What is autoimmune lymphoproliferative syndrome (ALPS)?

Updated: Jul 29, 2019
  • Author: Akaluck Thatayatikom, MD, RhMSUS; Chief Editor: Harumi Jyonouchi, MD  more...
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Answer

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of lymphocyte homeostasis. It is defined as a chronic (>6 months) non-malignancy and non-infectious uncontrolled proliferation of lymphocytes commonly accompanied by autoimmune manifestations, lymphadenopathy, splenomegaly, and susceptibility to malignancies. [1] ALPS is the first disease known to be caused by a primary defect in programmed cell death and the first description of a monogenic cause of autoimmune disease. The first genetic defect was described in 1995 by the discovery of the FAS gene mutation. [2] Other ALPS-associated genetic defects in the apoptotic pathway and ALPS-like disorders (ALPS-related syndromes) have subsequently been identified.

An illustrative case of ALPS is as follows:

  • A 10-year-old male presented with a history of lymphadenopathy, splenomegaly, and onset of multilineage cytopenias as an infant, with subsequent splenectomy at age 13 months

  • After undergoing the splenectomy, the patient developed pneumococcal meningitis, which led to hearing loss that required a cochlear implant

  • Subsequently, the patient experienced several episodes of pneumococcal sepsis, chronic osteomyelitis, profound neutropenia, vasculitis, autoimmune hemolytic anemia, and thrombocytopenia, with many hospitalizations and intensive care unit (ICU) admissions for treatment of these complications

This patient’s repeated infections with encapsulated organisms highlight the importance of maintaining the spleen in ALPS patients, if possible. The constellation of lymphadenopathy, splenomegaly, and autoimmune cytopenias necessitating long-term immunosuppressive treatment with mycophenolate mofetil makes diagnosis and management of these patients quite challenging.


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