Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and a proposed procedure for diagnosis
Shao-heng He, Hui-yun Zhang, Ping-chang Yang, et.al.
Acta Pharmacologica Sinica volume 34, pages1270–1283
Hi all of you Masterminds! We’re looking for doers and helpers!! See our call for volunteers below. 
- We are looking for a couple of additional FB Page editors and moderators with a professional research sciences or medical research background, research methods and indexes literate, love to read and summarize some of these arcane papers, and who can help dig out the best and latest science based mast cell research.
Please email me at: mast.don@bensfriends.org with a short vitae so we can start a dialogue.
…
…
- As you probably know, your wonderful Ben’s Friends community, Living With Mast Cell, is run by volunteers.
Because of fellow rare disease patients, their friends and family, who donate some of their time, we have safe and supportive space.
But so much still needs to be done such as
• Finding more individuals who could benefit from our secure website
• Better educating our members
• and of course, ensuring that our community continues to be here for us…
Would you like to join our team of wonderful volunteers who makes these things possible?
We’re hoping to gather a group of members with a variety of skills and talents who we can call on “just in case”.
What are we looking for?
• We’re looking for whatever you do well:
• Write promotional materials
• Organize or run fundraisers
• Act as a medical resource person
• Create music
• Email organizations to promote Ben’s Friends
• Organize or make instructional or promotional videos
• Create designs for use on our sites
• Provide a legal opinion if necessary
• Make a slick lesson for our online classroom
What’s your superpower?
Let us know, please join Ben’s Friends at the web address: http://www.livingwithmastcell.org/
and send a short email with contact information and reference Mast Cell Community if you want to help to : info@bensfriends.org
- Have you seen all the communities we support? WOW!. Here’s a link to other rare disease communities that Ben’s Friends helps with to share with friend or family that might need a safe group to talk with.
Reducing transmission of SARS-CoV-2
Kimberly A. Prather1, Chia C. Wang2,3, Robert T. Schooley4
1Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92037, USA.2Department of Chemistry, National Sun Yat-sen University, Kaohsiung, Taiwan 804, Republic of China
3Aerosol Science Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan 804, Republic of China
4Department of Medicine, Division of Infectious Diseases and Global Public Health, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Science 26 Jun 2020:
Vol. 368, Issue 6498, pp. 1422-1424
DOI: 10.1126/science.abc6197
https://science.sciencemag.org/content/368/6498/1422/tab-pdf
Article that goes with the paper
Systemic Mastocytosis Involving the Gastrointestinal Tract Case Report and Review
Amir Behdad, MD; Scott R. Owens, MD
Mastocytosis is rare, and is actually a heterogeneous group of diseases that may only involve the skin (urticaria pigmentosa) or that may have a systemic presentation with multiorgan involvement.
The gastrointestinal (GI) tract can be affected and symptoms related to GI involvement are often nonspecific. The diagnosis of systemic mastocytosis with primarily GI presentation can be challenging and requires familiarity with this entity and a high index of suspicion.
We report a case of systemic mastocytosis primarily diagnosed by the recognition of small intestinal and colonic involvement and review the diagnostic criteria, histopathology, and recent developments regarding this entity.
(Arch Pathol Lab Med. 2013;137:1220–1223; doi: 10.5858/arpa.2013-0271-CR)
https://www.archivesofpathology.org/doi/abs/10.5858/arpa.2013-0271-CR
Gastrointestinal manifestations in mastocytosis: A study of 83 patients
Harry Sokol, MD, PhD ∗,et.al.
MC neoplasms are related to the clonal proliferation of MCs secondary to a gain-of-function mutation of the proto-oncogene c-Kit.
Adults with mastocytosis usually present D816V mutations in c-Kit, the tyrosine kinase receptor of stem cell factor (SCF) expressed on MCs, but the mechanisms that drive the multiple phenotypic and clinical manifestations of this myeloproliferative disorder are not clear.
