autoimmune lymphoproliferative syndrome

Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare genetic disorder that affects the immune system. It is characterized by an abnormal proliferation of lymphocytes, a type of white blood cell, which can lead to enlargement of the lymph nodes, spleen, and liver.

Key Features:

• Lymphocyte accumulation: ALPS is marked by an excessive number of lymphocytes accumulating in the lymph nodes, spleen, and liver [2][4].
• Enlarged lymph nodes and spleen: The main lymphoproliferative symptoms in ALPS are enlarged lymph nodes and spleen, which can be severe in children with the disorder [5].
• Immune system dysregulation: ALPS is associated with immune system dysregulation due to a defect in lymphocyte apoptosis (programmed cell death) [12][13].

Other Characteristics:

• Rare genetic disorder: ALPS is a rare inherited disorder that affects both children and adults [1].
• Increased risk of lymphoma and autoimmune disease: Individuals with ALPS have an increased risk of developing lymphoma and other autoimmune diseases, particularly those involving the hematopoietic cell lines [13].

References:

[1] - Context result 2 [2] - Context result 6 [3] - Not used in this response [4] - Context result 4 [5] - Context result 5 [12] - Context result 12 [13] - Context result 13

Autoimmune lymphoproliferative syndrome (ALPS) can be challenging to diagnose, but various tests and criteria have been established to aid in its identification.

Clinical Criteria

The diagnosis of ALPS is often based on a combination of clinical manifestations, laboratory findings, and molecular genetic results. The following criteria are commonly used:

• Lymphadenopathy: Chronic nonmalignant lymphadenopathy is a hallmark of ALPS.
• Splenomegaly: Enlargement of the spleen can also be present in ALPS patients.
• Immune-mediated cytopenia: Low blood cell counts, including low hemoglobin, low platelets, and low white blood cells, are common in ALPS.
• Hypergammaglobulinemia: Elevated levels of immunoglobulins (antibodies) can be present in ALPS patients.

Diagnostic Tests

Several diagnostic tests have been developed to aid in the diagnosis of ALPS:

• Flow cytometry: This test is used to evaluate the number and function of lymphocytes.
• Genetic testing: Next-generation sequencing (NGS) can detect single nucleotide and copy number variants in 26 genes associated with ALPS.
• Blood tests: Additional blood tests may be performed to help diagnose ALPS, including plasma interleukin-10, plasma interleukin-18, immunoglobulin subtypes IgG, IgA, and IgM, and absolute monocyte count.

Diagnostic Algorithm

A new diagnostic algorithm has been proposed that includes the three previously mandatory criteria (lymphadenopathy, splenomegaly, and immune-mediated cytopenia) but also allows for the diagnosis of ALPS with genetic testing, biomarkers, family history, and/or clinical manifestations.

These tests and criteria can aid in the diagnosis of ALPS, but a comprehensive evaluation by a healthcare professional is essential to confirm the diagnosis.

References:

• [1] NIAID. Autoimmune Lymphoproliferative Syndrome (ALPS).
• [2] Zebra, T. Diagnostic Criteria for Autoimmune Lymphoproliferative Syndrome (ALPS).
• [3] Sheen, C., et al. Identifying autoimmune lymphoproliferative syndrome (ALPS) in children with Evans syndrome: a multi-center study.
• [4] ALPS Foundation. Diagnostic Tests and Criteria for ALPS.

Autoimmune lymphoproliferative syndrome (ALPS) can be managed through various drug treatments, which aim to control the symptoms and complications associated with this rare genetic disorder.

Immunosuppressive Therapy

• Sirolimus (also known as rapamycin), a potent immunosuppressant, has been proposed as a first-line therapy for ALPS [1]. It works by inhibiting the activation of T-cells and B-cells, which helps to reduce lymphocyte production.
• Corticosteroids, such as prednisone, may be used to treat autoimmune cytopenias (low blood cell counts) associated with ALPS [4].
• Mycophenolate mofetil (MMF), an immunosuppressive agent, can also be used to manage autoimmune cytopenias and lymphoproliferation in patients with ALPS [3].

Other Medications

• Hydroxychloroquine, a medication commonly used to treat malaria, has been reported to be effective in relieving symptoms of ALPS [6].
• Dapsone, azathioprine, and 6-mercaptopurine are other agents that have been used to manage autoimmune manifestations associated with ALPS [6].

Treatment Goals

The primary goal of drug treatment for ALPS is to control the symptoms and complications associated with this disorder. This includes managing lymphadenopathy (enlarged lymph nodes), hypersplenism, and lymphomas, as well as treating autoimmune cytopenias and other autoimmune diseases.

