Materiały źródłowe

• #1 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #2 Systemic mastocytosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/systemic-mastocytosis/

  Systemic mastocytosis occurs when white blood cells called mast cells, which are produced in bone marrow, abnormally accumulate in one or more tissues. In most cases of systemic mastocytosis, the accumulated mast cells have a mutation in a gene called KIT. The KIT gene provides instructions for making a protein that plays an important role in development and activity of mast cells. The KIT protein stimulates chemical signaling pathways that are involved in the growth and division (proliferation) of many types of cells, including mast cells. In systemic mastocytosis, KIT gene mutations are somatic, which means they are acquired during a person’s lifetime. These mutations result in a KIT protein that is always turned on (activated). As a result, signaling pathways are overactive, leading to increased production and accumulation of mast cells.

• #3 Mayo Clinic Health Library – Systemic mastocytosis | Swiss Medical Network

  https://www.swissmedical.net/en/healtcare-library/con-20306103

  Most cases of systemic mastocytosis are caused by a random change (mutation) in the KIT gene. Typically this flaw in the KIT gene is not inherited. Too many mast cells are produced and build up in tissues and body organs, releasing substances such as histamine, leukotrienes and cytokines that cause inflammation and symptoms.

• #4 Systemic Mastocytosis: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24386-systemic-mastocytosis

  Systemic mastocytosis is a type of mastocytosis a rare blood disorder that happens when your body makes abnormal mast cells. […] Research shows about 80% of people with systemic mastocytosis have a KIT gene variant (change). KIT genes play a role in developing certain cell types, including blood cells and mast cells. The gene change happens after conception and isnt hereditary. […] Systemic mastocytosis happens when you have the genetic change that causes it. That means you cant prevent it.

• #5 Systemic mastocytosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/systemic-mastocytosis/

  Systemic mastocytosis occurs when white blood cells called mast cells, which are produced in bone marrow, abnormally accumulate in one or more tissues. In most cases of systemic mastocytosis, the accumulated mast cells have a mutation in a gene called KIT. The KIT gene provides instructions for making a protein that plays an important role in development and activity of mast cells. The KIT protein stimulates chemical signaling pathways that are involved in the growth and division (proliferation) of many types of cells, including mast cells. In systemic mastocytosis, KIT gene mutations are somatic, which means they are acquired during a person’s lifetime. These mutations result in a KIT protein that is always turned on (activated). As a result, signaling pathways are overactive, leading to increased production and accumulation of mast cells.

• #6 Systemic Mastocytosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/203948-overview

  Mutations of the c-kit proto-oncogene may cause some forms of mastocytosis. […] Several types of somatic activating and nonactivating mutations in c-kit have been demonstrated to cause systemic mastocytosis. One of the common mutations found in systemic mastocytosis is an exon 17 D816V KIT receptor mutation. Most, if not all, adult patients with systemic mastocytosis carry this mutation. […] In the majority of patients, mastocytosis does not appear to be inherited, but rare familial cases with KIT mutations have been reported.

• #7 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Mastocytosis is a disorder in which abnormal mast cells are increased in one or more organs. […] The growth of mast cells is poorly controlled, sometimes as the result of mutations that produce clones, or identical copies, of cells. […] Mutations in KIT that keep the switch ON are the cause of mastocytosis. […] The most common mutation, called KIT D816V, produces a receptor that is constantly activated resulting in continuous growth and activation of mast cells. […] In addition to the increase in mediators as the result of increased numbers, abnormal mast cells in mastocytosis can be prone to release mediators more easily in general. […] Mastocytosis can occur in both children and adults, with a predominance for cutaneous mastocytosis in children and systemic mastocytosis in adults.

• #8 About Systemic Mastocytosis | Blueprint Medicines

  https://itssmthing.com/about-sm.php

  Systemic mastocytosis (pronounced mass-toe-sigh-TOE-sis), or SM for short, is a rare disease estimated to occur in approximately 32,000 people in the U.S. It is caused by an overproduction of abnormal mast cells (a type of white blood cell). […] In approximately 95% of cases, SM occurs due to a genetic mutation in the gene called KIT D816V. […] SM is caused by the activation of the KIT receptor protein, which drives the overproduction of abnormal mast cells and their buildup in a variety of organs. This buildup can result in symptoms such as rashes, diarrhea, anaphylaxis, heart palpitations, dizziness, and others. In approximately 95% of SM cases, the overactivation of this protein is associated with a mutation in the KIT gene called KIT D816V. […] SM is not thought to be a condition that is passed down through families. The mutation, KIT D816V, that causes SM in approximately 95% of cases is thought to be spontaneous, rather than inherited.

• #9 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Activating and inactivating mutations of KIT are implicated in the pathogenesis of systemic mastocytosis. The precise mechanism by which KIT-activating mutations improve signaling is not thoroughly understood, but these errors lead to stem cell factor (SCF)-independent activation. KITD816V is the most common driver mutation for systemic mastocytosis. KIT mutations are mostly somatic, so they don’t seem to be inherited although, they might be present at birth. They are rarely present in the germline cells, hence not passed down to the next generation. FIP1L1-PDGFRA mutation is associated with eosinophilia. Other mutations, namely TET2, IgE, JAK2V617F, and RAS, have associations with systemic mastocytosis as well.

• #10

  https://www.nhs.uk/conditions/mastocytosis/

  Mastocytosis is a rare condition caused by an excess number of mast cells gathering in the body’s tissues. […] The cause or causes of mastocytosis are not fully known, but there’s thought to be an association with a change in genes known as the KIT mutation. […] The KIT mutation makes the mast cells more sensitive to the effects of a signalling protein called stem cell factor (SCF). […] In very few cases of mastocytosis it appears the KIT mutation is passed down through families. However, in most cases the mutation happens for no apparent reason.

• #11 Mastocytosis and Mast Cell Activation Syndrome – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/mastocytosis-and-mast-cell-activation-syndrome

  Etiology in many cases of mastocytosis involves an activating mutation (D816V) in the gene coding for the stem cell factor receptor c-kit, which is present on mast cells. The result is autophosphorylation of the receptor, which causes uncontrolled mast cell proliferation. […] Genetic causes are suspected but not proved. Most cases do not involve clonal proliferation of mast cells but are due to a lower threshold for mast cells to degranulate.

• #12 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Systemic-Mastocytosis.aspx

  Systemic mastocytosis is usually linked to KIT somatic gain-of-function point mutations. […] The majority of adult SM patients have gain-of-function somatic mutations in the KIT tyrosine kinase domain, specifically the D816V mutation. […] Other somatic KIT variants seen in adult SM that are less prevalent, include D820G, D815K, D816Y, D816F, D816H, insVI815-816, and V560G.

• #13 Review and Updates on Systemic Mastocytosis and Related Entities

  https://www.mdpi.com/2072-6694/15/23/5626

  Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. […] The proliferation of neoplastic MCs is usually driven by KIT mutations that activate downstream pathways including PI3K, STAT5, NF-κB, mTORC2, and PKCδ. […] The KIT D816V mutation (exon 17) is frequently detected (>90%) in adult SM. Other less common mutations at codon 816 of KIT, including D816F, D816Y, D816G, D816H, D816I, and mutations such as F522C, V560G, I817V, N819Y, L799F, D820G, N822L, N822I, InsVI815-816, E839K, S840N, and S849I, have also been reported in SM. […] KIT mutations in the extracellular domain (e.g., deletion of codon 419 in exon 8 or p.A502_Y503dup in exon 9), TM domain (e.g., KIT p.F522C), or JM domain (e.g., KIT p.V560G) are found more frequently in indolent SM. […] Germline KIT mutations have been found to be associated with familial mastocytosis.

• #14 Review and Updates on Systemic Mastocytosis and Related Entities

  https://www.mdpi.com/2072-6694/15/23/5626

  Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. […] The proliferation of neoplastic MCs is usually driven by KIT mutations that activate downstream pathways including PI3K, STAT5, NF-κB, mTORC2, and PKCδ. […] The KIT D816V mutation (exon 17) is frequently detected (>90%) in adult SM. Other less common mutations at codon 816 of KIT, including D816F, D816Y, D816G, D816H, D816I, and mutations such as F522C, V560G, I817V, N819Y, L799F, D820G, N822L, N822I, InsVI815-816, E839K, S840N, and S849I, have also been reported in SM. […] KIT mutations in the extracellular domain (e.g., deletion of codon 419 in exon 8 or p.A502_Y503dup in exon 9), TM domain (e.g., KIT p.F522C), or JM domain (e.g., KIT p.V560G) are found more frequently in indolent SM. […] Germline KIT mutations have been found to be associated with familial mastocytosis.

• #15 Review and Updates on Systemic Mastocytosis and Related Entities

  https://www.mdpi.com/2072-6694/15/23/5626

  Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. […] The proliferation of neoplastic MCs is usually driven by KIT mutations that activate downstream pathways including PI3K, STAT5, NF-κB, mTORC2, and PKCδ. […] The KIT D816V mutation (exon 17) is frequently detected (>90%) in adult SM. Other less common mutations at codon 816 of KIT, including D816F, D816Y, D816G, D816H, D816I, and mutations such as F522C, V560G, I817V, N819Y, L799F, D820G, N822L, N822I, InsVI815-816, E839K, S840N, and S849I, have also been reported in SM. […] KIT mutations in the extracellular domain (e.g., deletion of codon 419 in exon 8 or p.A502_Y503dup in exon 9), TM domain (e.g., KIT p.F522C), or JM domain (e.g., KIT p.V560G) are found more frequently in indolent SM. […] Germline KIT mutations have been found to be associated with familial mastocytosis.

• #16 Unraveling the Rare Entity of KIT D816V-Negative Systemic Mastocytosis | Alyamany | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/1279/843

  Systemic mastocytosis (SM) is a rare type of myeloproliferative neoplasm characterized by abnormal proliferation and infiltration of different tissue by clonal mast cells. […] Around 95% of SM arise from a gain-of-function mutation at the KIT gene, specifically at codon 816, which highlights its essential role in SM and makes it an attractive target for therapy. […] Although KIT-negative SM is exceptionally rare, the increased number of cases documented in the literature makes it an intriguing dimension of this disorder. […] The occurrence of KIT-negative cases of SM is notably rare. […] However, their prevalence has gained increased recognition over the years, as evidenced by the cases reported in the literature. […] Research is still being done to understand better the complex interactions between different mutations, their capacity to change mast cells, and their influence on clinical manifestations and treatment of mastocytosis.

• #17 Unraveling the Rare Entity of KIT D816V-Negative Systemic Mastocytosis | Alyamany | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/1279/843

  The clinical manifestations include episodic flushing, diarrhea, hypotension, osteoporosis, and abdominal pain. […] In the context of KIT-negative SM, there is not enough evidence on the specific features seen in this entity; however, there is evidence expressing its association with advanced SM subtypes, such as MCL and MSC. […] The therapeutic approach to SM depends on the severity of symptoms. […] The high prevalence of KIT mutations in SM makes it an attractive therapeutic target. […] Regarding cases of true KIT-negative SM, it is theorized that therapies that selectively target KIT mutations are less effective when compared to their impact in cases of KIT-positive SM. […] Multiple medications are being investigated for efficacy in SM, including bezuclastinib, an orally administered potent and selective type I TKI targeting multiple loci, including D816V.

• #18 Systemic mastocytosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/systemic-mastocytosis/

  Mutations in additional genes seem to modify the severity of systemic mastocytosis, often resulting in a more aggressive disease and shorter survival. These genes primarily play roles in controlling the proliferation of cells or regulating the activity of other genes that are important in development.

• #19 Advanced Systemic Mastocytosis: Symptoms, Causes, Diagnosis, and Treatment

  https://www.everydayhealth.com/rare-diseases/advanced-systemic-mastocytosis/

  Systemic mastocytosis is often caused by changes (mutations) in a gene called KIT, which is responsible for regulating the growth and function of mast cells. This flaw in the KIT gene is usually not inherited. […] The bottom line is there’s no known, obvious predisposition to it, says Dr. Gotlib. […] It’s basically the random development of the KIT mutation in people who, over time, develop the overt, clinically evident disease, he says. […] Mastocytosis is no different, meaning that a person develops a mutation, and then in some cases, there are other mutations in addition to KIT that drive the development of mastocytosis, says Gotlib.

• #20 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Activating and inactivating mutations of KIT are implicated in the pathogenesis of systemic mastocytosis. The precise mechanism by which KIT-activating mutations improve signaling is not thoroughly understood, but these errors lead to stem cell factor (SCF)-independent activation. KITD816V is the most common driver mutation for systemic mastocytosis. KIT mutations are mostly somatic, so they don’t seem to be inherited although, they might be present at birth. They are rarely present in the germline cells, hence not passed down to the next generation. FIP1L1-PDGFRA mutation is associated with eosinophilia. Other mutations, namely TET2, IgE, JAK2V617F, and RAS, have associations with systemic mastocytosis as well.

• #21 Unraveling the Rare Entity of KIT D816V-Negative Systemic Mastocytosis | Alyamany | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/1279/843

  The prognosis of SM depends on different factors, including age, cytopenias, the WHO classification-defined subtype of SM, biochemical markers, and mutational profile. […] The presence of non-KIT mutations, such as SRSF2, ASXL1, RUNX1, and EZH2, has been associated with advanced SM subtypes and inferior prognosis. […] In cases of KIT-D816V-negative SM, these prognostic scores are controversial. […] Further and more comprehensive research is needed to expand our understanding of KIT-D816V-negative SM and determine the most appropriate management and prognosis.

• #22 Unraveling the Rare Entity of KIT D816V-Negative Systemic Mastocytosis | Alyamany | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/1279/843

  The prognosis of SM depends on different factors, including age, cytopenias, the WHO classification-defined subtype of SM, biochemical markers, and mutational profile. […] The presence of non-KIT mutations, such as SRSF2, ASXL1, RUNX1, and EZH2, has been associated with advanced SM subtypes and inferior prognosis. […] In cases of KIT-D816V-negative SM, these prognostic scores are controversial. […] Further and more comprehensive research is needed to expand our understanding of KIT-D816V-negative SM and determine the most appropriate management and prognosis.

• #23 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Activating and inactivating mutations of KIT are implicated in the pathogenesis of systemic mastocytosis. The precise mechanism by which KIT-activating mutations improve signaling is not thoroughly understood, but these errors lead to stem cell factor (SCF)-independent activation. KITD816V is the most common driver mutation for systemic mastocytosis. KIT mutations are mostly somatic, so they don’t seem to be inherited although, they might be present at birth. They are rarely present in the germline cells, hence not passed down to the next generation. FIP1L1-PDGFRA mutation is associated with eosinophilia. Other mutations, namely TET2, IgE, JAK2V617F, and RAS, have associations with systemic mastocytosis as well.

• #24 Mastocytosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863935/

  Mastocytosis is a disorder of abnormal mast cell proliferation with clinical features that include flushing, pruritus, abdominal pain, diarrhea, hypotension, syncope and musculoskeletal pain. […] Most patients with systemic disease have a somatically acquired activating mutation in the KIT oncogene. […] Most cases appear to be spontaneous. Inherited patterns of mastocytosis are unusual. […] Activating somatic mutations in c-kit that encodes for KIT, have been detected in the bone marrow as well as skin and peripheral blood cells in patients with mastocytosis. […] The most common somatic mutation, Asp816Val (D816V), is located in catalytic domain of KIT and results in augmented mast cell proliferation and survival. […] A subgroup of patients that present with hypereosinophillic syndrome have the FIP1L1/PDGRFA fusion tyrosine kinase, which can be found in multiple cell lineages including mast cells and eosinophils. This genetic abnormality is associated with increased mast cells in the bone marrow, an elevated tryptase and peripheral eosinophilia, thus highlighting a role for non-KIT dependent pathways in the pathogenesis of mastocytosis.

• #25 Mastocytosis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863935/

  Mastocytosis is a disorder of abnormal mast cell proliferation with clinical features that include flushing, pruritus, abdominal pain, diarrhea, hypotension, syncope and musculoskeletal pain. […] Most patients with systemic disease have a somatically acquired activating mutation in the KIT oncogene. […] Most cases appear to be spontaneous. Inherited patterns of mastocytosis are unusual. […] Activating somatic mutations in c-kit that encodes for KIT, have been detected in the bone marrow as well as skin and peripheral blood cells in patients with mastocytosis. […] The most common somatic mutation, Asp816Val (D816V), is located in catalytic domain of KIT and results in augmented mast cell proliferation and survival. […] A subgroup of patients that present with hypereosinophillic syndrome have the FIP1L1/PDGRFA fusion tyrosine kinase, which can be found in multiple cell lineages including mast cells and eosinophils. This genetic abnormality is associated with increased mast cells in the bone marrow, an elevated tryptase and peripheral eosinophilia, thus highlighting a role for non-KIT dependent pathways in the pathogenesis of mastocytosis.

• #26 Systemic Mastocytosis: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24386-systemic-mastocytosis

  Systemic mastocytosis is a type of mastocytosis a rare blood disorder that happens when your body makes abnormal mast cells. […] Research shows about 80% of people with systemic mastocytosis have a KIT gene variant (change). KIT genes play a role in developing certain cell types, including blood cells and mast cells. The gene change happens after conception and isnt hereditary. […] Systemic mastocytosis happens when you have the genetic change that causes it. That means you cant prevent it.