Currently, expression of CD2, CD25, or both by MCs is considered pathognomonic evidence for the pathologic status of MCs, and thus it is used as a minor criterion for the diagnosis of MC disorders.
https://www.jacionline.org/article/S0091-6749(13)00844-0/fulltext
The Staining of Mast Cells: A Historical Overview
Ribatti D.
The specificity of several staining methods for mast cells provides the pathologist with a useful means for the differential diagnosis of mast cell tumors. Mast cells stain metachromatically with toluidine blue with greater intensity in cells containing smaller granules. Most stains for mast cells rely on the cell’s content of heparin, other glycosaminoglycans, and esterase. As an alternative to histochemical stains, different antibodies have been used to identify mast cells in humans.
COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms
Robert Malone, et.al.
Very good paper on Adverse Drug Reactions with definitions to help you talk with your pharmacist and physician.
William Smith
Department of Clinical Immunology and Allergy, Royal Adelaide Hospital, South Australia.
Adverse drug reactions
Allergy? Side-effect? Intolerance?
Austrailian Fam Physician
Volume 42, No.1, January/February 2013 Pages 12-16
Assessment of an ADR may apply to a current reaction or a history of a past reaction. The main decision is whether to cease the drug and/or whether it can be used again.
Some ADRs are serious and likely to be reproducible and constitute absolute contraindications, whereas others are mild and may or may not occur on subsequent exposure.
The mechanism of the ADR may be helpful in risk assessment.
Drug allergy has immunological mechanisms: it may be severe, tends to be reproducible and may cross-react with structurally related drugs.
Drug side-effects are more common and predictable, vary in severity and depend on the drug’s pharmacological action.
Intolerance tends to be less severe, and may depend on susceptibility factors, which can vary.
The decision to prescribe a drug where there is a history of a previous ADR requires careful assessment of the risks and potential benefits.
Neuropsychological Features of Adult Mastocytosis
Daniela S. Moura, et.al.
2014, Immunology and Allergy Clinics of North America
Mastocytosis is defined as an excessive accumulation of mast cells in several organs or tissues. In most cases, the disease is indolent and does not reduce life expectancy. The disease is associated, however, with an underestimated chronic disability, presumably
linked to the release of mast cell mediators by abnormal mast cells that includes flushes and the well-defined gastrointestinal symptoms, cardiovascular instability, and skin involvement, in particular pruritus and esthetic concerns. In addition, it is well recognized that in almost one-third of the patients, general symptoms, including fatigue and musculoskeletal pain, could also have a major impact on the quality of life. Although less recognized and less attributed to mediators released from abnormal mast cells, symptoms, such as headache, anxiety, mood, and cognitive impairment, are frequent and should be specifically evaluated because they may require specific therapies and are associated with significant impairment of social life and professional activities. In this review, in addition to the authors’ studies on psychiatric and neurologic disorders, the major recent findings concerning neuropsychological symptoms in mastocytosis are reviewed
and data supporting the hypothesis that abnormal mast cell activation and to a less extent mast cell accumulation are involved in these disorders are discussed.
Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome
Theoharis C. Theoharides, Irene Tsilioni, and Mona Bawazeer
Fibromyalgia Syndrome (FMS) is a disorder of chronic, generalized muscular pain, accompanied by sleep disturbances, fatigue and cognitive dysfunction. There is no definitive pathogenesis except for altered central pain pathways.
We previously reported increased serum levels of the neuropeptides substance P (SP) and its structural analogue hemokinin-1 (HK-1) together with the pro-inflammatory cytokines IL-6 and TNF in FMS patients as compared to sedentary controls.
We hypothesize that thalamic mast cells contribute to inflammation and pain, by releasing neuro-sensitizing molecules that include histamine, IL-1β, IL-6 and TNF, as well as calcitonin-gene related peptide (CGRP), HK-1 and SP.
These molecules could either stimulate thalamic nociceptive neurons directly, or via stimulation of microglia in the diencephalon.
As a result, inhibiting mast cell stimulation could be used as a novel approach for reducing pain and the symptoms of FMS.
Strike 3! The Perturbed Axis of Mast Cells, Nerves, and Connective Tissues… - The Ehlers Danlos Society
Dr Anne Maitland
In a study published online May 14 in eLife, the scientists demonstrated for the first time that banishing mast cells — or blocking signals from the most common stimulus activating them in real life, or disabling a cartilage-degrading enzyme they release when activated — all protected mice from developing osteoarthritis induced by an experimental procedure. The results were supported by findings in human cells and tissues.
Mast Cells in Early Rheumatoid Arthritis
Felice Rivellese, Francesca Wanda Rossi, […], and Amato de Paulis
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation of the synovial membrane, with thickening of the synovial layer, cellular hyperplasia, and infiltration of immune cells.
Mast cells (MCs) are cells of the innate immunity present in healthy synovia and part of the cellular hyperplasia characterizing RA synovitis. Although their presence in synovia has been well described, the exact functions and the correlation of MCs with disease development and progression have been debated, particularly because of contradictory data obtained in animal models and from patients with longstanding disease.
Here, we present a revision of the literature on MCs in RA, including the most recent observations obtained from patients with early RA, indicating MCs as relevant markers of disease severity in early RA.
IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis
Qian Wang,et.al
Stanford University
RESEARCH COMMUNICATION May 14, 2019
Roles of mast cells in rheumatoid arthritis
Hong Ki Min, Kyoung-Woon Kim, […], and Hae-Rim Kim
ACTIVATION OF MAST CELL IN RHEUMATOID ARTHRITIS
MC is activated via various pathways, and the activated MC secretes mediators, stimulates other immune cells and local synoviocytes, and recruits circulating inflammatory cells into the RA synovium.
Preformed mediators (histamine, heparin, and proteases) are excreted from MCs by immediate immune response; however, MCs are also capable of producing and excreting various lipid-derived mediators, cytokines, and chemokines [24]. The aforementioned de novo production is mediated by several immunologic stimulations.
MCs are activated by various stimulants such as the immunoglobulins-Fc receptor interaction, toll-like receptors (TLRs), chemokines, cytokines, pathogen-associated molecular patterns (PAMP), or neuropeptides [11]. The MCs are mainly activated via IgE stimulations, and MCs from RA are also stimulated by the IgE-FcεR interaction [16,17].
The MCs possess not only FcεR, but also Fc gamma receptor (FcγR), and therefore, they can be activated even with IgG, which is the major immunoglobulin produced under chronic inflammatory status such as RA.
Mariella, Fusco & Skaper, Stephen & Coaccioli, Stefano & Paladini, Antonella & Varrassi, Giustino.
Degenerative Joint Diseases and Neuroinflammation.
Pain Practice. 17. 10.1111/papr.12551.
Accompanying osteoarthritis is rheumatoid arthritis, which is a chronic systemic disease that often causes pain and deformity. At least 50% of those affected are unable to remain gainfully employed within 10 years of disease onset.
A growing body of evidence now points to inflammation, locally and more systemically, as a promoter of damage to joints and bones, as well as joint-related functional deficits. The pathogenesis underlying joint diseases remains unclear; however, it is currently believed that crosstalk between cartilage and subchondral bone—and loss of balance between these 2 structures in joint diseases—is a critical element.
This view is amplified by the presence of mast cells, whose dysregulation is associated with alterations of junction structures (cartilage, bone, synovia, matrix, nerve endings, and blood vessels). In addition, persistent activation of mast cells facilitates the development of spinal neuroinflammation mediated through their interaction with microglia.
Unfortunately, current treatment strategies for rheumatic and articular disease are symptomatic and do little to limit disease progression.
Research now should be directed at therapeutic modalities that target osteoarticular structural elements and thereby delay disease progression and joint replacement.
Disorders of Flushing
STEVEN H. YALE, SHIKHA VASUDEVA,
JOSEPH J. MAZZA, LOREN ROLAK, JODI
ARROWOOD, SARA STICHERT, AND ERIK S.
STRATMAN
INTRODUCTION
Flushing is the term used to describe a warm, transient
redness of the skin caused by increased cutaneous blood
flow because of capillary dilatation. Flushing disorders
are distinguished on the basis of their frequency, duration, and temporal association with endogenous or
exogenous exposures such as drug and other organic
compounds (Table 1). A variety of chemical mediators
including endogenous enkephalins, endorphins,
prostaglandins, and histamine are known to induce
flushing (1–4). Recognizing the role that these chemical
mediators and other neurotransmitters play in the pathogenesis of flushing provides a rational basis for
management of clinical symptoms.
PATHOPHYSIOLOGY
Flushing has a predilection for the face, neck, and upper
chest where the upper dermis is the thinnest, capacitance
is greatest, and less tissue fluid is obstructing the superficial cutaneous vasculature (5). Neural, immunological,
and direct neurohumoral mechanisms are involved in the
pathogenesis of flushing. Neural-induced flushing (wet
flush) is distinguished from immunological and direct
humoral causes (dry flush) by the presence of sympathetic cholinergic neuronal activation of ecrine sweat
glands (6,7).
ORIGINAL ARTICLE
Disorders of flushing encompass a broad spectrum
of diverse acquired and inherited conditions. Chemical mediators involved in the flushing response are
incompletely understood. Flushing episodes rarely
can be associated with significant morbidity and
mortality. The goal of the physician is to separate
benign from potentially life-threatening conditions.
Accurate diagnosis requires a thorough history and
physical examination emphasizing the age of the
patient, temporal association of flushing with occupation, environmental, stress, food, or drug exposure, and the duration of the episode. In some
cases, despite a thorough evaluation, the etiology
for flushing remains unknown. Understanding the
distinct mechanisms that lead to flushing helps
provide a rational approach to treatment.
https://www.academia.edu/keypass/SHlpdGJIbTJZUGU3QkQ
1cFQyei84dzkyVVZsdHU2K2Z4NXVNNjBQUFB6cz0tLThWQlZWRFhEbHhrQWZtZ0pScFRSTEE9PQ==–8f2992160b7bde6b3e022ce0cf067708ffee30a9/t/fHyAR-NX75aQt-6EEFv/resource/work/32371339/Disorders_of_Flushing?email_work_card=view-paper
Flushing Disorders Associated With Gastrointestinal Symptoms: Part 2, Systemic Miscellaneous Conditions
Vaibhav Rastogi , Devina Singh , Joseph J Mazza , Dipendra Parajuli , Steven H Yale
PMID: 29650526 PMCID: PMC6108508 DOI: 10.3121/cmr.2017.1379b
Flushing disorders with involvement of the gastrointestinal tract represent a heterogeneous group of conditions.
In part 1 of this review series, neuroendocrine tumors (NET), mast cell activation disorders (MCAD), and hyperbasophilia were discussed. In this section we discuss the remaining flushing disorders which primarily or secondarily involve the gastrointestinal tract. This includes dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.
With the exception of paroxysmal pain disorders, panic disorders and some medications, these disorders presents with dry flushing. A detailed and comprehensive family, social, medical and surgical history, as well as recognizing the presence of other systemic symptoms are important in distinguishing the different disease that cause flushing with gastrointestinal symptoms.
Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila
Vaibhav Rastogi, MD,Devina Singh, MD, Joseph J. Mazza, MD, Dipendra Parajuli, MD, and Steven H. Yale, MD
Clin Med Res. 2018 Jun; 16(1-2): 16–28.
doi: 10.3121/cmr.2017.1379a
The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing.
This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.