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Splenomegaly: Investigation, Diagnosis and Management

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Splenomegaly: Investigation, Diagnosis and Management Blood Reviews 23 (2009) 105–111 Contents lists available at ScienceDirect Blood Reviews journal homepage: www.elsevier.com/locate/blre REVIEW Splenomegaly: Investigation, diagnosis and management Anna L. Pozo a,c, Edmund M. Godfrey b,d, Kristian M. Bowles a,* a Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, United Kingdom b Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom article info summary Keywords: Splenomegaly is a feature of a broad range of diseases, and presents to clinicians in many fields. This Spleen review examines the aetiology of splenomegaly in the developed world, and describes a logical approach Splenomegaly to the patient with splenomegaly. In some patients, extensive radiological and laboratory investigations Spleen radiology will fail to yield a diagnosis: these cases of ‘‘isolated” splenomegaly are not uncommon and can be par- Splenic biopsy ticularly challenging to manage. The risks of serious underlying disease must be balanced against the Diagnostic splenectomy risks of invasive investigations such as splenic biopsy and diagnostic splenectomy. We discuss the options in isolated splenomegaly and their evidence base, and incorporate them into a management strategy to aid the clinician in cases of diagnostic difficulty. Ó 2008 Elsevier Ltd. All rights reserved. Introduction assessment.4 While clinical examination can be convincing in mas- sive splenic enlargement, radiology is often needed to confirm the The patient with splenomegaly can present as a diagnostic chal- diagnosis. A single radiological definition of normal splenic size has lenge to a wide variety of clinicians. The list of conditions associ- not been adopted, and the assessment is often partly subjective.5–7 ated with splenomegaly is extensive, and as noted by William On ultrasound examination, ‘‘craniocaudal length” is used most Osler in 1908, ‘‘nearly all diseases of the spleen are of a secondary often to measure splenic size; this correlates well with splenic vol- nature”.1 A patient presenting with splenomegaly may therefore ume, particularly when the right lateral decubitus position is have a collection of symptoms, signs and test results that are com- adopted.5 However, the quoted upper limit of normal varies from mon to various diseases: some benign and self-limiting, some 11 to 14 cm.6,8 Other ultrasonographic indicators of splenomegaly infective and others malignant. The clinician must adopt a system- include an anteroposterior measure greater than two thirds of the atic approach to identify serious disease, whilst minimising unnec- distance between the anterior and posterior abdominal wall,6 or essary investigations and anxiety for the patient. A century after complex formulae can be used to estimate splenic volume.7 With Osler, this review examines the tools that are available in this diag- CT examination, splenic length, the ‘‘splenic index” (product of nostic pathway, and suggests a safe management strategy for those length, depth and width) and the sum of volumes of consecutive challenging patients with isolated splenomegaly. scan slices have all been used.6 Radiological confirmation of splenomegaly may therefore depend both on the radiologist’s pre- Defining splenomegaly ferred method and a degree of subjective judgement. A maximum length of 13 cm is a typical limit. The ‘‘gold-standard” definition of splenomegaly is splenic weight: the normal adult spleen weighs about 50–250 g, and this decreases with age.2 This can clearly only be established at sple- Aetiology and epidemiology of splenomegaly nectomy or post mortem examination, and it is surprisingly diffi- cult to establish a practical clinical definition of splenomegaly. The conditions associated with splenomegaly are shown in Ta- The clinical finding of a palpable spleen was previously consid- ble 1. There is limited recent information from developed countries ered to be evidence of splenic enlargement,3 but up to 16% of pal- on its epidemiology. Looking at unselected healthy populations, pable spleens have been found to be of normal size on radiological the prevalence of a palpable spleen in college freshmen was found to be 2.9% in 1966; none of these subjects developed malignant disease at follow-up of 10 years.9 Prospective studies in unselected * Corresponding author. Tel.: +44 01603 286286x6750; fax: +44 01603 286918. medical outpatients found palpable spleens in 2–5.6% of patients, E-mail addresses: [email protected] (A.L. Pozo), edgodfrey@doctors. org.uk (E.M. Godfrey), [email protected] (K.M. Bowles). with an unknown aetiology after basic investigations in 25–41% 3 c Tel.: +44 07780 603735; fax: +44 01603 286918. of cases. In many of