Splenomegaly – Causes, Symptoms, Treatment

The size and weight of spleen may vary and correlates with weight, height, and sex of an individual, with larger spleen size seen in men compared to women, and in heavier or taller individuals. A normally sized spleen measures up to 12 cm in craniocaudal length.  A length of 12 cm to 20 cm indicates splenomegaly, and a length greater than 20 cm is definitive of massive splenomegaly. The normal weight of the adult spleen is 70 g to 200 g; a spleen weight of 400 g to 500 g indicates splenomegaly and a spleen weight greater than 1000 g is definitive of massive splenomegaly. The normal-sized spleen is usually not palpable in adults. However, it may be palpable due to variations in body habitus and chest wall anatomy. Splenomegaly may be diagnosed clinically or radiographically using ultrasound?, CT imaging, or MRI.  Splenomegaly may be a transient condition due to acute? illness or may be due to serious underlying acute or chronic? pathology.[rx][rx][rx]

Splenomegaly is an enlargement of the spleen.^[rx] The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of hypersplenism which include: some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes, or platelets in any combination; a compensatory proliferative response in the bone marrow; and the potential for correction of these abnormalities by splenectomy. Splenomegaly is usually associated with increased workload (such as in hemolytic anemias), which suggests that it is a response to hyperfunction. It is therefore not surprising that splenomegaly is associated with any disease process that involves abnormal red blood cells being destroyed in the spleen. Other common causes include congestion due to portal hypertension? and infiltration by leukemias and lymphomas. Thus, the finding of an enlarged spleen, along with caput-medusae, is an important sign of portal hypertension.^[rx]

Types of Splenomegaly

Splenomegaly can be classified based on its pathophysiologic mechanism:

• Congestive – by pooled blood (e.g., portal hypertension?)
• Infiltrative – by invasion by cells foreign to the splenic environment (e.g., metastases, myeloid neoplasms, lipid storage diseases)
• Immune – by an increase in immunologic activity and subsequent hyperplasia (e.g., endocarditis, sarcoidosis, pain?, swelling?, stiffness?, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।" data-rx-term="arthritis" data-rx-definition="Arthritis means joint inflammation causing pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।">arthritis?: Rheumatoid arthritis is an autoimmune? joint disease causing infection?, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation?, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।" data-rx-term="rheumatoid arthritis" data-rx-definition="Rheumatoid arthritis is an autoimmune joint disease causing inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।">rheumatoid arthritis?)
• Neoplastic – when resident immune cells originate a neoplasm (e.g., lymphoma).

The standard system for classifying splenomegaly on radiography is:^[rx][rx]

• Normal (not splenomegaly) – the largest dimension is less than 11 cm
• Moderate splenomegaly – the largest dimension is between 11–20 cm
• Severe splenomegaly – the largest dimension is greater than 20 cm

Causes of Splenomegaly

There are several potential causes of splenomegaly.

