Which clinical history findings are characteristic of autoimmune lymphoproliferative syndrome (ALPS)?

Updated: Jul 29, 2019
  • Author: Akaluck Thatayatikom, MD, RhMSUS; Chief Editor: Harumi Jyonouchi, MD  more...
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The initial presentations of ALPS are often that of persistent lymphadenopathy (>95%) or splenomegaly (>90%) followed by autoimmunity (>70%) and hepatomegaly (50%) in an otherwise healthy child. [15, 16] Patients with germline FAS mutations typically present earlier than somatic FAS mutations; however, both mutations have the same clinical manifestations. [40]

The majority of patients develop lymphoproliferation at a young age (median age of 11.5 months) without associated constitutional symptoms. To meet the case definition of ALPS, a patient must have chronic, nonmalignant lymphadenopathy, or splenomegaly that lasts for 6 months or longer. The lymphoproliferation can wax and wane randomly before resolving in most patients after 20 years of age. [6]

Autoimmunity is the second most common clinical presentation, especially autoimmune cytopenias in one or more cell lineages. Autoimmune hemolytic anemia and autoimmune thrombocytopenia are more common than autoimmune neutropenia. The multilineage cytopenias often noticed in ALPS result from splenic sequestration, as well as from underlying autoimmune processes. [1] The symptoms related to cytopenia are pallor, petechiae, bleeding, icterus, fatigue, and recurrent infections. A family history of similar disorders may be noted; these are usually inherited in an autosomal dominant fashion. A thorough review of a patient’s extended family for a history of adenopathy, cytopenias, splenectomies, or lymphoma can provide clues in diagnosing ALPS.

Other autoimmune diseases occur in 10–20% of ALPS and can affect any organ system. The most common are skin rashes, immune-mediated pulmonary fibrosis, autoimmune thyroiditis, uveitis, Guillain-Barre syndrome, autoimmune hepatitis, nephristis, gastritis, pancreatitis, colitis, transverse myelitis, cerebellar ataxia, myocarditis, and arthritis. [6]

Careful attention to the development of systemic B symptoms (e.g., fever, drenching night sweats, pruritus, and weight loss) is essential for cancer surveillance in those at high-risk for B cell lymphoma.

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