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Blood Apr 2020Systemic mastocytosis (SM) has greatly benefited from the broad application of precision medicine techniques to hematolymphoid neoplasms. Sensitive detection of the... (Review)
Review
Systemic mastocytosis (SM) has greatly benefited from the broad application of precision medicine techniques to hematolymphoid neoplasms. Sensitive detection of the recurrent KIT D816V mutation and use of next-generation sequencing (NGS) panels to profile the genetic landscape of SM variants have been critical adjuncts to the diagnosis and subclassification of SM, and development of clinical-molecular prognostic scoring systems. Multilineage KIT involvement and multimutated clones are characteristic of advanced SM (advSM), especially SM with an associated hematologic neoplasm (AHN). A major challenge is how to integrate conventional markers of mast cell disease burden (percentage of bone marrow mast cell infiltration and serum tryptase levels) with molecular data (serial monitoring of both KIT D816V variant allele frequency and NGS panels) to lend more diagnostic and prognostic clarity to the heterogeneous clinical presentations and natural histories of advSM. The approval of the multikinase/KIT inhibitor midostaurin has validated the paradigm of KIT inhibition in advSM, and the efficacy and safety of second-generation agents, such as the switch-control inhibitor ripretinib (DCC-2618) and the D816V-selective inhibitor avapritinib (BLU-285) are being further defined in ongoing clinical trials. Looking forward, perhaps the most fruitful marriage of the advances in molecular genetics and treatment will be the design of adaptive basket trials that combine histopathology and genetic profiling to individualize treatment approaches for patients with diverse AHNs and relapsed/refractory SM.
Topics: Animals; Chromosome Aberrations; Hematopoietic Stem Cell Transplantation; Humans; Mastocytosis, Systemic; Mutation; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Pyrazoles; Pyrroles; Staurosporine; Triazines
PubMed: 32106312
DOI: 10.1182/blood.2019000932 -
The Journal of Small Animal Practice Jul 2022Cutaneous and subcutaneous mast cell tumours are common neoplasms in the dog. While the majority can be treated with adequate local therapy alone, a subset demonstrates... (Review)
Review
Cutaneous and subcutaneous mast cell tumours are common neoplasms in the dog. While the majority can be treated with adequate local therapy alone, a subset demonstrates a biologically aggressive behaviour associated with local recurrence or metastasis. This article reviews the diagnosis and tumour staging of canine mast cell tumours alongside treatment options and the evidence supporting their use. In addition, prognostic markers are evaluated to highlight how one can recognise mast cell tumours that may behave in a biologically aggressive manner as well as the challenges of tumours that are large, infiltrative or in locations not amenable to wide surgical excision.
Topics: Animals; Dog Diseases; Dogs; Mast Cells; Mastocytosis, Cutaneous; Neoplasm Staging; Skin; Skin Neoplasms
PubMed: 34671978
DOI: 10.1111/jsap.13444 -
Journal of Anesthesia Oct 2023Patients with mastocytosis have an increased risk of anaphylaxis during surgical procedures with general anesthesia. Therefore, we reviewed the anesthesia course of a... (Review)
Review
PURPOSE
Patients with mastocytosis have an increased risk of anaphylaxis during surgical procedures with general anesthesia. Therefore, we reviewed the anesthesia course of a large cohort of patients with mastocytosis.
METHODS
We retrospectively reviewed adult and pediatric patients with mastocytosis who underwent surgical procedures with general anesthesia at Mayo Clinic from January 1, 2000, through June 30, 2021. We also included any procedures with general anesthesia that occurred during the 3-year period preceding mastocytosis diagnosis and designated the patients who underwent these procedures as having an unknown diagnosis at the time of their surgical procedure. We analyzed whether patients received chronic antimediator treatment for mastocytosis and/or prophylactic medications before the procedures. We also determined whether medications indicative of mastocytosis-related adverse events were intraoperatively administered.
RESULTS
We identified 113 patients who underwent 219 procedures during the study period; 25 procedures were performed before mastocytosis diagnosis. Of 194 procedures in patients with known mastocytosis, patients received chronic antimediator therapy and/or perioperative prophylactic medications for 178 (91.8%) procedures. Among these procedures, 10 were potentially complicated by mast cell activation, which was inferred from administration of inhaled albuterol (n = 3) or intravenous diphenhydramine (n = 8). In addition, there was only one case of intraoperative anaphylaxis which occurred in a patient who underwent anesthesia before mastocytosis diagnosis and therefore did not receive prophylaxis.
CONCLUSION
Intraoperative anaphylaxis can be the first presenting sign of mastocytosis. Patients with mastocytosis who received chronic antimediator therapy and/or preoperative prophylactic medications had an uneventful surgical course.
Topics: Adult; Humans; Child; Anaphylaxis; Retrospective Studies; Mastocytosis; Anesthesia, General; Albuterol
PubMed: 37466804
DOI: 10.1007/s00540-023-03228-x -
Pediatrics in Review Aug 2021
Topics: Humans; Mastocytosis
PubMed: 34341090
DOI: 10.1542/PIR.2020-0108 -
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 -
Journal of Obstetrics and Gynaecology :... Oct 2020Mast cell activation syndrome (MCAS) is a chronic multisystem disease of aberrant constitutive and reactive mast cell mediator release causing generally inflammatory,... (Review)
Review
Mast cell activation syndrome (MCAS) is a chronic multisystem disease of aberrant constitutive and reactive mast cell mediator release causing generally inflammatory, allergic, and dystrophic issues. The pathobiology of MCAS drives extraordinary clinical complexity and heterogeneity, which led to only recent recognition despite increasingly apparent substantial prevalence, perhaps as high as 17%. It also has a strong female predilection. Thus, MCAS inescapably impacts pregnancy and the post-partum period in many women. No specific research in the pregnant or post-partum MCAS population has been performed yet. However, its prevalence and potential for driving substantial morbidity merit obstetric providers' acquaintance with this illness and its potential impacts on their patients during pregnancy, delivery, the post-partum period, and lactation. Extensive literature review across all medical specialities, plus direct experience in the authors' practices, provides guidance in recognising MCAS in pregnancy and diagnosing and effectively managing it. Described herein are manners in which MCAS, a protean multisystem disease, adversely affects all stages of pregnancy and post-partum. In order to reduce risks of MCAS causing complications before, during and after pregnancy, identifying and controlling the syndrome prior to pregnancy is best, but, even if the disease is not recognised until late, there may still be opportunities to mitigate its effects. There is precedent for improved outcomes if comorbid MCAS is recognised and controlled. This review provides the first comprehensive guide for obstetric providers regarding this emerging major comorbidity.
Topics: Delivery, Obstetric; Female; Humans; Labor, Obstetric; Lactation; Mast Cells; Mastocytosis; Postpartum Period; Pregnancy; Pregnancy Complications
PubMed: 32148151
DOI: 10.1080/01443615.2019.1674259 -
The Journal of Allergy and Clinical... Jul 2023Anaphylaxis results from massive mast cell activation. Mechanisms of mast cell activation may involve IgE- and non-IgE-mediated triggers, clonal mast cell disease, or be... (Review)
Review
Anaphylaxis results from massive mast cell activation. Mechanisms of mast cell activation may involve IgE- and non-IgE-mediated triggers, clonal mast cell disease, or be idiopathic and may be modified by several factors including but not restricted to hormonal status, stress, heritable factors, mast cell burden, and simultaneous exposure to more than 1 factor. Patients with recurrent anaphylaxis with a nonidentifiable trigger present a particular challenge in diagnosis and management. Presence of clonal disease may be suggested by hypotensive episodes with urticaria and angioedema, and high baseline tryptase levels. A number of scoring systems have been developed to identify patients who are at high risk to have underlying mastocytosis. This review provides an overview of anaphylaxis disorders and our current understanding of their mechanisms of action, evaluation, and management.
Topics: Humans; Anaphylaxis; Mastocytosis; Mast Cells; Hypotension; Urticaria; Tryptases
PubMed: 37220812
DOI: 10.1016/j.jaip.2023.05.012 -
Immunology and Allergy Clinics of North... Nov 2023To a large extent, the clinical picture of pediatric mastocytosis depends on the age at which it is diagnosed. A neonate with diffuse cutaneous mastocytosis may... (Review)
Review
To a large extent, the clinical picture of pediatric mastocytosis depends on the age at which it is diagnosed. A neonate with diffuse cutaneous mastocytosis may frequently present in a severe state requiring treatment. Toddlers may require long-term anti-mediator therapy, and this may lead to concerns such as organizing preschool education due to the need for epinephrine injections. A teenager may have to face cutaneous disease persistence or a diagnosis of systemic mastocytosis. Further studies are needed to refine the available treatment options and prognosis for different age groups.
Topics: Child, Preschool; Infant, Newborn; Adolescent; Child; Humans; Mastocytosis; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Prognosis
PubMed: 37758405
DOI: 10.1016/j.iac.2023.04.001 -
Immunology and Allergy Clinics of North... Nov 2023
Topics: Humans; Mast Cells; Mastocytosis
PubMed: 37758414
DOI: 10.1016/j.iac.2023.08.001 -
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