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Anaphylaxis
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
In some cases of anaphylaxis, a detailed history and extensive diagnostic evaluation, including testing for foods, medications, latex, exercise and insect stings are non-contributory. Idiopathic anaphylaxis is diagnosed when there is no identifiable cause or trigger for anaphylaxis (Greenberger and Lieberman 2014). To make this diagnosis, especially if there are recurrent episodes, underlying mast cell disorders (including systemic mastocytosis and monoclonal mast cell activation syndrome) should be ruled-out (Theoharides et al. 2015).
Pea
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Brain ischemia can result from a variety of disease states including trauma, hypoxia, toxicity, cytokines, etc. Mast cells are the human body’s defense against pathogens as well as inflammation. In brain ischemia, mast cells relocate to the site of damage and degranulate, causing the release of inflammatory mediators. Parrella et al.21 found that PEA, in addition to the flavonoid luteolin, exerts a mast cell modulatory effect in the context of brain ischemia cellular models. The addition of PEA-luteolin prevented the degranulation of mast cells in response to oxygen and glucose deprivation and provided a direct synergistic neuroprotective effect. This research provides a basis for the potential use of PEA in the treatment and management of brain ischemia.
Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, Dopamine, 2020
Mast cells, which are derived from myeloid progenitors, contain many secretory granules rich in histamine, serotonin, heparin, proteolytic enzymes, and cytokines [81,82]. Best known for their role in allergy and inflammation, mast cells are also involved with wound healing, angiogenesis, and in both innate and adaptive immune mechanisms. As presented in Figure 9.8, mast cells and basophils are the initiating cells for IgE-mediated allergic reactions, which are triggered when allergens cross-link preformed IgE bound to the high-affinity receptor on mast cells [81]. Once activated, mast cells induce inflammatory reactions by secreting the stored compounds, as well as by de novo synthesis of leukotrienes and cytokines. The consequences of mast cell activation depend on the dose of antigen and its route of entry (i.e., by inhalation, ingestion, or skin contact). Symptoms of allergic reactions range from the irritating sniffles of hay fever when pollen is inhaled, to the life-threatening circulatory collapse that occurs in systemic anaphylaxis. The immediate allergic reaction caused by mast cell degranulation is followed by a sustained inflammation, known as the late-phase response. The late response involves recruitment of other effector cells, notably Th2 lymphocytes, eosinophils, and basophils, which contribute to the immunopathology of an allergic response.
Drug delivery targets and strategies to address mast cell diseases
Published in Expert Opinion on Drug Delivery, 2023
Clayton H. Rische, Ariel H. Thames, Rebecca A. Krier-Burris, Jeremy A. O’Sullivan, Bruce S. Bochner, Evan A. Scott
Currently, the cutting edge of allergy and mastocytosis therapies are dominated by small molecules and biologics. Perhaps it is unsurprising, given that mast cells have proven difficult to manipulate and that some of their functions have been difficult to unravel. It has become increasingly clear that there are still gaps in the community’s approaches to treat allergy and mastocytosis. Even with the advent of new tyrosine kinase inhibitors with improved selectivity, there is a good chance that some forms of mastocytosis will be resistant to these types of drugs. Treatment of mast cell-mediated allergies and anaphylaxis has evaded the scientific community for decades. Drugs are available to manage allergic reactions and their symptoms, but therapeutic strategies to selectively, reliably, or directly ablate or modulate mast cells are lacking. Systemic mastocytosis likely requires a targeted multi-drug approach to tackle its multifarious biology across different patients. These shortcomings indicate a need for both improved methods of mast cell-selective drug delivery and a better understanding of mast cell-driven pathology. We propose that two key tools can play this role: targeted drug delivery and improved animal models.
Delayed diagnosis of adult-onset mastocytosis
Published in Baylor University Medical Center Proceedings, 2022
Annia Cavazos, Paul Subrt, Jaime A. Tschen
Mastocytosis is manifested as an increase in mast cells in various systems. Mast cells originate from pluripotent progenitor cells expressing the CD34 antigen and exist as two major phenotypes based on the presence of serine proteases tryptase and chymase.1 The diagnosis of systemic mastocytosis is made based on the presence of the major criterion—multifocal, dense infiltrates of mast cells detected in bone marrow or other extracutaneous organ—and one minor criterion or at least three minor criteria. The criteria are a) serum tryptase >20 ng/mL; b) mast cells in the bone marrow, blood, or extracutaneous organ expressing CD2 and/or CD25; c) detection of activating point mutation at codon 816 of KIT in bone marrow, blood, or extracutaneous organs; d) in biopsy >25% of mast cell infiltrate being spindle-shaped or atypical morphology or, among all mast cells in bone marrow aspirate smears, >25% being immature or atypical.2 In patients with insect sting anaphylaxis, an elevated serum tryptase level has been related to clonal mast cell disease. Thus, it is important to evaluate the clinical pattern at presentation as well as laboratory markers and consider a bone marrow biopsy for a specific diagnosis.3
Hypnotherapy in Treatment of Mastocytosis: A Prospective Study
Published in International Journal of Clinical and Experimental Hypnosis, 2021
Frédérique Retornaz, Michel Grino, Audrey Vanhaudenhuyse, Laurent Chiche, Chloé Stavris, Myriam Bennani, Marie Elisabeth Faymonville, Anouk Alitta
Mastocytosis is one of the orphan diseases (fewer than 5 to 10 cases per million per year) and is probably underdiagnosed (Barete, 2014). In France in 2006, 1300 cases of mastocytosis were reported by the Association Française pour les Initiatives de Recherche sur le Mastocyte et les Mastocytoses (AFIRMM: French Association for Research Initiatives on Mastocytes and Mastocytosis; Georgin-Lavialle et al., 2009). Mastocytosis is related to the activation and/or abnormal proliferation of mast cells in one or more organs (Pardanani, 2016). Mast cells are major effector cells of the immune system and play a major role in allergies and anaphylaxis, angiogenesis, bacterial and parasitological defenses, and blood-brain barrier function. Mast cells are characteristically found surrounding blood vessels and nerves and in the external and internal milieu (e.g., the skin, lungs and gastrointestinal tract). Mastocytosis is a mast cell clonal disorder leading to excessive proliferation and abnormal degranulation of mast cells. In 90% of adults and 35% of childhood mastocytosis cases, a C-KIT D816V point mutation (tyrosine kinase) can be detected (Bodemer. et al., 2010; Valent et al., 2017). In other childhood cases of mastocytosis, KIT mutations concern other loci.