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Allergic Mastocytic Gastroenteritis and Colitis: An Unexplained Etiology in Chronic Abdominal Pain and Gastrointestinal Dysmotility. Gastroenterology research and practice.

S. Glover, et.al.

Abdominal pain, bloating, early satiety, and changes in bowel habits are common presenting symptoms in individuals with functional GI disorders.

Emerging data suggests that these symptoms may be associated with mast cell excess and/or mast cell instability in the GI tract. The aim of this retrospective study was to evaluate the contribution of mast cells to the aforementioned symptomsinindividuals with a history of atopic disease.

A retrospective chart review of individuals seen in a university GI practice was conducted and twenty-four subjects were identified. The majority had abdominal pain, early satiety, and nocturnal awakening. 66.7% and 37.5% had a history of environmental and/or food allergy.

Solid gastric emptying was increased as were the mean number of mast cells reported on biopsies from the stomach, small bowel, and colon (>37/hpf) by CD117 staining.

Mean whole blood histamine levels were uniformly elevated.

This study suggests that in individuals with these characteristics, consideration should be given to staining their gastrointestinal biopsies for mast cells as this may provide them with relatively non-toxic but highly targeted treatment options.

Allergic gastroenteritis and colitis may represent a third type of GI mast cell disorder along with mast cell activation syndrome and mastocytic enterocolitis.

https://www.researchgate.net/profile/Pravin_Muniyappa/publication/224940537_Allergic_Mastocytic_Gastroenteritis_and_Colitis_An_Unexplained_Etiology_in_Chronic_Abdominal_Pain_and_Gastrointestinal_Dysmotility/links/554b87210cf29752ee7c8dcf/Allergic-Mastocytic-Gastroenteritis-and-Colitis-An-Unexplained-Etiology-in-Chronic-Abdominal-Pain-and-Gastrointestinal-Dysmotility.pdf

VooDoo and dishonest science is not just bad for political policymakers. It can kill you.

Our Mayo Jacksonville home away from home. Almost worth the trip for the gardens.

From the TMS folks another great opportunity webinar.

Our 2020 Rare Disease Day Initiative continues with our fourth in the new series of
TMS Patient Voice Forums!
We hope you will join us for the

Patient Voice Forum
for
Pediatric Mast Cell Diseases
Wednesday, June 3, 2020
8:00 pm (Eastern Time)

Featuring Dr. Marianna Castells, Dr. Ari Fried and
Dr. Anne Maitland

Please note other physicians may be added to the panel

We want to hear from you!

All TMS Members are invited to submit questions, comments and thoughts by emailing, nurses@tmsforacure.org with “Patient Voice Forum-Pediatrics” in the subject line. If you do not use this subject line your questions may be overlooked and not included.

Please note that only general medical questions/comments can be submitted/addressed about Pediatric Mast Cell Diseases; physicians cannot give one-on-one advice to patients in this forum.

All submissions must be received by Saturday May 30, 2020.

Additional call-in details will be provided as it nears.

Thank you so much for your participation in this meaningful event for our entire community.

For those who missed our other webinars a video recording can be found here.

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.

https://science.sciencemag.org/content/early/2020/05/27/science.abc6197

I want to share with you the recent study that we (Aristo Vojdani and myself) have been working on, and that is now in press in the journal “Clinical Immunology.” We identified which autoimmune target proteins cross-react with SARS-Co-V-2 spike and nuclear proteins. We have discovered that there is potential for the coronavirus infection to produce antibodies that may cross-react with the brain, thyroid gland, and the gut. This discovery may explain why some patients have a systemic disease with the infection, and some do not. We are still finalizing the complete study where we screen 50 autoimmune target proteins. Once we get that published, I will let you know. The bottom line is that, for some susceptible subgroups of people that get the coronavirus infection, it may trigger the onset of autoimmune disease or induce a flare-up of an existing autoimmune disease. I think we are about to see many patients develop Post-COVID-19 Syndrome, and it will involve autoimmunity to some of the target proteins that we have found cross-react with the virus. Please share this link and information. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases - ScienceDirect

Gut Microbes May Be Key to Solving Food Allergies

New therapeutics are testing whether protective bacteria can dampen harmful immune responses to food

“The peanut-allergy mice, another report showed, had a genetic glitch that damages a receptor called TLR4 that sits in the membranes of immune cells and recognizes microbes. It looked as though the peanut-allergy mice lacked the normal cross talk that takes place between gut microbes and immune cells.”

