Splenomegaly

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2], Gichoya Judy Wawira [3],

Synonyms and keywords: Spleen enlargement; enlarged spleen; spleen swelling

Causes

The causes of splenomegaly vary widely and range from increased splenic function (such as hemoglobinopathies), splenic congestion due to abnormal blood flow (such as venous obstruction), and splenic infiltration (such as storage disorders and malignancies).

Causes by Pathogenesis

Mechanism	Pathogenesis		Example
Increased function	Removal of defective RBCs		Spherocytosis Thalassemia Hemoglobinopathy Anemia Sickle cell anemia
	Immune hyperplasia	Response to infection (viral, bacterial, fungal, parasitic)	Mononucleosis AIDS Viral hepatitis Subacute bacterial endocarditis Bacterial septicemia Splenic abscess Typhoid fever Leptospirosis Tuberculosis Histoplasmosis Malaria leishmaniasis Trypanosomiasis Ehrlichiosis
		Disordered immunoregulation	Rheumatoid arthritis SLE Serum sickness Autoimmune hemolytic anemia Immune thrombocytopenia Sarcoidosis
		Drug reactions	Cidofovir Filgrastim
	Extramedullary hematopoiesis		Myelofibrosis Tumors Lukemias Marrow damage by radiation toxins
Abnormal blood flow	Organ Failure		Cirrhosis Congestive heart failure
	Vascular		Hepatic vein obstruction Portal vein obstruction Budd-Chiari syndrome Splenic vein obstruction
	Infections		Hepatic schistosomiasis Hepatic echinococcosis
Infiltration	Metabolic diseases		Gauchers disease Niemann-Pick disease Hurler syndrome Mucopolysaccharidoses Amyloidosis Tangier disease
	Benign and malignant infiltrations		Leukemias (acute, chronic, lymphoid and myeloid) Lymphomas (Hodgkins and non-hodgkins) Myeloproliferative disorders Metastatic tumors (commonly melanoma) Histiocytosis X Hemangioma Lymphangioma Splenic cyst Hamartomas Eosinophilic granuloma

Differentiating Splenomegaly from Other Diseases

Category	Disease		Etiology	Clinical manifestations												Para−clinical findings										Gold standard	Associated findings
				Demography	History	Symptoms					Signs					Lab Findings									Imaging
						Fever	Fatigue	Weight	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	CBC			Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology
																WBC	Hb	Plt
Congestive	Cirrhosis		Infection Alcohol Autoimmune	Any age, more common in elderly	Hepatitis Alcohol use NAFLD	–	+	↑↓	+	+	↓	Nl	+	+	Spider angiomata Palmar erythema Weakness	↓	↓	↓	Nl	↑	↑	↑	Dark urine	Pancytopenia Regenerating nodules of hepatocytes Fibrosis Deposition of connective tissue between these nodules	Small and nodular liver on ultrasound Fibrosis on liver scan	Liver biopsy	Hepatic encephalopathy Gynecomastia Hypogonadism Esophageal varices Caput medusa Dupuytren's contracture
	Heart failure		Coronary artery disease HTN	Elderly	Smoking Sedentary lifestyle Obstructive sleep apnea	–	+	↑↓	–	–	↑	↑	±	+	Dyspnea Weakness Chest pain Heart murmur	↓	↓	↑	Nl	↑	↑	↑	Nl	NA	Normal or low ejection fraction on echocardiography Cardiomegaly on chest x-ray	Echocardiography	Pulmonary edema Hyponatremia Elevated BNP
	Thrombosis of portal, hepatic, or splenic veins		Thrombosis	Any age	Inflammation Infection Cirrhosis Cancer	+	+	↑	+	+	↓	Nl	±	+	Weakness Hematemesis Melena	↓	↓	↓	Nl	↑	↑	↑	Dark urine	NA	Reduced or absent blood flow on doppler ultrasonography	Doppler ultrasonography	Portal hypertension Esophageal varices
Malignancy	Lymphoma		Unknown Mutation Infection	Any age, most common malignant splenic tumor	Epstein Barr virus Positive family history Smoking HIV Autoimmune diseases	+	+	↓	+	+	Nl	Nl	+	–	Lymphadenopathy Itching Night sweats Anorexia Dyspnea	↓	↓	↓	High ferritin	↑	↑	↑	Nl	Different histopathological features based on types and stages Reed-Sternberg cell Malignant cells	Peritoneal lymphomatosis on CT scan	Lymph node biopsy	Primary immune disorder Post-transplant
	Leukemia		Unknown Mutation Bone marrowinfiltration Ineffective hematopoiesis Immune mediated	Elderly, male>female	History of hematological disorder History of chemotherapy andionizing radiation	+	+	↓	+	+	Nl	Nl	±	+	Pallor Leukemia cutis Bruising Petechiae Ecchymosis Fatigue Bone tenderness Early satiety	↓	↓	↓	High ferritin	↑	↑	↑	Nl	Leukemic blasts Leukoerythroblastic features Giant platelets	NA	Bone marrow examination + clinical manifestation	Infections of variable severity Cranial nerve palsy
	Polycythemia Vera		Autonomous erythrocyteproduction JAK2mutation	Mean age >60 years old	Positive family history	–	+	Nl	+	–	Nl	Nl	–	–	Erythromelalgia Chest pain Stroke-like symptoms Pruritus Dizziness Visual disturbance Facial plethora Painful erythema Lymphadenopathy	Nl to ↑	↑	Nl to ↑	High ferritin	Nl	Nl	Nl	Nl	Elevated normochromic, normocytic RBCs Thrombocytosis Rarely immature cells Leukoerythroblastic picture	NA	WHO criteria for PV	Stroke Venous thrombosis Myelofibrosis Acute leukemia
	Disease		Etiology	Demography	History	Fever	Fatigue	Weight loss	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings
	Multiple myeloma		Unknown Mutation Infection	Any age, more common in adults	Exposure to chemicals Radiation Pre-existent blood disorders	+	+	↓	+	+	Nl	Nl	+	–	Lymphadenopathy Itching Night sweats Anorexia Dyspnea	↓	↓	↓	High ferritin	Nl	↑	↑	Hemoglobinuria	Blast cells		Bone marrow examination	Tumor lysis syndrome Infection CNS involvement DIC
	Essential thrombocythemia		Acquired mutation of JAK2, CALR, or MPL	Mean age >60 years old, female > male	Vascular occlusive events and hemorrhages	±	+	Nl	+	+	Nl	Nl	–	–	Flushing Erythromelalgia Transient ischemic attacks Priapism Decreased visual acuity	↑	↑	↑↑	Nl	Nl	Nl	Nl	Nl	Increased cellularity Hyperplasia and clustering of megakaryocytes Bone marrow reticulin may be increased with no collagen fibrosis	Splenomegaly on abdominal CT VTE on spiral chest CT DVT on ultrasound	Bone marrow biopsy	Thrombosis
	Primary myelofibrosis		Bone marrow fibrosis Mutation in JAK2, CALR, or MPL	Mean age >60 years old, male> female	Other myeloproliferativedisorders Radiation exposure Chemicals exposure	–	+	Nl	+	+	Nl	Nl	+	–	Pallor Bruising Skin nodules Insert paragraph Fatigue Abdominal pain Early satiety Dyspnea Lymphadenopathy	↓	↓	↑/↓	Low iron	Nl	↑	Nl	Dark urine	Proliferation and atypia of megakaryocytes Reticulin or collagen fibrosis Hypercellular bone marrow	Diffuse bone sclerosis on CT	Bone marrow biopsy	Thrombosis Variable risk for development of acute leukemia
	Primary splenic tumors		Lymphoid neoplasms Vascular neoplasms	Very rare	Positive family history	+	+	↓	+	–	Nl	Nl	–	–	Lymphadenopathy Dyspnea Shoulder pain Constipation Cachexia Pleural effusion	↓	↓	↓	Low iron, low ferritin	↑	↑	↑	Dark urine	Different histopathologic features depends on the type of tumor	Heterogeneous mass in the spleen on ultrasound Lymphomatous nodules and masses on CT scan	Biopsy	Metastasis to liver Poor prognosis
	Metastatic solid tumors		Bone marrowinfiltration Ineffective hematopoiesis Immune mediated	Any age, more in adults	Exposure to chemicals Radiation Pre-existent blood disorders	+	+	↓	+	+	↓	Nl	±	±	Petechiae Weakness	↓	↓	↓	Low iron, high ferritin	↑	↑	↑	Dark urine	Blast cells		Biopsy	Tumor lysis syndrome Infection CNS involvement DIC
	Disease		Etiology	Demography	History	Fever	Fatigue	Weight	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings
Infection	Viral	Hepatitis	Infection Autoimmune	Any age	High risk behaviors Close contact	+	+	↓	+	+	Nl	Nl	+	+	Lymphadenopathy Muscle weakness Joint swelling Focal neurologic signs Depends on etiology	↓	↓	↓	Nl	↑	↑	↑	Dark urine Hematuria	Pancytopenia	NA	Clinical manifestation + lab tests	Depends on etiology Encephalomyelitis
		Infectious mononucleosis	EBV	More common in children and young adults	Close contact	+	+	Nl	+	–	Nl	Nl	+	–	Sore throat Enlarged tonsils Lymphadenopathy Headache Maculopapular rash on the arms or trunk	↑	Nl	↑	Nl	↑	Nl	Nl	Nl	NA	NA	Clinical manifestation + heterophile antibody test	Splenic rupture Lymphocytosis Seizures
		Cytomegalovirus	CMV	More common in: Immunocompromised patients During pregnancy	Close contact	+	+	Nl	+	–	Nl	Nl	+	–	Exudative pharyngitis Symmetrical cervical adenopathy	↑	Nl	↑	Nl	↑	Nl	Nl	Nl	NA	NA	ELISA
	Bacterial	Salmonella	Salmonella	Any age	Eating contaminated meat, eggs, or milk	+	–	Nl	+	–	↓	Nl	–	–	Diarrhea Abdominal cramps Vomiting Dehydration	↑	Nl	↑	Nl	Nl	Nl	↑	Oliguria	NA	NA	Stool test	Typhoid fever Reactive arthritis Irritable bowel syndrome
		Brucella	Brucella	Any age	Ingesting contaminated food such as unpasteurized milk products Direct contact with an infected animal Inhalation of aerosols	+	+	Nl	+	–	↓	Nl	+	–	Headache Vomiting Diarrhea Constipation Arthralgia Night sweats Anorexia Foul-smelling perspiration	↑	Nl	↑	Nl	↑	Nl	Nl	Oliguria	NA	NA	Blood culture	Arthritis Epididymo-orchitis Spondylitis Neurobrucellosis Liver abscess formation Endocarditis
		Tuberculosis	Mycobacterium tuberculosis	Any age More common in developing countries and among immunocompromised patients	Close contact HIV	+	+	↓	+	–	↓	Nl	+	–	Chronic cough with blood-containing sputum Night sweats Anorexia Chest pain	↑	Nl	↑	Nl	↑	↑	↑	Oliguria	Acid-fast bacillus	Cavity on chest x ray	Identifying M. tuberculosis in a clinical sample	Tuberculous meningitis Urogenital tuberculosis Pott disease Miliary tuberculosis
	Parasitic	Malaria	Plasmodium	Worldwide More common in tropical and subtropical regions	Bitten by Anopheles mosquito	+	+	Nl	+	+	↓	Nl	+	–	Flu-like symptoms Headache Shivering Joint pain Vomiting	↑	↓	↑	Nl	↑	Nl	↑	Hemoglobinuria		NA
		Kala-azar	Leishmania	Any age	Bitten by sandflies	+	+	↓	+	+	↓	Nl	+	+	Asymptomatic Tender spleen Hepatomegaly	↓	↓	↓	Nl	↑	↑	↑	Hemoglobinuria	Visualization of the characteristic amastigote in smears or tissue	NA	Culture	Could be fatal
	Disease		Etiology	Demography	History	Fever	Fatigue	Weight	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings
Inflammation	Sarcoidosis		Immune mediated Unknown	Autoimmune disease More common in young African American women	Positive family history	+	+	↓	+	+	Nl	Nl	–	–	Bilateral hilar adenopathy Blurry vision Shortness of breath Cough Erythema nodosum	↑	↓	↑	Nl	Nl	Nl	Nl	Nl	NA	Bilateral hilar adenopathy on chest x-ray	Diagnosis of exclusion	Interstitial lung disease Systemic inflammatorydisease
	Serum sickness		Immune complex hypersensitivity (type III) to certain medications	Any age	Consumption of certain medications	+	+	Nl	+	–	↓	Nl	–	–	Rashes Itching Facial swelling Arthralgia Lymphadenopathy Dyspnea	↓ or ↑ Eosinophilia	↓	↑	Nl	Nl	Nl	↑	Proteinuria Hematuria	Plasma cells on peripheral blood smear Numerous histological changes including inflammation of arterial wall or fibrosis	NA	Clinical manifestation + recent medication consumption	Glomerulonephritis Shock
	Systemic lupus erythematosus		Immune mediated bone marrow failure	More common in young females	Positive family history	+	+	↓	+	+	Nl to ↓	Nl	+	+	Skin rash Mouth ulcers Chest pain Lymphadenopathy	↓	↓	↓		↑	↑	↑	Hemoglobinuria Proteinuria	Hypocellular bone marrow		Clinical findings + laboratory studies	Multi organ damage
	Felty syndrome		Immune mediated bone marrow failure	Rare autoimmune disease More common in females 50-70 years old	History of rheumatoid arthritis	+	+	↓	+	+	Nl to ↓	Nl	+	+	Pallor Skin hyperpigmentation Painful, stiff, and swollen joints Keratoconjunctivitis sicca	↓	↓	↓	Nl	Nl	Nl	Nl	Nl	Hypocellular bone marrow		Clinical findings + laboratory studies	Rheumatoid arthritis Infections
Infiltrative	Disease		Etiology	Demography	History	Fever	Fatigue	Weight	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings
	Gaucher disease		Accumulation of glucocerebroside	Autosomal recessive hereditary deficiency of the enzyme glucocerebrosidase More in Ashkenazi Jews	Positive family history	-	+	↓	+	+	Nl to ↓	Nl	+	+	Painful bone lesions Lymphadenopathy Yellowish-brown skin pigmentation	↓	↓	↓	Nl	Nl	↑	↑	Proteinuria Hematuria	Hypocellular bone marrow	NA	Enzyme testing	The most common of the lysosomal storage diseases Severe neurological complications Infections Osteoporosis
	Niemann-Pick disease		Mutations in the SMPD1 gene Deficiency in the activity of the lysosomal enzyme acid sphingomyelinase Accumulation of sphingomyelin	Autosomal recessive lysosomal storage disease More common in Ashkenazi Jews	Positive family history	-	+	↑	+	+	Nl to ↓	Nl	+	+	Unsteady gait Slurred speech Dysphagia Dystonia	↓	↓	↓	Nl	↑	↑	↑	Proteinuria Hematuria	Hypocellular bone marrow	NA	Genetic testing	CNS involvement Supranuclear gaze palsy Dementia Seizure Gelastic cataplexy Pulmonary infections Splenic rupture Coronary artery or valvular heart disease
	Langerhans cell histiocytosis		Clonal proliferation of Langerhans cells	Any age More common in children between 5-10 years old Boys>girls	-	-	+	↓	+	-	Nl	Nl	+	-	Painful bone swelling Scaly erythematous lesions Lymphadenopathy Cough Dyspnea	↓	↓	↓	Nl	↑	↑	↑	Proteinuria Hematuria	Birbeck granules on electron microscopy	Osteolytic lesions on imaging Lung nodules on imaging	Tissue biopsy	Diabetes insipidus
Category	Disease		Etiology	Demography	History	Fever	Fatigue	Weight	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings

Treatment

If the splenomegaly underlies hypersplenism, a splenectomy is indicated and it will correct the problem. After splenectomy, patients have an increased risk for infectious diseases. After splenectomy, patients should be vaccinated against Haemophilus influenzae and Streptococcus pneumoniae. They should receive annual influenza vaccination. Long-term prophylactic antibiotic should be given.