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What Is Mast Cell Activation Syndrome (MCAS)

Mast Cell Activation Syndrome (MCAS) is a condition involving repeated episodes of mast-cell mediator release that can affect the gut, skin, breathing, heart rate, and blood pressure.

Symptoms

• Flushing, itching, hives, or swelling
• Diarrhea, cramping, nausea, vomiting, bloating
• Fast heart rate, lightheadedness, fainting
• Wheezing, throat tightness, shortness of breath
• Headache, fatigue, or “brain fog”

Overview

Mast cells are immune cells that release histamine, prostaglandins, leukotrienes, and other chemical messengers. In MCAS, recurrent episodes may involve two or more body systems at once. GI symptoms may feel like sudden cramping, urgent diarrhea, nausea, food-related reactions, or bloating that occurs with flushing or racing heart. Histamine can influence gut motility, intestinal sensitivity, and signaling through the enteric nervous system. Stress and the gut-brain connection, including vagus nerve signaling, may amplify symptom perception but do not independently confirm MCAS. Diagnosis requires objective evidence of mast-cell mediator release during an episode and response to mediator-directed treatment.

Testing

Testing is most useful when collected during or soon after a significant episode and compared with a symptom-free baseline.

• Serum Tryptase: Acute and baseline levels; most specific routine marker.
• Urine N-Methylhistamine: Histamine metabolite.
• Urine Leukotriene E4: Leukotriene metabolite.
• Urine 11β-Prostaglandin F2α: Prostaglandin metabolite.
• KIT D816V Testing: Assesses for clonal mast-cell disease.
• Allergy Evaluation: Identifies IgE-mediated allergy or other triggers.

Common Pharmacological Treatments

• Cetirizine (Zyrtec), Fexofenadine (Allegra): H1 antihistamines for itching, hives, and flushing.
• Famotidine (Pepcid): H2 antihistamine often used for GI symptoms.
• Cromolyn Sodium: Mast-cell stabilizer that may reduce diarrhea, cramping, and bloating.
• Montelukast (Singulair): Leukotriene pathway blocker.
• Omalizumab (Xolair): Considered in selected refractory or allergic presentations.

Diet And Lifestyle

• Keep a symptom, food, medication, and trigger diary.
• Avoid clearly reproducible triggers rather than broadly restricting foods.
• Common reported triggers include alcohol, heat, temperature changes, infections, stress, NSAIDs, and certain foods.
• Use regular meals, hydration, sleep routines, and stress-regulation practices.
• Dietitian support can help prevent unnecessary food avoidance.

Sources

• Mast cell activation syndrome: current understanding and research needs. The Journal of Allergy and Clinical Immunology, 2024
• AAAAI mast cell disorders committee work group report: mast cell activation syndrome (MCAS) diagnosis and management. The Journal of Allergy and Clinical Immunology, 2019
• Anaphylaxis: a 2023 practice parameter update. Annals of Allergy, Asthma & Immunology, 2024

Lab Test (blood)

 7AlphaC4

Blood test for bile acid diarrhea, which is a condition when your digestive bile acid is released in excess in the colon leading to diarrhea. The aim is to look for Elevated concentrations (> 57 ng/mL) which is suggestive of bile acid diarrhea.

- labcorp can do it 

Transanal Irrigation (TAI) is used for neurogenic bowel dysfunction (NBD), low anterior resection syndrome (LARS), and refractory chronic constipation with fecal incontinence after conservative measures fail. 

- We often refer to Hopkins Colorectal CRNP 

- It is important to be educated on its use

- Patients should follow up a few times with provider to ensure proper use and outcomes

Common Devices:

Peristeen - Peristeen Transanal Irrigation Device Information (Click Here)

Sources 

• The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Fecal Incontinence

  https://pubmed.ncbi.nlm.nih.gov/40324433/

•   Peristeen® Plus Transanal Irrigation System. https://www.coloplastprofessional.us/coloplast/continence-care/peristeen/peristeen-plus-tai/peristeen-plus-transanal-irrigation-system/?legalconsented=true

What Is Intestinal Methanogen Overgrowth (IMO)?

Intestinal Methanogen Overgrowth (IMO) is excess methane-producing archaea in the digestive tract, often linked with constipation, bloating, and slow bowel motility.

Symptoms

• Constipation or infrequent stools
• Hard stools, straining, or incomplete evacuation
• Bloating and abdominal distention
• Abdominal discomfort or cramping
• Excess gas
• Symptoms that may overlap with Irritable Bowel Syndrome With Constipation (IBS-C)

Overview

IMO is not the same as Small Intestinal Bacterial Overgrowth (SIBO). Methane is produced by archaea, which are microorganisms distinct from bacteria and may be present in the small intestine and colon. Higher methane production is associated with slower intestinal transit, so patients often describe feeling “backed up,” bloated, and uncomfortable even when they are having bowel movements. The gut-brain connection can amplify symptoms: stress signaling through the vagus nerve and enteric nervous system may affect motility and visceral sensitivity. Serotonin helps coordinate intestinal movement, while stress-related changes in brain-gut signaling can worsen constipation and discomfort.

Testing

Breath testing measures hydrogen and methane after a carbohydrate drink. A methane level of 10 parts per million or higher at any point during testing supports IMO.

• Glucose Breath Test: Evaluates hydrogen and methane production.
• Lactulose Breath Test: Measures gas production across more of the intestinal tract.
• Anorectal Manometry: Assesses pelvic floor coordination when constipation is difficult to treat.
• Colon Transit Testing: Evaluates for slow-transit constipation.

Common Pharmacological Treatments

• Rifaximin (Xifaxan): Antibiotic commonly used for intestinal microbial overgrowth.
• Neomycin: Sometimes paired with Rifaximin for methane-predominant breath tests.
• Linaclotide (Linzess), Plecanatide (Trulance), Lubiprostone (Amitiza): May improve constipation and stool passage.
• Prucalopride (Motegrity): Supports colonic motility in selected patients.

Common Non-Pharmacological Options

• Dietitian Consultation: Helps individualize food changes without unnecessary restriction.
• Pelvic Floor Physical Therapy Or Anorectal Biofeedback: Helpful when dyssynergic defecation contributes to constipation.
• GI Psychology Or Nerva Digital App: Supports gut-brain symptom regulation.
• Motility Evaluation: Identifies constipation drivers that may coexist with IMO.

Common OTC Options

• Polyethylene Glycol 3350 (Miralax): Osmotic stool softening.
• Psyllium Husk: Soluble fiber that may support stool consistency.
• Kiwi Fruit: Some patients find two daily kiwis helpful for constipation.
• Peppermint Oil (IBgard): May ease bloating or cramping.

Diet And Lifestyle

• Eat regular meals and maintain adequate hydration.
• Increase fiber gradually; rapid increases can worsen bloating.
• Consider a structured, time-limited low-FODMAP approach with a dietitian.
• Support regular movement, sleep, and stress regulation, which can influence gut motility.
• Avoid overly restrictive diets unless there is a clear plan for reintroduction and nutrition.

Sources

• American College of Gastroenterology Clinical Guideline: Small Intestinal Bacterial Overgrowth — https://journals.lww.com/ajg/fulltext/2020/02000/acg_clinical_guideline__small_intestinal_bacterial.9.aspx
• North American Consensus on Hydrogen and Methane-Based Breath Testing — https://pmc.ncbi.nlm.nih.gov/articles/PMC5418558/
• International Foundation for Gastrointestinal Disorders: SIBO — https://iffgd.org/gi-disorders/other-disorders/small-intestinal-bacterial-overgrowth-sibo/