• #27 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Activating and inactivating mutations of KIT are implicated in the pathogenesis of systemic mastocytosis. The precise mechanism by which KIT-activating mutations improve signaling is not thoroughly understood, but these errors lead to stem cell factor (SCF)-independent activation. KITD816V is the most common driver mutation for systemic mastocytosis. KIT mutations are mostly somatic, so they don’t seem to be inherited although, they might be present at birth. They are rarely present in the germline cells, hence not passed down to the next generation. FIP1L1-PDGFRA mutation is associated with eosinophilia. Other mutations, namely TET2, IgE, JAK2V617F, and RAS, have associations with systemic mastocytosis as well.

• #28 Systemic Mastocytosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/203948-overview

  Mutations of the c-kit proto-oncogene may cause some forms of mastocytosis. […] Several types of somatic activating and nonactivating mutations in c-kit have been demonstrated to cause systemic mastocytosis. One of the common mutations found in systemic mastocytosis is an exon 17 D816V KIT receptor mutation. Most, if not all, adult patients with systemic mastocytosis carry this mutation. […] In the majority of patients, mastocytosis does not appear to be inherited, but rare familial cases with KIT mutations have been reported.

• #29 Systemic Mastocytosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/203948-overview

  Mutations of the c-kit proto-oncogene may cause some forms of mastocytosis. […] Several types of somatic activating and nonactivating mutations in c-kit have been demonstrated to cause systemic mastocytosis. One of the common mutations found in systemic mastocytosis is an exon 17 D816V KIT receptor mutation. Most, if not all, adult patients with systemic mastocytosis carry this mutation. […] In the majority of patients, mastocytosis does not appear to be inherited, but rare familial cases with KIT mutations have been reported.

• #30 Mastocytosis — DermNet

  https://dermnetnz.org/topics/mastocytosis

  Mastocytosis is caused by a mutation of the KIT gene on the 4q12 chromosome. This results in too many mast cells being produced. […] In rare cases, the KIT genetic defect is inherited. In most cases, it is sporadic, with no family history.

• #31 Review and Updates on Systemic Mastocytosis and Related Entities

  https://www.mdpi.com/2072-6694/15/23/5626

  Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. […] The proliferation of neoplastic MCs is usually driven by KIT mutations that activate downstream pathways including PI3K, STAT5, NF-κB, mTORC2, and PKCδ. […] The KIT D816V mutation (exon 17) is frequently detected (>90%) in adult SM. Other less common mutations at codon 816 of KIT, including D816F, D816Y, D816G, D816H, D816I, and mutations such as F522C, V560G, I817V, N819Y, L799F, D820G, N822L, N822I, InsVI815-816, E839K, S840N, and S849I, have also been reported in SM. […] KIT mutations in the extracellular domain (e.g., deletion of codon 419 in exon 8 or p.A502_Y503dup in exon 9), TM domain (e.g., KIT p.F522C), or JM domain (e.g., KIT p.V560G) are found more frequently in indolent SM. […] Germline KIT mutations have been found to be associated with familial mastocytosis.

• #32 Orphanet: Indolent systemic mastocytosis

  https://www.orpha.net/en/disease/detail/98848

  A rare, usually benign, chronic, form of systemic mastocytosis (SM) characterized by an abnormal accumulation of neoplastic mast cells (MCs) mainly in the bone marrow (BM) but also in other organs or tissues such as preferably the skin. […] Although the etiology of ISM is not fully understood, an activating mutation of KIT, usually KIT D816V, is found in the MCs of virtually all ISM cases. This mutation probably accounts for the abnormal accumulation of MCs in organ(s)/tissue(s). […] In some cases, the mutation is found primarily in the neoplastic MC compartment; in other cases, the mutation may be detected in other mature BM and peripheral blood cells such as basophils, eosinophils, neutrophils, as well as B- and T-lymphocytes. […] Furthermore, precursors of erythroid and myeloid cells as well as CD34+ progenitors may carry the KIT D816V mutation, suggesting the involvement of a pluripotent stem cell.

• #33 Orphanet: Indolent systemic mastocytosis

  https://www.orpha.net/en/disease/detail/98848

  A rare, usually benign, chronic, form of systemic mastocytosis (SM) characterized by an abnormal accumulation of neoplastic mast cells (MCs) mainly in the bone marrow (BM) but also in other organs or tissues such as preferably the skin. […] Although the etiology of ISM is not fully understood, an activating mutation of KIT, usually KIT D816V, is found in the MCs of virtually all ISM cases. This mutation probably accounts for the abnormal accumulation of MCs in organ(s)/tissue(s). […] In some cases, the mutation is found primarily in the neoplastic MC compartment; in other cases, the mutation may be detected in other mature BM and peripheral blood cells such as basophils, eosinophils, neutrophils, as well as B- and T-lymphocytes. […] Furthermore, precursors of erythroid and myeloid cells as well as CD34+ progenitors may carry the KIT D816V mutation, suggesting the involvement of a pluripotent stem cell.

• #34 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Indolent systemic mastocytosis (ISM) is the most common and typically less severe form of systemic mastocytosis. […] The main difference is that MCAS involves the inappropriate activation of normal mast cells, causing them to release their mediators excessively and inappropriately, leading to symptoms. […] However, with systemic mastocytosis, mast cells abnormally accumulate in various tissues, including the skin, bone marrow, and internal organs. […] ASM involves a rapid and extensive accumulation of abnormal mast cells in multiple organs, leading to severe symptoms such as organ dysfunction, bone fractures, and potentially life-threatening complications. […] MCL is an exceptionally rare and highly aggressive subtype in which mast cells rapidly multiply in the bone marrow and bloodstream.

