Mast cell activation syndrome
|Mast cell activation syndrome|
Mast cell activation syndrome (MCAS) is one type of mast cell activation disorder (MCAD), and 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, another type of MCAD, 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.
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, 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.
- easy bruising
- either a reddish or a pale complexion
- burning feeling
- diarrhea and/or constipation, cramping, intestinal discomfort
- nausea, vomiting
- swallowing difficulty, throat tightness
- congestion, coughing, wheezing
- Anaphylaxis 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.
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, 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.
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 ( The Mastocytosis Society). Some examples of tissue specific consequences of mast cell activation include urticaria, allergic rhinitis, and wheezing. Systemic mast cell activation presents with symptoms involving 2 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.
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 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:
- 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 has not published diagnostic criteria.
Common pharmacological treatments include:
- Mast cell stabilizers, including cromolyn sodium and natural stabilizers such as quercetin
- H1-antihistamines, such as cetirizine or ketotifen or fexofenadine or loratadine
- H2-antihistamines, such as ranitidine or famotidine
- 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
The prognosis of MCAS is uncertain because of lack of studies.
MCAS is a relatively new diagnosis, being unnamed until 2007, and is believed to be under-diagnosed.
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. and Akin et al., finally named in 2007.
Diagnostic criteria were proposed in 2010.
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A diverse range of mast cell stabilizing compounds have been identified in the last decade from; natural, biological and synthetic sources to drugs already in clinical uses for other indications. Although in many cases, the precise mode of action of these molecules is unclear, all of these substances have demonstrated mast cell stabilization activity and therefore may have potential therapeutic use in the treatment of allergic and related diseases where mast cells are intrinsically involved.Table 1: Naturally occurring mast cell stabilizers
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- 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