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| {{SI}} | | {{Autoimmune lymphoproliferative syndrome}} |
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| '''Editor-In-Chief:''' David Teachey, MD [mailto:TEACHEYD@email.chop.edu] | | '''Editor-In-Chief:''' David Teachey, MD [mailto:TEACHEYD@email.chop.edu] '''Associate editor in chief''': {{SharmiB}} |
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| {{SK}} Canale-Smith syndrome | | {{SK}} Canale-Smith syndrome; ALPS |
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| ==Overview== | | ==[[Autoimmune lymphoproliferative syndrome overview|Overview]]== |
| '''Autoimmune lymphoproliferative syndrome''' is a form of [[lymphoproliferative disorder]]. It affects [[lymphocyte]] [[apoptosis]].<ref name="pmid18193364">{{cite journal |author=Fleisher TA |title=The autoimmune lymphoproliferative syndrome: an experiment of nature involving lymphocyte apoptosis |journal=Immunol. Res. |volume=40 |issue=1 |pages=87–92 |year=2008 |pmid=18193364 |doi=10.1007/s12026-007-8001-1 |url=http://dx.doi.org/10.1007/s12026-007-8001-1}}</ref> Autoimmune Lymphoproliferative Syndrome ([[ALPS]]) is a rare disorder of abnormal [[lymphocyte]] survival caused by defective [[Fas]] mediated [[apoptosis]].<ref name="pmid16522544">{{cite journal| author=Rao VK, Straus SE| title=Causes and consequences of the autoimmune lymphoproliferative syndrome. | journal=Hematology | year= 2006 | volume= 11 | issue= 1 | pages= 15-23 | pmid=16522544 | doi=10.1080/10245330500329094 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16522544 }} </ref> 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.<ref name="pmid19930184">{{cite journal| author=Teachey DT, Seif AE, Grupp SA| title=Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS). | journal=Br J Haematol | year= 2010 | volume= 148 | issue= 2 | pages= 205-16 | pmid=19930184 | doi=10.1111/j.1365-2141.2009.07991.x | pmc=PMC2929682 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19930184 }} </ref>
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| ==Classification== | | ==[[Autoimmune lymphoproliferative syndrome historical perspective|Historical Perspective]]== |
| Old nomenclature<ref name="pmid12819469">{{cite journal| author=Sneller MC, Dale JK, Straus SE| title=Autoimmune lymphoproliferative syndrome. | journal=Curr Opin Rheumatol | year= 2003 | volume= 15 | issue= 4 | pages= 417-21 | pmid=12819469 | doi= | pmc= | url= }} </ref>
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| * IA - [[Fas]]
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| * IB - [[Fas ligand]]
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| * IIA - [[Caspase 10]]
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| * IIB - [[Caspase 8]]
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| * III - unknown
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| * IV - [[Neuroblastoma RAS viral oncogene homolog]]
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| Revised nomenclature (2010)<ref name="pmid20538792">{{cite journal| author=Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ et al.| title=Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. | journal=Blood | year= 2010 | volume= 116 | issue= 14 | pages= e35-40 | pmid=20538792 | doi=10.1182/blood-2010-04-280347 | pmc=PMC2953894 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20538792 }} </ref>
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| * ALPS-FAS: [[Fas]]. Germline FAS mutations. 70% of patients. Autosomal dominant. Dominant negative and haploinsufficient mutations described.<ref name="pmid21490157">{{cite journal| author=Kuehn HS, Caminha I, Niemela JE, Rao VK, Davis J, Fleisher TA et al.| title=FAS haploinsufficiency is a common disease mechanism in the human autoimmune lymphoproliferative syndrome. | journal=J Immunol | year= 2011 | volume= 186 | issue= 10 | pages= 6035-43 | pmid=21490157 | doi=10.4049/jimmunol.1100021 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21490157 }} </ref>
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| * ALPS-sFAS: [[Fas]]. Somatic FAS mutations in DNT compartment.<ref name="pmid15459302">{{cite journal| author=Holzelova E, Vonarbourg C, Stolzenberg MC, Arkwright PD, Selz F, Prieur AM et al.| title=Autoimmune lymphoproliferative syndrome with somatic Fas mutations. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 14 | pages= 1409-18 | pmid=15459302 | doi=10.1056/NEJMoa040036 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15459302 }} </ref> 10% of patients
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| * ALPS-FASL: [[Fas ligand]]. Germline FASL mutations. 3 reported cases
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| * ALPS-CASP10: [[Caspase 10]]. Germline CASP10 mutation. 2% of patients
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| * ALPS-U: Undefined. 20% of patients
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| * CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder
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| * RALD: [[NRAS]] , [[KRAS]]. Somatic mutations in NRAS and KRAS in lympocyte comparment. No longer considered a subtype of ALPS but distinct disesase
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| ==Clinical Manifestations== | | ==[[Autoimmune lymphoproliferative syndrome classification|Classification]]== |
| Lymphoproliferation: The most common clinical manifestation of ALPS is lymphoproliferation, affecting 100% of patients.
