What is the maximum number of days that can pass without a Fecal Microbiota Transplantation (FMT) dose before needing to restart the process in a patient with Mast Cell Activation Syndrome (MCAS) and high histamine levels?

FMT Dosing Intervals in MCAS: Clinical Guidance

Based on available evidence for severe/fulminant C. difficile infection requiring repeat FMT, dosing intervals of 3-5 days are recommended, and extending beyond 5 days may require restarting immune tolerance protocols, though no specific data exists for MCAS patients using micro-dosing protocols. 1

Evidence-Based Dosing Intervals

The 2024 AGA guidelines provide the most relevant framework for repeat FMT timing:

• Standard repeat FMT intervals: every 3-5 days for patients with severe or fulminant CDI not responding to initial treatment 1
• Timing should be based on patient response to treatment, local protocols, and multidisciplinary care 1
• Treatment response can be assessed by monitoring stool output, white blood cell count, and C-reactive protein 1

Critical Gap in Evidence for MCAS Micro-Dosing

No published data exists specifically addressing maximum intervals between micro-dose FMT administrations in MCAS patients. The guidelines focus on standard-dose FMT for CDI, not the micro-dosing protocol (0.50 grams every 4-5 days) described in this case. 1

Practical Recommendations for This Case

Dosing Schedule

• Maintain the 4-5 day interval currently being used, as this aligns with guideline recommendations for repeat FMT 1
• Do not exceed 5 days between doses to minimize risk of losing immune tolerance and requiring restart 1
• If MCAS symptoms prevent dosing at 5 days, consider this a potential restart scenario 2, 3

Antibiotic Considerations

• Minimum 24-hour washout period between last antibiotic dose and FMT administration is required 1
• Ideally, antibiotics should be stopped 1-3 days before FMT 1
• Consultation with infectious disease specialists is recommended when patients require antibiotics within 8 weeks of FMT 1

MCAS-Specific Concerns

This patient's MCAS complicates standard FMT protocols significantly:

• MCAS involves excessive mast cell mediator release (histamine, prostaglandins, leukotrienes, tryptase) in response to various triggers 2, 3, 4, 5
• Symptoms include gastrointestinal, cardiovascular, respiratory, and neurologic manifestations 4, 5
• Treatment typically requires H1/H2 antihistamines, leukotriene receptor blockers, mast cell stabilizers, and trigger avoidance 2, 5

The micro-dosing approach (0.50 grams vs. standard doses) appears to be an adaptation for MCAS sensitivity, though this is not evidence-based. 2, 3

Pre-Surgical Considerations

For the upcoming emergency oral surgery:

• Coordinate with anesthesia regarding MCAS management - premedication with H1/H2 blockers and corticosteroids may be necessary 2, 5
• Avoid known mast cell triggers in medications, antiseptics, and anesthetics 2, 3
• Have epinephrine immediately available for acute mast cell activation episodes 2
• Consider postponing non-emergent FMT doses around the surgical period to avoid compounding immune activation 2, 3

Key Caveats

• The spouse donor being previously tolerated does not guarantee continued tolerance after the C. difficile infection and development of MCAS 1
• Frozen FMT material has a maximum shelf life of 6 months at -80°C 1
• Thawing should occur at ambient temperature and be used within 6 hours 1
• No evidence supports FMT for MCAS treatment itself - this is solely for post-CDI microbiome restoration 1

Clinical Bottom Line

Maintain 4-5 day intervals maximum between micro-doses. Extending beyond 5 days risks requiring immune tolerance restart based on standard FMT protocols, though specific data for MCAS micro-dosing does not exist. Close monitoring for both CDI recurrence and MCAS exacerbation is essential, with multidisciplinary involvement including gastroenterology, infectious disease, and allergy/immunology. 1, 2, 3