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Autoimmune lymphoproliferative syndrome

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Related terms
Background
Signs and symptoms
Diagnosis
Complications
Treatment
Integrative therapies
Prevention
Author information
Bibliography
Causes
Risk factors

Related Terms
  • ALPS, antibody, autoimmune condition, Canale-Smith Syndrome, fas, immune system, lymph node, lymphocyte, platelet, red blood cell, spleen, steroids, white blood cell.

Background
  • Autoimmune lymphoproliferative syndrome (ALPS) is a rare autoimmune condition that usually develops in early childhood (before five years of age) and that affects both children and adults. In patients who develop the disease later in life, the symptoms are usually not as severe. ALPS is an inherited condition that affects both sexes.
  • Normally, the immune system attacks foreign invaders, such as bacteria. An autoimmune condition occurs when the immune system malfunctions and begins to attack normal components of the body. Antibodies are a normal component of the immune system that normally attack foreign invaders to help destroy them and protect the body. In patients with ALPS, there are increased numbers of lymphocytes, a type of white blood cell that makes antibodies. Some of the antibodies produced by the extra lymphocytes attack normal components of the body (because the antibodies are able to recognize proteins on these components), causing them to malfunction.
  • In patients with ALPS, antibodies commonly attack red blood cells, which transport oxygen throughout the body, and platelets, which help with clotting. However, the antibodies may attack cells in almost any location throughout the body, such as the skin, kidney, liver, or nerves. Patients with ALPS may have a wide spectrum of symptoms, depending on which components of the body have been attacked by the immune system. Some common symptoms may include weakness (due to reduced numbers of red blood cells), bruises or nosebleeds (due to reduced numbers of platelets), or increased risk of bacterial infection (due to decreased numbers of white blood cells).
  • ALPS generally does not lead to death and most individuals with ALPS are able to live normal lives. Currently, there is no known cure for ALPS. However, treatments exist that may help patients manage some of the symptoms of ALPS, including steroids that suppress the immune system.

Signs and symptoms
  • Patients with autoimmune lymphoproliferative syndrome (ALPS) may have a wide spectrum of symptoms, depending on which component(s) of the body have been compromised by the immune system. In individuals with ALPS, antibodies commonly attack red blood cells, which transport oxygen throughout the body, or platelets, which help in clotting. However, the antibodies may attack cells in almost any location throughout the body, such as the skin, kidney, liver, or nerves. Additional symptoms that patients may experience are highly specific based on the other type(s) of cells that are attacked.
  • If the immune system attacks red blood cells, patients with ALPS may have a reduction in red blood cell number. Because red blood cells normally transport oxygen to other cells in the body, this may lead to fatigue or weakness. Symptoms that patients with ALPS may develop include an enlarged spleen (due to more blood cells getting stuck there) or enlarged lymph nodes.
  • If the immune system attacks platelets, patients with ALPS will have a reduction in the number of platelets. Platelets are blood cells that help with the process of clotting. A reduction in platelets may lead to bruises, nosebleeds, increased risk of hemorrhage (excessive bleeding), or the formation of small red or purple spots on the skin called petechiae.
  • Skin rashes are frequently observed in patients with ALPS, likely due to autoimmune attacks on the skin.
  • In some patients with ALPS, antibodies may attack other white blood cells that normally fight disease or infection. This can lead to a reduction in the numbers of white blood cells, leaving an individual more susceptible to bacterial infection. Common symptoms of a bacterial infection include fever, sweating, chills, and fast breathing.