| | ==[[Autoimmune lymphoproliferative syndrome pathophysiology|Pathophysiology]]== |
| * [[Lymphadenopathy]]: >90% of patients present with chronic non-malignant lymphadenopathy. It can be mild to severe, affecting multiple nodal groups. Most commonly presents with massive non-painful hard cervical lymphadenopathy
| | ==[[Autoimmune lymphoproliferative syndrome causes|Causes]]== |
| * [[Splenomegaly]]: >80% of patients present with clinically identifiable splenomegaly. It can be massive.
| | ==[[Autoimmune lymphoproliferative syndrome differential diagnosis|Differentiating Autoimmune lymphoproliferative syndrome from other Diseases]]== |
| * [[Hepatomegaly]]: 30-40% of patients have enlarged livers.
| | ==[[Autoimmune lymphoproliferative syndrome epidemiology and demographics|Epidemiology and Demographics]]== |
| * Lymphoproliferation tends to present at a young age (median 11.5 months) and may improve with age.
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| Autoimmune disease: The second most common clinical manifestation and one that most often requires treatment.
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| * Autoimmune cytopenias: Most common. Can be mild to very severe. Can be intermittent or chronic.<ref name="pmid15542578">{{cite journal| author=Teachey DT, Manno CS, Axsom KM, Andrews T, Choi JK, Greenbaum BH et al.| title=Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS). | journal=Blood | year= 2005 | volume= 105 | issue= 6 | pages= 2443-8 | pmid=15542578 | doi=10.1182/blood-2004-09-3542 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15542578 }} </ref>
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| ** Autoimmune [[Hemolytic Anemia]]
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| ** Autoimmune [[Neutropenia]]
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| ** Autoimmune [[Thrombocytopenia]]
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| * Other: Can affect any organ system similar to [[systemic lupus erythematosis]] (most rare affecting <5% of patients)
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| ** Nervous: Autoimmune cerebellar [[ataxia]]; [[Guillain-Barre]]; [[Transverse myelitis]]
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| ** GI: Autoimmune esophagitis, gastritis, colitis, hepatitis, pancreatitis
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| ** Derm: Urticaria
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| ** Pulmonary: [[Bronchiolitis obliterans]]
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| ** Renal: Autoimmune glomerulonephritis, nephrotic syndrome
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| * Cancer: Secondary neoplasms affect approximately 10% of patients. True prevalence unknown as <20 reported cases of cancer. Most common EBER+ Non-Hodgkin's and [[Hodgkin's]] lymphoma
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| ** Unaffected family members with genetic mutations are also at increased risk of developing cancer
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| ==Laboratory Manifestations== | | ==[[Autoimmune lymphoproliferative syndrome risk factors|Risk Factors]]== |
| * Elevated peripheral blood Double Negative T cells (DNTs)<ref name="pmid12139944">{{cite journal| author=Bleesing JJ, Brown MR, Novicio C, Guarraia D, Dale JK, Straus SE et al.| title=A composite picture of TcR alpha/beta(+) CD4(-)CD8(-) T Cells (alpha/beta-DNTCs) in humans with autoimmune lymphoproliferative syndrome. | journal=Clin Immunol | year= 2002 | volume= 104 | issue= 1 | pages= 21-30 | pmid=12139944 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12139944 }} </ref>
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| ** Required for diagnosis
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| ** Immunophenotype: CD3+/CD4-/CD8-/TCRalpha/beta+
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| ** Measured by [[flow cytometry]]: Normal values <2.5% total T cells; <1% of total lymphocytes in peripheral blood
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| ** Marked elevations >5% virtually pathognomic for ALPS
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| ** Mild elevations also found in other autoimmune diseases
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| ** Thought to be cytotoxic T lymphocytes that have lost CD8 expression
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| ** ?Unknown if driver of disease or epiphenomenon
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| ** May be falsely elevated in setting of lymphopenia or falsely decreased with immunosuppressive treatment
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| * Defective in vitro Fas mediated apoptosis
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| ** Required for diagnosis under old definition. Now can be used to make diagnosis; however, not required to make diagnosis.
