Post Orgasmic Illness Syndrome (P.O.I.S.)

POIS Cause/Treatment Discussions => General Alternative Causes and Treatments of POIS => Topic started by: Muon on February 29, 2020, 06:56:19 AM

Title: MCAD Diagnostic Testing, Mediators & Treatment Options
Post by: Muon on February 29, 2020, 06:56:19 AM
See the Mast Cell Activation Syndrome thread (https://poiscenter.com/forums/index.php?topic=2301.msg18956#msg18956) for a discussion about mast cell disorders. Let me know in the comments below if you see interesting treatment in literature for Mast Cell Activation Disease (MCAD) especially for the MCAD subtype Mast Cell Activation Syndrome (MCAS) and non-IgE mediated mast cell activation.

Articles below that make use of sci-hub links and are not working: Change .tw to .se and vice versa in the URL.

Symptoms and Triggers

https://www.mastzellaktivierung.info/en/symptoms.html

https://www.mastzellaktivierung.info/en/therapy_triggers.html

Parameters for diagnostic testing

These are relatively/somewhat specific, tryptase is the only unique parameter but not useful in MCAS (https://en.wikipedia.org/wiki/Mast_cell_activation_syndrome). They are being tested when symptomatic. Urine samples need to be refrigerated at all times.

Heparin (https://journals.plos.org/plosone/article%3Fid%3D10.1371%252Fjournal.pone.0124912) (Plasma)

Chromogranin A (Serum)

Prostaglandin D2 (PGD2) (24h urine, D2 metabolites below are more stable)

11-beta-Prostaglandin F2alpha or 2,3-Dinor-11-beta-Prostaglandin F2alpha or 9alpha, 11beta-Prostaglandin F2 (24h urine, optional plasma)

N-Methylhistamine or N-Methylimidazoleacetic acid (https://hmdb.ca/metabolites/HMDB0002820) (24h urine) or Histamine (Plasma) (Warning: Histamine itself is stable for less than 1 minute)

LTE4 (https://en.wikipedia.org/wiki/Leukotriene_E4) (24h urine)(LTC4 holds the largest share of LTs in MCs. This will degrade to LTE4 which is stable for a longer time.)

Tryptase (Rarely shows up in MCAS, sometimes being tested in saliva when oral mucosal problems present)

Relative utility of assorted mast cell mediators in diagnosing mast cell activation syndrome (MCAS). (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T6/)

First morning urine can be used instead of 24h urine collection:
Dr. Theoharides: "We collected both 24-hour urine as well as first morning urine. Unless someone has nocturia, the results were about the same. That makes it much easier for a patient. Roughly the first morning urine collection about eight hours worth of urine during the night. We got the same results." Ref (https://www.drkarafitzgerald.com/2018/11/20/mast-cell-clinical-researcher-dr-theoharides/)

Medical terminology: Labs may use terminology like methylhistamine or urine histamine for N-methylhistamine or use PGF2 for PGD2 metabolites (Warning: there are PGF2 molecules that are not PGD2 metabolites). Ask them what kind of metabolite they are offering.

11-beta-Prostaglandin F2alpha seems to pop up in many papers as relatively more reliable compared to the other ones from the above selection. Although there are a few papers that make a case for Heparin.

Proposed diagnostic criteria and algorithms

Current provisional criteria to define mast cell activation syndrome (MCAS) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/table/Tab3/)

Table 2 & Figure 2 (https://www.tandfonline.com/doi/full/10.3109/07853890.2016.1161231):

1) Major criteria 1 + Major critera 2

Or

2) Major criteria 2 + at least one minor criterion

Proposed diagnostic rubric for mast cell mediator disorders (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/figure/F1/)

Mast Cell Mediator Release Syndrome Questionnaire:

Mast Cell Activation Syndrome: A Primer for the Gastroenterologist (https://sci-hub.se/10.1007/s10620-020-06264-9)

Surface-bound expression markers

CD117/CD2 and CD117/CD25

CD117: Classical mast cell marker (standard surface-bound molecule for mast cell recognition).
CD117/CD2: Looking for CD2 co-expression on CD117 mast cells. CD2 shouldn't be there.
CD117/CD25: Idem for CD25 which doesn't belong on CD117 mast cells.

Common routine tests

Common abnormalities in routine hematologic and serum chemistry tests found in the study population. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T5/)

Note:
"general laboratory abnormalities in these MCAS patients were common but typically modest in degree (i.e., only slightly above or below the upper or lower limit of normal, respectively) and thus less commanding of attention when viewed as isolated results rather than recurrent findings."

Selective vitamin deficiencies like Vitamin D is common among MCAS patients. Ref 1 (https://www.mastattack.org/2014/10/metabolic-issues-associated-with-mcas/), Ref 2 (https://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf)

Other ways to observe mast cell activity

"Single cell laser microcapture and qRT-PCR should be used to identify mast cell phenotype variability and mediator synthesis/release in situ." Ref (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/)

"Electron microscopy using time lapse photography on bladder biopsies from IC/BPS patients and controls to see if the mast cells in the biopsies of IC/BPS patients are degranulating at a more frequent rate, or releasing inflammatory mediators without degranulating compared to the control group."Ref (https://tau.amegroups.com/article/view/8090/8845)

Genetic alterations related to mast cell activation disease

Table 2 & figure 3 (https://sci-hub.se/10.1016/j.critrevonc.2014.09.001)

More papers discussing genetic alterations: Ref 1 (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2567.2012.03627.x), Ref 2 (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076241)

Eosinophil co-activation markers

Mast cells are known to communicate with eosinophils. Eosinophil activation could be probed by measuring unique eosinophil-derived mediators:

Charcot-Leyden crystals (https://en.wikipedia.org/wiki/Charcot%E2%80%93Leyden_crystals) composed of eosinophil protein galectin-10
Eosinophil cationic protein (ECP) (https://en.wikipedia.org/wiki/Eosinophil_cationic_protein)
Eosinophil-derived neurotoxin (EDN or Eosinophil protein X (EPX)) (https://en.wikipedia.org/wiki/Eosinophil-derived_neurotoxin)
Eosinophil peroxidase (https://en.wikipedia.org/wiki/Eosinophil_peroxidase)
*Major basic protein (MBP) (https://en.wikipedia.org/wiki/Major_basic_protein)
MBP homolog (MBP2)

*Also found in MCs but highly specific for eosinophils

Endothelial cells

Mast cells are sitting next to the endothelium of the inner lining of blood vessels and can interact easily with endothelial cells.
Endothelial degranulation via Weibel-Pallade bodies (https://en.wikipedia.org/wiki/Weibel%E2%80%93Palade_body):

Major components:

von Willebrand Factor (https://en.wikipedia.org/wiki/Von_Willebrand_factor) (vWF or Factor VIII related antigen, also found in MCs)
P-selectin (https://en.wikipedia.org/wiki/P-selectin)

Additional Weibel-Pallade components:

Interleukin-8
Eotaxin-3
Endothelin-1
Angiopoietin-2
Osteoprotegerin
P-selectin cofactor CD63/lamp3
?-1,3-fucosyltransferase VI

Other:
Plasminogen activator inhibitor type 1 (https://en.wikipedia.org/wiki/Plasminogen_activator_inhibitor-1) (PAI-1, by mast cell-derived exosomes (https://www.ahajournals.org/doi/full/10.1161/01.atv.0000172007.86541.76))

Comorbidity related testing

"Premature osteopenia/osteoporosis is frequently found in mast cell disease patients and is usually diffuse but may be focal."Ref (https://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf)
Osteoporosis/Osteopenia/Osteosclerosis: Bone mineral density measurements (DXA scan (https://en.wikipedia.org/wiki/Dual-energy_X-ray_absorptiometry))

Small intestinal bacterial overgrowth (SIBO) (https://journals.lww.com/ajg/Fulltext/2019/10001/Small_Intestinal_Bacterial_Overgrowth_Is_Common_in.1194.aspx) (Solution: Lactulose, gases: Hydrogen+Methane)

"Irritable/inflammatory bowel syndrome (IBS) is commonly diagnosed by gastroenterologists consulting on MCAS patients..."Ref (https://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf)
Irritable Bowel Syndrome (Table 2. Biomarker candidates in IBS (https://sci-hub.tw/10.1016/j.molmed.2009.08.001))

Conditions Often Comorbid With Mast Cell Diseases (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/table/T2/)

Supplementary Table 4. Allergic and non-allergic diseases for which pathogenetic involvement of mast cells has been demonstrated or suspected (https://www.tandfonline.com/doi/suppl/10.3109/07853890.2016.1161231?scroll=top)

Human mast cell types

Human MCs are classified by their content of serine proteases.

MCT: Tryptase-only, predominate in the alveolar septa (93%) and in the small intestinal mucosa (98%).
MCC: Chymase-only, present in synovial tissue.
MCTC: Both tryptase- and chymase-positive MCs, predominant subtype in skin (88%), tonsils and small intestinal submucosa (87%).

Mast Cell Mediators

Mast cells can release selectively. They could release/secrete one mediator or a small selection, that's why some authors suggest a new subtype of MCAD called Mast Cell Mediator Disease. Testing negative for the parameters used for diagnosis (at the top of this thread) doesn't exclude MCAD but diagnosis is less likely, other mediators below might be elevated but they aren't sufficient specific to aid diagnosis. Mediator profiles may vary among patients resulting in different symptomatology. Patients who have symptom overlap may share a mediator abnormality. This is an example (https://www.mastattack.org/2016/05/symptoms-mediators-and-mechanisms-a-general-review-part-1-of-2/) of how you could approach mediator testing.

MC mediators exclusive for rats or mice could have made it into the list below accidentally, not all papers make a distinction. And some have been detected only at the mRNA level.

