Mast cell activation syndrome

Not to be confused with Mastocytosis.

Immune Disorder
Classification and external resources
Specialty	Immunology
ICD-10	D89 (CDC Proposed as D89.40)
ICD-9-CM	757.33/202.60
Patient UK	Mast cell activation syndrome

Mast Cell Activation Syndrome (MCAS), also commonly referred to as mast cell activation disorder (MCAD), is an immunological condition in which mast cells inappropriately and excessively release chemical mediators, resulting in a range of chronic symptoms, sometimes including anaphylaxis or near-anaphylaxis attacks. Primary symptoms include cardiovascular, dermatological, gastrointestinal, neurological and respiratory problems.

Unlike mastocytosis, where patients have an abnormally increased number of mast cells, patients with MCAS have a normal number of mast cells that do not function properly and are defined as "hyperresponsive." MCAS is still a poorly understood condition and is a current topic of research.

MCAS is often found in patients with Ehlers-Danlos Syndrome (EDS) and Postural Orthostatic Tachycardia Syndrome (POTS). It is also found in subset groups of patients with Common Variable Immunodeficiency (CVID) and Lyme Disease.

Symptoms and Triggers

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, 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 and angioedema.

Common symptoms include:

Dermatological

-flushing

-easy bruising

-either a reddish or a pale complexion

-itchiness

Cardiovascular

-lightheadedness, dizziness, presyncope, syncope

Gastrointestinal

-diarrhea, cramping, intestinal discomfort

-nausea, vomitting

Psychological & Neurological

-brain fog, short term memory dysfunction, difficulty with recalling words

-headaches, migraines

Respiratory

-congestion, coughing, wheezing

Vision/Eyes

-ocular discomfort, conjunctivitis

Constitutional

-general fatigue and malaise

-food, drug, and chemical intolerances (especially fragrances)

-sense of being cold all the time

Musculoskeletal

-osteoporosis and osteopenia (including young patients)

Anaphylaxis If too many mediators are spilt into your system, patients 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.

Symptoms can be caused or worsened by triggers, which vary widely and are patient-specific.
Common triggers include:

-specific foods and drinks (especially alcohol, and high-histamine content foods)

-temperature extremes

-airborne smells including perfumes or smoke

-exercise or exertion

-emotional stress

Causes

There are no known causes, but the condition appears to be inherited. Symptoms of MCAS are caused by excessive chemical mediators inappropriately released by mast cells. Mediators include leukotrienes and histamines. The condition may be mild until exacerbated by stressful life events, or symptoms may develop and slowly trend worse with time.

Diagnosis

MCAS is often difficult to identify due to the heterogeneity of symptoms and the “lack of flagrant acute presentation.” The condition can also be difficult to diagnose, especially since many of the numerous symptoms may be considered “vague.” Patients often see many different specialties due to the inherent multisystem nature of the condition, and do not get diagnosed until a holistic view is taken by a diagnostician. Lack of awareness of MCAS by many medical professionals is currently a hurdle to proper diagnosis.

“Although different diagnostic criteria are published, a commonly used strategy to diagnose patients is to use all three of the following:

1. 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)

2. Laboratory evidence of mast cell mediator (N-methyl histamine, prostaglandin D2 or 11-beta- prostaglandin F2 alpha, leukotriene E4 and others)

3. Improvement in symptoms with the use of medications that block or treat elevations in these mediators”

The World Health Organization has not yet published diagnostic criteria.

Treatment

Common pharmacological treatments include:

• Mast cell stabilizers, including cromolyn sodium and natural product MC stabilizers such as quercetin
• H1-antihistamines, such as cetirizine or ketotifen
• H2-antihistamines, such as ranitidine
• Antileukotrienes, such as montelukast or zileuton as well as natural products (e.g., curcumin or St. John's wort extracts)
• Nonsteroidal anti-inflammatory drugs, including aspirin can be very helpful in reducing inflammation in some patients, while others can have dangerous reactions

Fillers, binders and dyes in many medications are often the culprit in causing reactions, not necessarily the active agent, so alternative formulations and compounding pharmacies should be considered.

Lifestyle changes may also be needed. Avoidance of triggers is important. It should be emphasized that MCAS patients can potentially react to any new exposure, including food, drink, medication, microbes and smoke via inhalation, ingestion or touch.

A low histamine diet and other elimination diets can be useful in identifying foods that trigger or worsen symptoms. Many MCAS patients already have high histamine levels, so ingesting foods with high histamine or histamine liberators can worsen many symptoms such as vasodilation that causes faintness and palpitations.

Prognosis

There is no cure for MCAS. For most, symptoms wax and wane, but many can experience a general worsening trend over time. Lifespan for those with MCAS appears to be normal, but quality of life can range from mild discomfort to severely impaired. Some patients are impaired enough to be disabled and unable to work.

Epidemiology

MCAS is a relatively new diagnosis, only being named in 2007, and is believed to be very under-diagnosed. New findings are revealing that MCAS is much more prevalent than previously thought. It's currently estimated that 4.5% of the general population has tryptasemia, which is associated with mast cell activation syndrome.

History

It has been suggested in the literature for decades; however diagnostic criteria have been proposed only in 2010. The condition was first recognized in 1991, and finally named in 2007.

See also

• Immunoglobulin E
• FcεRI

External links

Recent medical reviews on MCAS:

• The role of mast cells in functional GI disorders
• Mast Cell Activation Syndrome – May 2015
• Spectrum of mast cell activation disorders – 2014
• Mast cell activation syndromes: definition and classification – 2013
• Expanding Spectrum of Mast Cell Activation Disorders: Monoclonal and Idiopathic Mast Cell Activation Syndromes – 2013