Diagnosis
  • Autoimmune lymphoproliferative syndrome (ALPS) is a newly described disease and many of the symptoms are not specific to just ALPS. Therefore, it may be difficult for a doctor to diagnose ALPS without knowledge of the disease and its symptoms.
  • Clinical exam: A diagnosis is often made based on a clinical examination to check for symptoms of the disease. Symptoms that a doctor may look for to diagnose ALPS include an enlarged spleen (due to more blood cells getting stuck there), enlarged lymph nodes, skin rash, and frequent nose bleeds.
  • Blood tests: Patients with ALPS often have reduced numbers of red blood cells and increased numbers of certain types of white blood cells. Blood may be drawn from patients to check for these signs of the disease.
  • Genetic tests: Most patients with ALPS have a mutation, or error, in a gene called Fas. In patients who exhibit symptoms of ALPS, genetic testing may be used to look for a mutation in Fas and help diagnose the condition.
  • Cellular assays: Experiments may be performed on the lymphocytes of patients who are suspected to have ALPS to confirm a diagnosis. The lymphocytes of most patients with ALPS undergo decreased levels of cellular death, due to a defect, or mutation, in the Fas gene. A patient's lymphocytes can be tested in a laboratory using a cellular assay, to determine if the lymphocytes undergo decreased levels of death due to this mutation.

Complications
  • Enlarged spleen: In individuals with autoimmune lymphoproliferative syndrome (ALPS), red blood cells and platelets are often attacked by excess antibodies. When the antibodies become attached to red blood cells or platelets, they may become stuck in the spleen, an organ that filters the blood by removing cells that are no longer needed. Patients with ALPS may have enlarged spleens because of the large numbers of red blood cells and platelets that become stuck there, and these individuals are at a higher risk of having a rupture in the spleen, a potentially life-threatening condition in which a large amount of blood spills out of the spleen into the body.
  • Swollen lymph nodes: White blood cells such as lymphocytes are normally stored in the body in small capsules called lymph nodes. Because patients with ALPS have increased numbers of white blood cells, they may develop swelling of the lymph nodes. There are a large number of lymph nodes under the cheeks, which may cause patients with ALPS to appear as though they have swollen faces.
  • Autoimmune diseases: Patients with ALPS have a greater risk of developing other autoimmune diseases. These may include Guillain-Barre syndrome (a condition in which the immune system attacks parts of the nervous system) and systemic lupus erythematosus (an inflammatory condition in which the immune system attacks the skin, joints, kidneys, lungs, or other parts of the body).
  • Lymphoma: Patients with ALPS have an increased risk of developing lymphoma, a type of cancer caused by an abnormal growth of lymphocytes.

Treatment
  • Currently there is no known cure for autoimmune lymphoproliferative syndrome (ALPS). However, treatments exist that may help patients manage some of the symptoms. ALPS generally does not lead to death, and if treated properly, most individuals with ALPS are able to live normal lives.
  • Avoid heavy physical activity: Patients with ALPS may have an enlarged spleen and are at an increased risk for rupture of the spleen. Therefore, patients with ALPS are encouraged to avoid heavy physical activity, which may cause the spleen to rupture.
  • Spleen guard: Patients with enlarged spleens may wear a spleen guard to protect the spleen from external trauma and decrease the chance of rupture. A spleen guard is a piece of fiberglass that is molded to the shape of a person's body and worn under a shirt.
  • Splenectomy: Some patients with a severely enlarged spleen may have their spleen surgically removed. This will eliminate the possibility of having a ruptured spleen and will often lead to increased physical comfort. However, removal of the spleen may lead to an increased risk for bacterial infections, so patients who undergo a splenectomy must often remain on antibiotics for many years.
  • Blood transfusions: Patients with ALPS may have reduced numbers of red blood cells. In severe cases, a blood transfusion may be used to replace red blood cells. A blood transfusion is the transfer of someone else's compatible blood type into the patient's body through an intravenous line. Risks and complications associated with a blood transfusion include temporary fever, transmission of a viral infection, and the possibility of rejection if the blood types are not properly matched.
  • Vaccinations: Individuals with ALPS should receive typical childhood vaccinations (such as vaccinations against hepatitis B, tetanus, and measles), as well as yearly flu shots. This will help reduce the number of infections that an individual has to fight off, which is beneficial in patients who have impaired immune function.
  • Steroids: Steroids (such as prednisone) are a class of drugs known to suppress the activity of the immune system, in part by reducing lymphocyte function. Steroids may be effective in treating individuals with ALPS. Steroids may cause side effects, including weight gain, mood swings, thinning of the bones, and high blood sugar.
  • Immunosuppressants: Immunosuppressants (such as cyclosporine or Imuran®) are another class of drugs that may be effective in treating ALPS by reducing immune system activity. Immunosuppressants may cause side effects including headaches, heartburn, cramps, and muscle or joint pain.