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| ** Time and labor intensive assay.
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| ** T cells from patient and normal control supported in culture for >10 days with mitogen stimulation and IL-2 expansion and then exposed to anti-Fas IgM monoclonal antibody
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| ** ALPS patient T cells: Do not die with anti-Fas monoclonal antibody exposure. Normal T cells from unaffected patient do.
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| ** False negative in somatic Fas variant ALPS and FasL variant ALPS
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| * Genetic mutations in ALPS causative genes (see below)
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| * Biomarkers<ref name="pmid19176318">{{cite journal| author=Magerus-Chatinet A, Stolzenberg MC, Loffredo MS, Neven B, Schaffner C, Ducrot N et al.| title=FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function. | journal=Blood | year= 2009 | volume= 113 | issue= 13 | pages= 3027-30 | pmid=19176318 | doi=10.1182/blood-2008-09-179630 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19176318 }} </ref> <ref name="pmid20227752">{{cite journal| author=Caminha I, Fleisher TA, Hornung RL, Dale JK, Niemela JE, Price S et al.| title=Using biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome. | journal=J Allergy Clin Immunol | year= 2010 | volume= 125 | issue= 4 | pages= 946-949.e6 | pmid=20227752 | doi=10.1016/j.jaci.2009.12.983 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20227752 }} </ref>
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| ** Polyclonal [[hypergammaglobulinemia]]<ref name="pmid20068224">{{cite journal| author=Seif AE, Manno CS, Sheen C, Grupp SA, Teachey DT| title=Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study. | journal=Blood | year= 2010 | volume= 115 | issue= 11 | pages= 2142-5 | pmid=20068224 | doi=10.1182/blood-2009-08-239525 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20068224 }} </ref>
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| ** Elevated serum FASL
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| ** Elevated plasma [[IL-10]] and/or IL-18
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| ** Elevated plasma or serum [[vitamin B12]]
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| * [[Autoantibodies]]: Non-specific. Can have antibodies to blood cells (DAT, anti-neutrophil, anti-platelet). Also, can have positive ANA, RF, ANCA.
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| | ==[[Autoimmune lymphoproliferative syndrome screening|Screening]]== |
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| ==Diagnostic Algorithm== | | ==[[Autoimmune lymphoproliferative syndrome natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| Old criteria<ref name="pmid12819469">{{cite journal| author=Sneller MC, Dale JK, Straus SE| title=Autoimmune lymphoproliferative syndrome. | journal=Curr Opin Rheumatol | year= 2003 | volume= 15 | issue= 4 | pages= 417-21 | pmid=12819469 | doi= | pmc= | url= }} </ref>
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| * Required
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| ** Chronic non-malignant lymphoproliferation
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| ** Elevated peripheral blood DNTs
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| ** Defective in vitro Fas mediated apoptosis
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| New criteria<ref name="pmid20538792">{{cite journal| author=Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ et al.| title=Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. | journal=Blood | year= 2010 | volume= 116 | issue= 14 | pages= e35-40 | pmid=20538792 | doi=10.1182/blood-2010-04-280347 | pmc=PMC2953894 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20538792 }} </ref>
| | ==References== |
| *Required
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| ** Chronic non-malignant lymphoproliferation (>6 months lymphadenopathy and/or splenomegaly)
| | ==Diagnosis== |
| ** Elevated peripheral blood DNTs
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| *Accessory
| | [[Autoimmune lymphoproliferative syndrome criteria|Diagnostic Criteria]] | [[Autoimmune lymphoproliferative syndrome history and symptoms|History and Symptoms]] | [[ Autoimmune lymphoproliferative syndrome physical examination|Physical Examination]] | [[Autoimmune lymphoproliferative syndrome laboratory findings|Laboratory Findings]] | [[Autoimmune lymphoproliferative syndrome electrocardiogram|Electrocardiogram]] | [[Autoimmune lymphoproliferative syndrome chest x ray|Chest X Ray]] | [[Autoimmune lymphoproliferative syndrome CT|CT]] | [[Autoimmune lymphoproliferative syndrome MRI|MRI]] | [[Autoimmune lymphoproliferative syndrome echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Autoimmune lymphoproliferative syndrome other imaging findings|Other Imaging Findings]] | [[Autoimmune lymphoproliferative syndrome other diagnostic studies|Other Diagnostic Studies]] |
| ** Primary Accessory
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| *** Defective in vitro Fas mediated apoptosis
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| *** Somatic or germline mutation in ALPS causative gene (FAS, FASL, CASP10)
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| ** Secondary Accessory