• Liver disease (cirrhosis?, hepatitis?): Parenchymal liver disease causes increased vascular pressure leading to an increase in spleen size.
• Hematologic malignancies (lymphomas, leukemias, myeloproliferative disorders): Neoplastic cells cause infiltration of the spleen leading to splenomegaly.
• Venous thrombosis? (portal or hepatic vein thrombosis): This leads to an increase in vascular pressure leading to splenomegaly.
• Splenic congestion (venous thrombosis?, portal hypertension?, congestive heart failure).
• Cytopenias (Immune thrombocytopenic purpura, autoimmune? hemolytic anemia?, immune-mediated bacterial? infection?. সহজ বাংলা: ব্যাকটেরিয়ার বিরুদ্ধে লড়াই করা শ্বেত রক্তকণিকা।" data-rx-term="neutrophil" data-rx-definition="Neutrophil is a white blood cell important for fighting bacterial infection. সহজ বাংলা: ব্যাকটেরিয়ার বিরুদ্ধে লড়াই করা শ্বেত রক্তকণিকা।">neutrophil? count, which may increase infection risk. সহজ বাংলা: নিউট্রোফিল কম থাকা, সংক্রমণের ঝুঁকি বাড়তে পারে।" data-rx-term="neutropenia" data-rx-definition="Neutropenia means low neutrophil count, which may increase infection risk. সহজ বাংলা: নিউট্রোফিল কম থাকা, সংক্রমণের ঝুঁকি বাড়তে পারে।">neutropenia?, Felty syndrome): Immune-mediated destruction of red blood cells, white blood cells or platelets lead to functional splenomegaly.
• Splenic sequestration (pediatric sickle cell disease, hemolytic anemias, thalassemias).
• Acute? or chronic? infection? (bacterial? endocarditis, infectious mononucleosis, HIV, malaria, tuberculosis, histiocytosis, abscess?).
• Connective tissue diseases (systemic lupus erythematosus, stiffness?, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।" data-rx-term="arthritis" data-rx-definition="Arthritis means joint inflammation causing pain, swelling, stiffness, or reduced movement. সহজ বাংলা: জয়েন্টের প্রদাহ।">arthritis?: Rheumatoid arthritis is an autoimmune? joint disease causing infection?, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation?, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।" data-rx-term="rheumatoid arthritis" data-rx-definition="Rheumatoid arthritis is an autoimmune joint disease causing inflammation, pain, and swelling. সহজ বাংলা: রোগপ্রতিরোধ ব্যবস্থার ভুল আক্রমণে জয়েন্টের প্রদাহ।">rheumatoid arthritis?, Adult-onset Still’s disease, and some familial autoinflammatory syndromes).[rx][rx]
• Infiltrative disorders (sarcoidosis, amyloidosis, glycogen storage diseases).
• Splenic sequestration (pediatric sickle cell, hemolytic anemias, thalassemias).
• Focal lesions (hemangiomas, abscess, cysts, metastasis).
• malaria
• Hodgkin’s disease
• leukemia
• heart failure
• cirrhosis
• tumors in the spleen or from other organs that have spread to the spleen
• viral, bacterial, or parasitic infections
• inflammatory diseases, such as lupus or rheumatoid arthritis
• sickle cell disease

The mechanism underlying splenic enlargement varies based on the etiology. In the case of acute infectious illness, the spleen performs increased work in clearing antigens and producing antibodies and increases the number of reticuloendothelial cells contained within the spleen. These increased immune functions may result in splenic hyperplasia. In the case of liver disease and congestion, underlying illness causes increased venous pressure causing congestive splenomegaly. Extramedullary hematopoiesis exhibited in myeloproliferative disorders can lead to splenic enlargement (infiltrative splenomegaly).[rx][rx]

The possible causes of moderate splenomegaly (spleen <1000 g) are many and include

The causes of massive splenomegaly (spleen >1000 g) are

• chronic myelogenous leukemia
• myelofibrosis
• malaria
• Inflammatory diseases such as sarcoidosis, lupus, and rheumatoid arthritis
• Trauma, such as an injury during contact sports
• Cancer that has spread (metastasized) to the spleen
• A cyst, a noncancerous fluid-filled sac
  A large abscess, a pus-filled cavity usually caused by a bacterial infection
• Infiltrative diseases such as Gaucher disease, amyloidosis, or glycogen storage diseases splenic marginal zone lymphoma

Symptoms of Splenomegaly

An enlarged spleen may be caused by

• No symptoms in some cases
• Pain or fullness in the left upper abdomen that may spread to the left shoulder
• Feeling full without eating or after eating only a small amount from the enlarged spleen pressing on your stomach
• pressure or pain in the left upper part of your abdomen (near the stomach),
• feeling full without eating a large meal,
• or pain your left shoulder blade or shoulder area when taking a deep breath.
• Anemia
• Fatigue
• Frequent infections
• Easy bleeding

Diagnosis of Splenomegaly

History and Physical

The most common physical symptom associated with splenomegaly is vague abdominal discomfort. Patients may complain of pain in the left upper abdomen or referred pain in the left shoulder. Abdominal bloating, distended abdomen, anorexia, and/or early satiety may also occur. More commonly, patients will present with symptoms due to the underlying illness causing splenomegaly. Constitutional symptoms such as weakness, weight loss, and night sweats suggest malignant illness. Patients with splenomegaly due to acute infection may present with fever, rigors, generalized malaise, or focal infectious symptoms. Patients with underlying liver disease may present with symptoms related to cirrhosis or hepatitis. Symptoms of anemia (lightheadedness, dyspnea, or exertion), easy bruising, bleeding, or petechiae may indicate splenomegaly due to the underlying hemolytic process.

Physical examination of the spleen is performed with the patient in supine and right lateral decubitus position with neck, hips, and knees flexed. This positioning relaxes abdominal wall musculature and rotates the spleen more anteriorly. Light fingertip pressure is applied below the left costal margin during deep inspiration. The examiner may feel the rounded edge of the spleen pass underneath the fingertips at maximum inspiration. The exam is abnormal if the spleen is palpated more than 2 cm below the costal margin. In massive splenomegaly, the spleen may be palpated deep into the abdomen, crossing the midline of the abdomen and may even extend into the pelvis. Studies have shown that normal sized spleens may be palpable in approximately 3% of adults.

Patients may have an abnormally palpable spleen with or without exam findings of contributing underlying illness. Patients with splenomegaly due to acute infection may have exam findings consistent with infectious mononucleosis, endocarditis, or malaria. Exam findings of petechiae, abnormal mucosal bleeding, or pallor may accompany hematologic diseases. Jaundice, hepatomegaly, ascites, or spider angiomata may be present in patients with liver disease.  Patients with rheumatologic diseases may present with joint tenderness, swelling, rash, or an abnormal lung exam.

Evaluation

A combination of serum testing and imaging studies may definitively diagnose splenomegaly and the underlying cause. Derangement in the complete blood (cell) counts and morphology including WBC, RBC, and platelets will vary based on the underlying disease state. Abnormalities in liver function tests, lipase, rheumatologic panels, and disease-specific infectious testing aid in the diagnosis of causative disease.[rx] Hypersplenism may present with leukopenia, anemia, and thrombocytopenia.

Investigations

Investigations for splenomegaly should be targeted to the most likely underlying cause and include:

• Blood tests – FBC/blood film/U+E/LFTs/LDH/autoimmune screen/blood culturesHIV test
• CXR – looking for bihilar lymphadenopathy which may suggest an underlying lymphoproliferative process or infection. Malaria film if recent foreign travel to a malaria-endemic area Echo if infective endocarditis is suspected
• CT thorax abdop Elvis  – if underlying malignancy suspected. Bone marrow aspirate and trephine if an underlying hematological process is likely
• Lymph node biopsy – Imaging may be used to diagnose splenomegaly and elucidate its underlying cause. The spleen has a similar attenuation as the liver when measured on CT imaging. In addition to diagnosing splenomegaly (a splenic measurement of greater than 10 cm in craniocaudal length), abdominal CT may detect splenic abscess, mass lesions, vascular abnormalities, cysts, inflammatory changes, traumatic injury, intra-abdominal lymphadenopathy, or liver abnormalities.
• Sonography in trauma (FAST) exam – uses ultrasound to assess for the presence of fluid where it should not be in trauma evaluation. A FAST exam looks at four windows: pericardial window, Morrison’s pouch (right upper quadrant between liver and right kidney), left upper quadrant (between the spleen and left kidney), and the suprapubic region to look at the bladder and pelvis. The exam is considered positive with fluid in any of these spaces, and combination with hemodynamic instability is an indication for exploratory laparotomy. With positive fluid in the pericardial window, a pericardiocentesis is an appropriate followup.[rx]
• Computed tomography (CT) – are beneficial tools to visualize and characterize the spleen. Both modalities function to measure the spleen and identify physical abnormalities. While not necessary, the use of contrast can aid in tracing blood flow and help identify any leaks or pathologic fluid collection.[rx]
• Ultrasound – is a useful imaging modality in measuring the spleen and spares the patient radiation from CT imaging. Normal spleen size measured via ultrasound is less than 13 cm superior to the inferior axis, 6 cm to 7 cm in medial to lateral axis and 5 cm to 6 cm in anterior to the posterior plane.
• MRI, PET scans – liver-spleen colloid scanning, and splenectomy and splenic biopsy may be indicated in certain cases.

