I will add more explanations and commentary in the future, but for now I want to make this information available, so I am posting this as a sorted list of links.
Good summary of the basics from a pamphlet from The Mastocytosis Society Canada
"Mast cell (MC) activation disorders present with multiple symptoms including flushing, pruritus, hypotension, gastrointestinal complaints, irritability, headaches, concentration/memory loss and neuropsychiatric issues. These disorders are classified as: cutaneous and systemic mastocytosis with a c-kit mutation and clonal MC activation disorder, allergies, urticarias and inflammatory disorders and mast cell activation syndrome (MCAS), idiopathic urticaria and angioedema. MCs are activated by IgE, but also by cytokines, environmental, food, infectious, drug and stress triggers, leading to secretion of multiple mediators. The symptom profile and comorbidities associated with these disorders, such as chronic fatigue syndrome and fibromyalgia, are confusing. We propose the use of the term 'spectrum' and highlight the main symptoms, useful diagnostic tests and treatment approaches."
Mast Cell Activation Symptomatology (Part 1 of 3), Part 2, and Part 3
These short videos on YouTube are a good introduction to mast cells and mast cell disease.
Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome by Dr. L. Afrin
Immunology and clinical manifestations of Non-Clonal Mast Cell Activation Syndrome
Autoimmune progesterone anaphylaxis.
One of the ways that MCAS has been differentiated from SM (Systemic Mastocytosis) has been whether or not a mutation has been found in the C-KIT gene. This has resulted in SM and one rare form of MCAS being considered "monoclonal" disorders, while MCAS has not been seen this way. In a presentation given by Dr Afrin he explains that current evidence points to MCAS also being a clonal disorder of the c-kit gene. This is significant because it means there may not be "one" MCAS, but many different related disorders that differ in symptoms and treatment needs.
"What Dr. Molderings discovered back in 2007, and there was a follow-up paper just last summer (2010) confirming and further extending these findings, is that just as systemic mastocytosis is a clonal disease largely of the D816V mutation in KIT, mast cell activation syndrome is a clonal disease, too, but it is a pool of many different clones. There are many different mutations. Dozens of mutations have been found, and they are scattered across all pieces of KIT [slide 37]. Each mutation leads KIT to behave in a different way, driving the cells to produce different aberrant mediator expression patterns leading to different clinical presentations. And it gets worse (with respect to trying to understand MCAS as a single entity): most patients have multiple KIT mutations, and so far there has been little apparent linkage amongst the different mutations. And then there’s another twist that makes the situation worse yet: we’ve also learned that most of these patients also have mutations in other genes and proteins that are integral to mast cell function."
These cells produce and express dozens of mediators. One mutation leads to aberrant expression of maybe not all mediators in the mast cell but probably a sizable subset. But there are multiple mutations in most patients with mast cell disease including mast cell activation syndrome. How any one mutation might interact with any other one or multiple mutations remains to be determined. And there are multiple genes beyond just KIT that are mutated in most myeloproliferative disease
patients. And when you go to that “COPE with Cytokines” website, it will really hit this home for you. Each mediator doesn’t cause just one problem. Each mediator has an entire array, a unique array, of effects – direct effects, indirect effects, local effects, and remote effects – so when you do all the multiplying implicit in all of this biology math, you begin to understand why this disease could present with such extreme heterogeneity."
Mast Cell: A Multi-Functional Master Cell
Mast Cells and Disease Processes
Mast Cell Regulation of the Immune Response
The Role of Mast Cells in the Defense Against Pathogens
The Role of Mast Cells in Bacterial Infection
Development, migration, and survival of mast cells
Electron microscopicol evidence for a direct contact between nerve fibres and mast cells
“mast cells may play an important part in the function of neurons.”
What Causes Mast Cell Disease?
The genetic basis of mast cell activation disease
Transgenerational transmission of systemic mast cell activation disease—genetic and epigenetic features
Genetic cause of Vibratory Urticaria found and here
Testing and Diagnosis of Mast Cell Diseases
The Physician's Guide to Laboratory Testing for Mast Cell Disorders
24-hour N-methylhistamine urine test
"NMH levels may be depressed in individuals who have a polymorphism in the histamine-N-methyl transferase gene, which encodes the enzyme that catalyzes NMH formation. This polymorphism results in an amino acid change that decreases the rate of NMH synthesis."
Testing for Prostaglandin D2 in urine
Bone Marrow Biopsies for the Diagnosis of Systemic Mastocytosis
(found that one biopsy is not sufficient to detect SM in all cases)
What triggers mast cells to react (degranulate)?
List of common mast cell triggers from the site MastoKids
Mitochondrial calcium and mast cell degranulation
Silver nanoparticles are mast cell triggers
Environmental estrogens induce mast cell degranulation and increase IgE allergy
The Lyme Disease spirochete Borrelia burgforgeri induces mast cell degranulation
Systemic hypoxia induces mast cell degranulation (altitude for example)
Ragweed pollen induces mast cell release of mediators by inducing mito dysfunction
Stress can trigger mast cells
Many infections can trigger mast cells, including yeast, strep, staph, herpes infections and Lyme.
