Bruton's Agammaglobulinemia Defect: Bruton's tyrosine kinase (BTK gene on X chr) -> blocks B cell differentiation and maturation (prevents Pre-B -> immature B transition) Presentation: recurrent bacterial infections after 6 months (maternal IgG) -> opsonization [quizlet.com]

Small lymphoid follicles are also present. ALPS involving lymph node. The paracortex is populated by small lymphocytes and many large immunoblasts with prominent nucleoli. [basicmedicalkey.com]

Presentation [ 4 ] Onset and time course Most patients present with lymphoproliferation (see below) in early childhood (median age approximately 1 year). [patient.info]

Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. [tititudorancea.com]

The patient's sister and brother presented with SLE features at the age of 10 and 6 years, respectively, but without lymphoproliferative disorder. Literature This section has been translated automatically. [altmeyers.org]

• Splenomegaly

  It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child. [pediatrics.aappublications.org]

  50%) in an otherwise healthy child. [15, 16] To meet the case definition of ALPS, a patient must have chronic, nonmalignant lymphadenopathy or splenomegaly that lasts for 6 months or longer. [emedicine.medscape.com]

  Comprises lymphadenopathy, hepatomegaly or splenomegaly. Autoimmunity Autoimmune destruction of blood cells is the most common feature, varying from mild and asymptomatic to severe. [patient.info]

  ALPS is characterized by: Anemia due to excessive destruction of red blood cells hemolytic anemia), Decreased platelets in the blood ( thrombocytopenia ), Enlargement of lymph nodes (lymphadenopathy), and Enlargement of the spleen (splenomegaly). [medicinenet.com]

  The laboratory finding of increased alpha beta TCR+DNT cells is consistent with ALPS only with the appropriate clinical picture (nonmalignant lymphadenopathy, splenomegaly, and autoimmune cytopenias). [mayomedicallaboratories.com]

• Lymphadenopathy

  At 3 years of age, he developed hepatosplenomegaly and generalized lymphadenopathy associated with herpesviremia. [altmeyers.org]

  It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child. [pediatrics.aappublications.org]

  Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. [tititudorancea.com]

  Medical College and KEM Hospital, Parel, Mumbai India Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.81873 A 50-year-old male patient presented with fever, epistaxis and multiple lymphadenopathy since 15 days. [jpgmonline.com]

  Comprises lymphadenopathy, hepatomegaly or splenomegaly. Autoimmunity Autoimmune destruction of blood cells is the most common feature, varying from mild and asymptomatic to severe. [patient.info]

• Anemia

  Anemia For chronic anemia, the underlying disease (infection, arthritis, heart, lung or kidney disease) is attended to, often improving the anemia. [my.clevelandclinic.org]

  Myelodysplastic Syndromes Refractory Anemia with Unilineage Dysplasia Refractory Anemia with Ring Sideroblasts Refractory Cytopenia with Multilineage Dysplasia Refractory Anemia with Excess Blasts (RAEB) Myelodysplastic Syndrome (MDS) with Isolated del [euro-libris.ro]

  Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. [tititudorancea.com]

  ALPS is characterized by: Anemia due to excessive destruction of red blood cells hemolytic anemia), Decreased platelets in the blood ( thrombocytopenia ), Enlargement of lymph nodes (lymphadenopathy), and Enlargement of the spleen (splenomegaly). [medicinenet.com]

  Autoimmune Hemolytic Anemia. In: Nathan and Oski’s Hematology of Infancy and Childhood, 7th ed. Orkin SH, Nathan DG, Ginsburg D, Look AL, Fisher DE, Lux SE, editors. 2009 Saunders Elsevier, Philadelphia, PA. pp. 633-634. Cassell D, Rose N. Eds. [rarediseases.org]

• Hodgkin Lymphoma

  The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma. (NCI Thesaurus) ALSO IN ENCYCLOPEDIA : [tititudorancea.com]

  lymphoma and non-Hodgkin lymphoma 51x increased risk of Hodgkin lymphoma 14x increased risk of non-Hodgkin lymphoma Usually not related to Epstein-Barr virus infection Increased risk of carcinomas Thyroid, breast, liver, tongue, skin Increased risk of [basicmedicalkey.com]

  ALPS-affected patients have a lifelong increased risk of Hodgkin's and non-Hodgkin's lymphoma 1. [centogene.com]

  Lymphoproliferation in ALPS patients is generally benign, but they are at increased risk for the development of Hodgkin’s and non-Hodgkin’s lymphoma. [karger.com]

  German High-Grade Non-Hodgkin’s Lymphoma Study Group Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. [ncbi.nlm.nih.gov]

• Fatigue

  Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. [tititudorancea.com]

  Healthy Lifestyles Physical Activity Nutrition and Weight Management Supplement Use Immunizations and Infections Late Effects/Long-Term Psychosocial and Physical Problems Anthracycline-Induced Cardiac Toxicity Anxiety and Depression Cognitive Function Fatigue [nccn.org]

  increased infections in patients suffering from rheumatoid arthritis blood disorder after transplant surgery foul smelling stools which are bulky, loose and greasy hair loss (alopecia) liver problems in patients with rheumatoid arthritis paleness, fatigue [netmeds.com]

  :: Case Report A 50-year-old male presented with a 15-day history of fever, fatigue, epistaxis, petechial hemorrhages and multiple cervical lymph adenopathy. [jpgmonline.com]

  Patients with ALPS may present initially with episodes of fatigue, pallor and icterus due to haemolytic anaemia. They may also be more likely to have easy bruising and mucocutaneous bleeding caused by thrombocytopenia. [casereports.bmj.com]

• Recurrent Infection

  The patient suffered from recurrent infections affecting most systems (respiratory, urinary, gastrointestinal) since the age of one year. [altmeyers.org]

  Some patients have recurrent infections, and there may be an increased risk of hematologic malignancy (summary by {2:Oliveira, 2013} and {1:Niemela et al., 2010}). [diseaseinfosearch.org]

  Infection Syndrome, Autosomal Dominant Hies, Autosomal Dominant Hyper-IgE Syndrome, Autosomal Dominant Job Syndrome 147060 Genetic Test Registry Hyper-IgE Recurrent Infection Syndrome, Autosomal Recessive HIES, Autosomal Recessive Hyper-IgE Syndrome, [ukgtn.nhs.uk]

  Thus, ALPS should be considered in individuals with the following signs and symptoms: Chronic non-malignant lymphoproliferation signs that includes: Chronic and/or recurrent lymphadenopathy Splenomegaly with/without hypersplenism Hepatomegaly Lymphocytic [centogene.com]

  infections including chronic mucocutaneous candidiasis (CMC), recurrent Staphylococcus aureus, recurrent herpes, Mycobacterium, autoimmunity, cytopenia and aneurysm [30] GOF mutations in STAT3 Autosomal dominant/ GOF mutation in STAT3 gene (17q21.2) [emedicine.medscape.com]

• Hepatosplenomegaly

  Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. [tititudorancea.com]

  At 3 years of age, he developed hepatosplenomegaly and generalized lymphadenopathy associated with herpesviremia. [altmeyers.org]

  Clinical findings Prominent lymphadenopathy, hepatosplenomegaly and Coombs-positive haemolytic anaemia; loss of immunologic self-tolerance resulting in hypergammaglobulinaemia with multiple autoantibodies, such as anti-erythrocyte, anti-RNP, anti-SM, [medical-dictionary.thefreedictionary.com]

  Clinical description ALPS is clinically heterogeneous with the following primary clinical signs: lymphoproliferation, manifesting as lymphadenopathy and hepatosplenomegaly with or without hypersplenism, often improving with age, autoimmune disease, mostly [orpha.net]

• Platyspondyly

  Aseptic arthritis, platyspondyly, phalangeal anomaly, and clinodactyly have been observed in Schimke syndrome [35,36]. [symbiosisonlinepublishing.com]

• Guillain-Barré Syndrome

  […] pneumonia Autoimmune diseases, including: Cytopenia, particularly combinations of autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and autoimmune neutropenia Autoimmune hepatitis Autoimmune glomerulonephritis Autoimmune thyroiditis Guillain-Barré [centogene.com]

  […] destruction of erythrocytes and platelets Subset of these patients has ALPS Other less common autoimmune phenomena in ALPS include Skin rash: Often of urticarial nature Autoimmune hepatitis Autoimmune glomerulonephritis Autoimmune thyroiditis Uveitis and Guillain-Barré [basicmedicalkey.com]

  Other signs can affect organ systems similar to systemic lupus erythematosus (least common, affecting ataxia ; Guillain–Barré syndrome ; transverse myelitis. [en.wikipedia.org]

In the light of the above presentation a complete workup was initiated to exclude common conditions like tuberculosis, acquired immunodeficiency syndrome, lymphoid malignancy and sarcoidosis. [jpgmonline.com]

[…] in the intrinsic pathway is extremely rare. [1, 8] Although 20% of ALPS patients have no identifiable mutation that leads to their defective lymphocyte apoptosis, they may still meet the diagnostic criteria for ALPS or an ALPS-related disorder (see Workup [emedicine.medscape.com]

• Neutropenia

  Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. [tititudorancea.com]

  Investigations [ 4 ] General investigations Blood tests These may show: Autoimmune-type haemolytic anaemia, thrombocytopenia, neutropenia and hypergammaglobulinaemia. T- and B-cell lymphocytosis. [patient.info]

  ALPS can also cause anemia (low level of red blood cells), thrombocytopenia (low level of platelets), and neutropenia (low level of neutrophils, the most common type of white blood cell in humans). [niaid.nih.gov]

  Get Update Overview RAS-associated leukoproliferative disorder is characterized by lymphadenopathy, splenomegaly, and variable autoimmune phenomena, including autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and neutropenia. [diseaseinfosearch.org]

  It is always prudent to check CBCs to rule out neutropenia and provide antibiotic prophylaxis as needed before dental work and other elective surgeries in some of these patients with significant neutropenia. [frontiersin.org]

• Leukopenia

  Low numbers of white cells (leukopenia or neutropenia) can cause repeated bacterial infections. When a particular blood count is only mildly decreased, it may not cause any symptoms whatsoever. [my.clevelandclinic.org]

• Chlamydia

  In a cohort of 243 patients with Common Variable Immunodeficiency (CVID), 2% had rheumatoid arthritis, 1.6% juvenile idiopathic arthritis, 0.8% septic arthritis (Mycoplasma pneumoniae, Chlamydia pneumoniae), 0.8% septic osteomyelitis [66-70]. [symbiosisonlinepublishing.com]

• Staphylococcus Aureus

  aureus, recurrent herpes, Mycobacterium, autoimmunity, cytopenia and aneurysm [30] GOF mutations in STAT3 Autosomal dominant/ GOF mutation in STAT3 gene (17q21.2) Hypogammaglobulinemia, autoimmunity, cytopenia, lymphadenopathy, splenomegaly, enteropathy [emedicine.medscape.com]

The NCCN Templates are not exhaustive and do not represent the full spectrum of care or treatment options described in the NCCN Guidelines or the NCCN Compendium or include all appropriate approaches or combinations of drugs or biologics for the treatment [nccn.org]

[…] with AZORAN 50MG and for at least 3 months after the treatment is discontinued AZORAN 50MG has been reported to interfere with the effectiveness of intrauterine contraceptive devices (IUCD) therefore additional contraceptive measures are recommended [netmeds.com]

This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy. It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement. [en.wikipedia.org]

Some patients do not need any treatment. [ 9 ] In many cases, treatment for autoimmunity is required. This is usually given as short bursts of immunosuppressive medication. [patient.info]

CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [diseaseinfosearch.org]

Prognosis The prognosis for ALPS patients remains guarded. ALPS-FAS patients have a significantly increased risk of non-Hodgkin's and Hodgkin's lymphoma which can occur at any age and responds to conventional chemotherapy. [orpha.net]

Prognosis The mortality and morbidity of ALPS vary widely. [emedicine.medscape.com]

Prognosis Long-term prognostic data are lacking, because this is a rare and recently identified disease. ALPS patients can live into adulthood. [ 5 ] Symptoms may improve as the patient ages. [patient.info]

[…] post-splenectomy sepsis despite vaccination and antibiotic prophylaxis No long-term effect to control cytopenia(s) Bone marrow (hematopoietic stem cell) transplantation carries risks Reduced-intensity transplant can reduce transplant-associated risks Prognosis [basicmedicalkey.com]

Etiology ALPS is caused by defective lymphocyte homeostasis. Germline mutations in the FAS (10q24.1), FASLG (1q23), or CASP10 (2q33-q34) genes are known to be associated with ALPS. 75% of cases are associated with heterozygous mutations in FAS. [orpha.net]

Autoimmune lymphoproliferative syndrome: etiology, diagnosis, and management. van der Werff ten Bosch J. van der Werff ten Bosch J. Paediatr Drugs. 2003;5(3):185-93. doi: 10.2165/00128072-200305030-00005. Paediatr Drugs. 2003. PMID: 12608883 Review. [pubmed.ncbi.nlm.nih.gov]

TERMINOLOGY Abbreviations Autoimmune lymphoproliferative syndrome (ALPS) Definitions Disease of disrupted lymphocyte homeostasis as result of defective Fas-mediated apoptosis ETIOLOGY/PATHOGENESIS Genetic Mutations in FAS Pathway FAS pathway mutations [basicmedicalkey.com]

The etiology of the lymphadenopathy in most patients with ALPS is related to an impairment of apoptosis due to inherited heterozygous mutations in the fas gene (tumor necrosis factor receptor gene superfamily member 6-TNFRSF6, CD95, APO-1, APT-1), which [jpgmonline.com]

Summary Epidemiology The prevalence of ALPS is unknown. It has been characterized in more than 500 patients to date and has been reported worldwide in various ethnic groups. [orpha.net]

Registry data has been used in epidemiological studies to gauge PID prevalence: 5.38/100,000 in France, 5.6/100,000 in Australia, USA 86.3/100,000 inhabitants [8]. [symbiosisonlinepublishing.com]

Epidemiology The initial presentations of ALPS include persistent lymphadenopathy (>95%) or splenomegaly (>90%) followed by autoimmune cytopenias (>70%) such as autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), and hepatomegaly [emedicine.medscape.com]

This finding supports the idea that the pathophysiology of ALPS is multifactorial, with an autosomal dominant inheritance pattern and variable penetrance. [12] [emedicine.medscape.com]

Useful For Suggests clinical disorders or settings where the test may be helpful Diagnosing autoimmune lymphoproliferative syndrome, primarily in patients Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they [mayomedicallaboratories.com]

Pathophysiology of Arthus Reaction A local subacute antibody-mediated hypersensitivity (type III hypersensitivity) reaction. Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin. [quizlet.com]

In addition to the main pathophysiologic finding of fibro-osseous bone formation, craniosynostosis has been reported in Cherubism syndrome, where a mutation in SH3BP2 causes bone degeneration in the jaws [137]. [symbiosisonlinepublishing.com]

[…] cancer: American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. [nccn.org]

Pro-T -> immature T), ADA deficiency (XR, prevents lymphoid stem cell -> Pro-B/Pro-T) OR failure to synthesize MHC II antigens (prevents formation of CD4+ T cells) Presentation: Recurrent viral, bacterial, fungal and protozoal infections -> treat with [quizlet.com]

Hughes PD, Betz GT, Fortner KA et al. (2008) Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity 28: 197–205. [els.net]

[…] inflammation of the gut (Crohn’s disease or ulcerative colitis) treat some diseases where your immune system is reacting against your own body (autoimmune diseases) including severe inflammatory diseases of the skin, liver, arteries and some blood disorders prevent [netmeds.com]

The essential role Fas plays in maintaining lymphocyte homeostasis and peripheral immune tolerance to prevent autoimmunity was first clarified by studying Fas-deficient MRL/lpr-/- mice. [emedicine.medscape.com]