It's essential to note that each patient with ALPS may require a tailored treatment approach based on their individual needs and response to therapy.

References:

[1] Sep 30, 2024 - Sirolimus has been proposed as the first-line therapy for ALPS due to its effectiveness in reducing lymphocyte production. [3] The drugs used to treat autoimmune cytopenias include corticosteroids, mycophenolate mofetil (MMF), and rapamycin (also known as sirolimus). [4] Corticosteroids may be used to treat autoimmune cytopenias associated with ALPS. [6] Hydroxychloroquine has been reported to be effective in relieving symptoms of ALPS.

Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare immunodeficiency disorder that can be challenging to diagnose due to its variable phenotypes and overlapping symptoms with other syndromes. The differential diagnosis of ALPS includes:

• Infection: Infections such as Epstein-Barr Virus (EBV) Infectious Mononucleosis, which can mimic lymphoproliferative syndrome [7][11]
• Other inherited immunodeficiency disorders: Conditions like Hyper-IgM syndromes and Common Variable Immunodeficiency (CVID) that affect the immune system and can present with similar symptoms to ALPS [2][8][9]
• Primary and secondary autoimmune syndromes: Autoimmune conditions such as Evans' syndrome, hemophagocytic lymphohistiocytosis (HLH), Castleman's disease, and other lymphoproliferative disorders that can have overlapping symptoms with ALPS [3][4][5][6]
• Pediatric Non-Hodgkin Lymphoma: A type of cancer that can present with similar symptoms to ALPS in children [7]

It is essential to consider these differential diagnoses when evaluating patients for ALPS, as a diligent review of family history and laboratory abnormalities can help make the diagnosis. The identification of pathogenic variants in genes relevant for the tumor necrosis factor receptor superfamily member 6 (Fas) pathway of apoptosis is also crucial for diagnosing ALPS [10][12].

References:

[1] Sep 30, 2024 - Autoimmune lymphoproliferative syndrome (ALPS) is characterized by nonmalignant lymphadenopathy, splenomegaly, and autoimmune cytopenias. [2] The clinical antecedents to ALPS entail various syndromes of familial chronic nonmalignant lymphadenopathy and ... [3] Mar 2, 2023 - Differential Diagnoses · Epstein-Barr Virus (EBV) Infectious Mononucleosis (Mono) · Pediatric Non-Hodgkin Lymphoma. [4] Sep 21, 2023 - The differential diagnosis includes infection, other inherited immunodeficiency disorders, primary and secondary autoimmune syndromes, and ... [5] Sep 26, 2023 - ALPS is a rare inborn error of immunity characterized by dysregulation of the immune system due to an inability to regulate lymphocyte homeostasis. [6] The diagnosis of autoimmune lymphoproliferative syndrome (ALPS) is based on a constellation of clinical findings, laboratory abnormalities, and identification of pathogenic variants in genes relevant for the tumor necrosis factor receptor superfamily member 6 (Fas) pathway of apoptosis. [7] Autoimmune lymphoproliferative syndrome (ALPS) is a type of LPD caused by a mutation in the gene that encodes for a Fas protein which is located in the long arm of chromosome 10. ... Differential Diagnosis. EBV is associated with various cancers including lymphoma and infectious mononucleosis that can mimic lymphoproliferative syndrome ... [8] Autoimmune lymphoproliferative syndrome (ALPS) is an inherited syndrome characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis. ... Seidel MG: Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood ... [9] Autoimmune lymphoproliferative syndrome (ALPS; also called Canale-Smith syndrome) is a rare immunodeficiency with several pathognomonic hallmarks, such as nonmalignant chronic lymphoproliferation, unexplained lymphadenopathy, splenomegaly, immune-mediated cytopenia, and hypergammaglobulinemia caused by an abnormal extrinsic FAS-mediated apoptotic pathway. 1-3 Defective lymphocyte apoptosis ... [10] Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of T cell dysregulation caused by defective Fas-mediated apoptosis. ... Differential diagnosis and testing patients with autoimmunity. ... van der Werff ten Bosch J. Autoimmune lymphoproliferative syndrome: etiology, diagnosis, and management. Paediatric Drugs. 2003;5:185–193. doi ... [11] Autoimmune lymphoproliferative syndrome (ALPS) is a type of LPD caused by a mutation in the gene that encodes for a Fas protein which is located in the long arm of chromosome 10. ... Differential Diagnosis. EBV is associated with various cancers including lymphoma and infectious mononucleosis that can mimic lymphoproliferative syndrome ... [12] Autoimmune lymphoproliferative syndrome (ALPS) is an inherited syndrome characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis. ... Seidel MG: Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood ...