Mast cell activation syndrome (MCAS) is a 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.
|Mast cell activation syndrome|
Multiple diagnostic schemes for MCAS have been proposed, and the condition is increasingly over-diagnosed or misdiagnosed.
Signs and symptomsEdit
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:
- easy bruising
- either a reddish or a pale complexion
- burning feeling
- diarrhea and/or constipation, cramping, intestinal discomfort
- nausea, vomiting, acid reflux
- 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.[medical citation needed]
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.[medical citation needed] Some examples of tissue specific consequences of mast cell activation include urticaria, 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.
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 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.
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., named in 2007.
- Valent P (April 2013). "Mast cell activation syndromes: definition and classification". Allergy. 68 (4): 417–24. doi:10.1111/all.12126. PMID 23409940. S2CID 43636053.
- Akin C, Valent P, Metcalfe DD (December 2010). "Mast cell activation syndrome: Proposed diagnostic criteria". The Journal of Allergy and Clinical Immunology. 126 (6): 1099–104.e4. doi:10.1016/j.jaci.2010.08.035. PMC 3753019. PMID 21035176.
- Akin C (May 2015). "Mast cell activation syndromes presenting as anaphylaxis". Immunology and Allergy Clinics of North America. 35 (2): 277–85. doi:10.1016/j.iac.2015.01.010. PMID 25841551.
- Gülen T, Akin C, Bonadonna P, et al. (November 2021). "Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review". J Allergy Clin Immunol Pract. 9 (11): 3918–3928. doi:10.1016/j.jaip.2021.06.011. hdl:10261/268013. PMID 34166845. S2CID 235634993.
- [better source needed] Afrin LB, Molderings GJ (February 2014). "A concise, practical guide to diagnostic assessment for mast cell activation disease". World Journal of Hematology. 3 (1): 1–7. doi:10.5315/wjh.v3.i1.
- Frieri M (June 2018). "Mast Cell Activation Syndrome". Clinical Reviews in Allergy & Immunology. 54 (3): 353–365. doi:10.1007/s12016-015-8487-6. PMID 25944644. S2CID 5723622.
- [better source needed] Afrin L (2013). "Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome.". Mast Cells: Phenotypic Features, Biological Functions and Role in Immunity. Nova Science. pp. 155–232. Archived from the original on 2018-08-18. Retrieved 2015-10-13.
- Akin C (August 2017). "Mast cell activation syndromes". The Journal of Allergy and Clinical Immunology. 140 (2): 349–355. doi:10.1016/j.jaci.2017.06.007. PMID 28780942.
- Finn DF, Walsh JJ (September 2013). "Twenty-first century mast cell stabilizers". British Journal of Pharmacology. 170 (1): 23–37. doi:10.1111/bph.12138. PMC 3764846. PMID 23441583.
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
- Weiler CR, Austen KF, Akin C, et al. (October 2019). "AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management". The Journal of Allergy and Clinical Immunology. 144 (4): 883–896. doi:10.1016/j.jaci.2019.08.023. PMID 31476322.
- [non-primary source needed] Sonneck K, Florian S, Müllauer L, Wimazal F, Födinger M, Sperr WR, Valent P (2007). "Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: Monoclonal mast cell activation syndrome". International Archives of Allergy and Immunology. 142 (2): 158–64. doi:10.1159/000096442. PMID 17057414. S2CID 25058981.
- [non-primary source needed] Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P, Metcalfe DD (October 2007). "Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis". Blood. 110 (7): 2331–3. doi:10.1182/blood-2006-06-028100. PMC 1988935. PMID 17638853.