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What Is Mast Cell Activation Syndrome (MCAS)?

Long Covid is characterized by immune activation and inflammation. Mast Cell Activation Syndrome (MCAS) is proposed as part of the puzzle. Mast cells act as part of the immune system to help to fight infections. They are also involved in allergic reactions in which they release chemicals such as histamine. Mast cell activation syndrome happens when mast cells release too many of these chemicals resulting in allergic or anaphylactic symptoms. Although the symptoms of MCAS are similar to those of allergy it is usually more prolonged and without an obvious allergic trigger. In classical allergy, an immune protein IgE is needed to release histamine but not in MCAS.

Symptoms

Symptoms of MCAS, such as itching skin with hives and wheezing are typical of allergy. In addition, patients may have fast heart rate, passing out, or low blood pressure. In extreme cases there could be anaphylaxis with difficulty breathing due to throat swelling and very low blood pressure. Some patients experience abdominal pain, diarrhea and others neurological symptoms including headache, confusion and extreme tiredness. When the symptoms involve 2 or more organ systems, such as wheezing, diarrhea, and or/ flushing, patient should be evaluated for MCAS. Patients often initially enjoy symptom-free intervals interspersed with symptomatic periods. Over time, symptom-free intervals shorten, and finally symptoms become chronic with intensity which fluctuates but with an overall trend toward steadily increasing intensity.

Diagnosis & Tests

A few mediators or chemicals have been found to be consistently elevated in episodes of MCAS, and hence have been designed as measurable biomarkers in commercial laboratory tests. Some of the useful tests in diagnosis of MCAS include:

  • Serum mast cell tryptase
  • Urine levels of N-methylhistamine
  • Urine levels of 11B-Prostaglandin F2α (11B-PGF-2α)
  • Urine levels of Leukotriene E4 (LTE4)

Ideally, the measurement of these biomarkers should be done shortly after the onset of the anaphylactic event. Moreover, having a baseline level to compare with the acute level may be helpful in the interpretation of some of these biomarkers.

Treatment

Treatment of patients with MCAS is highly individualized and targeted to bothersome symptoms and the underlying pathology. Based on the causes of MCAS, several treatments have been proposed, mostly either blocking the release of histamine or blocking the effects of histamine. Part of the diagnostic criteria is that the symptoms should resolve with therapies directed at the increased mediator.

The treatment of acute episodes should follow the recommendations for treatment of anaphylaxis depending on the severity of symptoms.

The goal for long term treatment is mainly for patient relief. Low histamine diets have been used to reduce the total body load of histamine. Choice of drug therapy include antihistamines, mast cell stabilizers, and leukotriene antagonists:

Antihistamines

  • Histamine type 1 receptor (H1R) blockers can be effective for itching, abdominal discomfort and flushing. Non-sedating second-generation H1R antihistamines (e.g. Loratadine or Cetirizine) are generally preferred and can be increased to 2 to 4 times the standard dose.
  • Histamine type 2 receptor (H2R) blockers (e.g. ranitidine or famotidine) can be helpful for abdominal pain and nausea. They may also help H1R antihistamines attenuate cardiovascular symptoms.

Montelukast

Montelukast blocks the effects of leukotriene, which is an inflammatory chemical, to reduce symptoms like wheezing and abdominal cramping. Some evidence showed that it may be particularly effective in those with increased urinary LTE4 levels.

Corticosteroids

Oral corticosteroids (e.g. prednisolone) is used to treat hives and wheezing but should only be used with medical supervision.

Others

Other drug such as Quercetin is a plant pigment that has been shown to have anti-histamine effect as well.

Depending on the country many of these treatments are available over the counter, but they should be ideally used with medical supervision.

 

Reference

1. Mast Cell Activation Syndrome (MCAS). American Academy of Allergy Asthma & Immunology. (n.d.). Retrieved October 5, 2021, from https://www.aaaai.org/conditions-treatments/related-conditions/mcas.

2. Molderings, G. J., Brettner, S., Homann, J., & Afrin, L. B. (2011, March 22). Mast cell activation disease: A concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology & Oncology. Retrieved October 5, 2021, from https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-4-10.

3. Weiler CR; Austen KF; Akin C; Barkoff MS; Bernstein JA; Bonadonna P; Butterfield JH; Carter M; Fox CC; Maitland A; Pongdee T; Mustafa SS; Ravi A; Tobin MC; Vliagoftis H; Schwartz LB; (n.d.). AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management. The Journal of Allergy and Clinical Immunology. Retrieved October 5, 2021, from https://pubmed.ncbi.nlm.nih.gov/31476322/.

Topics: Long COVID

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