Integrative therapies
  • Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of autoimmune lymphoproliferative syndrome (ALPS).

Prevention
  • There are currently no known ways to prevent autoimmune lymphoproliferative syndrome (ALPS).

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Bi LL, Pan G, Atkinson TP, et al. Dominant inhibition of Fas ligand-mediated apoptosis due to a heterozygous mutation associated with autoimmune lymphoproliferative syndrome (ALPS) Type Ib. BMC Med Genet. 2007 Jul 2;8:41.
  2. Bleesing JJ, Brown MR, Straus SE, et al. Immunophenotypic profiles in families with autoimmune lymphoproliferative syndrome. Blood. 2001 Oct 15;98(8):2466-73.
  3. Holzelova E, Vonarbourg C, Stolzenberg MC, et al. Autoimmune lymphoproliferative syndrome with somatic Fas mutations. N Engl J Med. 2004 Sep 30;351(14):1409-18.
  4. National Human Genome Research Institute. . Accessed February 5, 2008.
  5. National Institute of Allergy and Infectious Diseases. . Accessed February 5, 2008.
  6. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2008.
  7. Orphanet Rare Diseases and Orphan Drugs Database. . Accessed February 5, 2008.
  8. Rieux-Laucat F, Le Deist F, Fischer A. Autoimmune lymphoproliferative syndromes: genetic defects of apoptosis pathways. Cell Death Differ. 2003 Jan;10(1):124-33.
  9. Wei A, Cowie T. Rituximab responsive immune thrombocytopenic purpura in an adult with underlying autoimmune lymphoproliferative syndrome due to a splice-site mutation (IVS7+2 T>C) affecting the Fas gene. Eur J Haematol. 2007 Oct;79(4):363-6.

Causes
  • Autoimmune lymphoproliferative syndrome (ALPS) is an autoimmune condition caused by an inherited defect in the immune system. Normally, the immune system attacks foreign invaders, such as bacteria. Antibodies are a component of the immune system that normally attack foreign invaders to help destroy them. In patients with ALPS, there are increased numbers of lymphocytes, which are a type of white blood cell that make antibodies. Some of the antibodies produced by the extra lymphocytes attack normal components of the body (such as red blood cells or platelets), causing them to malfunction.
  • Many patients with ALPS have a mutation, or error, in a gene called Fas. Individuals have two copies of most genes, and in 83% of patients with ALPS, at least one copy of the Fas gene appears to be defective. The Fas gene normally functions to cause specific cells to die (such as lymphocytes). A defect in the Fas gene could reduce the amount of cell death among lymphocytes after they are done fighting an infection, leading to higher numbers of lymphocytes that continue to create antibodies. These extra antibodies then begin to attack the body's normal components, resulting in ALPS. However, because some patients with ALPS do not have a defective Fas gene, researchers believe that additional genetic or environmental factors may lead to the disease.

Risk factors
  • Many patients with autoimmune lymphoproliferative syndrome (ALPS) have a mutation, or error in a gene called Fas. Individuals have two copies of most genes, and in 83% of patients with ALPS, at least one copy of the Fas gene appears to be defective. If an individual has a parent with one mutant Fas gene, that individual has a 50% chance of inheriting the mutant Fas gene. Individuals with a mutant Fas gene have an increased risk of developing ALPS. Because only one defective gene is needed for ALPS to develop, ALPS is considered an autosomal dominant inheritance condition. However, because not all individuals with a mutant Fas gene develop ALPS, researchers believe that additional genetic or environmental factors may be involved in the disease.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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