a. Splenomegaly is defined as pathologic enlargement of the spleen.
i. A normal spleen has a craniocaudal length of no more than 12 cm and weighs less than 200 g. It is surrounded by a thin capsule. The spleen is usually not palpable unless it is enlarged; therefore, a palpable spleen is almost always abnormal.
ii. At times the spleen may be difficult to palpate, but dullness to percussion during inspiration in the area of the lower left intercostal space (Traube’s space) in the left anterior axillary line suggests splenic enlargement (Castell’s sign).
iii. Massive splenomegaly (weight >1000 g) occurs in lymphoma, myeloproliferative disorders, visceral leishmaniasis, and malaria.
b. Hypersplenism is the term given to any clinical situation in which the spleen inappropriately removes excess amounts of leukocytes, platelets, or erythrocytes from the circulation.
i. Hypersplenism and splenomegaly are not synonymous. Patients with hypersplenism generally all have splenomegaly; however, only a small percentage of those with splenomegaly have hypersplenism. Hypersplenism denotes a physiologic derangement, whereas splenomegaly purely refers to anatomic enlargement of the organ regardless of cause.
ii. Characteristics of hypersplenism include the following:
2. Splenic destruction/sequestration of one or more cell lines
3. Normal or hyperplastic bone marrow
4. Reversal of cytopenia following splenectomy
B. Clinical Manifestations of Splenomegaly
a. Nonacute splenomegaly is most common. Clinical presentations include:
i. Early satiety (because of impaired gastric filling), which may lead to weight loss if present for a prolonged time
ii. Cytopenias (as a result of hypersplenism), which may present with unusual infections (e.g., fulminant infections with pneumococcus or meningococcus), bleeding, or fatigue
iii. Symptoms of the underlying disease
iv. Many patients have no symptoms referable to splenomegaly.
b. Acute splenomegaly
i. Clinical signs include sudden onset of left upper quadrant pain with a tender, enlarged spleen.
ii. Differential diagnosis
C. Causes of Splenomegaly
a. Congestive causes. This category includes any disease that leads to disordered splenic blood flow, so that the blood “backs up” in the spleen. Causes are always anatomically distal to the spleen.
i. Splenic vein thrombosis/obstruction
ii. Portal vein obstruction
iii. Hepatic schistosomiasis
iv. Hepatic cirrhosis leading to portal hypertension
v. Hepatic vein obstruction
vi. Constrictive pericarditis
vii. Congestive heart failure (CHF)
b. Reactive causes. This category includes diseases that lead to splenic hyperplasia. Because the spleen is a lymphoid gland (i.e., a giant lymph node), many diseases that cause a systemic immunologic response can cause splenomegaly. In addition, blood disorders that lead to hemolysis can also cause the spleen to enlarge.
1. Bacterial (e.g., endocarditis, tuberculosis, sustained bacteremia)
2. Viral (e.g., mononucleosis, viral hepatitis)
3. Parasitic (e.g., malaria, leishmaniasis, trypanosomiasis)
4. Fungal (e.g., disseminated histoplasmosis)
ii. Collagen vascular diseases
1. Rheumatoid arthritis. Felty’s syndrome is the triad of rheumatoid arthritis, leukopenia, and splenomegaly.
Rheumatoid arthritis—like CHF, systemic lupus erythematosus (SLE), and endocarditis—usually causes mild splenomegaly
2. SLE. SLE can often cause splenomegaly by chronic inflammation, similar to rheumatoid arthritis.
iii. Serum sickness. This immune complex disorder—usually caused by a drug hypersensitivity reaction—occurs 1–3 weeks after primary exposure (or within 36 hours of reexposure) to an offending agent.
MNEMONIC: Clinical Manifestations of Serum Sickness (“SALT”)
Skin rash (morbilliform, urticarial, or palpable purpura)
Arthralgias or Arthritis
iv. Work hypertrophy (i.e., enlargement due to increased functional demand) can be caused by hemolysis.
3. Gaucher’s disease, an autosomal recessive disorder characterized by an accumulation of sphingolipid within phagocytic cells throughout the body
3. Myeloproliferative disorders
4. Primary splenic tumors
5. Metastatic tumors
MNEMONIC: Causes of Massive Splenomegaly (“Hopefully, My Medical Students Can Learn Gastroenterology”)
Hairy cell leukemia (uncommon, resembles chronic lymphocytic leukemia)
Myeloid metaplasia with myelofibrosis (one of four myeloproliferative disorders)
Chronic myelogenous leukemia (another myeloproliferative disorder)
Lymphoma (primarily splenic lymphoma)
D. Approach to the Patient
a. Patient history. When taking the history, focus on finding an underlying cause. Things to look for include:
i. Alcohol use, viral hepatitis, or cirrhosis
iii. Febrile illness (current or recent)
iv. Arthralgias, arthritis, or joint stiffness
v. Fever, weight loss, diaphoresis, or lymph node swelling
vi. Family history of anemia or splenomegaly
b. Physical examination. Look for evidence of hepatomegaly, lymphadenopathy, skin rash, subcutaneous nodules, CHF, liver disease, or an infectious process (e.g., fever, leukocytosis, hypotension).
c. Laboratory tests usually include a complete blood count (CBC) with platelets and analysis of the peripheral smear and liver tests.
d. Massive splenomegaly, when the spleen crosses the midline, is seen only in a handful of diseases.
e. Other tests. Blood cultures may be warranted if infection is suspected. An ultrasound is useful to confirm the presence of splenomegaly, evaluate portal pressures by Doppler, and estimate liver size. Abdominal computed tomography (CT) scanning may add to information from ultrasound. Bone marrow biopsy, lymph node biopsy, serologies, exploratory laparotomy, and other imaging studies may also be performed if the workup is otherwise nondiagnostic.
f. Splenectomy may be considered in patients with splenomegaly that remains idiopathic and associated with cytopenia because a significant number of these patients may have an occult lymphoma. Vaccination against encapsulated organisms (e.g., pneumococcus) must be considered in those that are functionally asplenic or undergo splenectomy.
Suggested Further Readings
Grover SA, Barkun AN, Sackett DL. The rational clinical examination. Does this patient have splenomegaly? JAMA 1993;270:2218–21. (Classic Article.)Find this resource:
Harmanci O, Bayraktar Y. Clinical characteristics of idiopathic portal hypertension. World J Gastroenterol 2007;13:1906–11.Find this resource:
Pozo AL, Godfrey EM, Bowles KM. Splenomegaly: investigation, diagnosis and management. Blood Rev 2009;23:105–11.Find this resource:
Smith C, Saint S, Price R, Al-Zoubi A, Callaghan B. Clinical problem-solving. Diagnosing one letter at a time. N Engl J Med 2015;372:67–73.Find this resource: