Mast Cell Activation Syndrome (MCAS)

Mast cell activation syndrome (MCAS) is a relatively recently recognized syndrome that continues to be debated about in the medical community. MCAS was first characterized in 1991 and diagnostic criteria were not first classified until 2010. Some consider it very rare while others believe it affects approximately 17% of the population.

Dermatographia — hive lines that immediately pop up after scratching the skin.

What is a Mast Cell?

A mast cell is a type of white blood cell that plays a key role in the body's immune response, particularly in allergic reactions and defense against parasites. Mast cells are found in tissues throughout the body, especially in areas close to the outside world like the skin, lungs, digestive tract, and around blood vessels and nerves. The contain and release granules that are filled with histamine, heparin, and other inflammatory chemicals. When triggered—often by allergens binding to IgE antibodies on their surface—they release these chemicals in a process called degranulation. They function in allergic reactions, inflammation, wound healing, and in defense against pathogens, specifically parasites. They are most known for producing itching, swelling, and mucus production all by releasing histamine.

Mast cells are central players in conditions such as asthma, anaphylaxis, eczema, and mastocytosis (a rare malignancy). People who have chronic allergic symptoms do experience increased activation of mast cells increased histamine.

What is MCAS? Two Very Different Definitions

Currently there are two recognized definitions of MCAS with the first being published in 2011 by a hematologist, Peter Valent, MD, of Vienna, Austria. Over the years his description of MCAS has been revised and adoptions by the American Academy of Allergy, Asthma & Immunology (AAAAI). Current criteria include:

• Typical clinical signs of severe, recurrent systemic mast cell activation present in at least two organ systems

• Anaphylaxis is common

• Increased mast cell activity is confirmed by laboratory tests, typically by a isignificant increased in serum tryptase level at the time of active symptoms

• Response of symptoms to medications that block mast cells or there produced biochemical signals (histamine)

In 2012, Gerhard J. Molderings, MD and his colleagues of Germany, define MCAS based on organ system symptoms. There definition was also revised in later years but continues to focus on clinical complaints that are related to mast cell activity plus the presence of at least one laboratory, tissue test, genetic, or radiologic study consistent with mast cell activity. Response to medication may or may not be used to confirm the diagnosis. It is this definition of MCAS that produced the population estimation of approximately 17%. The list of clinical symptoms recognized in this list is broad and includes:

• Constitutional: Chronic fatigue, flushing, or sweats

• Dermatologic: Rashes or lesions

• Ophthalmologic: dry eyes

• Oral: Burning or itching in mouth

• Pulmonary: Airway inflammation at any/all levels

• Cardiovascular: Blood pressure lability or co-diagnosis of POTS is common

• Gastrointestinal: Reflux, dysphagia, or malabsorption

• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia

• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common

• Neurologic: Headaches or sensory neuropathies

• Psychiatric: Depression or anxiety

• Endocrinologic: Thyroid disease or dyslipidemia

• Hematologic: Polycythemia or anemia (after ruling out other causes)

MCAS has been linked to other chronic conditions that have an inflammatory component including chronic fatigue syndrome (also called myalgic encephalomyelitis), Elhers-Danilo’s Syndrome, fibromyalgia, postural Orthostatic tachycardia syndrome (POTS), and long COVID.

MCAS or CIRS (chronic inflammatory response syndrome)?

Both conditions result in a person having chronic multisymptom multisystem illness meaning they have been sick for a long time with many symptoms. MCAS will almost always have clear allergic symptoms or symptoms attributed to relased products of mast cell granules. CIRS may also have dermatographia (scratched skin will form a hive in the shape of the scratch) which is the result of mast cell (and basophil) granules being released.

MCAS is often best evaluated by an allergist familiar with the full range of laboratory tests and diagnostic criteria to determine whether it is a likely differential diagnosis. Functional medicine or CIRS-trained physicians can help identify underlying root causes, support mitigation of reactions, and assess whether CIRS may be a coexisting condition.

Reference: Does Mast Cell Activation Syndrome Underlie Multiple Ills?

Miriam E. Tucker; Miriam E. Tucker

October 15, 2024