Autoimmune lymphoproliferative syndrome (ALPS) is a form of lymphoproliferative disorder (LPDs). It affects lymphocyte apoptosis.It is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Normally, after infectious insult, the immune system down-regulates by increasing Fas expression on activated B and T lymphocytes and Fas-ligand on activated T lymphocytes. Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this apoptotic pathway, leading to chronic non-malignant lymphoproliferation, autoimmune disease, and secondary cancers. Signs and symptoms
All people with ALPS have signs of lymphoproliferation, which makes it the most common clinical manifestation of the disease. The increased proliferation of lymphoid cells can cause the size of lymphoid organs such as the lymph nodes and spleen to increase (lymphadenopathy and splenomegaly, present in respectively over 90% and over 80% of patients). The liver is enlarged (hepatomegaly) in 30–40% of patients.Autoimmune disease is the second most common clinical manifestation and one that most often requires treatment. The most common autoimmune presentations include autoimmune cytopenias, which can be mild to very severe and intermittent or chronic. These include autoimmune hemolytic anemia, autoimmune neutropenia, and autoimmune thrombocytopenia. Other autoimmune manifestations can be similar to systemic lupus erythematosus (least common, affecting <5% of patients). Manifestations within the nervous system can include autoimmune cerebellar ataxia, Guillain–Barré syndrome, and transverse myelitis. Manifestations in the gastrointestinal system can include atrophic gastritis, and autoimmune hepatitis, esophagitis, colitis, and pancreatitis.
A probable diagnosis is the same but with one secondary accessory criterion. Classification
2003 nomenclature
IA - Fas
IB - Fas ligand
IIA - Caspase 10
IIB  - Caspase 8
III - unknown
IV - Neuroblastoma RAS viral oncogene homologRevised nomenclature (2010)
ALPS-FAS: Fas. Germline FAS mutations. 70% of patients. Autosomal dominant. Dominant negative and haploinsufficient mutations described. ALPS-sFAS: Fas. Somatic FAS mutations in DNT compartment. 10% of patients
ALPS-FASL: Fas ligand. Germline FASL mutations. 3 reported cases
ALPS-CASP10: Caspase 10. Germline CASP10 mutation. 2% of patients
ALPS-U: Undefined. 20% of patients
CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder
RALD: NRAS, KRAS. Somatic mutations in NRAS and KRAS in lymphocyte compartment. No longer considered a subtype of ALPS but distinct disease

Treatment
Treatment is most commonly directed at autoimmune disease and may be needed to treat bulky lymphoproliferation. First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes.Second line therapies include: mycophenolate mofetil (cellcept) which inactivates inosine monophosphate, most studied in clinical trials with responses varying (relapse, resolution, partial response). It does not affect lymphoproliferation or reduce DNTs, with no drug-drug interactions. This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy.