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Immunology and Allergy Clinics of North... Feb 2014Mastocytosis is a disorder of abnormal mast cell proliferation, with clinical features that include flushing, pruritus, abdominal pain, diarrhea, hypotension, syncope,... (Review)
Review
Mastocytosis is a disorder of abnormal mast cell proliferation, with clinical features that include flushing, pruritus, abdominal pain, diarrhea, hypotension, syncope, and musculoskeletal pain. These features are the result of mast cell mediator release and infiltration into target organs. Patients of all ages may be affected, although in children, manifestations primarily involve the skin. Most patients with systemic disease have a somatically acquired activating mutation in the KIT oncogene. This article discusses the causes and pathogenesis of mastocytosis, with an overview of the clinical features and the approach to diagnosis, evaluation, and therapy in adults and pediatric patients.
Topics: Disease Progression; Humans; Mastocytosis; Prognosis; Treatment Outcome
PubMed: 24262698
DOI: 10.1016/j.iac.2013.09.001 -
International Journal of Molecular... Nov 2020Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory... (Review)
Review
Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual's baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where -mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor -mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where -mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.
Topics: Diagnosis, Differential; Genetic Predisposition to Disease; Humans; Mast Cells; Mastocytosis; Precision Medicine
PubMed: 33261124
DOI: 10.3390/ijms21239030 -
International Journal of Molecular... May 2021Mastocytosis is a heterogeneous group of hematologic neoplasms defined by an accumulation of neoplastic mast cells (MC) in the skin, bone marrow, and other visceral...
Mastocytosis is a heterogeneous group of hematologic neoplasms defined by an accumulation of neoplastic mast cells (MC) in the skin, bone marrow, and other visceral organs [...].
Topics: Bone Marrow; Diagnosis, Differential; Hematologic Neoplasms; Humans; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Skin
PubMed: 34068468
DOI: 10.3390/ijms22095024 -
Medicina (Kaunas, Lithuania) Jan 2021Mast cell disorders comprise a wide spectrum of syndromes caused by mast cells' degranulation with acute or chronic clinical manifestations. In this review article we... (Review)
Review
Mast cell disorders comprise a wide spectrum of syndromes caused by mast cells' degranulation with acute or chronic clinical manifestations. In this review article we reviewed the latest findings in scientific papers about mast cell disorders with a particular focus on mast cell activation syndrome and mastocytosis in pediatric age. Patients with mast cell activation syndrome have a normal number of mast cells that are hyperreactive upon stimulation of various triggers. We tried to emphasize the diagnostic criteria, differential diagnosis, and therapeutic strategies. Another primary mast cell disorder is mastocytosis, a condition with a long-known disease, in which patients have an increased number of mast cells that accumulate in different regions of the body with different clinical evolution in pediatric age. Mast cell activation syndrome overlaps with different clinical entities. No consensus was found on biomarkers and no clearly resolutive treatment is available. Therefore, a more detailed knowledge of this syndrome is of fundamental importance for a correct diagnosis and effective therapy.
Topics: Biomarkers; Child; Diagnosis, Differential; Humans; Mast Cells; Mastocytosis; Syndrome
PubMed: 33573161
DOI: 10.3390/medicina57020124 -
Chemical Immunology and Allergy 2010It is known that patients with mastocytosis have an increased risk of anaphylaxis. This also appears to be the case with patients with evidence of a clonal mast cell... (Review)
Review
It is known that patients with mastocytosis have an increased risk of anaphylaxis. This also appears to be the case with patients with evidence of a clonal mast cell disorder resulting in the monoclonal mast cell activation syndrome (MMAS) who do not express the full mastocytosis phenotype. Most patients with mastocytosis are recognized by their characteristic skin lesions. An increased level of baseline serum mast cell tryptase is also an indicator for a possible clonal mast cell disorder including mastocytosis. Other markers for mast cell clonality and for mastocytosis include abnormal immunostaining of mast cells with CD25 and CD2, clustering of mast cells in tissues, abnormal mast cell morphology, and the presence of a mutation in the proto-oncogene c-kit encoding for the mast cell growth receptor KIT. As recognition depends on an understanding of mastocytosis, and this disease should be considered in patients with recurrent anaphylaxis, we describe the features of mast cell clonality, MMAS and mastocytosis, and review recent findings.
Topics: Anaphylaxis; Antigens, CD; Biomarkers; Cell Degranulation; Cell Movement; Cell Proliferation; Clone Cells; Humans; Mast Cells; Mastocytosis; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins c-kit; Skin Diseases; Tryptases
PubMed: 20519885
DOI: 10.1159/000315946 -
Blood Oct 2022Avapritinib, a highly selective inhibitor of KIT D816V, was approved by the Food and Drug Administration in 2021 for treatment of advanced systemic mastocytosis (AdvSM)...
Avapritinib, a highly selective inhibitor of KIT D816V, was approved by the Food and Drug Administration in 2021 for treatment of advanced systemic mastocytosis (AdvSM) and by the European Medicines Agency in 2022 for AdvSM after prior systemic therapy. The phase 1 EXPLORER and phase 2 PATHFINDER trials demonstrated that avapritinib can elicit complete and durable clinical responses and molecular remission of KIT D816V. Key management challenges relate to the complex mutational landscape of AdvSM, often found with an associated hematologic neoplasm.
Topics: Humans; Mastocytosis; Mastocytosis, Systemic; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Pyrazoles; Pyrroles; Triazines
PubMed: 35877999
DOI: 10.1182/blood.2021014612 -
Journal of Investigational Allergology... 2014Mastocytosis is a clonal disorder characterized by proliferation and accumulation of mast cells in various tissues, mainly skin and bone marrow. It can cause a wide... (Review)
Review
Mastocytosis is a clonal disorder characterized by proliferation and accumulation of mast cells in various tissues, mainly skin and bone marrow. It can cause a wide variety of clinical manifestations-other than urticaria pigmentosa-that can lead to inappropriate release of mediators by mast cells. The most severe manifestation is anaphylaxis. The triggers of anaphylaxis in adults with mastocytosis are numerous, but Hymenoptera stings seem to be the most frequent, followed by foods and drugs. Therefore, to prevent severe reactions, it is very important to recognize and avoid potential triggers; in addition, venom-allergic patients must receive lifelong immunotherapy, which has proven very effective. Given that published data on drug anaphylaxis in patients with mast cell disorders are scarce, it is not currently possible to provide clear recommendations. The risk of systemic reactions during general anesthesia can be reduced by assessing risk on an individual basis (previous reaction to a drug or reaction during surgery) and by avoiding specific trigger factors (patient temperature changes, infusion of cold solution, tissue trauma, friction, and other mechanical factors).
Topics: Anaphylaxis; Animals; Arthropod Venoms; Drug Hypersensitivity; Humans; Hymenoptera; Mastocytosis; Tryptases
PubMed: 25345299
DOI: No ID Found -
Ugeskrift For Laeger Feb 2016Mastocytosis is a heterogeneous disease with an increased number and activation of mast cells. Subtypes range from benign to rare aggressive forms, and the disease may... (Review)
Review
Mastocytosis is a heterogeneous disease with an increased number and activation of mast cells. Subtypes range from benign to rare aggressive forms, and the disease may affect people of all ages. The pathogenesis involves mutations in the KIT gene in both children and adult patients. Estimated prevalence is one per 10,000, but the disease is very likely underdiagnosed. The diagnosis may be challenging and patients may present to several medical specialties. This article presents an overview of clinical signs and symptoms as well as a diagnostic algorithm and treatment options of mastocytosis.
Topics: Adult; Algorithms; Anaphylaxis; Child; Humans; Mastocytosis; Osteoporosis
PubMed: 27063008
DOI: No ID Found -
Dermatologie (Heidelberg, Germany) May 2023Mastocytosis in children is a rare disease characterized by an abnormal accumulation of tissue mast cells. Mastocytosis in children presents with typical skin... (Review)
Review
Mastocytosis in children is a rare disease characterized by an abnormal accumulation of tissue mast cells. Mastocytosis in children presents with typical skin alterations that are classified as maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis, or mastocytoma. Some patients also develop mast cell mediator symptoms, such as pruritus, flush, and anaphylaxis. In many children, the disease is characterized by a benign and usually self-limiting course; systemic mastocytosis with extracutaneous involvement and a chronic or progressive course is found only rarely. Therapeutically, H1 antihistamines are primarily used on an as-needed basis or as continuous treatment, depending on the severity. Children, parents and caregivers should be thoroughly educated about the clinical picture and possible trigger factors of mast cell mediator release. For children with extensive skin alterations and severe symptoms, the prescription of an epinephrine auto-injector is recommended for emergency treatment.
Topics: Humans; Child; Mastocytosis; Mast Cells; Urticaria Pigmentosa; Mastocytosis, Systemic; Mastocytosis, Cutaneous
PubMed: 37140636
DOI: 10.1007/s00105-023-05168-9 -
Blood Feb 2013Mast cell leukemia (MCL) is a very rare form of aggressive systemic mastocytosis accounting for < 1% of all mastocytosis. It may appear de novo or secondary to previous... (Review)
Review
Mast cell leukemia (MCL) is a very rare form of aggressive systemic mastocytosis accounting for < 1% of all mastocytosis. It may appear de novo or secondary to previous mastocytosis and shares more clinicopathologic aspects with systemic mastocytosis than with acute myeloid leukemia. Symptoms of mast cell activation-involvement of the liver, spleen, peritoneum, bones, and marrow-are frequent. Diagnosis is based on the presence of ≥ 20% atypical mast cells in the marrow or ≥ 10% in the blood; however, an aleukemic variant is frequently encountered in which the number of circulating mast cells is < 10%. The common phenotypic features of pathologic mast cells encountered in most forms of mastocytosis are unreliable in MCL. Unexpectedly, non-KIT D816V mutations are frequent and therefore, complete gene sequencing is necessary. Therapy usually fails and the median survival time is < 6 months. The role of combination therapies and bone marrow transplantation needs further investigation.
Topics: Disease Progression; Humans; Leukemia, Mast-Cell; Mast Cells; Mastocytosis, Systemic
PubMed: 23243287
DOI: 10.1182/blood-2012-07-442400