Mast Cell Activation Syndrome (MCAS)

Mast Cell Activation Syndrome (MCAS) is a condition in which mast cells, a type of white blood cell involved in the immune system, release excessive amounts of chemicals such as histamine, prostaglandins, and other inflammatory substances inappropriately or excessively. This abnormal activation leads to symptoms affecting multiple organs and systems.  Mast cells are part of the immune system and are found in tissues throughout the body, especially near the skin, lungs, gastrointestinal tract, and blood vessels.

Histamine is a compound involved in local immune responses and regulating physiological functions in the gut. It is released by mast cells and basophils and plays a pivotal role in allergic reactions, causing symptoms such as itching, swelling, and vasodilation.

Causes of MCAS

In MCAS, these mast cells become overactive and release mediators too often or at the wrong times, causing a wide variety of symptoms. The causes of MCAS can include:

• Genetic factors: Some individuals may have genetic predispositions that make their mast cells hyper-responsive.
• Environmental triggers: Infections, stress, allergens, and certain medications or foods can activate mast cells inappropriately.
• Idiopathic: In many cases, the exact cause is unknown.

MCAS is different from mastocytosis, where there is an abnormal increase in the number of mast cells. In MCAS, the problem is that the existing mast cells release too many mediators rather than there being too many mast cells.

Symptoms of MCAS

The symptoms of MCAS are highly variable, as mast cells are present throughout the body and can affect multiple organs and systems. Common symptoms include:

1. Skin Symptoms:  flushing, hives, itching, swelling
2. Gastrointestinal Symptoms:  nausea, vomiting, diarrhea or constipation, abdominal pain, heartburn
3. Cardiovascular Symptoms:  low blood pressure, dizziness, rapid or irregular heartbeat
4. Respiratory Symptoms:  wheezing, shortness of breath, nasal congestion
5. Neurological Symptoms:  headaches, brain fog, fatigue
6. Other Symptoms:  anaphylaxis, joint or muscle pain, difficulty regulating body temperature

Histamine Blockers

• OTC H1 Blocker, eg Zyrtec, Claritin, Allegra, Benadryl, Ketotifen
• OTC H2 Blockers, eg Pepcid, Tagamet, Zantac
• Rx H1 Blockers, Ketotifen 0.5mg PO QHS

Mast Cell Stabilizers

• Cromolyn solution 100mg/5mL 200mg 4x/day before meals and at bedtime
• Ketotifen

Leukotriene Inhibitors

• Montelukast (brand name Singulair) 10mg daily (selectively binds to cysteinyl leukotriene receptors)
  • Montelukast Black Box Warnings:  Serious Neuropsychiatric Events
• Zafirlukast (Accolate) 20mg bid (antagonizes leukotriene D4 and E4 receptors)

Midodrine

Midodrine can help patients with mast cell activation syndrome by stabilizing blood pressure, improving blood flow, and reducing orthostatic stress, which can indirectly help to reduce mast cell activation and associated symptoms of flushing and hives.  It is particularly useful for managing symptoms related to orthostatic hypotension, which is a common issue in MCAS.  However, midodrine is typically part of a broader treatment plan that includes other medications targeting mast cell activity directly.

Black Box Warnings:  Midodrine can cause marked supine blood pressure elevations, use in patients whose lives are considerably impaired despite standard clinical care

Low Dose Naltrexone (LDN) 0.5-4.5 mg per day

Mechanisms of Low-Dose Naltrexone (LDN)

1. Immune Modulation:
   • LDN is thought to exert its effects by modulating the immune system. It temporarily blocks opioid receptors, leading to a rebound increase in the production of endorphins and enkephalins, which are natural opioids produced by the body. These endogenous opioids can modulate the immune response, potentially leading to reduced inflammation and mast cell stabilization.
2. Reduction in Pro-Inflammatory Cytokines:
   • LDN has been shown to reduce the production of pro-inflammatory cytokines, which are signaling molecules that can activate mast cells and promote histamine release. By lowering these cytokines, LDN might help to reduce the activation and degranulation of mast cells.
3. Regulation of TLR4 (Toll-Like Receptor 4):
   • LDN might exert some of its effects through the modulation of Toll-Like Receptor 4 (TLR4), which plays a role in the immune system’s response to pathogens. TLR4 is involved in the activation of mast cells. By modulating TLR4, LDN could potentially reduce inappropriate mast cell activation and histamine release.

Supplements

Supplements including luteolin, quercetin, vitamin C, local raw honey, bromelain, probiotics, astragalus, butterbur, D-HIST, PEA may reduce microglial activation

Luteolin calms/inhibits the mast cell response; has anti- inflammatory, anti-carcinogenic, and anti-viral properties; “inhibits interleukin (IL)-6, IL-8 and VEGF

Low Histamine Diet

A histamine avoidance diet can help reduce the amount of histamine the body needs to deal with.