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| *** Elevated biomarkers
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| **** Plasma sFASL >200pg/ml
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| **** Plasma IL-10 >20pg/ml
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| **** Plasma or serum vitamin B12 >1500ng/L
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| **** Plasma IL-18 >500pg/ml
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| *** Immunohistochemical findings on biopsy consistent with ALPS as determined by experienced hematopathologist
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| *** Autoimmune cytopenias and polyclonal hypergammaglobulinemia
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| *** Family history of ALPS or non-malignant lymphoproliferation
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| * Definitive diagnosis: Required plus one primary accessory criteria
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| * Probable diagnosis: Required plus one secondary accessory criteria
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| * Definitive and Probable ALPS should be TREATED THE SAME and patients counseled that they have ALPS if definitive or probable
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| ==Treatment== | | ==Treatment== |
| * Mostly commonly directed at autoimmune disease
| | [[Autoimmune lymphoproliferative syndrome medical therapy|Medical Therapy]] | [[Autoimmune lymphoproliferative syndrome surgery |Surgery]] | [[Autoimmune lymphoproliferative syndrome primary prevention|Primary Prevention]] | [[Autoimmune lymphoproliferative syndrome secondary prevention|Secondary Prevention]] | [[Autoimmune lymphoproliferative syndrome cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Autoimmune lymphoproliferative syndrome future or investigational therapies|Future or Investigational Therapies]] |
| * Maybe needed to treat bulky lymphoproliferation
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| * First line therapies
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| ** [[Corticosteroids]]
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| *** Very active but toxic with chronic use
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| ** [[IVIgG]]
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| *** Not as effective as in other immune cytopenia syndromes
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| * Second line therapies
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| ** [[Mycophenolate mofetil]] (cellcept)<ref name="pmid15877736">{{cite journal| author=Rao VK, Dugan F, Dale JK, Davis J, Tretler J, Hurley JK et al.| title=Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome. | journal=Br J Haematol | year= 2005 | volume= 129 | issue= 4 | pages= 534-8 | pmid=15877736 | doi=10.1111/j.1365-2141.2005.05496.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15877736 }} </ref>
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| *** Inactivates inosine monophosphate
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| *** Active in most patients
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| *** Most studied medicine in clinical trials
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| *** Some patients have complete resolution of autoimmune disease
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| *** Some patients have partial responses
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| *** Some patients relapse
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| *** Does not affect lymphoproliferation or reduce DNTs
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| *** Well-tolerated: Side effects: Diarrhea, neutropenia
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| *** Does not require therapeutic drug monitoring
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| *** No drug-drug interactions
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| *** Can cause hypogammaglobulinemia (transient) requiring IVIgG replacement
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| *** Consider PCP prophylaxis but usually not needed
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| ** [[Sirolimus]] (rapamycin, rapamune)
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| *** mTOR ([[mammalian target of rapamycin]]) inhibitor<ref name="pmid16757690">{{cite journal| author=Teachey DT, Obzut DA, Axsom K, Choi JK, Goldsmith KC, Hall J et al.| title=Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS). | journal=Blood | year= 2006 | volume= 108 | issue= 6 | pages= 1965-71 | pmid=16757690 | doi=10.1182/blood-2006-01-010124 | pmc=PMC1895548 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16757690 }} </ref>
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| *** Active in most patients
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| *** Second most studied agent in clinical trials
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| *** Most patients have complete resolution of autoimmune disease (>90%)<ref name="pmid19208097">{{cite journal| author=Teachey DT, Greiner R, Seif A, Attiyeh E, Bleesing J, Choi J et al.| title=Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. | journal=Br J Haematol | year= 2009 | volume= 145 | issue= 1 | pages= 101-6 | pmid=19208097 | doi=10.1111/j.1365-2141.2009.07595.x | pmc=PMC2819393 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19208097 }} </ref> <ref name="pmid19588524">{{cite journal| author=Janić MD, Brasanac CD, Janković JS, Dokmanović BL, Krstovski RN, Kraguljac Kurtović JN| title=Rapid regression of lymphadenopathy upon rapamycin treatment in a child with autoimmune lymphoproliferative syndrome. | journal=Pediatr Blood Cancer | year= 2009 | volume= 53 | issue= 6 | pages= 1117-9 | pmid=19588524 | doi=10.1002/pbc.22151 | pmc= | url= }} </ref>