• #35 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #36 Mastocytosis: Types, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/5908-mastocytosis

  Mastocytosis is an acquired genetic disorder, meaning you dont inherit the condition. It happens when KIT genes mutate (change). KIT genes play a role in developing certain cell types, including blood cells and mast cells. In mastocytosis, mutated KIT genes order mast cells to multiply uncontrollably. […] Mastocytosis happens when mast cells that protect your body from allergens and bacteria mutate (change) and become abnormal cells that set up a continuous allergic response. […] Mastocytosis is considered an incurable disease that healthcare providers manage with treatments to ease symptoms and treat complications.

• #37 Rare diseases | Systemic Mastocytosis

  https://www.istitutogentili.com/en/rare-diseases/systemic-mastocytosis/

  Systemic mastocytosis (SM) is a rare disease resulting from the clonal expansion and accumulation of abnormal mast cells in various organs and tissues throughout the body. […] Mutations in the c-KIT gene activate the KIT receptor, even in the absence of its ligand. […] This mechanism favours cell proliferation, reduces programmed cell death and, consequently, the accumulation of mast cells in certain organs and tissues of the human body.

• #38 Rare diseases | Systemic Mastocytosis

  https://www.istitutogentili.com/en/rare-diseases/systemic-mastocytosis/

  Systemic mastocytosis (SM) is a rare disease resulting from the clonal expansion and accumulation of abnormal mast cells in various organs and tissues throughout the body. […] Mutations in the c-KIT gene activate the KIT receptor, even in the absence of its ligand. […] This mechanism favours cell proliferation, reduces programmed cell death and, consequently, the accumulation of mast cells in certain organs and tissues of the human body.

• #39 Review and Updates on Systemic Mastocytosis and Related Entities

  https://www.mdpi.com/2072-6694/15/23/5626

  Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. […] The proliferation of neoplastic MCs is usually driven by KIT mutations that activate downstream pathways including PI3K, STAT5, NF-κB, mTORC2, and PKCδ. […] The KIT D816V mutation (exon 17) is frequently detected (>90%) in adult SM. Other less common mutations at codon 816 of KIT, including D816F, D816Y, D816G, D816H, D816I, and mutations such as F522C, V560G, I817V, N819Y, L799F, D820G, N822L, N822I, InsVI815-816, E839K, S840N, and S849I, have also been reported in SM. […] KIT mutations in the extracellular domain (e.g., deletion of codon 419 in exon 8 or p.A502_Y503dup in exon 9), TM domain (e.g., KIT p.F522C), or JM domain (e.g., KIT p.V560G) are found more frequently in indolent SM. […] Germline KIT mutations have been found to be associated with familial mastocytosis.

• #40 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Mastocytosis is a disorder in which abnormal mast cells are increased in one or more organs. […] The growth of mast cells is poorly controlled, sometimes as the result of mutations that produce clones, or identical copies, of cells. […] Mutations in KIT that keep the switch ON are the cause of mastocytosis. […] The most common mutation, called KIT D816V, produces a receptor that is constantly activated resulting in continuous growth and activation of mast cells. […] In addition to the increase in mediators as the result of increased numbers, abnormal mast cells in mastocytosis can be prone to release mediators more easily in general. […] Mastocytosis can occur in both children and adults, with a predominance for cutaneous mastocytosis in children and systemic mastocytosis in adults.

• #41 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #42 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #43 Mast cell activation syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Mast_cell_activation_syndrome

  There are many causes of mast cell activation, including allergy. Genetics may play a role. In particular, mutations of the KIT gene (which codes for the KIT protein that regulates cell growth), specifically around codon 816 with the common one being asp816val, have been suspected to be associated with MCAS and is also associated to most systemic mastocytosis patients. […] It has been found that people with MCAS tend to have a wider range of KIT mutations around all domains of the protein and multiple at the same time rather than a single one, which could be a potential cause of the heterogeneity of the presenting symptoms of MCAS. […] Symptoms of MCAS are caused by excessive chemical mediators released by mast cells. […] Mediators include leukotrienes, histamines, prostaglandin, and tryptase.

• #44 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #45 Mast cell activation syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Mast_cell_activation_syndrome

  There are many causes of mast cell activation, including allergy. Genetics may play a role. In particular, mutations of the KIT gene (which codes for the KIT protein that regulates cell growth), specifically around codon 816 with the common one being asp816val, have been suspected to be associated with MCAS and is also associated to most systemic mastocytosis patients. […] It has been found that people with MCAS tend to have a wider range of KIT mutations around all domains of the protein and multiple at the same time rather than a single one, which could be a potential cause of the heterogeneity of the presenting symptoms of MCAS. […] Symptoms of MCAS are caused by excessive chemical mediators released by mast cells. […] Mediators include leukotrienes, histamines, prostaglandin, and tryptase.

• #46 Mayo Clinic Health Library – Systemic mastocytosis | Swiss Medical Network

  https://www.swissmedical.net/en/healtcare-library/con-20306103

  Most cases of systemic mastocytosis are caused by a random change (mutation) in the KIT gene. Typically this flaw in the KIT gene is not inherited. Too many mast cells are produced and build up in tissues and body organs, releasing substances such as histamine, leukotrienes and cytokines that cause inflammation and symptoms.

• #47 Systemic Mastocytosis: Causes, Symptoms, Diagnosis, and Treatment

  https://www.webmd.com/allergies/systemic-mastocytosis

  Systemic mastocytosis doesn’t usually run in families. A random change (mutation) in the KIT gene shows up in mast cells in people with mastocytosis. This gene helps program a protein that’s in charge of how cells grow. It also plays a role in the way mast cells develop. […] If you have systemic mastocytosis, certain triggers cause mast cells to release chemicals and cause symptoms. They aren’t the same for everyone, but common triggers include: Alcohol, Spicy foods, Changes in temperature, Insect stings, Stress or anxiety, Surgery, Vaccines, Certain medicines, such as aspirin, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs). […] It’s also possible to get symptoms without any triggers.

