From Facebook

The emerging role of mast cells in liver disease

Veronica Jarido, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Joanne Thomson, Kristen Stephenson, and Heather Francis

Published Online:01 AUG 2017https://doi.org/10.1152/ajpgi.00333.2016

The purpose of this review is to refresh the reader’s knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review focuses primarily on liver diseases and mast cells during autoimmune disease, hepatitis, fatty liver disease, liver cancer, and aging in the liver. Overall, these studies demonstrate the potential role of mast cells in disease progression.

Mast Cells Cause Liver Disease through Protein Shuttled via Extracellular Sacs, NIH Research Suggests

NIAID Now | November 19, 2018

New research by NIH investigators demonstrates for the first time that a bone marrow-derived cell, the mast cell, can cause disease in a solid organ through the transmission of small sacs of molecules through the bloodstream.

Specifically, the study shows that in people with a rare disorder called systemic mastocytosis, some of these sacs, known as extracellular vesicles, travel from mast cells to liver cells and deliver a protein that causes liver disease.

Published online in the Proceedings of the National Academy of Sciences (PNAS) in October, the study adds to a growing body of evidence that extracellular vesicles can enable one type of cell to influence the behavior of an entirely different cell type.

Dean Metcalfe, M.D., chief of the Mast Cell Biology Section in the NIAID Laboratory of Allergic Diseases, and Ana Olivera, Ph.D., a staff scientist in the same laboratory section, led the new research conducted by Do-Kyun Kim, Ph.D., a visiting fellow in the section. The study included 21 patients with systemic mastocytosis and 10 healthy volunteers.

Mast Cell-Derived Histamine Regulates Liver Ketogenesis via Oleoylethanolamide Signaling

Alessandra Misto, Daniele Piomelli, et.al.

Cell Metabolism, Volume 29, Issue 1, 8 January 2019, Pages 91-102.e5

Here, we present evidence that mast cells contribute to the control of fasting-induced ketogenesis via a paracrine mechanism that involves secretion of histamine into the hepatic portal circulation, stimulation of liver H1 receptors, and local biosynthesis of the high-affinity PPAR-α agonist, oleoylethanolamide (OEA).

Genetic or pharmacological interventions that disable any one of these events, including mast cell elimination, deletion of histamine- or OEA-synthesizing enzymes, and H1 blockade, blunt ketogenesis without affecting lipolysis.

The results reveal an unexpected role for mast cells in the regulation of systemic fatty-acid homeostasis, and suggest that OEA may act in concert with lipolysis-derived fatty acids to activate liver PPAR-α and promote ketogenesis.

https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(18)30579-5&ved=2ahUKEwini6yuvuHrAhUDL6wKHbrrCYYQFjAOegQIBhAB&usg=AOvVaw2g8SwLePr4gdNX_djAzkEn&cshid=1599840906591

Happy Friday Dance Party!!! Everybody Dance Now!!!

A Practical Guide for Treatment of Pain in Patients with Systemic Mast Cell Activation Disease

Stefan Wirz, MD, PhD and Gerhard J. Molderings, MD, PhD

Pain Physician 2017; 20:E849-E861 • ISSN 2150-1149

Systemic mast cell activation disease (MCAD, a subclass of mastocytosis), which has a prevalence of around 17% (at least in the German population), is characterized by accumulation of genetically altered dysfunctional mast cells with abnormal release of these cells’ mediators.

Since mast cells affect functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing, this disease has to be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity of a generally inflammatory and allergic theme.

Pain in its different manifestations is a common symptom in MCAD found in more than three-quarters of the MCAD patients. Because of the specific mast cell-related causes of pain in MCAD it should be treated specifically, if possible, deduced from their putative mast cell mediator-related causes.

As yet, there is no official guideline for treatment of MCAD at all. The present review focuses on mast cell mediator-induced acute and chronic pain and the current state of analgesic drug therapy options in MCAD.

Due to the high prevalence of MCAD, many physicians are often faced with the issue of pain management in MCAD patients. Hence, our practical guide should contribute to the improvement of patient care.

