Mast cell activation syndrome

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.[6] It has many overlapping characteristics with recurrent idiopathic anaphylaxis, although there are distinguishing symptoms, specifically hives and angioedema.[7]

Common symptoms include:[4][8]

• Dermatological
  • flushing
  • hives
  • easy bruising
  • either a reddish or a pale complexion
  • itchiness
  • burning feeling
  • dermatographism
• Cardiovascular
  • lightheadedness, dizziness, presyncope, syncope, arrhythmia, tachycardia
• Gastrointestinal
  • diarrhea and/or constipation, cramping, intestinal discomfort
  • nausea, vomiting
  • swallowing difficulty, throat tightness
• Genitourinary
  • interstitial cystitis; burning in the bladder and urinary tract
• Psychiatric & Neurological
  • brain fog, short term memory dysfunction, difficulty with recalling words
  • headaches, migraines
  • co-morbid psychiatric and behavioral symptoms as a result of mast cell mediators being released in the brain (i.e.: anxiety, depression, mood swings, etc.)
• Respiratory
  • congestion, coughing, wheezing
  • Nonallergic rhinitis with eosinophilia syndrome (NARES) [9]
  • Obstructive Sleep Apnea
• Vision/Eyes
  • ocular discomfort, conjunctivitis
  • redness
• Constitutional
  • general fatigue and malaise
  • food, drug, and chemical allergies or intolerances (especially fragrances)
  • Cold and Heat Intolerance
• Musculoskeletal
  • osteoporosis and osteopenia are possible symptoms of mast cell activation disorders
• Anaphylaxis If too many mediators are split 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.

Symptoms can be caused or worsened by triggers, which vary widely and are patient-specific. Common triggers include:[8]

• specific foods and drinks (especially alcohol, high-histamine content foods, and histamine releasing additives such as sulfites)
• temperature extremes
• airborne smells including perfumes or smoke
• exercise or exertion
• emotional stress
• hormonal changes, particularly during adolescence, pregnancy and menstruation.

There are no known causes, but the condition appears to be inherited in some patients.[5] Symptoms of MCAS are caused by excessive chemical mediators inappropriately released by mast cells. Mediators include leukotrienes, histamines, prostaglandin, and tryptase. The condition may be mild until exacerbated by stressful life events, or symptoms may develop and slowly trend worse with time.[4][5]

MCAS is often difficult to identify due to the heterogeneity of symptoms and the "lack of flagrant acute presentation."[8] The condition can also be difficult to diagnose, especially since many of the numerous symptoms are non-specific in nature. Mast cell activation was assigned an ICD 10 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:

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 (elevated serum tryptase, 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"[4]

The World Health Organization has not published diagnostic criteria.

Common pharmacological treatments include:

• Mast cell stabilizers,[7] including cromolyn sodium and natural stabilizers such as quercetin[10][11]
• H1-antihistamines,[7] such as cetirizine or ketotifen or fexofenadine or loratadine
• H2-antihistamines,[7] such as ranitidine or famotidine
• Antileukotrienes,[7] such as montelukast or zileuton as well as natural products (e.g., curcumin or St. John's wort extracts)
• Nonsteroidal anti-inflammatory drugs,[6] including aspirin can be very helpful in reducing inflammation in some patients, while others can have dangerous reactions[6]

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.[6]

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.[6]

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.

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.[6] Some patients are impaired enough to be disabled and unable to work.

MCAS is a relatively new diagnosis, being unnamed until 2007, and is believed to be under-diagnosed. (Dr. Lawrence Afrin describes it as "likely quite prevalent" and having "increasingly apparent prevalence").[6]

Diagnostic criteria were proposed in 2010.[2] The condition was hypothesized by the pharmacologists John Oates and Jack Roberts of Vanderbilt University in 1991, and following a build-up of evidence featured in papers by Sonneck et al.[12] and Akin et al.,[13] finally named in 2007.[6]

• FcεRI
• Histamine intolerance
• Immunoglobulin E

• Characterization of Mast Cell Activation Syndrome - 2016 Lawrence Afrin, M.D et al.
• The role of mast cells in functional GI disorders FFT at Gut/BMJ
• 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