Diagnostic approach to the child with unexplained splenomegaly*

EBV: Epstein-Barr virus; CMV: cytomegalovirus; CXR: chest radiograph; LCH: Langerhans cell histiocytosis; HLH: hematophagocytic lymphohistiocytosis; ALPS: autoimmune lymphoproliferative syndrome; POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes; CT: computed tomography; ALL: acute lymphoblastic leukemia; AML: acute myelogenous leukemia; CBC: complete blood count; TB: tuberculosis; IV: intravenous; SLE: systemic lupus erythematosus; ANA: antinuclear antibody; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; CVID: common variable immunodeficiency; LFTs: liver function tests; U/S: ultrasound; RBC: red blood cell; G6PD: glucose-6-phosphate dehydrogenase; LDH: lactate dehydrogenase; MRI: magnetic resonance imaging.
* The evaluation of a child with unexplained splenomegaly generally includes history, physical examination, CBC (with platelet count and differential), reticulocyte count, review of the peripheral smear, LFTs, serologies for EBV and CMV, CXR, and abdominal U/S (with Doppler imaging). The diagnosis may be apparent from the initial evaluation (eg, physical examination may reveal clear signs mononucleosis; CBC may reveal peripheral blasts; abdominal U/S may reveal portal hypertension, portal thrombosis, or discrete splenic lesion). In most cases, additional testing is needed to confirm the specific diagnosis. If the work-up for the suspected etiology is negative, additional evaluation for other etiologies is generally warranted.