Key words: Pain therapy, mast cell activation disease, mast cell activation syndrome, systemic mastocytosis, mast cell Pain Physician 2017; 20:E849-E861

https://www.painphysicianjournal.com/current/pdf?article=NDYxNQ%3D%3D&journal=107

A probabilistic approach for links between rheumatic diseases and weather

Hiroshi Morimoto

The graduate school of informatics, Nagoya University, Japan

DOI: 10.15761/IMC.1000104

Since rheumatic disease is one of autoimmune diseases, it is related to immune reaction, inflammatory responses and cytokine network.

Therefore, relation between weather and cytokines becomes an important problem in order to identify mechanisms behind rheumatic diseases. Our finding of the pattern (a) is closely related to cytokines including tumour necrosis factor (TNF-alpha) and interleukin 6 (IL-6).

If the barometric pressure decreases, the hydrostatic pressure (HP) between cells increases, causing edema or swelling.

The increase of HP induced mRNA expressions of IL-6 and TNF- alpha [9]. Our pattern (a) is also related to interleukin 8 (IL-8). The research found that mechanical stress induced expression of IL-8 and IL-6 in human periodontal ligament cells.

Mast cells may be influenced by barometric pressure and be an important source of TNF- alpha and IL-6 [10,11].

Mast Cells in Liver Fibrogenesis

Ralf Weiskirchen, Steffen K. Meurer, Christian Liedtke, and Michael Huber

Cells 2019, 8, 1429
doi:10.3390/cells8111429

Today, there is first evidence demonstrating that MCs are important cellular regulators in human liver disease. In a normal human liver, MCs are associated with the connective tissue and are mainly found along the portal tracts.

The number of MCs in human liver is significantly increased during the pathogenesis of PBC, PSC, bile duct obstruction, hepatitis, alcohol-induced liver injury, steatosis, steatohepatitis, congenital and non-congenital liver fibrosis, liver cancer, liver rejection upon liver transplant, and liver aging.

Although the cellular and sub-cellular linkages of MCs to all these diseases remain unresolved, it is most likely that these cells are critically involved in the liver’s fibrotic response to chronic inflammation.

On the other side, MCs can exert immunomodulatory effects on other immune cells, thereby enhancing or suppressing the initiation, magnitude, and/or duration of immune cells within the liver, preventing diminished hepatobiliary functions during disease progression, or by acting as a first effector cell in an innate response to encounter antigens.

However, the knowledge of MC.
function in the human liver is still very limited and further fundamental studies are urgently needed to understand the full biological repertoire and activities mediated by these important immune cells in human liver homeostasis and disease.

https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.mdpi.com/2073-4409/8/11/1429/pdf&ved=2ahUKEwi55bfkq-brAhVQY6wKHduxCpEQFjANegQIBRAB&usg=AOvVaw3YiKr20NdIygDyAvOAeYam

TRYPTASE+SCF+MAST CELL ACCUMULATION IN THE HUMAN LIVER CORRELATES WITH FIBROSIS IN NON-ALCOHOLIC FATTY LIVER DISEASE

A.C. De LaCruz, A. Omidian, M.Wilson, M.Altintas, N. DeLa Cruz Munoz, M. Nadji, M. Garcia-Buitrago, A. Nayer.

Journal of Hepatology 2016 vol. 64 | S425–S630

Inflammation promotes progression of nonalcoholic fatty liver disease (NAFLD). We have previously shown that mast cells accumulate in the human liver in NAFLD. Mast cells can expresstryptase that has been implicated in fibrogenesis. We studied mast cells present in the liver of humans with NAFLD and determined whether: (1) mast cells express tryptase; (2) mast cell tryptase expression correlates with fibrosis; (3) tryptase+ mast cells express stem cell factor (SCF), a growth factor critical for recruitment, proliferation, and functions of mast cells.