“That was my lightbulb moment,” Nagler says. Perhaps the trillions of microbes that live in us suppress immune responses to food by stimulating the TLR4 receptor. And perhaps perturbations in that teeming microbiome alter the suppression and cause a rise in allergies."

The Mastocytosis Society, Inc. (TMS) 2020 Patient Survey to Assess Impact of COVID-19 in Patients with Mast Cell Disease

This survey will remain open for the foreseeable future

You are invited to participate in a survey being conducted by Middle Tennessee State University (MTSU) researchers, in collaboration with The Mastocytosis Society, Inc. (TMS), designed to assess the impact of COVID-19 in patients with Mast Cell Disease. Data obtained from this survey will be used for discussion, investigation, presentation, and publications in medical journ ls to share knowledge gained about managing patients affected by both COVID-19 and pre-existing Mast Cell Disease. This survey is expected to take approximately 25 minutes to complete.

Adult patients and caregivers of adult and pediatric patients under age 18 who have been diagnosed with Mast Cell Disease, including Mastocytosis, Mast Cell Activation Syndrome (MCAS), and Hereditary Alpha Tryptasemia (HaT), by any physician or clinic, may take this survey if they have had any possible exposure to COVID-19, or have had symptoms of COVID-19, regardless of COVID-19 test results or COVID-19 diagnosis.

If in doubt, take the survey.

If you would like to participate in this survey,
please click here.

If your experience with COVID-19 changes after taking the survey, you may retake the survey. Please visit the TMS 2020 COVID-19 Survey webpage for important instructions on how to retake the survey.

TMS appreciates the collaborative effort and expertise of members of the TMS Medical Advisory Board/Mast Cell Disease specialists, as well as scientists from Middle Tennessee State University, in the development of this survey.

For any questions, please contact: research@tmsforacure.org.

TMS 2020 Mast Cell Disease COVID-19 Survey Team
The Mastocytosis Society, Inc.

Asprin therapy can get some folks in trouble

https://www.jacionline.org/article/S0091-6749(16)30440-7/pdf

You know you have Mast Cell disease when …

Sjogren’s Syndrome in a Patient with Maculopapular Cutaneous Mastocytosis

Dalvir Gill, et.al.

An absence of well-defined histopathological features and a lack of clinical awareness can delay its diagnosis and treatment, clinicians need to be aware that even the milder form of mastocytosis, cutaneous type, can also be associated with Sjogren’s syndrome.

Histamine transport and metabolism are deranged in salivary glands in Sjögren’s syndrome

Vasily Stegaev, Anne T. Nies, Pauliina Porola, et.al.

Rheumatology, Volume 52, Issue 9, September 2013, Pages 1599–1608, https://doi.org/10.1093/rheumatology/ket188

Mast Cells Are Involved in the Pathogenesis of Sjögren Syndrome By Inducing Tissue Fibrosis

Shinjiro Kaieda, et.al.

These results suggest a novel role for mast cells in the development of sialadenitis and interstitial lung disease in patients with Sjögren syndrome via induction of tissue fibrosis. An amplification loop between mast cells and fibroblasts enhances production of the pro-fibrotic factor, TGF-β, and angiogenic factor, VEGF, which may contribute to tissue fibrosis in sialadenitis and interstitial lung disease.

Cutaneous mastocytosis in a patient with primary Sjögren’s syndrome.

Shebnem Kalay Erbay, Carol Stewart, Ashraf Hassanein, Andrew Fletcher, et.al.

