From the Guidelines
Autoimmune Lymphoproliferative Syndrome (ALPS) is characterized by symptoms including lymphadenopathy, splenomegaly, and autoimmune cytopenias, which can lead to significant morbidity and mortality if left untreated. The primary symptoms of ALPS include:
- Enlarged lymph nodes (lymphadenopathy)
- An enlarged spleen (splenomegaly)
- Autoimmune conditions, particularly autoimmune cytopenias such as hemolytic anemia, thrombocytopenia, and neutropenia, which can cause fatigue, easy bruising, and increased susceptibility to infections 1
- Some patients may experience skin rashes or other dermatological manifestations
- ALPS patients have an increased risk of developing lymphoma and other cancers, as noted in the 2010 study published in Blood 1
These symptoms occur because ALPS is caused by genetic mutations affecting the FAS-mediated apoptosis pathway, which normally regulates lymphocyte death, leading to the accumulation of unusual double-negative T cells and impaired lymphocyte homeostasis, resulting in immune dysregulation 1. The diagnosis of ALPS is based on revised diagnostic criteria, which include required criteria such as chronic lymphadenopathy or splenomegaly and elevated CD3+TCRαβ+ CD4-CD8- DNT cells, as well as accessory criteria such as defective lymphocyte apoptosis and somatic or germline pathogenic mutation in FAS, FASLG, or CASP10 1.
The diagnosis and treatment of ALPS should be guided by the most recent and highest quality evidence, with a focus on reducing morbidity, mortality, and improving quality of life. Treatment is typically supportive and may include immunosuppressive medications like corticosteroids, mycophenolate mofetil, or sirolimus to control autoimmune manifestations, though specific treatment depends on the severity and specific symptoms present 1.
From the Research
Symptoms of Autoimmune Lymphoproliferative Syndrome (ALPS)
The symptoms of ALPS include:
- Noninfectious and nonmalignant lymphadenopathy 2, 3, 4
- Splenomegaly 2, 3, 5, 4
- Autoimmune pathology, most commonly autoimmune cytopenias 2, 3, 4
- Multilineage cytopenias due to splenic sequestration and/or autoimmune destruction 3, 5
- Hepatosplenomegaly 3, 5
- Autoimmune hemolytic anemia (AIHA) 3, 5
- Immune-mediated thrombocytopenia 3, 5
- Autoimmune neutropenia 3
Rare Complications
Rarely, patients with ALPS may develop: