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X-linked lymphoproliferative disease

Author
Jack JH Bleesing, MD, PhD
Section Editor
Jennifer M Puck, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

X-linked lymphoproliferative disease (XLP, also called Duncan disease) is a rare disorder that was first identified by Purtillo, et al in the Duncan family, in which 6 of 18 males died of lymphoproliferative disease, including fulminant infectious mononucleosis (FIM) and lymphoma [1,2]. It is caused by mutations in the signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) gene [3,4].

XLP is characterized by severe dysregulation of the immune system, often but not always in response to Epstein-Barr virus (EBV) infection. The three most common clinical manifestations are FIM, dysgammaglobulinemia, and lymphoma, usually of B cell origin [5]. Additional presentations include lymphocytic vasculitis, aplastic anemia, and lymphomatoid granulomatosis [6,7].

X-linked inhibitor of apoptosis (XIAP) deficiency was initially considered a form of XLP (XLP type 2, or XLP2) [8,9]. However, after further characterization of the disorder, it appears that XIAP deficiency may be better classified as X-linked familial hemophagocytic lymphohistiocytosis (HLH) [10,11]. (See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis", section on 'Genetics'.)

This topic will review the pathogenesis, clinical manifestations, diagnosis, and management of XLP. Other combined immunodeficiencies are discussed separately. (See "Combined immunodeficiencies".)

EPIDEMIOLOGY

XLP is estimated to affect one to three of every million males [12,13]. However, the disease is probably underreported since males with fatal fulminant infectious mononucleosis (FIM) are not always evaluated for XLP [14]. There is no racial or ethnic predilection [12,13].

                     

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Literature review current through: Nov 2016. | This topic last updated: Tue Jun 14 00:00:00 GMT 2016.
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References
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