Mast cells have been linked to rheumatoid arthritis (RA) and are essential to the pathogenesis of RA-like disease in a mouse model. We describe a 34-year-old woman who developed Sjögren’s syndrome concurrently with telangiectasia macularis eruptiva perstans (TMEP), a rare form of cutaneous mastocytosis. The patient had sicca symptoms with an abnormal minor salivary gland biopsy and decreased salivary flow, peripheral neuropathy, an 80 pound weight loss, and a macular erythematous rash that exhibited superficial perivascular mast cell infiltrates on biopsy of lesional skin. This case further underscores the link between mast cells and the development of autoimmunity.

Overactive bladder and bladder pain syndrome/interstitial cystitis in primary Sjögren’s syndrome patients: A nationwide population-based study

Chun-Kang Lee, Ching-Pei Tsai, Tsai-Ling Liao, et.al.

In our study, we observed a 2.34-fold increased hazard ratio of BPS/IC in pSS patients. Van de Merve et al. also proposed that clinicians should be aware of an increased risk of BPS/IC in patients with pSS.[6] In addition, BPS/IC patients had relatively higher risks of developing pSS than the general population.[5] Anti-M3R IgG of pSS patients might also be crucial to the development of IC in both the early and late stages.[5] The detrusor muscle cells could produce interleukin(IL)-8, IL-6, and CCL5/RANTES in response to tumor necrosis factor(TNF)-α, and IL-1β.[13] In human airway smooth muscle cells, muscarinic receptor agonist may stimulate M3R, leading to the secretion of IL-6 and CXCL8.[14] Similarly, an increased inflammatory cytokines secretion from detrusor muscle cells was observed after a compensatory increase in M3R expression caused by anti-M3R IgG. Moreover, In a murine model, the mast cells may induce IL-6, IL-8, and RANTES after the release of TNF-α and IL-1β.[15] Consequently, the increase of inflammatory cytokines induced by autoantibodies may drive mast cells to the bladder lamina propria of detrusor muscle, which is related to the pathogenesis of BPS/IC.

https://www.mdlinx.com/news/new-effective-treatment-for-inflammatory-diseases-found/5MR8TEQAASn0rEuOXYWZtv?utm_medium=email&publish_dt=06-01-2020&utm_source=alert&utm_campaign=ajm_49939

APPA (apocynin and paeonol) modulates pathological aspects of human neutrophil function, without supressing antimicrobial ability, and inhibits TNFα expression and signalling

A. L. Cross, J. Hawkes, S. W. Edwards, et.al.

Inflammopharmacology

Neutrophils are key players in the pathophysiological process underlying inflammatory conditions not only by release of tissue-damaging cytotoxic enzymes, reactive oxygen species (ROS) but also by secretion of important immunomodulatory chemokines and cytokines.

Here, we report the effects of the novel agent APPA, undergoing formal clinical development for treatment of osteoarthritis, and its constituent components, apocynin (AP) and paeonol ¶ on a number of neutrophil functions, including effects on TNFα- expression and signalling. Neutrophils were treated with APPA (10–1000 µg/mL) prior to the measurement of cell functions, including ROS production, chemotaxis, apoptosis and surface receptor expression. Expression levels of several key genes and proteins were measured after incubation with APPA and the chromatin re-modelling agent, R848. APPA did not significantly affect phagocytosis, bacterial killing or expression of surface receptors, while chemotactic migration was affected only at the highest concentrations.

However, APPA down-regulated neutrophil degranulation and ROS levels, and decreased the formation of neutrophil extracellular traps. APPA also decreased cytokine-stimulated gene expression, inhibiting both TNFα- and GM-CSF-induced cell signalling. APPA was as effective as infliximab in down-regulating chemokine and IL-6 expression following incubation with R848.

Whilst APPA does not interfere with neutrophil host defence against infections, it does inhibit neutrophil degranulation, and cytokine-driven signalling pathways (e.g. autocrine signalling and NF-κB activation), processes that are associated with inflammation.

These observations may explain the mechanisms by which APPA exerts anti-inflammatory effects and suggests a potential therapeutic role in inflammatory diseases in which neutrophils and TNFα signalling are important in pathology, such as rheumatoid arthritis.