Splenomegaly and hypersplenism

What is splenomegaly?

Splenomegaly is an enlarged spleen. The spleen is involved in producing protective humoral antibodies, the production and maturation of B and T cells and plasma cells, and removal of unwanted particulate matter (for example, bacteria); it also acts as a reservoir for blood cells, especially white cells and platelets. When the spleen is palpable it has usually reached at least twice its normal size.

What is hypersplenism?

• This is a pancytopenia occurring in patients with an enlarged spleen. It is due to large numbers of cells being pooled and destroyed in the spleen's reticulo-endothelial system, and haemodilution because of an increased plasma volume.

• It can present with symptoms of anaemia, infection, or bleeding.

• Bone marrow biopsy shows normal or hyperplastic marrow.

• Splenic sequestration crisis may develop in young children with sickle cell anaemia, which can precipitate hypovolaemic shock and death, and is an indication for splenectomy.

How common is splenomegaly? (Epidemiology)

Splenomegaly is a rare condition. An incidence of 2% has been reported in the USA.¹

One study reported that 0.3% of all hospital admissions were found to have splenomegaly. Haematological diseases were the underlying causal diagnosis in 39%; hepatic diseases in 18%, infectious disease in 10% and other diseases in 8%.²

Symptoms of splenomegaly (presentation)¹

• Presentation depends on the underlying cause. For example, constitutional symptoms such as weakness, weight loss and night sweats may occur in malignancy. Acute infection may present with fever, rigors and malaise. Underlying liver disease may present with symptoms related to cirrhosis or hepatitis. Symptoms of anaemia or petechiae may indicate an underlying haemolytic process.

• Left upper quadrant (LUQ) mass or 'uncomfortable' abdominal pain is a common presentation. Early satiety from a compressed stomach may occur.

• Pancytopenia due to hypersplenism (see 'Hypersplenism' heading, below).

Examination

When considering whether an LUQ mass is an enlarged spleen, features of an enlarged spleen include that:

• It moves with respiration.

• It enlarges towards the right iliac fossa (RIF) - always start palpation in the RIF and move across towards the right upper quadrant (or a massive splenomegaly may be missed).

• You cannot palpate above it - the upper margin lies under the ribs.

• You may feel a notch.

• It is dull to percussion.

Always remember to check for any accompanying lymphadenopathy and/or features of liver disease.

Diagnosing splenomegaly (investigations)¹

• Liver biopsy.

• Bone marrow biopsy.

• Lymph node biopsy.

• Imaging by MRI or PET scan may be required.

• Splenic biopsy may be indicated in some cases.

• Next generational sequencing - this is a technique in which an entire chromosome can be genetically sequenced in a short period of time. It has been used to review genetic mutations in people with idiopathic splenomegaly.³

Causes of splenomegaly (aetiology)²

• Haematological:

  • Haemolytic anaemias (for example, thalassaemia, red cell defects, sickle cell anaemia).

  • Acute leukaemias, chronic leukaemias.

  • Polycythaemia rubra vera.

  • Macroglobulinaemia.

  • Lymphoma (Hodgkin's disease and non-Hodgkin's lymphoma).

  • Essential thrombocythaemia.

  • Myelofibrosis.

• Infections:

  • Malaria.

  • Schistosomiasis.

  • Visceral leishmaniasis (kala-azar).

  • Tuberculosis, brucellosis.

  • Glandular fever, viral hepatitis.

  • Infective endocarditis.

• Tumours and cysts:

  • Splenic abscesses.

  • Splenic metastases.

  • Cysts - for example, hydatid, dermoid.

  • Tumours - for example, haemangioma.

• Congestive splenomegaly:

  • Liver cirrhosis.

  • Budd-Chiari syndrome.⁴

  • Portal or splenic vein obstruction.

  • Heart failure.

• Connective tissue disorders:

  • Systemic lupus erythematosus.

  • Felty's syndrome.

• Other disorders:

  • Gaucher's disease.

  • Niemann-Pick disease.

  • Amyloidosis.

In about 5% of cases, no cause can be found.³

Causes of massive splenomegaly

• Chronic myeloid leukaemia.

• Myelofibrosis, malaria (hyper-reactive malarial splenomegaly).

• Leishmaniasis.

• 'Tropical splenomegaly' (idiopathic; Africa, Southeast Asia).

• Gaucher's disease.⁴

Splenomegaly in children

This is most commonly caused by infection, autoimmune disorders or haemolysis. It may be a presenting feature of neoplasia (for example, metastatic neuroblastoma). Causes include:

• Infection: glandular fever, cytomegalovirus (CMV), other viral infections, often accompanied by lymphadenopathy; bacterial, protozoal, and fungal infections.

• Autoimmune: juvenile idiopathic arthritis.

• Haemolysis: hereditary spherocytosis, sickle cell anaemia, thalassaemia.

• Neoplasia: acute lymphoblastic leukaemia (ALL), Hodgkin's disease and non-Hodgkin's lymphoma (NHL), acute or chronic myeloblastic leukaemia, neuroblastoma.

• Inherited diseases: Gaucher's disease and other storage disorders.

Management of splenomegaly

• Treatment of the cause.

• Blood transfusions may be required.

• Open or laparoscopic splenectomy may be indicated to control or stage the disease (for example, hereditary spherocytosis, Hodgkin's disease).

• Patients with impaired splenic function need prophylactic vaccinations, etc (see the separate Splenectomy and hyposplenism article).