Autoimmune lymphoproliferative syndrome overview: Difference between revisions
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==Historical Perspective== | ==Historical Perspective== | ||
ALPS was first reported in 1967 by Canale and Smith; thus it was named initially as Canale and Smith syndrome. According to the 2010 revised guidelines, now [[ALPS]] is defined by the presence of [[chronic]], non-malignant, and non-infectious [[lymphadenopathy]] along with [[autoimmune]] [[cytopenias]]. ALPS was first explained in 1990 in a cohort of patients with chronic lymphoproliferation and increased numbers of double-negative T cells (DNTs). Also [[ALPS]] is associated with increased level of IL-10,IL-12,[[vitamin]] B 12, soluble FAS [[ligand]] and [[IgG]] in [[serum]]. [[In vitro]] [[evidence]] of defective FAS mediated [[apoptosis]] is also found in [[ALPS]]. | |||
==Classification== | ==Classification== | ||
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===Laboratory Findings=== | ===Laboratory Findings=== | ||
There is no single [[laboratory]] test to [[diagnose]] [[ALPS]]. [[Patients]] with suspected [[ALPS]] should get investigated for [[ALPS]] related [[mutations]]. | |||
===Imaging Findings=== | ===Imaging Findings=== | ||
Revision as of 02:30, 6 July 2021
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] David Teachey, MD [2]
Overview
Autoimmune lymphoproliferative syndrome is a form of lymphoproliferative disorder. It affects lymphocyte apoptosis. Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of abnormal lymphocyte survival caused defective Fas mediated apoptosis. ALPS was first reported in 1967 by Canale and Smith; thus it was named initially as Canale and Smith syndrome. According to the 2010 revised guidelines, now ALPS is defined by the presence of chronic, non-malignant, and non-infectious lymphadenopathy along with autoimmune cytopenias. ALPS was first explained in 1990 in a cohort of patients with chronic lymphoproliferation and increased numbers of double-negative T cells (DNTs). Also ALPS is associated with increased level of IL-10,IL-12,vitamin B 12, soluble FAS ligand and IgG in serum. In vitro evidence of defective FAS mediated apoptosis is also found in ALPS. For proper development of immune system and regulation of apoptosis FAS receptor pathway is very important. Heterozygous mutation in genes in the FAS pathway cause ALPS. Other different kinds of mutations also identified and gene based nomenclature is recommended nowadays to describe new cases. The true incidence and prevalence of ALPS are still not known due to the high rate of misdiagnosis or remain undiagnosed. FAS plays an important role in controlling the malignant transformation of lymphocytes. Hence, ALPS patients are at high risk of developing lymphoma. Germline FAS mutation is the most common while somatic mutation is the second most common cause. Many of the patients with ALPS have unidentified genetic defects. ALPS mostly occur in early childhood with a median age of 18 months. Common clinical features are chronic lymphadenopathy(95% of patients), splenomegaly(90% of patients), or hepatomegaly(40-50% of patients). Lymphoproliferation is the earliest symptom with a median age of onset is 11.5 months. Lymphoproliferation can get worsen in adolescence and eventually get resolved in early 20s.Most of the ALPS patients have non tender, enlarged lymph nodes for a prolonged duration. In ALPS, second most common clinical manifestations are related to autoimmunity as hemolytic anemia, thrombocytopenia and neutropenia. Cytopenias are accompanied with elevated or reduced serum IgG. Autoimmune cytopenias might be absent in the intital periods of ALPS but Coombs positive autoimmune hemolytic anemia and thrombocytopenia with or without autoantibodies might get detected even before any clinical manifestations. Autoimmune cytopenias can be asymptomatic to life threatening illiness. Treatment of cytopenias in ALPS may range from periodic treatment to chronic. Similar to lymphoproliferation, autoimmune cytopenias may improve with age but less chance of complete resolution by adulthood.10-20% of patients with ALPS can have autoimmune manifestations involving other organ systems such as skin rashes, pulmonary fibrosis, hepatitis, uveitis,colitis,pancreatitis,Systemic lupus erythematosus,Guillain-Barre syndrome, transverse myelitis, cerebellar ataxia and arthritis. Anticardiolipin antibodies are also commonly found but thromboembolic events are rare. The symptoms of lymphadenopathy, splenomegaly and autoimmune cytopenias in ALPS create a challenge to reach proper diagnosis as these symptoms overlap with other childhood hematologic disorders as histiocytosis,lymphoma,heredietary spherocytosis, Evans syndrome and Rosai-Dorfman syndrome. Immune disorders with autoimmune componenet as common variable immunodeficiency and Wiskott-Aldrich syndrome also should be excluded. According to the revised guideline in 2010, to diagnose ALPS there should be 2 required and 6 additional criterias.Required criterias are chronic Lymphadenopathy with or without splenomegaly and increased TCRαβ+ DNT cells in circulation. Primary additional criterias are abnormal lymphocyte apoptosis assay and the presence of pathogenic mutations in FAS gene.Definitive diagnosis of ALPS requires 2 required criteria and one of the two primary additional criteria. There is no single laboratory test to diagnose ALPS. Patients with suspected ALPS should get investigated for ALPS related mutations.Treatment of ALPS is focused mainly on immunosuppression to treat autoimmune symptoms as cytopenias and to avoid splenectomy. In severe cases of ALPS which are refractory to immunosuppressors, hematopoietic stem cell transplant is the final treatment of choice.
Historical Perspective
ALPS was first reported in 1967 by Canale and Smith; thus it was named initially as Canale and Smith syndrome. According to the 2010 revised guidelines, now ALPS is defined by the presence of chronic, non-malignant, and non-infectious lymphadenopathy along with autoimmune cytopenias. ALPS was first explained in 1990 in a cohort of patients with chronic lymphoproliferation and increased numbers of double-negative T cells (DNTs). Also ALPS is associated with increased level of IL-10,IL-12,vitamin B 12, soluble FAS ligand and IgG in serum. In vitro evidence of defective FAS mediated apoptosis is also found in ALPS.
Classification
Pathophysiology
Causes
Differentiating [Disease] from Other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
There is no single laboratory test to diagnose ALPS. Patients with suspected ALPS should get investigated for ALPS related mutations.
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Treatment of ALPS is focused mainly on immunosuppression to treat autoimmune symptoms as cytopenias and to avoid splenectomy. In severe cases of ALPS which are refractory to immunosuppressors, hematopoietic stem cell transplant is the final treatment of choice.