• #48 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #49 Advanced systemic mastocytosis

  https://www.medicalnewstoday.com/articles/advanced-systemic-mastocytosis

  Genetic mutation of the KIT genes plays a role in the development of advanced systemic mastocytosis, leading to the atypical buildup of mast cells in one or more tissues. […] The KIT genes control chemical signaling pathways that instruct the growth of different cells in the body, including mast cells. […] Certain factors may activate the mast cells. Possible triggers include: friction, minor injury, surgery, temperature changes, insect stings, some vaccines, anxiety or stress, certain medications, such as opioids, aspirin, and nonsteroidal anti-inflammatory drugs.

• #50 Systemic Mastocytosis: Causes, Symptoms, Diagnosis, and Treatment

  https://www.webmd.com/allergies/systemic-mastocytosis

  Systemic mastocytosis doesn’t usually run in families. A random change (mutation) in the KIT gene shows up in mast cells in people with mastocytosis. This gene helps program a protein that’s in charge of how cells grow. It also plays a role in the way mast cells develop. […] If you have systemic mastocytosis, certain triggers cause mast cells to release chemicals and cause symptoms. They aren’t the same for everyone, but common triggers include: Alcohol, Spicy foods, Changes in temperature, Insect stings, Stress or anxiety, Surgery, Vaccines, Certain medicines, such as aspirin, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs). […] It’s also possible to get symptoms without any triggers.

• #51 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #52 Advanced systemic mastocytosis

  https://www.medicalnewstoday.com/articles/advanced-systemic-mastocytosis

  Genetic mutation of the KIT genes plays a role in the development of advanced systemic mastocytosis, leading to the atypical buildup of mast cells in one or more tissues. […] The KIT genes control chemical signaling pathways that instruct the growth of different cells in the body, including mast cells. […] Certain factors may activate the mast cells. Possible triggers include: friction, minor injury, surgery, temperature changes, insect stings, some vaccines, anxiety or stress, certain medications, such as opioids, aspirin, and nonsteroidal anti-inflammatory drugs.

• #53 Systemic Mastocytosis: Causes, Symptoms, Diagnosis, and Treatment

  https://www.webmd.com/allergies/systemic-mastocytosis

  Systemic mastocytosis doesn’t usually run in families. A random change (mutation) in the KIT gene shows up in mast cells in people with mastocytosis. This gene helps program a protein that’s in charge of how cells grow. It also plays a role in the way mast cells develop. […] If you have systemic mastocytosis, certain triggers cause mast cells to release chemicals and cause symptoms. They aren’t the same for everyone, but common triggers include: Alcohol, Spicy foods, Changes in temperature, Insect stings, Stress or anxiety, Surgery, Vaccines, Certain medicines, such as aspirin, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs). […] It’s also possible to get symptoms without any triggers.

• #54 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #55 Systemic Mastocytosis: Causes, Symptoms, Diagnosis, and Treatment

  https://www.webmd.com/allergies/systemic-mastocytosis

  Systemic mastocytosis doesn’t usually run in families. A random change (mutation) in the KIT gene shows up in mast cells in people with mastocytosis. This gene helps program a protein that’s in charge of how cells grow. It also plays a role in the way mast cells develop. […] If you have systemic mastocytosis, certain triggers cause mast cells to release chemicals and cause symptoms. They aren’t the same for everyone, but common triggers include: Alcohol, Spicy foods, Changes in temperature, Insect stings, Stress or anxiety, Surgery, Vaccines, Certain medicines, such as aspirin, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs). […] It’s also possible to get symptoms without any triggers.

• #56 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #57 Mastocytosis: Testing & Treatment | Frontier Allergy Austin

  https://www.frontierallergist.com/conditions/mastocytosis/

  Mastocytosis is a rare disorder in which an abnormally high level of mast cells build up throughout the body. […] Most cases of mastocytosis are caused by a mutation in the KIT gene. The KIT gene normally encodes a protein that helps control important cellular processes, such as cell growth, cell division, and cell movement. The KIT gene mutation that causes mastocytosis causes the overproduction of mast cells. In most cases, this mutation is spontaneous without a very clearly defined genetic component. […] Symptoms of mastocytosis can be triggered by a variety of different substances or environmental factors. Although triggers vary from person to person, the common triggers include: Consumption of alcohol and/or certain foods, Fatigue, stress, or pain, Skin irritation, Changes in temperature, Exercise, Insect bites or stings, Use of certain medications, Infections, Odors, Exposure to sunlight, Friction or vibration.

• #58 Systemic Mastocytosis: Causes, Symptoms, Diagnosis, and Treatment

  https://www.webmd.com/allergies/systemic-mastocytosis

  Systemic mastocytosis doesn’t usually run in families. A random change (mutation) in the KIT gene shows up in mast cells in people with mastocytosis. This gene helps program a protein that’s in charge of how cells grow. It also plays a role in the way mast cells develop. […] If you have systemic mastocytosis, certain triggers cause mast cells to release chemicals and cause symptoms. They aren’t the same for everyone, but common triggers include: Alcohol, Spicy foods, Changes in temperature, Insect stings, Stress or anxiety, Surgery, Vaccines, Certain medicines, such as aspirin, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs). […] It’s also possible to get symptoms without any triggers.

• #59 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #60 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #61 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #62 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #63 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #64 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Mastocytosis is a disorder in which abnormal mast cells are increased in one or more organs. […] The growth of mast cells is poorly controlled, sometimes as the result of mutations that produce clones, or identical copies, of cells. […] Mutations in KIT that keep the switch ON are the cause of mastocytosis. […] The most common mutation, called KIT D816V, produces a receptor that is constantly activated resulting in continuous growth and activation of mast cells. […] In addition to the increase in mediators as the result of increased numbers, abnormal mast cells in mastocytosis can be prone to release mediators more easily in general. […] Mastocytosis can occur in both children and adults, with a predominance for cutaneous mastocytosis in children and systemic mastocytosis in adults.

