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Recognition and Management of Medication Excipient Reactivity in Patients With Mast Cell Activation Syndrome

Jill R. Schofield, MD1,2 and Lawrence B. Afrin, MD

Mast cell activation syndrome (MCAS) is a complex disorder hallmarked by chronic multisystem inflammatory, allergic and growth dystrophic phenomena caused by inappropriate mast cell activation.

MCAS has been estimated to affect as many as 17% of the population with a severity ranging from mild to life-threatening.

MCAS patients are more sensitive than the average person to chemicals in the environment, including the nondrug (“inactive”) ingredients (excipients) in medications and supplements. Excipient reactivity may explain unusual side effects to medications health professionals often find puzzling, such as the patient who appears intolerant of prednisone, acetaminophen, levothyroxine, or a vitamin.

We present a series of patients with MCAS to illustrate important points regarding excipient reactivity which may be useful in everyday practice.

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I said I was Zebra Doc, I didn’t say I was a Wuss. #zebrastrong

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FDA double nested study on anticholinergic medications and dementia. Good read.

"There were no significant increases in risk associated with antihistamines, skeletal muscle relaxants, gastrointestinal antispasmodics, antiarrhythmics, or antimuscarinic bronchodilators, although the numbers of patients exposed were small for skeletal muscle relaxants and antiarrhythmics. "

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2736353

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The perioperative period is the time period of a patient’s surgical procedure. It commonly includes ward admission, anesthesia, surgery, and recovery.

https://anesthesiology.pubs.asahq.org/article.aspx?articleid=1917908

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Horner, Chelsey G., “Anesthesia for the Patient with Mast Cell Activation Disease” (2018). Nursing Capstones. 182.

https://commons.und.edu/cgi/viewcontent.cgi?article=1181&context=nurs-capstones

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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

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

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"Mast cells mainly function as immediate hypersensitivity in the early phase of allergic inflammation, whereas basophils, although their precursor cells are the same as mast cells, largely circulate in the blood and are recruited in the late phase of allergic response [42].

The locations of intestinal mast cells are primarily tissues at the interface like blood vessels or intestinal surfaces, and their granule contents are variable depending on factors surrounding them.

They are mainly located in the lamina propria and the submucosa but are also found in the intraepithelial, smooth muscle, and serosal layers of the intestine [43].

According to their granule contents, mast cells can be grouped as those containing tryptase but no chymase and those containing tryptase, chymase, and carboxypeptidase [13, 44, 45], each predominating in different locations [46].

The functions of intestinal mast cells include regulating permeability, secretion, peristalsis, nociception, innate and adaptive immunity, and angiogenesis and affecting many diverse GI diseases such as not only functional GI disorders but also organic diseases [47]."

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From Jonathon

Extensive references. WAO guideline (tome) for IgE skin test.

Of note is their recommendation for discontinuance of H1 and H2 meds 4 to 5 days prior to testing that contravenes recommendations of a number of prominent mast cell practitioners for highly reactive patients.

Consult your physician(s) prior to discontinuing any treatment prior to test. If highly reactive, request/ensure you have rescue meds on hand and avoid triggers.

345

Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence, diagnosis and treatment

Comorbidity discussion.

“Motility and absorptive disorders are highly prevalent in IBD patients, particularly in those with persistent GI symptoms despite quiescent disease. Timely diagnosis and appropriate treatment of these conditions significantly improves care and well-being of IBD patients. Despite the high prevalence and significant impact of these disorders in IBD patients, evidence in diagnosis and treatment is critically lacking. Future controlled studies are needed to address motility and absorptive disorders specially in IBD patients.”

https://www.wjgnet.com/1007-9327/full/v25/i31/4414.htm

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Fascinating Bioscience of the day. Preliminary experiments in mice show macrophages can refuel neuron mitochondria relieving inflammation induced pain.

(Air Force fighter pilots hear it all the time from the tanker community…“You Can’t Kick Ass Without Tanker Gas”)

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Detection of c-kit mutation Asp 816 to Val in microdissected bone marrow infiltrates in a case of systemic mastocytosis associated with chronic myelomonocytic leukaemia

K Sotlar, Marafioti, H Griesser, J Theil, C Aepinus, R Jaussi, H Stein, P Valent, H-P Horny

https://mp.bmj.com/content/molpath/53/4/188.full.pdf

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Mast Cells in Lung Inflammation

https://page-one.springer.com/pdf/preview/10.1007/978-1-4419-9533-9_13

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Mast Cells in Lung Homeostasis: Beyond Type I Hypersensitivity

Marcia Campillo-Navarro, et.al.

