MAST CELL ACTIVATION - AIMA€¦ · SANDEEP GUPTA. WHAT ARE MAST CELLS? Found in all tissues of...
Transcript of MAST CELL ACTIVATION - AIMA€¦ · SANDEEP GUPTA. WHAT ARE MAST CELLS? Found in all tissues of...
DR. SANDEEP GUPTAM A S T C E L L A C T I V A T I O N
WHAT ARE MAST CELLS?Found in all tissues of body, especially(around) blood vessels & nerves
Skin, Lungs
Digestive tract
Mouth, Nose
Blood brain barrier
Triggered byIgE & IgG antibodies
Antigens (allergens, bacteria, viruses, fungi, toxins)
Cytokines (inflammation)
Drugs, Physical activity, Hormones
C3a, C5a
When triggered releaseHistamines
Prostaglandins
Heparin
Tryptase
Cytokines (IL-6 et al, MMP-9, TGF-b1)
Other (VEGF, PAI-1)
WHAT IS MAST CELL ACTIVATION SYNDROME?
Mast Cell Disorders
Primary
Mastocytosis
Monoclonal mast cell activation syndrome
Secondary
Allergic disorders
Chronic inflammation or cancer
physical / autoimmune urticarias
Idiopathic
MCAS
Anaphylaxis
Angiodema
Urticarias
First described in early ‘90s but
Not named until 2007
SYMPTOMS OF MCAS
Skin
Flushing, itching, heat, hives, pain
Cardiovascular
Hypotension or hypertension, POTS,
tachycardia
Head
Headaches, migraines, brain fog, anxiety,
depression, vertigo, irritability
GI
Nausea, stomach aches, bloating, cramping,
constipation, loose stools, leaky gut, dysbiosis,
crohn’s disease
Menstrual
Pelvic pain, PMS, endometriosis
Respiratory
Nasal congestion, runny nose, sneezing,
itchy/watery eyes, mucous, wheezing
Systemic
Fatigue, food, drug, chemical sensitivities
NEUROLOGICAL EFFECTS OF MAST CELLS
“MCs play a critical role in neuroinflammation, which is facilitated by their close proximity to nerve fibres in the periphery and meninges of the spinal cord and the
brain”.
“Multifaceted activation of MCs releasing neuropeptides, cytokines and other mediators has direct effects on the neural system as well as neurovascular
interactions. Emerging studies have identified the release of extracellular traps, a phenomenon traditionally meant to ensnare invading pathogens, as a cause of MC-
induced neural injury”.
Extracellular traps involve citrullination of histone proteins and are dependent on ROS formation and engagement of toll-like receptor 4 (TLR4)
Reference: Mittal, A. et al. (2019). Mast Cell Neural Interactions in Health and Disease. Front Cell Neuro.
NEUROLOGICAL SYMPTOMS OF MCAS
Headaches Brain fog
Insomnia
Difficulties with tinnitus, balance and
co-ordination
A N E C D O T A L L Y M C A S H A S B E E N A S S O C I A T E D W I T H A L M O S T
E V E R Y C A S E 0 F S E V E R E S E N S I T I V I T Y I H A V E S E E N
BIOMARKER TESTING
Tryptase(serum)
Chromogranin A (serum)
Eosinophilic Cationic Protein (ECP)
Histamine(chilled plasma or whole blood)
Matrix Metalloproteinase-9
N-methylhistamine(24 hr urine)
Increase over baseline of 20% (+ 2 ng/mL)
OR baseline > 15 (NR < 11.5 ng/mL)
No definitive test(s)
MCAS is a clinical diagnosis
Can aid diagnosis and help to
track treatment
Can be elevated but rule out heart failure, renal
problems, tumors and PPI use
WB NR 28-51 ug/L
NR < 200 mcg/g
Abnormal is above 350mg/dl
PGF2a NR < 1000 ng/24h
MCAS AND OTHER CONDITIONS
CIRSMCAS 30-50%
MCAS also involved in
Allergies & Asthma
Autism
Autoimmune disorders
(hasthimoto’s, lupus, MS, RA,
eczema)
Celiac disease
ME/CFS, Fibromyalgia
Food allergy and intolerances
GERD
Infertility
Interstitial cystitis
IBS
Migraines
Mood disorders
MCS
POTS
& more
TREATMENT – REMOVE TRIGGERS
mold illnessS IM P L EMADE
MCAS
Metals, plastics,
pesticides
Allergens, foods,
physical triggers
CIRS/mold, stealth
infections
Block the mediator
Stablisemast cells
Remove triggers
TREATMENT OF MCAS – FINDING & TREATING CAUSATIVE FACTORS
Mould exposure
(internal or external)
Oxalosis
Glyphosate & heavy metal
toxicity
Mould exposure
(internal or external)
Oxalosis
Bartonella and other bacterial infections
Parasitic infections
Glyphosate and heavy
metal toxicity
Anti-histamines
H1 blockers
Doxepine
Diphenydramine(Benadryl, Unisom)
Cetririzine(Zyrtec)
Loratadine(Clarityne)
H2 blockers
Famotidine (Pepcid)Cimetidine (Tagamet)
Ranitidine(Zantac)
TREATMENT OF MCAS –PHARMACEUTICALS
Can be administered IV as a
rescue therapy
TREATMENT OF MCAS – PHARMACEUTICALS (CONT.)
mold illnessS IM P L EMADE
Mast cell stabilizers
Cromolyn Ketotifen Hyroxyurea
Leukotriene inhibitors
Montelukast(Singulair)
Zafilukast(Accolate)
Tyrosine kinase inhibitors
Imatinib
Often agents of choice
TREATMENT – SUPPLEMENTS
Natural anti-histamines & mast cell stabilizers
DAO Enzymes
Probiotics
Medicinal cannabis
•Quercetin, luteolin rutin, blackseed oil
•B6 / P5P
•Omega 3s, curcumin Alpha lipoic acid
•NAC / SAMe, B12, methylfolate
•Umbrellux DAO(15-20 min before meals)
•Lactobacillus rhamnosus
•Bifidobacter sppSpore-based probiotics
•TCH & CBD combined products (eg 60% CBD, 40% THC)
TREATMENT – LOW HISTAMINE DIET
mold illnessS IM P L EMADE
• Raw and cured meats
• Processed and smoked fish
CuredMeat
• Alcohol
• Chocolate
• NutsTreats
• Soy sauce and fermented soy
• Aged cheese
• Pickles
Fermented foods
• Spinach (large quantities) / Citrus fruits
• Tomatoes, ketchup/tomato sauces
• Artificial food colorings & preservatives
• Yeast, yeast extracts
Other
Avoid/reduce
TREATMENT - PRIORITIZATION
Removal from Mold
MCAS(Mast Cell Activation Syndrome)
Nutrient Support (KPU etc)
VirusesParasitesBabesia/Bartonella
Ehrlichia/Anaplasma
Borrelia Other
Stealth infectionsMARCoNS
Questions and Answers
mold illnessS IM P L EMADE