Mast cell activation syndrome (MCAS) is a type of mast cell activation disorder (MCAD), and is an immunological condition in which

mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...

s inappropriately and excessively release chemical mediators, resulting in a range of chronic symptoms, sometimes including

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

or near-anaphylaxis attacks. Primary symptoms include cardiovascular, dermatological, gastrointestinal, neurological and respiratory problems. Multiple diagnostic schemes for MCAS have been proposed, and the condition is increasingly over-diagnosed or misdiagnosed.

Signs and symptoms

MCAS is a condition that affects multiple systems, generally in an inflammatory manner. Symptoms typically wax and wane over time, varying in severity and duration. Many signs and symptoms are the same as those for

mastocytosis Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells (also called ''mastocytes'') and CD34+ mast cell precursors. People affected by mas ...

, because both conditions result in too many mediators released by mast cells. It has many overlapping characteristics with recurrent idiopathic anaphylaxis, although there are distinguishing symptoms, specifically

hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...

and

angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...

. Common symptoms include: * Dermatological ** flushing ** hives ** easy bruising ** either a reddish or a pale complexion ** itchiness ** burning feeling ** dermatographism * Cardiovascular ** lightheadedness, dizziness,

presyncope Lightheadedness is a common and typically unpleasant sensation of dizziness or a feeling that one may faint. The sensation of lightheadedness can be short-lived, prolonged, or, rarely, recurring. In addition to dizziness, the individual may feel ...

, syncope,

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

* Gastrointestinal ** diarrhea and/or constipation, cramping, intestinal discomfort ** nausea, vomiting, acid reflux ** swallowing difficulty, throat tightness * Respiratory ** congestion, coughing, wheezing * ''

Anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

'' If too many mediators are released into a patient's system, they may also experience anaphylaxis, which primarily includes: difficulty breathing, itchy hives, flushing or pale skin, feeling of warmth, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.

Causes

There are no known causes, but the condition appears to be inherited in some patients. Symptoms of MCAS are caused by excessive chemical mediators inappropriately released by mast cells. Mediators include

leukotrienes Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotri ...

histamines Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...

prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deriv ...

, and

tryptase Tryptase (, ) is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. Club cells contain tryptase, which is believed to be responsible for cleaving the hemag ...

. The condition may be mild until exacerbated by stressful life events, or symptoms may develop and slowly trend worse with time.

Pathophysiology

Mast cell activation can be localized or systemic. MCAS can present with a wide range of symptoms in multiple body systems, these symptoms may range from digestive discomfort to chronic pain, mental issues as well as an anaphylactic reaction. Some examples of tissue specific consequences of mast cell activation include

urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...

, allergic rhinitis, and wheezing. Systemic mast cell activation presents with symptoms involving two or more organ systems (skin: urticaria, angioedema, and flushing; gastrointestinal: nausea, vomiting, diarrhea, and abdominal cramping; cardiovascular: hypotensive syncope or near syncope and tachycardia; respiratory: wheezing; naso-ocular: conjunctival injection, pruritus, and nasal stuffiness). This can result from the release of mediators from a specific site, such as the skin or mucosal tissue, or activation of mast cells around the vasculature.

Diagnosis

MCAS is often difficult to identify due to the heterogeneity of symptoms and the "lack of flagrant acute presentation". Many of the numerous symptoms are non-specific in nature. Mast cell activation was assigned an

ICD-10 ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms ...

code (D89.40, along with subtype codes D89.41-43 and D89.49) in October 2016. Although different diagnostic criteria are published, a commonly used strategy to diagnose patients is to use all three of the following: # Symptoms consistent with chronic/recurrent mast cell release:
Recurrent abdominal pain, diarrhea, flushing, itching, nasal congestion, coughing, chest tightness, wheezing, lightheadedness (usually a combination of some of these symptoms is present) # Laboratory evidence of mast cell mediator (elevated serum tryptase, N-methyl histamine, prostaglandin D2 or 11-beta- prostaglandin F2 alpha, leukotriene E4 and others) # Improvement in symptoms with the use of medications that block or treat elevations in these mediators" The

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...

has not published diagnostic criteria.

Treatment

Common pharmacological treatments include: *

Mast cell stabilizer Mast cell stabilizers are medications used to prevent or control certain allergic disorders. They block mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. One suspected pharmaco ...

s, including

cromolyn sodium Cromoglicic acid (INN)—also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate—is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. ...

and

natural Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans ar ...

stabilizers such as

quercetin Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor ...

Table 1: Naturally occurring mast cell stabilizers
/ref> * H1-antihistamines, such as

cetirizine Cetirizine, sold under the brand name Zyrtec among others, is a second-generation antihistamine used to treat allergic rhinitis (hay fever), dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty minutes a ...

or ketotifen or fexofenadine or loratadine * H2-antihistamines, such as

ranitidine Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome ...

or famotidine *

Antileukotriene An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor ( arachidonate 5-lipoxygenase) or leukotriene receptor antagonist (cysteinyl leuko ...

s, such as montelukast or zileuton as well as natural products (e.g.,

curcumin Curcumin is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal curcuminoid of turmeric (''Curcuma longa''), a member of the ginger family, Zingiberaceae. It is sold as a herbal supplement, cosmet ...

or St. John's wort extracts) *

Nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration o ...

s, including

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

can be very helpful in reducing inflammation in some patients, while others can have dangerous reactions

Prognosis

The prognosis of MCAS is uncertain because of lack of studies.

History

The condition was hypothesized by the pharmacologists John Oates and Jack Roberts of

Vanderbilt University Vanderbilt University (informally Vandy or VU) is a private research university in Nashville, Tennessee. Founded in 1873, it was named in honor of shipping and rail magnate Cornelius Vanderbilt, who provided the school its initial $1-million ...

in 1991, and following a build-up of evidence featured in papers by Sonneck et al. and Akin et al., named in 2007. Diagnostic criteria were proposed in 2010 and revised in 2019.

References

External links

{{Medical resources , DiseasesDB = , ICD10
D89.4
, ICD9 = 279.8 , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = Immune system disorders Syndromes