"Influenza is a frequent infectious disease of the human respiratory tract, which is caused by a group of viruses from the Orthomyxoviridae family; the most common of these viruses is influenza A.

These viruses have attracted attention because they are associated with pandemics that have severely affected human health, like the ‘Spanish flu’ of 1918 [42].

Interestingly, studies with this strain have reported alterations in lung architecture, which are caused by an excessive inflammatory response promoted by an uncontrolled production of inflammatory cytokines and chemokines, also known as ‘cytokine storm’ [43]"

351

Asthma: Eosinophil Disease, Mast Cell Disease, or Both?

Peter Bradding DM, FRCP

"Although this article focuses on the role of mast cells and eosinophils in asthma pathogenesis, it is important to appreciate that most, if not all, elements of the asthmatic airway are dysfunctional.

There is epithelial damage with failure of healing and overproduction of growth factors and proinflammatory cytokines, [1] mucous gland hyperplasia with associated mucus hypersecretion, [2] airway smooth muscle (ASM) remodelling with hypertrophy, hyperplasia, BHR and cytokine secretion, [3–5] and activation of inflammatory cells, including mast cells, [6] T cells, [7] eosinophils, [8] and neutrophils [2]. "

"Mast cells have long been considered to play a significant role in the pathophysiology of asthma through their ability to release a host of pleiotropic autacoid mediators, proteases, and cytokines in response to activation by both immunoglobulin E (IgE)-dependent and diverse nonimmunologic stimuli [6, 34].

Within the first few minutes following laboratory allergen challenge, secretion of the autacoid mediators histamine, prostaglandin D2 (PGD2) and LTC4 induces bronchoconstriction, mucus secretion, and mucosal edema, which account for the acute symptoms [35].

Mast cells also release preformed and newly generated cytokines with the potential for a wide range of biological effects in the airways. "

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Apoptosis and Pro-inflammatory Cytokine Response of Mast Cells Induced by Influenza A Viruses

Bo Liu, et.al.

“Influenza A virus (IAV) is one of the most common respiratory pathogens. It is notorious for its unique potential to cause global pandemics and epidemics in animals and humans of all age groups. It has considerable morbidity and high fatality rates. Several studies suggest that fatal lung tissue injury triggered by the cytokines dysregulation (called “cytokine storm”), which is produced by excessive immune inflammation response, makes a critical contribution to the mortality of influenza.”

“Collectively, the results of the present study suggest that virus-induced hyper-production of pro-inflammatory cytokines and chemokines (cytokine storm) and apoptosis are intrinsically linked in mast cells during IAV infection. H5N1 viral RNA was detected in the lungs and tracheas, where apoptosis and inflammation were both prominent, but little viral RNA was found in the livers, where apoptosis and inflammation were not observed [47].”

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Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis

Lisa E. Gralinski, et.al.

"The anaphylatoxins produced by the activated complement pathway, C4a, C3a, and C5a, have important immunostimulatory roles in vascular permeability and inflammatory cell recruitment (35, 48).

C3a and C5a in particular are noted for their roles in causing mast cell degranulation, initiating a cytokine storm, promoting vascular permeability, and contributing to acute lung injury (36, 49, 50).

Furthermore, a C5a antibody blockade was recently shown to protect in a model of highly susceptible MERS-CoV mice (16).

Although there are no reports of mast cell activation following SARS-CoV or MERS-CoV infection, activation has been observed both in vitro and in vivo following infection with influenza virus (51) and may occur following other severe respiratory infections, including coronaviruses.

Mast cells release cytokines, including IL-6, IL-1, and TNF-α, consistent with the inflammatory profile observed following SARS-CoV MA15 infection.

While this work cannot definitively conclude that the complement anaphylatoxins and mast cell activation contribute to SARS-CoV MA15 pathogenesis, the data are consistent with this possibility, and the concept warrants further investigation."

https://mbio.asm.org/content/9/5/e01753-18

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Chronically Ill and Elderly

Amid a coronavirus outbreak in the United States, the US Centers for Disease Control and Prevention is encouraging older people and people with severe chronic medical conditions to “stay at home as much as possible.”

This advice is on a CDC website that was posted Thursday, according to a CDC spokeswoman.

Early data suggests older people are twice as likely to have serious illness from the novel coronavirus, according to the CDC.

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Dr. Zubin Damania (AKA ZDoggMD) with 6:30 of common sense and what the hospital community are thinking.