these patients splenomegaly was not d Tel.: +44 07971 475645. confirmed radiologically. More recent small studies describe 0268-960X/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.blre.2008.10.001 106 A.L. Pozo et al. / Blood Reviews 23 (2009) 105–111 Table 1 recognise multi-system disorders such as the collagen diseases Diseases associated with splenomegaly. and sarcoidosis. The past medical history may suggest the cause Category Groups Examples of splenomegaly, though further investigations will be indicated Infection Acute Infectious mononucleosis, viral hepatitis, if the presentation is unusual (e.g. massive splenomegaly in a pa- septicaemia, typhoid, cytomeglalovirus, tient with mild congestive cardiac failure). A family history should toxoplasmosis be carefully elicited, such as of malignancy or anaemia, while Subacute/chronic Tuberculosis, subacute bacterial remembering that individuals with autosomal recessive conditions endocarditis, brucellosis, syphilis, HIV like Gaucher’s disease often have no affected family members. Risk Tropical/parasitic Malaria, leishmaniasis, schistosomiasis factors should be identified for liver disease, particularly alcohol Haematological Myeloproliferative Myelofibrosis, chronic myeloid leukaemia intake, and for infectious diseases (travel, sexual contacts, intrave- (CML), polycythaemia vera, essential thrombocytosis nous drug use, exposure to animals and predisposition to infective Lymphoma Non-Hodgkin lymphoma (NHL), Hodgkin endocarditis). lymphoma Physical examination will typically confirm palpable spleno- Leukaemia Acute leukaemia, chronic lymphocytic megaly, depending on the degree of enlargement and body habitus. leukaemia (CLL), hairy cell leukaemia, prolymphocytic leukaemia General examination may reveal fever, lymphadenopathy, anae- Congenital Hereditary spherocytosis, thalassaemia, mia, signs of hepatic or inflammatory disease, stigmata of endocar- HbSC disease ditis, or involvement of any other organ system. The difficulty with Others Autoimmune haemolysis, megaloblastic splenomegaly is that many signs and symptoms that may be elic- anaemia ited are common to various conditions. Most patients require at Congestive Cirrhosis, splenic/portal/hepatic vein least preliminary laboratory and radiological investigations, as thrombosis or obstruction, congestive shown in Table 2. This list is not exhaustive, and additional inves- cardiac failure tigations may be indicated by specific clinical findings. Inflammatory Collagen diseases Systemic lupus erythematosus, rheumatoid Even if initial assessment does not identify the cause of spleno- arthritis (Felty’s) Granulomatous Sarcoidosis megaly, certain parameters may narrow the differential diagnosis. In studies of inpatients with splenomegaly, haematological dis- Neoplastic Haemangioma, metastases (lung/breast carcinoma, melanoma) eases were positively associated with lymphadenopathy, massive Infiltrative Gaucher’s disease, amyloidosis splenomegaly and ‘‘cytoses” (erythrocytosis, leucocytosis, throm- Miscellaneous Cysts bocytosis, marked left shift of the neutrophilic leucocytes or marked reticulocytosis).12 84% of cases with progressive splenic enlargement were associated with haematological disease, pre- dominantly malignancy.11 Infectious diseases showed positive asymptomatic young men in whom significant, persistent spleno- associations with fever, and hepatic diseases with abnormal liver megaly was detected on clinical and radiological examination, with normal investigations including bone marrow, liver and rectal biopsies.10 Since many of these patients remained well for over 10 years, there does seem to be a group of individuals with benign Table 2 Initial investigations in the patient with splenomegaly. splenomegaly, but the prevalence is not clear. The frequency and causes of splenomegaly have now been stud- In most patients In selected patients (depending on clinical ied retrospectively in US hospital inpatients.11–13 The estimated features) incidence from 1963 to 1995 was 0.3% of admissions and a diagno- Haematology sis was reached in 98%, but 12% required a diagnostic splenec- Full blood count Direct antiglobulin test Peripheral blood film Reticulocyte count tomy.11 Of all patients with splenomegaly, haematological ESR Malaria blood film disease was found in 16–66%, hepatic disease in 9–41%, infectious Clotting screen Haemoglobin electrophoresis/HPLC disease in 9–36%, congestive or inflammatory disease in 4–10% and Biochemistry 11–13 primary splenic disease (e.g. storage disease) in 1–6%. Within Urea and electrolytes Serum ACE the haematological disorders, the most common diagnoses were Liver function tests Serum protein electrophoresis lymphoma (16–44% of all splenomegaly), CML (8–29%), haemoglo- C-reactive protein Urine Bence Jones protein binopathy (7–25%),
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