5-hydroxyeicosatetraenoicacid (5-HETE) (https://en.wikipedia.org/wiki/5-Hydroxyeicosatetraenoic_acid)  (Ref) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520518/figure/fig3/)
?-D-galactosidase (https://en.wikipedia.org/wiki/Beta-galactosidase)
Beta-glucosaminidase
Beta-glucuronidase (https://en.wikipedia.org/wiki/Beta-glucuronidase)
Beta-Hexosaminidase (https://en.wikipedia.org/wiki/Hexosaminidase) ( Carbohydrate processing)
ACTH (https://en.wikipedia.org/wiki/Adrenocorticotropic_hormone)
ADAMTSs (https://en.wikipedia.org/wiki/ADAMTS)
Adenosine triphosphate (ATP) (https://en.wikipedia.org/wiki/Adenosine_triphosphate)
Annexin A1 (https://en.wikipedia.org/wiki/Annexin_A1) (Lipocortin I, Ref (https://www.ncbi.nlm.nih.gov/pubmed/26803520))
Angiogenin (Ribonuclease 5) (https://en.wikipedia.org/wiki/Angiogenin)
Angiopoietin (https://en.wikipedia.org/wiki/Angiopoietin)
Arylsulfatase A (https://en.wikipedia.org/wiki/Arylsulfatase_A) (Cerebroside sulfatase)
Arylsulfatase B (https://en.wikipedia.org/wiki/Arylsulfatase_B)
Antizyme inhibitor 2 (AzI2) (https://en.wikipedia.org/wiki/AZIN2)
Bradykinin (https://en.wikipedia.org/wiki/Bradykinin)
BDNF (https://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor) (Premature ejaculation, depression, burnout, sensitivity to stress)
Calcitonin gene-related peptide (https://en.wikipedia.org/wiki/Calcitonin_gene-related_peptide)
Carboxypeptidase A3 (https://en.wikipedia.org/wiki/CPA3) (CPA3)
Cathelicidin antimicrobial peptide LL-37 (https://en.wikipedia.org/wiki/Cathelicidin)
Cathepsins (https://en.wikipedia.org/wiki/Cathepsin) B, C, D, E, G, L
CCL1 (https://en.wikipedia.org/wiki/CCL1)
CCL16 (https://en.wikipedia.org/wiki/CCL16)
CCL17 (https://en.wikipedia.org/wiki/CCL17) (TARC)
CXCL1 (https://en.wikipedia.org/wiki/CXCL1)
CXCL4 (https://en.wikipedia.org/wiki/Platelet_factor_4) (Platelet Factor 4)
CXCL10 (https://en.wikipedia.org/wiki/CXCL10) (IP-10)
Chondroitin sulfate (https://en.wikipedia.org/wiki/Chondroitin_sulfate)
Chromogranin A (https://en.wikipedia.org/wiki/Chromogranin_A)
Chymase (https://en.wikipedia.org/wiki/Chymase)
Complement factor C3 (https://en.wikipedia.org/wiki/Complement_component_3)
Complement factor C5 (https://en.wikipedia.org/wiki/Complement_component_5)
Collagen type VIII (https://en.wikipedia.org/wiki/Collagen,_type_VIII,_alpha_1)
CRH (https://en.wikipedia.org/wiki/Corticotropin-releasing_hormone)
CXCL5 (https://en.wikipedia.org/wiki/CXCL5) (Epithelial-derived neutrophil-activating peptide 78, ENA78)
Dopamine (https://en.wikipedia.org/wiki/Dopamine)
EGF (https://en.wikipedia.org/wiki/Epidermal_growth_factor)
Endorphins (https://en.wikipedia.org/wiki/Endorphins)
Endothelin (https://en.wikipedia.org/wiki/Endothelin)
Eotaxin-1 (https://en.wikipedia.org/wiki/CCL11) (CCL11)
Factor VIII (https://en.wikipedia.org/wiki/Factor_VIII)
Factor VIII related antigen (https://en.wikipedia.org/wiki/Von_Willebrand_factor) (=von Willebrand Factor)
FGF2 (https://en.wikipedia.org/wiki/Basic_fibroblast_growth_factor) (Basic fibroblast growth factor, bFGF)
Fractalkine (https://en.wikipedia.org/wiki/CX3CL1) (CX3CL1)
G-CSF (https://en.wikipedia.org/wiki/Granulocyte_colony-stimulating_factor)
M-CSF (https://en.wikipedia.org/wiki/Macrophage_colony-stimulating_factor)
GM-CSF (https://en.wikipedia.org/wiki/Granulocyte-macrophage_colony-stimulating_factor)
Gonadotropin-releasing hormone (https://en.wikipedia.org/wiki/Gonadotropin-releasing_hormone) (GnRH, Ref (https://www.sciencedirect.com/science/article/pii/S0079612302411028))
Granzyme B (https://en.wikipedia.org/wiki/Granzyme_B)
H3-corticosterone (Ref (https://pubmed.ncbi.nlm.nih.gov/6057021/))
Heat shock protein 70 (https://en.wikipedia.org/wiki/Hsp70) (HSP70)
Heat shock protein 90 (https://en.wikipedia.org/wiki/Hsp90) (HSP90)
Hemokinin-1
Heparanase (https://en.wikipedia.org/wiki/Heparanase)
Heparan sulfate (https://en.wikipedia.org/wiki/Heparan_sulfate)
Heparin (https://en.wikipedia.org/wiki/Heparin)
Histamine (https://en.wikipedia.org/wiki/Histamine)
Hyaluronic acid (https://en.wikipedia.org/wiki/Hyaluronic_acid)
IGF-1 (https://en.wikipedia.org/wiki/Insulin-like_growth_factor_1)
IFN-alpha (https://en.wikipedia.org/wiki/Interferon_type_I#IFN-%CE%B1) (Response to viral infections regulated by IFN-?, flu type symptoms, such as fever, muscle aches and lethargy.)
IFN-beta (https://en.wikipedia.org/wiki/Interferon_type_I#IFN-%CE%B2) (Response to viral infections regulated by IFN-?, flu type symptoms, such as fever, muscle aches and lethargy.)
IFN-gamma (https://en.wikipedia.org/wiki/Interferon_gamma)
IL-1alpha (https://en.wikipedia.org/wiki/IL1A)
IL-1beta (https://en.wikipedia.org/wiki/Interleukin_1_beta)
IL-1RA (https://en.wikipedia.org/wiki/Interleukin_1_receptor_antagonist)
IL-2 (https://en.wikipedia.org/wiki/Interleukin_2)
IL-3 (https://en.wikipedia.org/wiki/Interleukin_3)
IL-4 (https://en.wikipedia.org/wiki/Interleukin_4)
IL-5 (https://en.wikipedia.org/wiki/Interleukin_5) (major driver of eosinophilia)
IL-6 (https://en.wikipedia.org/wiki/Interleukin_6)
IL-8 (https://en.wikipedia.org/wiki/Interleukin_8) (CXCL8, Seminal plasma IL-8 (https://sci-hub.se/10.1016/j.jri.2013.02.004) in male genital tract inflammation, "the most abundant cytokine of human mast cells"Ref (https://sci-hub.se/10.1111/j.1600-0897.2004.00224.x))
IL-9 (https://en.wikipedia.org/wiki/Interleukin_9)
IL-10 (https://en.wikipedia.org/wiki/Interleukin_10)
IL-11 (https://en.wikipedia.org/wiki/Interleukin_11)
IL-12 (https://en.wikipedia.org/wiki/Interleukin_12)
IL-13 (https://en.wikipedia.org/wiki/Interleukin_13) (IL-13 can induce IgE release from B cells, IgE-->IgG4 class switching)
IL-14 (https://en.wikipedia.org/wiki/Alpha-taxilin)
IL-15 (https://en.wikipedia.org/wiki/Interleukin_15)
IL-16 (https://en.wikipedia.org/wiki/Interleukin_16) (Crohn's disease (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230976/))
IL-17 (https://en.wikipedia.org/wiki/Interleukin_17) (IL17A)
IL-17F
IL-18 (https://en.wikipedia.org/wiki/Interleukin_18)
IL-22 (https://en.wikipedia.org/wiki/Interleukin_22) (IL-TIF)
IL-25 (https://en.wikipedia.org/wiki/Interleukin_25) (IL-17E)
IL-31 (https://en.wikipedia.org/wiki/Interleukin_31)
IL-33 (https://en.wikipedia.org/wiki/Interleukin_33)
Leukemia inhibitory factor (https://en.wikipedia.org/wiki/Leukemia_inhibitory_factor) (LIF)
Leptin (https://en.wikipedia.org/wiki/Leptin)
LTB4 (https://en.wikipedia.org/wiki/Leukotriene_B4)
LTC4 (https://en.wikipedia.org/wiki/Leukotriene_C4)
Major basic protein (https://en.wikipedia.org/wiki/Major_basic_protein) (MBP)
Mast cell kininogenase (https://en.wikipedia.org/wiki/Plasma_kallikrein)
Mast cell-derived exosomes (https://www.frontiersin.org/articles/10.3389/fimmu.2014.00569/full#h4) (crosses BBB, Nonspecific B and T Cell-Stimulatory Activity (https://sci-hub.se/10.1159/000053691))
Melatonin (https://en.wikipedia.org/wiki/Melatonin)
Mitochondrial DNA (https://en.wikipedia.org/wiki/Mitochondrial_DNA) (Ref (https://www.jimmunol.org/content/190/1_Supplement/43.39)) (Possible immune response by release of anti-mitochondrial DNA antibodies)
MCP-1 (https://en.wikipedia.org/wiki/CCL2) (CCL2)
MCP-3 (https://en.wikipedia.org/wiki/CCL7) (CCL7)
MCP-4 (https://en.wikipedia.org/wiki/CCL13) (CCL13)
MCP-5 (https://en.wikipedia.org/wiki/CCL12) (CCL12)
MCP-6 (is this a tryptase enzyme?)
MIF (https://en.wikipedia.org/wiki/Macrophage_migration_inhibitory_factor)
MIP-1alpha (https://en.wikipedia.org/wiki/CCL3) (CCL3, fever)
MIP-1beta (https://en.wikipedia.org/wiki/CCL4) (CCL4)
MIP-2alpha (https://en.wikipedia.org/wiki/CXCL2) (CXCL2)
MIP-2beta (https://en.wikipedia.org/wiki/CXCL3) (CXCL3)
MIP-3alpha (https://en.wikipedia.org/wiki/CCL20) (CCL20)
MIP-3beta (https://en.wikipedia.org/wiki/CCL19) (CCL19)
MMP2 (https://en.wikipedia.org/wiki/MMP2) (degrades collagen I)
MMP9 (https://en.wikipedia.org/wiki/MMP9) (degrades collagen IV and V)
NGF (https://en.wikipedia.org/wiki/Nerve_growth_factor)
Neurolysin (https://en.m.wikipedia.org/wiki/Neurolysin)
Neurotensin (https://en.wikipedia.org/wiki/Neurotensin)
Neurotrophin 3 (https://en.wikipedia.org/wiki/Neurotrophin-3)
Neurotrophin-4 (Ref (https://pubmed.ncbi.nlm.nih.gov/11750074/?dopt=Abstract))
Nitric oxide (https://en.wikipedia.org/wiki/Nitric_oxide) (NO)
Nitric oxide synthase (https://en.wikipedia.org/wiki/Nitric_oxide_synthase) (NOS)
Norepinephrine
Oncostatin M (https://en.wikipedia.org/wiki/Oncostatin_M) (T cell-induced mast cell activation)
PAF (https://en.wikipedia.org/wiki/Platelet-activating_factor)
Peroxidase (https://en.wikipedia.org/wiki/Peroxidase)
PLA2 (https://en.wikipedia.org/wiki/Phospholipase_A2)
Platelet derived growth factor (https://en.wikipedia.org/wiki/Platelet-derived_growth_factor) (PDGF, PDGF-AA & PDGF-BB)
Pro-caspase 3, 4
PGD2 (https://en.wikipedia.org/wiki/Prostaglandin_D2) (flushing, hair loss)
PGE2 (https://en.wikipedia.org/wiki/Prostaglandin_E2) (Fever, pain)
RANKL (https://en.wikipedia.org/wiki/RANKL) (Driver of Osteoporosis)
RANTES (https://en.wikipedia.org/wiki/CCL5) (CCL5)
Renin (https://en.wikipedia.org/wiki/Renin) (Angiotensinogenase, Ref (https://www.pnas.org/content/101/37/13607.short))
ROS (https://en.wikipedia.org/wiki/Reactive_oxygen_species)
Secretogranin III
SCF (https://en.wikipedia.org/wiki/Stem_cell_factor)
Serglycin (https://en.wikipedia.org/wiki/Serglycin)
Serotonin (https://en.wikipedia.org/wiki/Serotonin)
Somatostatin (https://en.wikipedia.org/wiki/Somatostatin) (Growth hormone inhibiting hormone, GHIH)
Spermidine (https://en.wikipedia.org/wiki/Spermidine)
Spermine (https://en.wikipedia.org/wiki/Spermine)
Sphingosine-1-phosphate (https://en.wikipedia.org/wiki/Sphingosine-1-phosphate) (S1P)
Substance P (https://en.wikipedia.org/wiki/Substance_P)
Superoxide dismutase (https://en.wikipedia.org/wiki/Superoxide_dismutase)
Superoxide (https://en.wikipedia.org/wiki/Superoxide)
TGF-beta1 (https://en.wikipedia.org/wiki/TGF_beta_1)
TGF-beta2 (https://en.wikipedia.org/wiki/TGF_beta_2)
Thromboxane (https://en.wikipedia.org/wiki/Thromboxane)
Tissue plasminogen activator (https://en.wikipedia.org/wiki/Tissue_plasminogen_activator)   
TNF-alpha (https://en.wikipedia.org/wiki/Tumor_necrosis_factor_alpha)
TNF-related apoptosis-inducing ligand (https://en.wikipedia.org/wiki/TRAIL) (TRAIL)
Tryptase-alpha
Tryptase-betaI
Tryptase-betaII
Tryptase-betaIII
Tryptase-gamma
Tryptase-delta
TSLP (https://en.wikipedia.org/wiki/Thymic_stromal_lymphopoietin)
Urocortin (https://en.wikipedia.org/wiki/Urocortin)
VEGF-A (https://en.wikipedia.org/wiki/Vascular_endothelial_growth_factor) (Opens up BBB, Released 6-12 hours after MC stimulation (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288), stress (CRH) and mercury)
VIP (https://en.wikipedia.org/wiki/Vasoactive_intestinal_peptide)

Non-IgE mediated mast cell activation

Non-IgE mediated mast cell activation (https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S0014299915301448)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/table/T3/

Differential release of mast cell mediators and the pathogenesis of inflammation (https://sci-hub.se/10.1111/j.1600-065X.2007.00519.x)

Sources

https://www.mastattack.org/mast-cell-mediators/

Table 3:
Differential release of mast cell mediators and the pathogenesis of inflammation (https://sci-hub.se/10.1111/j.1600-065X.2007.00519.x)

https://www.frontiersin.org/articles/10.3389/fimmu.2014.00569/full

https://sci-hub.tw/10.1007/s12016-019-08769-2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730566/

https://sci-hub.tw/10.1007/s00018-010-0587-0

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701915/

https://sci-hub.se/10.1134/S000629791612018X

Mast Cell Function A New Vision of an Old Cell (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230976/)

Mast Cell Cytokine and Chemokine Responses to Bacterial and Viral Infection (https://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/12570671/)

Tables of MC mediators sorted by CC and CXC structure:
Mast cell: an emerging partner in immune interaction (https://www.frontiersin.org/articles/10.3389/fimmu.2012.00120/full)

BDNF production in mast cells: https://www.atsjournals.org/doi/pdf/10.1165/ajrcmb.21.4.3670

Oxylipin production ratio's vs time, figure 3:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520518/

https://sci-hub.se/https://www.nature.com/articles/ni1158
https://static-content.springer.com/esm/art%3A10.1038%2Fni1158/MediaObjects/41590_2005_BFni1158_MOESM1_ESM.pdf

https://www.frontiersin.org/articles/10.3389/fimmu.2011.00037/full

Heat shock proteins: Ref 1 (https://www.sciencedirect.com/science/article/abs/pii/S0190962213013054), Ref 2 (https://www.sciencedirect.com/science/article/abs/pii/S0301472X05005199)

Factor VIII (https://www.thieme-connect.com/products/ejournals/pdf/10.1160/TH11-05-0351.pdf), Factor VIII related antigen (https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1699-0463.1982.tb00119_90A.x), Type VIII collagen (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001916/pdf/ijexpath00012-0016.pdf), Oncostatin M (https://www.ncbi.nlm.nih.gov/pubmed/18028996)

Eosinophil link 1 (https://books.google.nl/books?id=qefTAAAAQBAJ&pg=PA267&lpg=PA267&dq=unique+eosinophil+mediators&source=bl&ots=8WFioQUhvl&sig=ACfU3U1gS8u1Kx4CVmLjz3nagnCxskbfXA&hl=nl&sa=X&ved=2ahUKEwismKS9_fbnAhVVIMUKHRBuBowQ6AEwEnoECAgQAQ#v=onepage&q=unique%20eosinophil%20mediators&f=false)

CC and CXC chemokine overview (https://en.wikipedia.org/wiki/Chemokine#Types_by_structure)

Osteoporosis/osteosclerosis:
"On the other hand mast cell products, possibly via tryptase release, were shown to activate osteoblasts and to increase osteoprotegerin production, thereby limiting osteoclast-mediated bone resorption. The authors have no obvious explanation for the findings of both increased and decreased bone formation markers in the same disease." Page 390: Ref (https://books.google.nl/books?id=wSqiAwAAQBAJ&pg=PA390&lpg=PA390&dq=Osteoprotegerin+mast+cells&source=bl&ots=n7FPj4Mqj1&sig=ACfU3U2GlYppwhZ_i0_Hv6HK3xyY36YmDQ&hl=nl&sa=X&ved=2ahUKEwit1s-1qo3oAhWS26QKHSn5BB8Q6AEwBnoECAoQAQ#v=onepage&q=Osteoprotegerin%20mast%20cells&f=false)
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Muon on February 29, 2020, 07:30:07 AM
Potential treatment options


Prescriptions Abbreviations (https://www.d.umn.edu/medweb/Modules/Prescription/Abbreviations.html)


Various tables with options, see figure 3 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/figure/Fig3/) first for treatment approach before moving on to the tables:
Pharmacological treatment options for mast cell activation disease (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/)


