Gastrointestinal Symptoms of Mast Cell Activation Syndrome 

Background: Mast Cell Activation Syndrome (MCAS), is a condition marked by the aberrant mast cell activation in a variety of tissues.  It’s a complex disorder characterized by abnormal mast cell activation.  

Mast cells are essential parts of the immune system of the body, normally tasked with protecting the body from infections, these cells become hyper responsive in MCAS. There’s production of copious amounts of chemical mediators like cytokines and histamine which results in the manifestation of numerous symptoms affecting not only respiratory, cardiovascular, skin, gastrointestinal but also other organ systems. 

Diagnosis is often challenging due to its heterogenous nature and overlap with other illnesses. 

What Are The Gastrointestinal Symptoms? 

MCAS is characterized by a variety of gastrointestinal symptoms such as: 

• Bloating 
• Diarrhoea 
• Constipation 
• Nausea 
• Vomiting 
• Abdominal pain 
• Gastroesophageal reflux disease/heart burn. 

These symptoms can vary from minor discomfort to severe and incapacitating episodes. While specific manifestations of gastrointestinal symptoms may vary among MCAS patients, they are frequently brought on by the release of mast cell mediators like histamines and cytokines. These cause the gastrointestinal smooth muscles to contract, increase vascular permeability, secrete mucus, and experience neurogenic inflammation. 

These symptoms can seriously lower a person's quality of life and can happen either episodically or continuously. 

While gastrointestinal symptoms are common, patients may also experience symptoms involving the skin (such as flushing, itching, and hives), respiratory system (such as wheezing and shortness of breath), cardiovascular system (such as palpitations and low blood pressure), neurological system (such as headaches and cognitive impairment), and musculoskeletal system (such as joint pain and muscle weakness). 

Mechanisms Underlying the GI symptoms 

Histamine Release: In reaction to a variety of stimuli, mast cells release histamine, which causes smooth muscle contraction, an increase in vascular permeability, and the secretion of mucus. These actions can all be linked to gastrointestinal symptoms like cramps, diarrhea, and bloating. 

Pro-inflammatory Cytokines: TNF-α and interleukin-6 (IL-6) are two examples of pro-inflammatory cytokines that mast cells can produce. These cytokines can worsen tissue damage and inflammation in the gastrointestinal tract. 

Neurogenic Inflammation: Mast cell activation can stimulate the release of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP), leading to neurogenic inflammation and visceral hypersensitivity, which are associated with symptoms like abdominal pain and discomfort. 

Dysregulation of Gut Microbiota: Emerging evidence suggests that MCAS may disrupt the balance of gut microbiota, leading to dysbiosis and subsequent gastrointestinal symptoms. Additionally, mast cell mediators can influence the permeability of the intestinal barrier, contributing to increased mucosal inflammation and immune activation. 

Diagnosis 

Clinical History:  A detailed history is very important and this should include; the onset, course, features of the symptoms, along with any possible aggravating factors. Patients with MCAS frequently describe a history of recurrent or chronic symptoms that impact several organ systems. These symptoms can get worse in response to specific triggers like stress, infections, drugs, or allergens in the environment. 

Physical Examination: Findings such as skin findings (e.g., flushing, hives), respiratory symptoms (e.g., wheezing), cardiovascular symptoms, orthostatic hypotension (sudden drop in blood pressure while standing), or abdominal tenderness may indicate mast cell activation. 

Laboratory Tests:  During episodes of mast cell activation, the levels of mast cell mediators in the blood or urine may be elevated. These tests are used to measure these levels. Serum tryptase levels, serum histamine levels, 24-hour urine histamine metabolites, and other markers of mast cell activation are examples of tests that may be performed. It is crucial to remember that normal levels of these mediators do not necessarily rule out MCAS because they can vary and remain normal in between mast cell activation episodes. For further information about testing, please click here. 

Reaction to Therapy: The diagnosis of MCAS may be supported by a favorable reaction to targeted therapy using drugs like mast cell stabilizers and antihistamines. If these drugs help their patients' symptoms, they may still benefit from continued treatment if their symptoms are mast cell-mediated. 

Management Strategies 

H1 and H2 Antihistamines: These drugs relieve symptoms like nausea, diarrhea, and abdominal pain by preventing the effects of histamine that is released by mast cells. 

Mast Cell Stabilizers: Medications like Ketotifen and sodium cromoglicate function by stabilizing the membranes of mast cells, stopping the release of inflammatory mediators, and lessening symptoms related to the gastrointestinal tract. 

PPIs, or Proton Pump Inhibitors: By lessening the production of gastric acid and easing the symptoms of acid reflux and heartburn, PPIs are frequently used to treat GERD symptoms in patients with MCAS. 

Dietary Adjustments: To relieve gastrointestinal symptoms, some patients may find relief from dietary adjustments such as avoiding trigger foods, cutting back on histamine-rich foods, and adhering to a low-FODMAPS diet. This should be done with expert guidance to avoid overly restrictive diets. 

Symptom Management: To control bowel movements and ease discomfort, anti-diarrheal drugs, laxatives, and prokinetic agents can also be used to relieve symptoms. 

Conclusion 

One of the main characteristics of mast cell activation syndrome is gastrointestinal symptoms, which greatly increases the burden of illness that affected people endure.  

Comprehending the intricate relationship between gastrointestinal dysfunction and mast cell activation is essential for precise diagnosis and efficient treatment of this difficult ailment. Healthcare professionals can enhance the prognosis and quality of life for patients with MCAS by utilizing a holistic strategy that targets both gastrointestinal inflammation and mast cell activation. 

References 

• https://www.icliniq.com/articles/gastro-health/gastrointestinal-symptoms-in-mast-cell-activation-syndrome 
• Mast Cells in Gastrointestinal Disease 
• Gastrointestinal Manifestations in Systemic Mastocytosis: The Need of a Multidisciplinary Approach 
• Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside 

Author: Dr Nathaniel Eni (MBBS; MRCGP) 

General Practitioner

West End Road Surgery, Southampton 

Peer Reviewer: Mr. Oluwaseyi Adebola (MBBS, MSc, MRCS).  

Neurosurgery Specialty registrar, Walton Centre, Liverpool 

Medical Lead for Mast Cell Action, UK. 

Society of British Neurological Surgeons Collaborative Research Lead, Walton Centre