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Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis

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

INTRODUCTION

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by dysregulation of the immune system due to an inability to regulate lymphocyte homeostasis through the process of lymphocyte apoptosis (a form of programmed cell death). The consequences of this include lymphoproliferative disease, manifested by lymphadenopathy, hepatomegaly, splenomegaly, and an increased risk of lymphoma, as well as autoimmune disease, typically involving blood cells.

This topic reviews the clinical features and diagnosis of ALPS. The epidemiology, genetics, pathogenesis, management, and prognosis of ALPS are discussed separately. (See "Autoimmune lymphoproliferative syndrome (ALPS): Epidemiology and pathogenesis" and "Autoimmune lymphoproliferative syndrome (ALPS): Management and prognosis".)

CLINICAL MANIFESTATIONS

In the two largest cohorts of patients with ALPS, the French cohort and National Institutes of Health (NIH) cohort, disease onset was most commonly marked by lymphoproliferation with generalized adenopathy and hepatosplenomegaly at a median age of 2.7 to 3 years [1,2]. Patients with later disease onset often presented with autoimmune manifestations rather than lymphoproliferative disease.

ALPS due to mutations in the FAS gene that encodes an apoptosis-associated antigen (ALPS-FAS) is the most common and best-characterized type of ALPS, although it is nonetheless a rare condition. The following are the main consequences of perturbed lymphocyte homeostasis in ALPS-FAS.

Chronic nonmalignant lymphoproliferation — Expansion and persistence of lymphocyte populations that are not eliminated through apoptosis affect the lymphoid compartment, resulting in chronic lymphadenopathy, splenomegaly with or without premature destruction of blood cells (hypersplenism), and, less frequently, hepatomegaly. The lymphoproliferation typically manifests in the first years of life in individuals with ALPS-FAS. In some individuals, splenomegaly is the predominant or only manifestation of lymphoproliferation [3,4].

                         

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Literature review current through: Jun 2017. | This topic last updated: Dec 20, 2016.
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