persistent fevers, weight loss, malaise, and/or diffuse lymphadenopathy. The travel and exposure history may also provide clues for certain systemic infections (eg, tuberculosis, malaria, babesiosis). Suggestive laboratory findings for systemic infection include leukocytosis with or without increased numbers of bands ("left shift"). In some cases, the peripheral blood smear may be diagnostic (eg, malaria (picture 4), babesiosis (picture 5)). Chest radiograph findings may be noted in patients with tuberculosis. Additional testing depends on the clinical circumstances and may include:

Tuberculin skin testing to evaluate for tuberculosis (see "Tuberculosis disease in children", section on 'Screening tests')

Serial blood cultures to evaluate for infective endocarditis (see "Infective endocarditis in children", section on 'Diagnosis')

Malaria blood smear (see "Laboratory tools for diagnosis of malaria", section on 'General principles')

HIV testing (see "Screening and diagnostic testing for HIV infection" and "Diagnostic testing for HIV infection in infants and children younger than 18 months")

Bartonella titers (see "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease", section on 'Diagnostic tests')

Blood smear and/or polymerase chain reaction testing for babesiosis (see "Babesiosis: Clinical manifestations and diagnosis", section on 'Diagnosis')

Suspected hematologic malignancy – Hematologic malignancy may be suggested by a clinical history of persistent fevers, anorexia, weight loss, decreased activity level, bone pain, and/or easy bruising. On physical examination, lymphadenopathy may be noted in addition to splenomegaly. Laboratory findings may include cytopenias; however, these are nonspecific findings and may be seen in other conditions associated with splenomegaly. In contrast, abnormal immature cells (blasts) in the peripheral blood are specific and indicate hematologic malignancy (eg, acute lymphocytic leukemia (picture 6), acute myeloid leukemia (picture 7)). Bone marrow examination is required for morphologic evaluation coupled with special staining and immunocytochemical techniques to establish the specific diagnosis. (See "Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children" and "Acute myeloid leukemia in children and adolescents".)

Suspected lymphoproliferative disease – Lymphoproliferative disease may be suggested by diffuse lymphadenopathy, particularly if lymph nodes are massively enlarged and/or rapidly increasing in size (table 5). Chest radiograph findings of hilar adenopathy or mediastinal mass are also of concern. Additional evaluation may include contrast-enhanced computed tomography of the chest and abdomen, lymph node biopsy, and/or bone marrow biopsy. (See "Peripheral lymphadenopathy in children: Evaluation and diagnostic approach", section on 'Lymph node biopsy'.)

The evaluation for specific causes of lymphoproliferative disease is reviewed separately:

(See "Clinical manifestations, pathologic features, and diagnosis of precursor T cell acute lymphoblastic leukemia/lymphoma", section on 'Diagnosis'.)

(See "Overview of Hodgkin lymphoma in children and adolescents", section on 'Diagnostic evaluation'.)

(See "Overview of non-Hodgkin lymphoma in children and adolescents", section on 'Diagnosis'.)

(See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis", section on 'Diagnosis'.)

(See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis", section on 'Evaluation and diagnostic testing'.)

(See "Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis".)

(See "HHV-8/KSHV-associated multicentric Castleman disease", section on 'Diagnostic evaluation'.)

Suspected hemolytic anemia – Hemolytic anemia is suggested by the combination of low hemoglobin, unconjugated hyperbilirubinemia, and reticulocytosis. The peripheral blood smear may show polychromasia, reflecting reticulocytosis (picture 8). In addition, certain congenital red blood cell (RBC) disorders may have specific findings on the blood smear (eg, elliptocytosis (picture 9), spherocytes (picture 10), xerocytosis (picture 11), sickle cell disease [SCD] (picture 2), and thalassemia (picture 12)). Additional testing to evaluate for hemolytic anemia includes reticulocyte count and serum markers of hemolysis (eg, lactate dehydrogenase, plasma free hemoglobin, and haptoglobin). The diagnostic evaluation for hemolytic anemia in children is discussed in detail separately. (See "Overview of hemolytic anemias in children", section on 'Diagnostic approach'.)

Suspected liver disease and/or portal hypertension – Liver disease is suggested by findings of jaundice, hepatomegaly, firm liver edge, ascites, and/or spider angiomata. Abnormal liver function tests and abnormal findings on abdominal imaging help to identify liver disease as the cause of splenomegaly. Further testing is warranted to identify the cause of liver disease; liver biopsy may be warranted in some cases. The approach to evaluating patients with suspected liver disease is discussed separately. (See "Approach to the patient with abnormal liver biochemical and function tests" and "Acute liver failure in children: Etiology and evaluation".)

Suspected autoimmune disease – Autoimmune disease may be suggested by findings of rashes and/or joint swelling. Laboratory findings include nonspecific markers of inflammation (eg, leukocytosis, elevated erythrocyte sedimentation rate, or C-reactive protein). Additional evaluation includes antinuclear antibody titers as a screening test and further evaluation based on the findings:

(See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Diagnosis'.)

(See "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications".)

Suspected immunodeficiency – Primary immunodeficiency may be suggested by a history of recurrent sinopulmonary infections and/or failure to thrive. Lymphopenia may be noted on the complete blood count; however, more commonly, the complete blood count is normal. Additional evaluation includes measurement of immunoglobulin levels and antibody functional studies (ie, vaccine response). (See "Common variable immunodeficiency in children".)

Suspected storage disease – Storage disease may be suspected based on other organ involvement (eg, hepatomegaly, skeletal abnormalities, neurologic involvement). Bone abnormalities may be seen on plain radiographs, and focal splenic masses may be noted on ultrasound. The diagnosis is confirmed by demonstrating a specific enzyme deficiency and/or genetic mutation. The approach is discussed in greater detail separately. (See "Inborn errors of metabolism: Classification", section on 'Lysosomal storage disorders' and "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Overview of Niemann-Pick disease", section on 'Diagnosis' and "Mucopolysaccharidoses: Clinical features and diagnosis", section on 'Diagnosis'.)

Nonspecific findings – If the initial workup does not suggest a specific etiology, computed tomography of the chest and abdomen should be performed to evaluate for disseminated or intraabdominal malignancy (eg, lymphoma, neuroblastoma), advanced liver disease, or portal hypertension.

In addition, a reasonable approach for children with nonspecific findings is to perform bone marrow aspiration with biopsy and culture. Conditions such as lipid storage diseases (picture 13 and picture 14), disseminated mycobacterial or granulomatous disease, hemophagocytic syndrome (picture 15), and occult tumors (picture 16) may be diagnosed in this way.

SUMMARY AND RECOMMENDATIONS

Definition – A splenic edge felt >2 cm below the left costal margin is an abnormal finding. A spleen is considered to be massively enlarged if its lower pole is within the pelvis or if it crosses the midline. (See 'Definitions' above.)

Causes of hepatomegaly – The most common causes of splenomegaly in children include infection (eg, Epstein-Barr virus [EBV] or cytomegalovirus [CMV], though many infectious agents can cause splenomegaly), malignancy, disorders of immune regulation (eg, autoimmune disease or primary immunodeficiency), and hemolytic anemias. Other important considerations include portal hypertension, heart failure, storage diseases, and space-occupying lesions (eg, hemangioma, cyst, hamartoma) (table 1). (See 'Causes of splenomegaly' above.)

Evaluation

History – The history may provide valuable clues as to the possible cause of splenomegaly (table 1). A history of recent febrile illness, pharyngitis, and fatigue suggests a viral etiology (eg, infectious mononucleosis, CMV, hepatitis). More pronounced constitutional symptoms (eg, persistent fevers, night sweats, weight loss, decreased activity level) suggest systemic diseases such as leukemia, lymphoma, systemic lupus erythematosus, malaria, or tuberculosis. (See 'History' above.)

Physical examination – Other physical examination findings that are important to note when evaluating a child with splenomegaly include lymphadenopathy, jaundice, hepatomegaly, rashes, joint swelling, petechiae, and ecchymoses (See 'Physical examination' above.)

Initial diagnostic testing – Initial testing for children with unexplained splenomegaly includes (algorithm 1) (see 'Initial diagnostic testing' above):

-Complete blood count including platelet count and differential

-Reticulocyte count

-Review of the peripheral blood smear

-Liver function tests

-Lactate dehydrogenase

-C-reactive protein and/or erythrocyte sedimentation rate

-EBV and CMV serologies

-Chest radiograph

-Abdominal ultrasound

Imaging – Ultrasonography (including Doppler imaging to evaluate splenic and portal blood flow) is usually the initial imaging test to evaluate a child with unexplained splenomegaly. It accurately defines spleen size and volume and identifies focal or diffuse pathologic changes. A finding of slow or reversed portal blood flow suggests portal hypertension. Focal lesions identified on ultrasound should generally be further evaluated with computed tomography or magnetic resonance imaging. (See 'Imaging' above.)

Diagnostic approach – For most children who present with unexplained splenomegaly, a likely diagnosis (or diagnostic category) can be arrived at based upon the history, physical examination, and initial imaging and laboratory findings. In most cases, additional testing is needed to establish the specific diagnosis (algorithm 1 and table 1). (See 'Diagnostic approach' above.)

  1. Hosea SW, Burch CG, Brown EJ, et al. Impaired immune response of splenectomised patients to polyvalent pneumococcal vaccine. Lancet 1981; 1:804.
  2. Giebink GS, Le CT, Schiffman G. Decline of serum antibody in splenectomized children after vaccination with pneumococcal capsular polysaccharides. J Pediatr 1984; 105:576.
  3. Heath HW, Pearson HA. Thrombocytosis in pediatric outpatients. J Pediatr 1989; 114:805.
  4. McIntyre OR, Ebaugh FG Jr. Palpable spleens in college freshmen. Ann Intern Med 1967; 66:301.
  5. Suttorp M, Classen CF. Splenomegaly in Children and Adolescents. Front Pediatr 2021; 9:704635.
  6. O'Reilly RA. Splenomegaly in 2,505 patients in a large university medical center from 1913 to 1995. 1913 to 1962: 2,056 patients. West J Med 1998; 169:78.
  7. Tamayo SG, Rickman LS, Mathews WC, et al. Examiner dependence on physical diagnostic tests for the detection of splenomegaly: a prospective study with multiple observers. J Gen Intern Med 1993; 8:69.
  8. Vancauwenberghe T, Snoeckx A, Vanbeckevoort D, et al. Imaging of the spleen: what the clinician needs to know. Singapore Med J 2015; 56:133.
  9. Rosenberg HK, Markowitz RI, Kolberg H, et al. Normal splenic size in infants and children: sonographic measurements. AJR Am J Roentgenol 1991; 157:119.
  10. Pelizzo G, Guazzotti M, Klersy C, et al. Spleen size evaluation in children: Time to define splenomegaly for pediatric surgeons and pediatricians. PLoS One 2018; 13:e0202741.
  11. Gielchinsky Y, Elstein D, Hadas-Halpern I, et al. Is there a correlation between degree of splenomegaly, symptoms and hypersplenism? A study of 218 patients with Gaucher disease. Br J Haematol 1999; 106:812.
Topic 5928 Version 32.0