• #65 Mastocytosis and Mast Cell Activation Syndrome – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/mastocytosis-and-mast-cell-activation-syndrome

  Etiology in many cases of mastocytosis involves an activating mutation (D816V) in the gene coding for the stem cell factor receptor c-kit, which is present on mast cells. The result is autophosphorylation of the receptor, which causes uncontrolled mast cell proliferation. […] Genetic causes are suspected but not proved. Most cases do not involve clonal proliferation of mast cells but are due to a lower threshold for mast cells to degranulate.

• #66 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #67 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #68 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #69 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #70 Orphanet: Indolent systemic mastocytosis

  https://www.orpha.net/en/disease/detail/98848

  A rare, usually benign, chronic, form of systemic mastocytosis (SM) characterized by an abnormal accumulation of neoplastic mast cells (MCs) mainly in the bone marrow (BM) but also in other organs or tissues such as preferably the skin. […] Although the etiology of ISM is not fully understood, an activating mutation of KIT, usually KIT D816V, is found in the MCs of virtually all ISM cases. This mutation probably accounts for the abnormal accumulation of MCs in organ(s)/tissue(s). […] In some cases, the mutation is found primarily in the neoplastic MC compartment; in other cases, the mutation may be detected in other mature BM and peripheral blood cells such as basophils, eosinophils, neutrophils, as well as B- and T-lymphocytes. […] Furthermore, precursors of erythroid and myeloid cells as well as CD34+ progenitors may carry the KIT D816V mutation, suggesting the involvement of a pluripotent stem cell.

• #71 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #72 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #73 Review and Updates on Systemic Mastocytosis and Related Entities

  https://www.mdpi.com/2072-6694/15/23/5626

  Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. […] The proliferation of neoplastic MCs is usually driven by KIT mutations that activate downstream pathways including PI3K, STAT5, NF-κB, mTORC2, and PKCδ. […] The KIT D816V mutation (exon 17) is frequently detected (>90%) in adult SM. Other less common mutations at codon 816 of KIT, including D816F, D816Y, D816G, D816H, D816I, and mutations such as F522C, V560G, I817V, N819Y, L799F, D820G, N822L, N822I, InsVI815-816, E839K, S840N, and S849I, have also been reported in SM. […] KIT mutations in the extracellular domain (e.g., deletion of codon 419 in exon 8 or p.A502_Y503dup in exon 9), TM domain (e.g., KIT p.F522C), or JM domain (e.g., KIT p.V560G) are found more frequently in indolent SM. […] Germline KIT mutations have been found to be associated with familial mastocytosis.

• #74 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #75 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #76 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #77 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #78 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #79 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #80 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Indolent systemic mastocytosis (ISM) is the most common and typically less severe form of systemic mastocytosis. […] The main difference is that MCAS involves the inappropriate activation of normal mast cells, causing them to release their mediators excessively and inappropriately, leading to symptoms. […] However, with systemic mastocytosis, mast cells abnormally accumulate in various tissues, including the skin, bone marrow, and internal organs. […] ASM involves a rapid and extensive accumulation of abnormal mast cells in multiple organs, leading to severe symptoms such as organ dysfunction, bone fractures, and potentially life-threatening complications. […] MCL is an exceptionally rare and highly aggressive subtype in which mast cells rapidly multiply in the bone marrow and bloodstream.

• #81 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #82 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #83 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Indolent systemic mastocytosis (ISM) is the most common and typically less severe form of systemic mastocytosis. […] The main difference is that MCAS involves the inappropriate activation of normal mast cells, causing them to release their mediators excessively and inappropriately, leading to symptoms. […] However, with systemic mastocytosis, mast cells abnormally accumulate in various tissues, including the skin, bone marrow, and internal organs. […] ASM involves a rapid and extensive accumulation of abnormal mast cells in multiple organs, leading to severe symptoms such as organ dysfunction, bone fractures, and potentially life-threatening complications. […] MCL is an exceptionally rare and highly aggressive subtype in which mast cells rapidly multiply in the bone marrow and bloodstream.

• #84 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #85 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #86 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  SM-AHN is a rare subtype in which systemic mastocytosis coexists with another health condition, such as acute myeloid leukemia (AML). […] The onset of systemic mastocytosis symptoms can vary. […] Symptom variability in systemic mastocytosis is further influenced by the specific subtype of the disease. […] The subtype dictates not only the intensity of symptoms but also the overall prognosis and response to treatment. […] Mastocytosis can worsen due to triggers that prompt mast cells to release histamine and other chemicals.

• #87 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #88 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #89 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  SM-AHN is a rare subtype in which systemic mastocytosis coexists with another health condition, such as acute myeloid leukemia (AML). […] The onset of systemic mastocytosis symptoms can vary. […] Symptom variability in systemic mastocytosis is further influenced by the specific subtype of the disease. […] The subtype dictates not only the intensity of symptoms but also the overall prognosis and response to treatment. […] Mastocytosis can worsen due to triggers that prompt mast cells to release histamine and other chemicals.

• #90 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #91 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #92 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Indolent systemic mastocytosis (ISM) is the most common and typically less severe form of systemic mastocytosis. […] The main difference is that MCAS involves the inappropriate activation of normal mast cells, causing them to release their mediators excessively and inappropriately, leading to symptoms. […] However, with systemic mastocytosis, mast cells abnormally accumulate in various tissues, including the skin, bone marrow, and internal organs. […] ASM involves a rapid and extensive accumulation of abnormal mast cells in multiple organs, leading to severe symptoms such as organ dysfunction, bone fractures, and potentially life-threatening complications. […] MCL is an exceptionally rare and highly aggressive subtype in which mast cells rapidly multiply in the bone marrow and bloodstream.

