Splenomegaly in Children and Adolescents

Abstract

In contrast to other lymphoid tissues making up the immune system, the spleen as its biggest organ is directly linked into the blood circulation. Beside its main task to filter out microorganism, proteins, and overaged or pathologically altered blood cells, also humoral and cellular immune responses are initiated in this organ. The spleen is not palpable during a physical examination in most but not all healthy patients. A correct diagnosis of splenomegaly in children and adolescents must take into account age-dependent size reference values. Ultrasound examination is nowadays used to measure the spleen size and to judge on reasons for morphological alterations in associated with an increase in organ size. An enormous amount of possible causes has to be put in consideration if splenomegaly is diagnosed. Among these are infectious agents, hematologic disorders, infiltrative diseases, hyperplasia of the white pulp, congestion, and changes in the composition and structure of the white pulp by immunologically mediated diseases. This review attempts to discuss a comprehensive list of differential diagnoses to be considered clinically in children and young adolescents.

Keywords: adolescence; childhood; hematologic disorders; immunological disorders; infections; infiltrative diseases; pathophysiology; splenomegaly.

Figure 1

Range of spleen size (longitudinal diameter) assessed by ultrasound examination according to age in Caucasians (For details see Table 2, normal range denotes the 2.5th to 97.5th percentiles). Figure modified from (3).

Figure 2

(A) Organization of macroscopic visible structures in the human spleen and schematic presentation of blood vessels and white and red pulp. Original photo from (6). (B) Schematic diagram of the microstructure of the spleen. For details see text. (C) Schematic drawing of a venous sinus located in the red pulp cords. Blood cells from the cords are only collected into the venous sinuses if they manage to pass the slits between the endothelial cells (shown by red arrows). Figure modified from (7).

Figure 3

Algorithms for a non-evidence based diagnostic approach toward a pediatric or adolescent patient presenting with splenomegaly on physical examination. Diagnostic steps are grouped into 1st line, 2nd line, and 3rd line approaches. The extensive list of differential diagnoses excludes more detailed information in this flow chart for which the reader is kindly referred to the text and to Table 3 of this review. ALPS, autoimmune lymphoproliferative syndrome; CRP C, reactive protein; EMA, eosin-5'-maleimide; FMF, familial Mediterranean fever; Hb, hemoglobin; HLH, hemophagocytic lymphohistiocytosis; juv., juvenile; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; SLE, systemic lupus erythematosus; SSc, systemic sclerosis.