Treatment of Splenomegaly

Treatment of splenomegaly is targeted at treating the underlying disease and protecting the patient from complications of splenomegaly itself.  Patients with splenomegaly from any cause are at increased risk of splenic rupture, and increased attention must be made to protect the patient from abdominal trauma. Treatment ranges from abdominal injury avoidance in the young healthy patient with splenomegaly due to infectious mononucleosis, to splenectomy of a massively enlarged spleen in a patient with hairy cell leukemia. Likewise, the prognosis is largely dependent on the underlying disease state.[rx][rx]

• Splenic sequestration – is seen in sickle cell anemia is often managed with blood transfusions/exchange transfusions. Sometimes splenectomy is required for ITP. Low dose radiation therapy can also shrink the spleen size in patients with primary myelofibrosis.
• Patients who undergo splenectomy – are at increased risk of infections secondary to encapsulated organisms such as Haemophilus Influenzae, Streptococcus pneumonia, and Neisseria meningitides. Vaccinations against these organisms are highly recommended in patients who have undergone splenectomy. Careful attention must be paid to post-splenectomy patients presenting with febrile illnesses as they may require more aggressive, empiric antibiotic therapy.
• If the splenomegaly underlies hypersplenism – splenectomy is indicated and will correct the hypersplenism. However, the underlying cause of hypersplenism will most likely remain; consequently, a thorough diagnostic workup is still indicated, as, leukemia, lymphoma and other serious disorders can cause hypersplenism and splenomegaly. After splenectomy, however, patients have an increased risk for infectious diseases.
• Infective endocarditis suspected – TTE (transthoracic) +/- TOE (transoesophageal) for vegetations, at least 3 different sets of blood cultures from different sites at the different time should be sent and discuss with cardiology and microbiology for appropriate treatment

Patients undergoing splenectomy should be vaccinated against Haemophilus influenzae, Streptococcus pneumoniae, and Meningococcus. They should also receive annual influenza vaccinations. Long-term prophylactic antibiotics may be given in certain cases.

Differential Diagnosis

There are several potential causes of splenomegaly, and careful and thorough evaluation is often needed to find the underlying cause of splenomegaly.

These include:

• Cirrhosis
• Hepatitis
• Rheumatoid arthritis
• Felty syndrome
• Systemic lupus erythematosus
• Lymphoma
• Sickle cell anemia

Liver disease (cirrhosis, hepatitis) is one of the most common causes and history of liver disease, abnormal physical exam findings and elevated liver enzymes in addition to abnormal liver imaging can help diagnose liver diseases.

Hematologic malignancies and metastasis shall be especially considered in patients with constitutional symptoms and weight loss. Abnormal peripheral blood smear and biopsy can assist in diagnosing malignancies.

Autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) frequently are associates with splenomegaly. In RA, the presence of splenomegaly in addition to neutropenia is termed Felty syndrome.

Acute and chronic infections including viral, bacterial, fungal, and mycobacterial infections can all cause splenomegaly and shall be carefully ruled out.

Cytopenias and diseases causing splenic sequestration can be ruled out by complete blood counts, peripheral blood smear and hemoglobin electrophoresis.

Infiltrative disorders such as glycogen storage diseases are a rare cause of splenomegaly and shall be considered if other more common causes are ruled out in patients with other clinical features consistent with these glycogen storage diseases.

References