https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.researchgate.net/profile/Mehmet_Altintas/publication/308571093_Tryptase_SCF_Mast_Cell_Accumulation_in_the_Human_Liver_Correlates_with_Fibrosis_in_Non-Alcoholic_Fatty_Liver_Disease/links/5ba3c71c45851574f7d978bc/Tryptase-SCF-Mast-Cell-Accumulation-in-the-Human-Liver-Correlates-with-Fibrosis-in-Non-Alcoholic-Fatty-Liver-Disease.pdf&ved=2ahUKEwjerc_Yq-brAhUEc60KHTv6DwgQFjAMegQIBBAB&usg=AOvVaw0ApRXlfVWdfTbWHnsHWIWS&cshid=1600010979939

NAFLD Tied To Mast Cells

By Michael Vlessides

Mast cells, which have been implicated in a variety of illnesses, also appear to play a role in nonalcoholic fatty liver disease (NAFLD), according to Florida researchers, who also found that the density of hepatic mast cells correlated directly with necroinflammatory activity and fibrosis.

“Traditionally, mast cells have been implicated in conditions such as allergies, hypersensitivity reactions and asthma,” said Anna Christina dela Cruz, MD, who was a liver fellow at the University of Miami when the study was conducted.

“However, there’s been recent interest in the role of mast cells in liver regeneration, liver inflammation and other metabolic syndromes. Although mast cells have been found to accumulate in the liver of rodents with NAFLD, there have not been studies exploring the involvement of mast cells in NAFLD in humans.”

The researchers hypothesized that since inflammation plays a critical role in the progression of NAFLD and mast cells have been shown to accumulate in the liver of rodents with NAFLD, the cells may contribute to the progression of liver disease.

Dr. dela Cruz reported at the 2015 annual meeting of the American Association for the Study of Liver Diseases (abstract 914), there was significant interobserver correlation with respect to mast cell quantification (r=0.78; P<0.001).

Mast cells were roughly four times more abundant in patients with NAFLD than in controls (17.0 ± 2.4 vs. 4.4 ± 1.3/mm2; P<0.05). Plus, the greater the density of hepatic mast cells, the more necroinflammatory activity and fibrosis that the patients had (Figure 1).

https://www.gastroendonews.com/Article/PrintArticle?articleID=35233

Alcoholic liver disease and mast cells: What’s your gut got to do with it?

Julie Ann Tolefree , Abigail Joy Garcia a, Jenee Farrell , Vik Meadows, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville , Nicole Francis a, Julia Mirabel, Heather Francis

Liver Research
Volume 3, Issue 1, March 2019, Pages 46-54
https://doi.org/10.1016/j.livres.2019.02.002

Alcoholic liver disease (ALD) remains one of the leading causes of liver injury and death when left un-treated. The gut microbiota has been recognized as a key regulator of a number of pathologies, including ALD.

The role of mast cells (MCs) during liver disease progression has been demonstrated in a number of animal models and in human liver diseases.

The interaction between the gut microbiota and MCs has been investigated, and links between the gut and these immune cells are being uncovered.

The interplay between the gut microbiota and MCs during ALD has been evaluated and studies suggest that there couldbe an important link between MCs, their mediators and gut inflammation during the progression of ALD.

Hepatic MC markers.

MCs contribute to liver disease progression via a number of traditional and unconventional receptor subtypes.

Using a novel technique for isolating pure hepatic MCs from cholestatic livers, Hargrove et al., concluded that isolated hepatic MCs exhibit a similar morphology compared to cultured, activated MCs.

Both hepatic and cultured MCs express typical markers: c-Kit, FcεRI,chymase, tryptase, and histamine receptors H1-H4.

However, hepatic MCs also express vascular endothelial growth factor receptors (VEGF-R2/R3) and angiopoietin receptors (TIE1/2), which are not traditionally found in cultured MCs.

A concise, practical guide to diagnostic assessment for mast cell activation disease

Lawrence B Afrin, Gerhard J Molderings

World J Hematol. Feb 6, 2014; 3(1): 1-17
doi: 10.5315/wjh.v3.i1.1

Mast cell activation disease (MCAD) is characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells’ mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing.

Recent data suggest a high prevalence of MCAD. Thus, MCAD should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity of a generally inflammatory theme or patients in whom established diagnoses do not well account for the patient’s presentation of symptoms consistent with mast cell mediator release.

Mediator testing can be challenging but typically is manageable. Diagnostic efforts are worthwhile, as diagnosis often leads to effective therapy.

AAAAI Ask the Expert

ANTIHISTAMINES AND WEIGHT GAIN

It has long been known that the administration of antihistamines can cause weight gain. In fact, one antihistamine, cyproheptadine, has been used for this purpose. There are many postulations as to why this occurs. One reason, which may be the most reasonable, is that histamine is known to reduce the appetite, and antihistamines, therefore, counteract this effect.

In a recent NHANES survey, antihistamine use was associated with obesity, and a study in the journal “Obesity,” (see abstract copied below) confirmed this and analyzed the use of over-the-counter antihistamines and their effect on weight gain. They found, as in the NHANES survey, that the use of over-the-counter antihistamines, including both fexofenadine and cetirizine, was associated with obesity.

Unfortunately, we know more about this association and the potential underlying reasons for it than we do about which antihistamines may be less likely to produce this effect. I know of no study comparing the effects of available antihistamines on weight gain and could find none on a literature search. Therefore, although it is not unlikely that some antihistamines may be more potent than others in this regard, the effect appears to be more class-related rather than drug-specific.

But because we have no available information on relative potency of antihistamines regarding their effect on weight gain, there is, to my knowledge, no information available to assist you in selecting a specific antihistamine that might be helpful and not produce this side effect. Therefore the only strategy available to you, if you wish to continue to use antihistamines, is to employ various agents via “trial and error.”

The other strategy of course would be to use alternative agents to supplement or replace antihistamine use. A thorough discussion of these drugs are available in two articles.

1.Morgan M and Khan DA. Annals of Allergy, Asthma, and Immunology 2008; 100:403-411.

2.Morgan M and Khan DA. Annals of Allergy, Asthma, and Immunology 2008; 100:51-526.

In summary, to my knowledge, there is no specific antihistamine which will not potentially cause the well-documented side effect of weight gain with regular use, and therefore the only alternative for you is to try different antihistamines in a “trial and error” fashion, or to supplement or substitute the use of antihistamines with alternative therapies. References and abstracts of references are copied below should you wish to read further about the issue of antihistamines and weight gain.

Thank you again for your inquiry and we hope this response is helpful to you.

Obesity
Volume 18, Issue 12, pages 2398–2400, December 2010

Abstract

The incidence of obesity in the United States has reached epidemic proportions. Previous research has shown several medications exert noticeable effects on body-weight regulation.

Histamine-1 (H1) receptor blockers commonly used to alleviate allergy symptoms are known to report weight gain as a possible side effect. Therefore, we investigated the association between prescription H1 antihistamine use and obesity in adults using data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES).

Adults taking prescription H1 antihistamines were matched by age and gender with controls and compared on the basis of body measurements, plasma glucose, insulin concentrations, and lipid levels. Prescription H1 antihistamine users had a significantly higher weight, waist circumference, and insulin concentration than matched controls. The odds ratio (OR) for being overweight was increased in prescription H1 antihistamine users. H1 antihistamine use may contribute to the increased prevalence of obesity and the metabolic syndrome in adults given these medications are also commonly used as over-the-counter remedies.

Expert Opin Pharmacother. 2012 Dec;13(18):2613-24. doi: 10.1517/14656566.2012.742887. Epub 2012 Nov 10.
Potential benefits of cyproheptadine in HIV-positive patients under treatment with antiretroviral drugs including efavirenz.
Dabaghzadeh F, Khalili H, Ghaeli P, Dashti-Khavidaki S.

https://www.aaaai.org/ask-the-expert/antihistamines-weight-gain

Histamine H2-Receptor Antagonists Use Is Associated with Lower Prevalence of Nonalcoholic Fatty Liver Disease

Huafeng Shen, MD MPH and Suthat Liangpunsakul, MD MPH

J Clin Gastroenterol. 2016 Aug; 50(7): 596–601.
doi: 10.1097/MCG.0000000000000503
PMCID: PMC4935666
NIHMSID: NIHMS754566
PMID: 26905606

Recent basic mechanistic studies found that proton pump inhibitors (PPIs) or histamine antagonists inhibited multiple pathways involved in non-alcoholic fatty liver disease (NAFLD) development.

The aim of this study was to investigate an association between PPIs or H1/H2-receptor antagonists (H1RAs/H2RAs) use and NAFLD prevalence in the general US population.

In conclusion, we found that the use of H2RAs may be associated with a lower prevalence of NAFLD, primarily among men with insulin resistance. Further studies are needed to confirm our observation.

Histamine Type-2 Receptor Antagonists (H2 Blockers)

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Histamine Type-2 Receptor Antagonists (H2 Blockers) [Updated 2018 Jan 25

The selective histamine type 2 receptor antagonists/blockers (H2 blockers) are widely used in the treatment of acid-peptic disease, including duodenal and gastric ulcers, gastroesophageal reflux disease and common heartburn.

The four H2 blockers in current use are available by prescription as well as over-the-counter, and are some of the most widely used drugs in medicine.

The H2 blockers are very well tolerated, but have been linked to rare instances of clinically apparent liver injury.

The H2 receptor blockers act by binding to histamine type 2 receptors on the basolateral (antiluminal) surface of gastric parietal cells, interfering with pathways of gastric acid production and secretion.

The selectivity of H2 blockers is of key importance, as they have little or no effect on the histamine type 1 receptors, which are blocked by typical antihistamines that are used to treat allergic reactions and have little effect on gastric acid production.

The selective H2 blockers are less potent in inhibiting acid production than the proton pump inhibitors (which block the common, final step in acid secretion) but, nevertheless, suppress 24 hour gastric acid secretion by about 70%.

The H2 receptor blockers are metabolized in the liver by the cytochrome P450 system. Among the four agents, cimetidine is distinctive in its potent inhibition of the P450 system (CYP 1A2, 2C9 and 2D6), which can result in significant drug interactions.

All four H2 receptor blockers have been implicated in rare cases of clinically apparent, acute liver injury. The most cases have been linked to ranitidine and cimetidine, but these two agents are also the most commonly used. The four H2 receptor blockers in clinical use are discussed separately, with references given after each.

Famotidine

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Famotidine.

Famotidine is a histamine type 2 receptor antagonist (H2 blocker) which is commonly used for treatment of acid-peptic disease and heartburn. Famotidine has been linked to rare instances of clinically apparent acute liver injury.

Chronic therapy with famotidine has been associated with minor elevations in serum aminotransferase levels in 1% to 4% of patients, but similar rates were reported in placebo recipients.

The ALT elevations are usually asymptomatic and transient, and may resolve without dose modification.

Rare instances of clinically apparent liver injury have been reported in patients receiving famotidine, but few cases have been reported and clinical characteristics in published cases have varied in the time to onset and pattern of injury.

Onset has ranged from 1 to 14 weeks and serum enzyme pattern has typically been hepatocellular. The injury resolves within 4 to 12 weeks of stopping famotidine. Immunoallergic features (rash, fever, eosinophilia) are uncommon, as is autoantibody formation.

Likelihood score: C (probable rare cause of clinically apparent liver injury).

Mechanism of Injury

Famotidine is metabolized by the microsomal P450 drug metabolizing enzymes and injury may be the result of its activation to a toxic intermediate.

Outcome and Management

The hepatic injury caused by famotidine is usually rapidly reversible with stopping the medication (Case 1). Famotidine has not been definitively linked to cases of acute liver failure, chronic hepatitis, prolonged cholestasis or vanishing bile duct syndrome.

The results of rechallenge have not been reported. There appears to be cross reactivity in hepatic injury with cimetidine (Case 2). If acid suppression is required, use of an unrelated proton pump inhibitor is probably prudent for patients with clinically apparent famotidine induced liver injury.

The H2 receptor blockers include cimetidine, famotidine, nizatidine, and ranitidine. Combined general references on the H2 receptor blockers are given together after this overview section, while specific references are provided in the separate section on each drug.

See also the Proton Pump Inhibitors.

Cimetidine

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-Cimetidine.

Introduction

Cimetidine is a histamine type 2 receptor antagonist (H2 blocker) which is widely used for treatment of acid-peptic disease and heartburn. Cimetidine has been linked to rare instances of clinically apparent acute liver injury.