Download the supplemental material Figure 1:
https://www.tandfonline.com/doi/suppl/10.3109/07853890.2016.1161231?scroll=top&

Quote from: Dr. Theoharides
No matter what the trigger, I will use some antihistamine. As I said, I'll go through at least three before I give up, just in case I'm missing something. Ref (https://www.drkarafitzgerald.com/2018/11/20/mast-cell-clinical-researcher-dr-theoharides/)
Treatment Approach for Mast Cell Mediator Disorders (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/table/T9/)


Page 207, Table 3. Management of mast cell activation syndrome (https://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf)


Naturally occuring mast cell stabilizers, Table 1:
Twenty-first century mast cell stabilizers (https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.12138)


Mast cell stabilizers (https://sci-hub.se/10.1016/j.ejphar.2015.05.071)


Herbal and dietary supplements, Table 1:
Mast cells and mast cell mediators as targets of dietary supplements (https://sci-hub.se/10.1016/s1081-1206(10)61484-6)


Cannabinomimetic compounds (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2826.2008.01674.x) (THC, CBD, PEA (https://en.wikipedia.org/wiki/Palmitoylethanolamide))


Dexamethasone rapidly suppresses IL-33-stimulated mast cell function by blocking transcription factor activity (https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.3A0316-125R)


Short Chain Fatty Acids Modulate Mast Cell Activation (https://sci-hub.se/https://onlinelibrary.wiley.com/doi/abs/10.1111/all.14313) (butyrate and propionate)


Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment (https://casereports.bmj.com/content/2018/bcr-2017-221405?int_source=trendmd&int_medium=cpc&int_campaign=usage-042019)


"The rank order of potency was diazepam > 4'-chlorodiazepam > flunitrazepam > clonazepam with clonazepam causing only a minor effect at a high concentration." Inhibitory effects of benzodiazepines on the adenosine A2B receptor mediated secretion of interleukin-8 in human mast cells (https://sci-hub.se/10.1016/j.ejphar.2012.12.003)


Erythromelalgia in a Patient with Mast Cell Activation Syndrome: Response to Low Dose Naltrexone (https://www.jofskin.org/index.php/skin/article/view/722/pdf)


Osthole, a Natural Plant Derivative Inhibits MRGPRX2 Induced Mast Cell Responses (https://www.frontiersin.org/articles/10.3389/fimmu.2020.00703/full)


Alpha1-adrenergic receptor antagonists?:
?1-Adrenergic Receptor Blockade by Prazosin Synergistically Stabilizes Rat Peritoneal Mast Cells (https://www.hindawi.com/journals/bmri/2020/3214186/)


Medical-grade Manuka honey inhibits mast cell degranulation by downregulating protein kinase-B (Akt) phosphorylation: Potential role as intravesical agent in interstitial cystitis/bladder pain syndrome (https://www.eu-openscience.europeanurology.com/article/S2666-1683(20)32900-1/pdf)


Dr. Dempsey had some good results with:
Dynamic Neural Retraining System
Carnivore diet
Ketogenic diet

Other diets that may be beneficial:
Low histamine diet (https://www.mastzellaktivierung.info/en/therapy_dietarychange.html)
Low FODMAP diet

Read this first before buying a supplement containing Luteolin: Luteolin supplements: All that glitters is not gold (https://sci-hub.se/10.1002/biof.1689)

Comparative Characteristics of Algonot Dietary Supplements (https://www.mastcellmaster.com/dietary-supplements/Flavonoid-Formulation.pdf)

https://algonot.com/products/

NeuroProtek FAQs (https://www.mastcellmaster.com/dietary-supplements/NeuroProtek-Frequently-Asked-Questions-Pg-2.pdf)

1. Allergies/mast cell diseases: FibroProtek 2 caps BID plus GenteDerm for skin irritation
2. Chronic fatigue syndrome/fibromyalgia: FibroProtek 2 caps BID plus GenteDerm for skin irritation
3. Interstitial cystitis/chronic prostatitis: CystoProtek 2 caps BID
4. Alzheimer's/BrainFog: NeuroProtek 2 caps BID plus BrainGain 1 cap BID or BrainGain 2 caps BID
5. Autism: NeuroProtek-Low phenol starting with 1 cap am, advancing to 1 cap am and pm in two weeks, then slowly advancing to 2 caps BID in two months, then advancing to 2 caps BID regular NeuroProtek
6. Arthritis/tendonitis: Algonot-plus 2 caps BID
7. Skin sensitivities/allergies/eczema/psoriasis: GentleDerm apply 2-4 per day as needed
8. Allergies: Hydroxyzine (Atarax) 25 mg at night up to 50 mg QSH and 25 mg am
9. IBS/migraines: Cyproheptadine (Periactin) 4 mg per day
10. Anxiety/irritability: Propranolol (Inderal) 40 mg per day (except in cases of asthma, diabetes, low BP)
Ref (https://www.mastcellmaster.com/testimonials.php)


Cromoglicid acid is available as Allergoval (Germany), Cromolyn (USA), Nalcrom (various countries). Oral, nasal spray or eye drops.


Quercetin Phytosome (https://www.thorne.com/products/dp/quercetin-phytosome) (Absorption (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418071/))

Aller-7 (https://myvagina.com/mast-cell-activation-syndrome/)? (see treatment section)

Natural products targeting Fc?RI receptor for anti-allergic therapeutics (https://sci-hub.se/https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.13335)

Stress, inflammation:
Luteolin + Ashwagandha (https://pubmed.ncbi.nlm.nih.gov/30574737/)

Catechin synergistically potentiates mast cell-stabilizing property of caffeine (https://link.springer.com/article/10.1186/s13223-020-00502-5)

Echinacea purpurea water extracts suppress the release of chemical mediators from mast cells (https://academic.oup.com/bbb/advance-article/doi/10.1093/bbb/zbaa125/6066522?login=true)

Cardiovascular symptoms

Table 1 and 2:
Cardiovascular symptoms in patients with systemic mast cell activation disease (https://sci-hub.se/10.1016/j.trsl.2015.12.012)

Neurologic and Psychiatric Symptoms

Table 3:
Mast Cell Activation Disease: An Underappreciated Cause of Neurologic and Psychiatric Symptoms and Diseases (https://sci-hub.se/10.1016/j.bbi.2015.07.002)

Atopic Dermatitis:

A Natural Compound Mixture Containing Arctigenin, Hederagenin, and Baicalein Alleviates Atopic Dermatitis in Mice by Regulating HPA Axis and Immune Activity (https://www.hindawi.com/journals/ecam/2020/1970349/)

Pseudoephedrine alleviates atopic dermatitis-like inflammatory responses in vivo and in vitro (https://www.sciencedirect.com/science/article/abs/pii/S0024320520308900)

Mastocytosis

Fentanyl buccal tablet for the treatment of breakthrough pain in systemic mastocytosis - a case study (https://www.termedia.pl/Fentanyl-buccal-tablet-for-the-treatment-of-breakthrough-pain-in-systemic-mastocytosis-a-case-study,59,42690,0,1.html)

Endocrine

Estradiol Augments while Tamoxifen Inhibits Rat Mast Cell Secretion (https://www.karger.com/article/Abstract/236217)

Strategy

Synergies (Example Figure 4 (https://sci-hub.se/10.1016/s1081-1206(10)61484-6))
Indirect MC inhibition (Increasing Parameters (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288#exd13288-fig-0001) that inhibit mast cells by indirect methods)
Receptor activation/blockage (Ref1 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/table/T1/), Ref2 (https://www.frontiersin.org/files/Articles/25962/fimmu-03-00120-HTML/image_m/fimmu-03-00120-t001.jpg))
MC mediator binding
Diagnostic testing
Identifying triggers and minimalize exposure
Addressing neurohormonal imbalances that favor a mast cell stimulatory state. Ref (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288#exd13288-tbl-0001)

Notes

Any drug can induce intolerance symptoms in the individual MCAD patient. It is very important to note that such patients often demonstrate even a greater propensity to react to medication excipients (i.e., fillers, binders, dyes, preservatives) than to the active ingredients. When the patient tries one or more alternative formulations of a medication with the same active ingredient but sharing as few as possible (preferably none) of the excipients in the offending formulation, the patient may discover the medication to be at least tolerable and perhaps even quite effective. Recognition and Management of Medication Excipient Reactivity in Patients With Mast Cell Activation Syndrome (https://sci-hub.se/10.1016/j.amjms.2019.03.005)

All drugs should be tested for tolerance in a low single dose before therapeutic use, if their tolerance in the patient is not known from an earlier application.

The tolerability and efficacy of most therapies tried in MCAD (starting, and escalating in dosage and composition, cautiously) become clinically evident within 1-2 months.

Successful regimens appear highly personalized.

Compilation of drugs associated with a high risk of release of mediators from mast cells and their therapeutic alternatives (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/table/Tab12/)

Duration
Phenol intolerance gives problems with flavonoids.
Salicylate intolerance (may also be an indication of leukotriene overproduction)

Videos and podcasts

Mast Cell Activation Disease: Current Concepts ("MCAS 101") (https://www.youtube.com/watch?v=lrKqlv6VK_w)

Dr. Lawrence Afrin presents "Mast Cell Activation Syndrome" (https://www.youtube.com/watch?v=82dmZhCBuBo)

Episode 51: All Things Mast Cell with World-Renowned Clinical Researcher Dr. Theoharides. (https://www.drkarafitzgerald.com/2018/11/20/mast-cell-clinical-researcher-dr-theoharides/) (including full transcript)

BetterHealthGuy: Episode #58: Mast Cell Master with Dr. T.C. Theoharides, PhD, MD (https://www.youtube.com/watch?v=6gfTFwJgIVQ)

BetterHealthGuy: Episode #106: Bartonella and MCAS with Dr. Tania Dempsey, MD (https://www.youtube.com/watch?v=937sZJDNVGw)

IIMEC13 Anne Ortegren Memorial Lecture Professor Theoharis C Theoharides (https://www.youtube.com/watch?v=HNNPsZlDTEQ)

'Brain Allergy' and ASD - T. Theoharides, MD, PhD (https://www.youtube.com/watch?v=9QbZp3WcC1Q)

Brain Inflammation in Autism and How to Calm It by Prof T Theoharides (https://www.youtube.com/watch?v=Z7eqEHphCOg)

The Coffee Klatch: Dr. Theoharides - Mast Cell Disorders (https://www.blogtalkradio.com/thecoffeeklatch/2015/02/04/dr-theoharides--mast-cell-disorders-1)

Dr. hoffman: A Promising Neuro-Protective Nutraceutical, Part 1 (https://drhoffman.com/podcast/a-promising-neuro-protective-nutraceutical-part-1/)

Dr. hoffman: A Promising Neuro-Protective Nutraceutical, Part 2 (https://drhoffman.com/podcast/a-promising-neuro-protective-nutraceutical-part-2/)

Scientific articles (Flavonoids)

(Mast cell inhibition in %, Ref (https://youtu.be/6gfTFwJgIVQ?t=5669)):

Tetramethoxyluteolin (90-100%) > Luteolin (75%) > Quercetin (55%) > Cromolyn (15%)

The Role of Quercetin, Flavonols and Flavones in Modulating Inflammatory Cell Function (https://sci-hub.se/https://www.ingentaconnect.com/content/ben/iadt/2010/00000009/00000004/art00006)