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| *** Most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%)
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| *** Some patients have near complete response (disease flares with viral illness)
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| *** A few patients have had partial responses (most commonly patient with non-cytopenia autoimmune disease)
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| *** Most patients have elimination of peripheral blood DNTs
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| *** mTOR/Akt/PI3K pathway may be activated in abnormal ALPS cells: mTOR inhibitors may be targeted therapy
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| *** May not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune function with transition from cellcept to rapamycin<ref name="pmid21475130">{{cite journal| author=Teachey DT| title=Autoimmune lymphoproliferative syndrome: new approaches to diagnosis and management. | journal=Clin Adv Hematol Oncol | year= 2011 | volume= 9 | issue= 3 | pages= 233-5 | pmid=21475130 | doi= | pmc= | url= }} </ref>
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| *** Not reported to cause hypogammaglobulinemia
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| *** Hypothetically, may have lower risk of secondary cancers as opposed to other immune suppressants
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| **** Always a risk with any agent in pre-cancerous syndrome as immune suppression can decreased tumor immunosurvellence
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| **** mTOR inhibitors active against lymphomas, especially EBV+ lymphomas. Thus, THEORETICALLY could eliminate malignant clones.
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| *** Requires therapeutic drug monitoring
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| **** Goal serum trough 5-15ng/ml
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| *** Drug-drug interactions
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| *** Well tolerated: Side effects: mucositis, diarrhea, hyperlipidemia, delayed wound healing
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| *** Consider PCP prophylaxis but usually not needed
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| ** Other agents:
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| *** Fansidar,<ref name="pmid11918552">{{cite journal| author=van der Werff Ten Bosch J, Schotte P, Ferster A, Azzi N, Boehler T, Laurey G et al.| title=Reversion of autoimmune lymphoproliferative syndrome with an antimalarial drug: preliminary results of a clinical cohort study and molecular observations. | journal=Br J Haematol | year= 2002 | volume= 117 | issue= 1 | pages= 176-88 | pmid=11918552 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11918552 }} </ref> <ref name="pmid17674358">{{cite journal| author=Rao VK, Dowdell KC, Dale JK, Dugan F, Pesnicak L, Bi LL et al.| title=Pyrimethamine treatment does not ameliorate lymphoproliferation or autoimmune disease in MRL/lpr-/- mice or in patients with autoimmune lymphoproliferative syndrome. | journal=Am J Hematol | year= 2007 | volume= 82 | issue= 12 | pages= 1049-55 | pmid=17674358 | doi=10.1002/ajh.21007 | pmc= | url= }} </ref> mercaptopurine: More commonly used in Europe. Good ancedotal data
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| *** Rituximab: AVOID. Can cause life long hypogammaglobulinemia<ref name="pmid19214977">{{cite journal| author=Rao VK, Price S, Perkins K, Aldridge P, Tretler J, Davis J et al.| title=Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS). | journal=Pediatr Blood Cancer | year= 2009 | volume= 52 | issue= 7 | pages= 847-52 | pmid=19214977 | doi=10.1002/pbc.21965 | pmc=PMC2774763 | url= }} </ref>
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| *** Splenectomy: AVOID. >30% risk of pneumococcal sepsis even with vaccination and antibiotic prophylaxis<ref name="pmid21885601">{{cite journal| author=Rao VK, Oliveira JB| title=How I treat autoimmune lymphoproliferative syndrome. | journal=Blood | year= 2011 | volume= | issue= | pages= | pmid=21885601 | doi=10.1182/blood-2011-07-325217 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21885601 }} </ref> <ref name="pmid21885602">{{cite journal| author=Neven B, Magerus-Chatinet A, Florkin B, Gobert D, Lambotte O, De Somer L et al.| title=A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. | journal=Blood | year= 2011 | volume= | issue= | pages= | pmid=21885602 | doi=10.1182/blood-2011-04-347641 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21885602 }} </ref>
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| | ==Case Studies== |
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| ==References==
| | [[Autoimmune lymphoproliferative syndrome case study one|Case #1]] |
| {{reflist|2}}
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| [[Category:Disease]] | | [[Category:Disease]] |