Immunology 101

Mast cells are a type of white blood cell that resides in connective tissue, containing small granules (small little packets) of compounds that play a role in immunity. The most well known is histamine, but others include leukotrienes (which also play a role in allergies), serotonin, ATP (your body’s primary energy currency), inflammatory cytokines such as TNF-alpha and interleukin-4, reactive oxygen species (like H2O2, which help kill off foreign invaders), and enzymes like tryptase.

Mast cells just carry all these compounds around in the bloodstream, selectively releasing their contents when triggered. Triggers include binding with two or more IgE molecules (the “hypersensitivity” immunoglobulin, characteristic of true allergies), physical injury, or pathogenic microbes. When mast cells release all their contents at once, that’s called anaphylaxis, and it can be life-threatening.

Mast Cell Diseases

Mastocytosis is when a patient has too many mast cells due to a genetic mutation. This can be cutaneous (skin only—also called urticaria pigmentosa) or systemic (in other forms of connective tissue also, especially the stomach and intestinal linings). Cutaneous mastocytosis is diagnosed by skin biopsy, while systemic mastocytosis is diagnosed via bone marrow biopsy.

Mast Cell Activation Syndrome (MCAS) looks very similar to mastocytosis, but in this case, patients have a normal number of mast cells. They’re just hyperresponsive, meaning they release their contents inappropriately.

Symptoms and Testing for MCAS

Symptoms common to MCAS include itchiness, easy bruising, lightheadedness, diarrhea, intestinal cramping, nausea and vomiting, brain fog, headaches and migraines, fatigue, food and chemical sensitivities.

All symptoms worsen in response to certain triggers, different for each patient, but they tend to be things like high histamine foods, chemical exposure, hormone fluctuations (like before menses), exertion, temperature changes, an stress. Sometimes the triggers are the fillers or additives in medications.

MCAS is determined by meeting three criteria: 1) presenting with the symptoms above, without a diagnosis of systemic mastocytosis or a previous episode of anaphylaxis, 2) increase in serum tryptase (one of the enzymes contained in mast cells—it should be in the cells, not in the bloodstream), or increase in other mast cell mediators like histamine; and 3) improvement with treatment with mast cell stabilizers (mentioned below.)

Causes and Associations of MCAS

MCAS can show up as a concomitant condition with POTS, with Lyme, and with CIRS (Chronic Inflammatory Response Syndrome), a biotoxin-related illness. I also often see symptoms consistent with MCAS associated with multiple chemical sensitivity.

Melanocyte-stimulating hormone (MSH), usually low after exposure to water-damaged buildings, helps to modulate the allergenic immune response when levels are adequate and even causes mast cells to undergo apoptosis, or programmed cell death. The lack of sufficient MSH in the presence of CIRS may be part of the reason why CIRS and MCAS are related.

Treatments for MCAS

In addition to a low histamine diet, there are both pharmaceutical and natural approaches. Pharmaceuticals include anti-histamines and anti-leukotrienes, as well as mast cell stabilizers.

Natural mast cell stabilizers include quercetin and Vitamin C.

I’ll usually also work on the pathways by which histamine gets out of the body. One enzyme that directly degrades histamine is DAO (diamine oxidase), which you can take with meals. There are two other routes of excretion: one is an enzyme called NAT, which requires Vitamin B5, and the other is a three-step enzyme process involving the methylation cycle and another enzyme called MAO. (A lot of my patients have mutations in this one.) I’d highly suggest getting genetics testing to support these pathways.

Of course, if MCAS is secondary to biotoxin exposure or Multiple Chemical Sensitivity, the real treatment is detoxification and addressing the cause.