Flavonoids Inhibit COX-1 and COX-2 Enzymes and Cytokine/Chemokine Production in Human Whole Blood (https://sci-hub.se/https://link.springer.com/article/10.1007/s10753-014-9995-x)

Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314669/)

The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells (https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S0091674914015747)

Antimicrobial activity of flavonoids (https://www.sciencedirect.com/science/article/pii/S0924857905002554)

Flavonoids: an overview (https://www.cambridge.org/core/journals/journal-of-nutritional-science/article/flavonoids-an-overview/C0E91D3851345CEF4746B10406908F52)

Natural compounds with dual antimicrobial and antiinflammatory effects (https://sci-hub.se/https://link.springer.com/article/10.1007/s11101-020-09694-5)

Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708423/)
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Muon on February 29, 2020, 07:51:14 AM
Reserved 2
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Muon on February 29, 2020, 08:19:42 AM
Reserved 3
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Muon on February 29, 2020, 11:27:54 AM
Reserved 4
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Muon on February 29, 2020, 11:31:42 AM
Reserved 5
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Muon on February 29, 2020, 11:33:48 AM
Reserved 6
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Muon on March 02, 2020, 07:15:10 AM
Reserved Final
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Muon on March 02, 2020, 07:37:45 AM
Muon, you seem to have some insights about MCAS and POIS. I still haven't had the chance and time to read in depth about it. Could you think of some marker that can be tested in a lab that you suspect would turn out abnormal in us, compared to healthy subjects? If yes, well, we can do a self-study, a bunch of us on our own testing for that marker, maybe before as well as 24 hours after orgasm, and compare? Lab tests for immune markers are not even expensive. Maybe IFN-gamma? Or you can make some list. If it's not super fancy stuff, most labs in the various countries where we live would do it. But it would be great if we have an actual lab-measured marker that is off in POIS sufferers compared to a control group.

Unfortunately as you can see, the super fancy stuff is all over the place. Perhaps this a reason why common routine lab results barely show abnormalities despite the large amount of different symptoms. Labs offering these mediators could be hard to find, that's why it's important to share labs via this thread (even if it's anonymous via private message): https://poiscenter.com/forums/index.php?topic=3207.0

I can't recommend a parameter because parameter distribution, if we are dealing with selective release, may vary from person to person based on symptomatology (type, duration, onset, intensity etc.). People could do their own investigation.

Clinical trials could be organized via Synevo (https://www.synevo-ssl.de/en.html).
Title: Re: MCAD Diagnostic Testing & Mediators
Post by: Simon66 on March 12, 2020, 10:53:03 AM
What is the recommended treatment for this? Cromolyn?
Title: Re: MCAD Diagnostic Testing, Mediators & Treatment Options
Post by: Muon on March 12, 2020, 02:22:28 PM
What is the recommended treatment for this? Cromolyn?

There is no straightforward answer to that question. Yes cromolyn is part of treatment algorithms. I have made a new header, treatment options, and will update it bit by bit. You will get a better insight and an answer to your question once I'm done with it.
Title: Re: MCAD Diagnostic Testing, Mediators & Treatment Options
Post by: Muon on March 28, 2020, 11:09:57 AM
Could you think of some marker that can be tested in a lab that you suspect would turn out abnormal in us, compared to healthy subjects?

Well, I actually suspect one being elevated at average for a group of POIS patients when symptomatic compared to controls. That's VEGF.

It's being selectively released from mast cells when triggered by CRH and/or PGE2. Quite some poisers have stated over the years they can't tolerate stress that well. A few even mentioned it will generate POIS symptoms. Even the POIS symptoms itself could generate stress leading to more CRH.

From what I understand CRH is the first molecule being released by stress. CRH ---> CRH receptor activation on MCs ---> VEGF (selectively).

Now there are also some poisers getting a good response from COX inhibitors and there are a few theories floating around where PGE2 is involved in inflammatory behaviour regarding POIS (in MCAS as well btw). PGE2 can selectively release VEGF from MCs as well.

Human Mast Cells Express Corticotropin-Releasing Hormone (CRH) Receptors and CRH Leads to Selective Secretion of Vascular Endothelial Growth Factor (https://www.jimmunol.org/content/174/12/7665.short)

Prostaglandin E2 Induces Degranulation-Independent Production of Vascular Endothelial Growth Factor by Human Mast Cells (https://www.jimmunol.org/content/172/2/1227.short)
Title: Re: MCAD Diagnostic Testing, Mediators & Treatment Options
Post by: Muon on October 12, 2020, 05:35:42 PM
KiminOrlando (https://www.dinet.org/forums/topic/31575-mast-cell-activation-disease-mcad-mini-compilation/):

"My Allergy and Immunologist dismissed Mast Cell issues for me because my tryptase levels were normal. This looks like so much data. What should I print and hand him for my next 10 minute appointment to see if I can get him to look further?"

I would show this one:

Current provisional criteria to define mast cell activation syndrome (MCAS; modified from Afrin and Molderings 2014) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/table/Tab3/)

Or Table 2 from this link (basically a small modification of the link above):

Criteria proposed to define mast cell activation disease (for references, see text) when all other diagnoses that could better explain the full range and chronicity of the findings in the case have been excluded. (https://www.tandfonline.com/doi/figure/10.3109/07853890.2016.1161231?scroll=top&needAccess=true#)

If you pick one of the above you can add this one to that:

Relative utility of assorted mast cell mediators in diagnosing mast cell activation syndrome (MCAS). (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T6/)

Note that most MCAS patients get diagnosed by major criterion 1 + evidence of above-normal levels of MC mediators. And some by major criterion 1 + minor criterion: symptomatic response to inhibitors of mast cell activation. You can see the flexibility here. A video fragment talking about MCAS criteria: https://youtu.be/lrKqlv6VK_w?t=2485