• #93 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #94 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. […] In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. […] When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the „on” position. […] Mast cells in systemic mastocytosis are triggered by changes in temperature, rubbing or injury, surgeries, insect bites, vaccines, anxiety, and certain medicines like aspirin or painkillers. […] There are five subtypes of systemic mastocytosis: Indolent Systemic Mastocytosis (ISM), Smoldering Systemic Mastocytosis (SSM), Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN).

• #95 Systemic Mastocytosis: Symptoms, Subtypes, Treatment

  https://www.verywellhealth.com/systemic-mastocytosis-8669227

  Indolent systemic mastocytosis (ISM) is the most common and typically less severe form of systemic mastocytosis. […] The main difference is that MCAS involves the inappropriate activation of normal mast cells, causing them to release their mediators excessively and inappropriately, leading to symptoms. […] However, with systemic mastocytosis, mast cells abnormally accumulate in various tissues, including the skin, bone marrow, and internal organs. […] ASM involves a rapid and extensive accumulation of abnormal mast cells in multiple organs, leading to severe symptoms such as organ dysfunction, bone fractures, and potentially life-threatening complications. […] MCL is an exceptionally rare and highly aggressive subtype in which mast cells rapidly multiply in the bone marrow and bloodstream.

• #96 Mayo Clinic Health Library – Systemic mastocytosis | Swiss Medical Network

  https://www.swissmedical.net/en/healtcare-library/con-20306103

  Most cases of systemic mastocytosis are caused by a random change (mutation) in the KIT gene. Typically this flaw in the KIT gene is not inherited. Too many mast cells are produced and build up in tissues and body organs, releasing substances such as histamine, leukotrienes and cytokines that cause inflammation and symptoms.

• #97 Systemic Mastocytosis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/203948-overview

  Mutations of the c-kit proto-oncogene may cause some forms of mastocytosis. […] Several types of somatic activating and nonactivating mutations in c-kit have been demonstrated to cause systemic mastocytosis. One of the common mutations found in systemic mastocytosis is an exon 17 D816V KIT receptor mutation. Most, if not all, adult patients with systemic mastocytosis carry this mutation. […] In the majority of patients, mastocytosis does not appear to be inherited, but rare familial cases with KIT mutations have been reported.

• #98 Unraveling the Rare Entity of KIT D816V-Negative Systemic Mastocytosis | Alyamany | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/1279/843

  The prognosis of SM depends on different factors, including age, cytopenias, the WHO classification-defined subtype of SM, biochemical markers, and mutational profile. […] The presence of non-KIT mutations, such as SRSF2, ASXL1, RUNX1, and EZH2, has been associated with advanced SM subtypes and inferior prognosis. […] In cases of KIT-D816V-negative SM, these prognostic scores are controversial. […] Further and more comprehensive research is needed to expand our understanding of KIT-D816V-negative SM and determine the most appropriate management and prognosis.

• #99 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Mast cells are immune cells derived from myeloid lineage. They are usually located in the connective tissues. They are activated through immunoglobulin (Ig)E mediated and non-IgE mechanisms and thus act as effector cells in hypersensitivity and allergic reactions. In the IgE mediated mechanism, the allergen forms a cross-link with the IgE receptor, which then activates the mast cells, resulting in degranulation. Non-IgE mediated mechanisms include emotional and physical stimuli, food, drugs like opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, heat, exercise, cytokines, venoms, and hormones. The most common mediators released are histamines, proteases, cytokines, growth hormones, tumor necrosis factors, and phospholipases. Tryptases and chymases form an abundant portion of the mast cell granules. Tryptase is almost always secreted by mast cells and therefore it is used as an important diagnostic factor.

• #100 Systemic Mastocytosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/41138

  Activating and inactivating mutations of KIT are implicated in the pathogenesis of systemic mastocytosis. The precise mechanism by which KIT-activating mutations improve signaling is not thoroughly understood, but these errors lead to stem cell factor (SCF)-independent activation. KITD816V is the most common driver mutation for systemic mastocytosis. KIT mutations are mostly somatic, so they don’t seem to be inherited although, they might be present at birth. They are rarely present in the germline cells, hence not passed down to the next generation. FIP1L1-PDGFRA mutation is associated with eosinophilia. Other mutations, namely TET2, IgE, JAK2V617F, and RAS, have associations with systemic mastocytosis as well.

• #101 Systemic Mastocytosis

  https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis

  Most adult patients fit into the indolent systemic mastocytosis category. […] While they may be symptomatic, indolent systemic mastocytosis patients generally have low morbidity and normal life expectancy not different from their peers. […] Smoldering systemic mastocytosis patients have an inferior survival compared to indolent systemic mastocytosis, but the advanced age of those patients account for most of the difference. […] Indolent systemic mastocytosis patients have a low risk of progression to more severe disease, while the risk of progression to more severe disease is higher for Smoldering systemic mastocytosis patients. […] Aggressive systemic mastocytosis patients have more significant symptoms, including enlarged liver and lymph nodes, as well as blood abnormalities such as anemia and low platelets. […] Patients with systemic mastocytosis with an associated hematologic neoplasm suffer from additional problems caused by the associated blood malignancy. […] Mast cell leukemia is very rare, but comes with a difficult prognosis and shorter life span.

• #102 Unraveling the Rare Entity of KIT D816V-Negative Systemic Mastocytosis | Alyamany | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/1279/843

  The prognosis of SM depends on different factors, including age, cytopenias, the WHO classification-defined subtype of SM, biochemical markers, and mutational profile. […] The presence of non-KIT mutations, such as SRSF2, ASXL1, RUNX1, and EZH2, has been associated with advanced SM subtypes and inferior prognosis. […] In cases of KIT-D816V-negative SM, these prognostic scores are controversial. […] Further and more comprehensive research is needed to expand our understanding of KIT-D816V-negative SM and determine the most appropriate management and prognosis.

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