Cimetidine is metabolized by and can inhibit several isoforms of the hepatic cytochrome P450 system (CYP 1A2, 2C9 and 2D6), which can result in significant drug-drug interactions if administered with agents that rely upon their metabolism by these microsomal enzymes (such as digoxin, warfarin, oral contraceptives, isoniazid and phenytoin).

Hepatotoxicity

Chronic therapy with cimetidine has been associated with minor elevations in serum aminotransferase levels in 1% to 4% of patients, but similar rates were reported in placebo recipients.

The ALT elevations were usually asymptomatic and transient and usually resolved even without dose modification.

Several instances of clinically apparent liver injury have been reported in patients receiving cimetidine, but the time to onset and pattern of injury has varied greatly.

Onset can be as short as a few days to as long as 7 months, and the serum enzyme pattern varies from hepatocellular to cholestatic, most cases having a “mixed” hepatocellular-cholestatic pattern of injury (Cases 1 and 2).

The injury is rarely severe and resolves within 4 to 12 weeks of stopping cimetidine. Liver biopsy histology often shows prominent centrolobular necrosis. Immunoallergic features (rash, fever, eosinophilia) are uncommon, as is autoantibody formation.
Likelihood score: B (highly likely cause of clinically apparent liver injury).

Mechanism of Injury

Cimetidine is metabolized by and inhibits the function of the microsomal P450 drug metabolizing enzymes, and injury may be the result of its activation to a toxic intermediate. Rapid recurrence with rechallenge is typical, but features of hypersensitivity are uncommon.

Outcome and Management

The hepatic injury caused by cimetidine is usually rapidly reversible with stopping the medication (Case 1). Cimetidine has not been definitively linked to cases of acute liver failure, but there has been at least one case of prolonged cholestasis with probable vanishing bile duct syndrome after an episode of cholestatic hepatitis attributed to cimetidine.

Rechallenge usually causes recurrence which can be more severe than the initial episode. There appears to be little cross susceptibility to hepatic injury between ranitidine and cimetidine, but instances have been reported of recurrence after famotidine (Case 2).

If acid suppression is required, use of an unrelated proton pump inhibitor is probably prudent for patients with clinically apparent cimetidine induced liver injury.

Covid-19 Hyperinflammation and Post-Covid-19 Illness May Be Rooted in Mast Cell Activation Syndrome

Lawrence B. Afrin, Leonard B. Weinstock, Gerhard J. Molderings
International Journal of Infectious Diseases
DOI:S1201-9712(20)30732-3 Redirecting
IJID 4599

:black_small_square:︎Much of Covid-19 hyperinflammation is concordant with mast-cell-driven inflammation.

:black_small_square:︎Prevalence of severe Covid approximates that of mast cell activation syndrome (MCAS).

:black_small_square:︎ Drugs inhibiting mast cells (MCs) and their mediators show promise in Covid-19.

:black_small_square:︎None of our treated MCAS patients suffering Covid-19 had severe courses or mortality.

:black_small_square:︎ The dysfunctional MCs of MCAS may underlie severe acute and chronic Covid-19 illness.

Covid-19 Hyperinflammation and Post-Covid-19 Illness May Be Rooted in Mast Cell Activation Syndrome

Lawrence B. Afrin, Leonard B. Weinstock, Gerhard J. Molderings
International Journal of Infectious Diseases
DOI:S1201-9712(20)30732-3 Redirecting
IJID 4599

:black_small_square:︎Much of Covid-19 hyperinflammation is concordant with mast-cell-driven inflammation.

:black_small_square:︎Prevalence of severe Covid approximates that of mast cell activation syndrome (MCAS).

:black_small_square:︎ Drugs inhibiting mast cells (MCs) and their mediators show promise in Covid-19.

:black_small_square:︎None of our treated MCAS patients suffering Covid-19 had severe courses or mortality.

:black_small_square:︎ The dysfunctional MCs of MCAS may underlie severe acute and chronic Covid-19 illness.

https://www.jacionline.org/article/S0091-6749(14)02923-6/fulltext