Role of female sex hormones, estradiol and progesterone, in mast cell behaviorMast cells have "clock genes" that make them more reactive at night
Mast cell mediators (what they release):
Introduction to Prostaglandins
More on prostaglandins and how to inhibit them
Neural circuitry engaged by prostaglandins during the sickness syndrome
Mast cells produce and release serotonin
Serotonin in immune and neuroimmune function
Serotonin is a chemotactic factor for eosinophils
Polyamines are selective regulators of serotonin release from mast cells
Serotonin reduces allergic inflammation
Treating mast cell disease
Medications used to help mast cell patients tend to address symptoms rather than cause, such as antihistamines and the anti-leukotriene med Singulair. There are 4 known histamine receptors, labeled H1 through H4. The antihistamine meds that most of us are familiar with, such as Benadryl, Claritin and Zyrtec are examples of H1 blockers. H2 receptors are associated with stomach acid production when stimulated, which is why H2 blockers are used to reduce acid fro treatment of acid reflux. These receptors are also involved in smooth muscle relaxation, antibody production,
Antihistamines by Receptor Activity
The use of continuous benadryl infusion via pump to control severe MCAS
What stabilizes mast cells so they react less:
The prescription medications that are commonly used to stabilize mast cells include Cromolyn Sodium (also called Gastrocrom) and Ketotifen (which is not FDA approved and needs to be obtained through a compounding pharmacy). Other medications including medical cannabis and the benzodiazepines are thought to also stabilize mast cells but the exact mechanism isn't fully understood. They do bring a lot of relief to a lot of mast cell patients.
Immunomodulation of mast cells by nutrients
Mast cells and mast cell mediators as targets of dietary supplements
Quercetin more effective than Cromolyn
How quercetin and luteolin help brain inflammation from mast cells
Green tea contains a mast cell stabilizer
Chondroitin sulphate inhibits connective tissue mast cells
Chondroitin Sulfate as a mast cell stabilizer
Mast cell stabilizing potential of Camel milk
Anti-inflammatory and anti-oxidative effect of curcumin in connective tissue type mast cell
Antihistamine foods (be aware that many of these foods can also be potent mast cell triggers)
Progesterone may stabilize mast cells
Vitamin D stabilizes mast cells
Emergency Room Information and Resources
Emergency Care for Patients with Mast Cell Disorders
Emergency Room Protocols
A handy reference guide to provide everything you need for emergency room visits as a patient with a Mast Cell Disorder (from The Mastocytosis Society)
Mast Cell Activation Disease and methylation
Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy?
Mast cells and adrenal function
Mast cells in the brain and psychiatric effects:
Mast Cells and Stress- a psychoneuroimmunological perspective
Mast cell disease causes neurological and psychiatric symptoms and diseases
Mast cells regulate blood-brain-barrier permeability from acute stress
Mast cells can cause permeability of the blood-brain-barrier and contribute to neurological disorders
The Role of Mast Cells in Alzheimer's Disease.
Mast cells and migraine pathways
Microglia and mast cells: two tracks on the road to neuroinflammation.
Mast Cell Disease can manifest as Mixed Organic Brain Syndrome (psychiatric symptoms)
Brain mast cells link the immune system to anxiety-like behavior.
Mast cell activation and autism
Neuro-inflammation, blood-brain barrier, seizures and autism
“Allergic Symptoms” in Children with Autism Spectrum Disorders. More than Meets the Eye?Activated mast cells excrete mitochondrial components, triggering autoimmunity
Children with autism have elevated levels of mast cell mediators in their blood
Mercury causes mast cells to release pro-inflammatory mediators
Is a subtype of autism an allergy of the brain?
Focal Brain Inflammation in Autism
Neuroinflammation and Autism
In the gut:
Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside.Intestinal mast cells in gut inflammation and motility disturbances
Mast Cell Activation in Gallbladder Disease
Mast cell–nerve axis with a focus on the human gut
Mast cells and Cyclic Vomiting Syndrome (also migraine and leaky gut)
In neurological conditions:
Mast Cells, histamine, and hydroxyzine in MS
Mast cells may lead to abnormal nerve growth such as Neurofibromatosis
Mast cells are involved in the pathogenesis of neurofibromas
In the heart
Cardiovascular symptoms in patients with systemic mast cell activation disease
Evidence for a Role of Mast Cells in the Evolution to Congestive Heart Failure
"These observations suggest that mast cells play a critical role in the progression of heart failure. Stabilization of mast cells may represent a new approach in the management of heart failure."
Cardiac mast cells: the centerpiece in adverse myocardial remodelling
Mast Cell Disease and Ehlers-Danlos Syndrome
(these are the slides from a presentation done by Dr Anne Maitland, with good info on mast cell disease as well as discussing the EDS connection)
Role and Relevance of Mast Cells in Fungal Infections
Interstitial Cystitis more on MCAS and Interstitial Cystitis/Bladder Pain Syndrome
Mast Cells in Intersitial Cystitis
The role of mast cells in atherosclerosis
Mast Cells and Myelofibrosis
Mast Cells and Spondyloarthritis