Mast cell disease in the age of COVID-19: Part 1

If you are currently alive on this planet, you are aware that we are currently experiencing a worldwide pandemic the likes of which have not been seen in decades. We are still early into this event and there is a lot of uncertainty. However, the scientific and medical communities have come together to share data and resources to protect the lives of people around the world. In the meantime, day to day life will change for most people, including mast cell patients.

A lot of patients are concerned about the intersection of COVID-19 and mast cell disease.

I wrote this monster post but think people would be better served by taking smaller bites so I sectioned the article into several smaller posts. This is the first one. Watch for the rest in the next few days.

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COVID-19 can cause severe respiratory distress, requiring use of a ventilator to sustain life.

It is extremely common for mast cell patients to have increased mast cell reaction in pulmonary tissues at baseline. Chronic airway inflammation is sometimes associated with increased mast cell population in pulmonary tissues. [i] Chronic dry, unproductive cough, similar to the one seen with COVID-19, sometimes occurs in mast cell patients. [ix] Mast cell patients frequently have reactive airways, creating an environment of persistent mast cell activation. [ix] Physical stimuli in the respiratory tract, such as coughing, can also be activating. [ii] Persistent coughing and inflammation of the respiratory tract are painful, further contributing to mast cell activation. [iii]

Several mast cell mediators contribute to airway inflammation and subsequent symptoms including cough. Histamine and prostaglandin D2 promote bronchoconstriction, mucus production, and airway edema. Leukotrienes C4 and D4 and chymase also contribute to mucus production and edema. Tryptase release promotes overall increased reactivity of the airway. [i]

A number of medications routinely used to mitigate airway inflammation are well tolerated in mast cell patients. This includes beta-2 adrenergic agonists, like albuterol; inhaled and oral steroids, like fluticasone or prednisone; and inhaled cromolyn [vi] are frequently used in mast cell patients [vi]. Oral theophylline, benzonatate, and nebulized racemic epinephrine can provide relief from pulmonary symptoms. [viii]

Guaifenesin is commonly used for cough. Patients should be vigilant that the guaifenesin preparation they use does not contain other medications. It is commonly sold in preparations that include dextromethorphan, which causes mast cell degranulation, and phenylephrine, a decongestant that can affect heart rate and blood pressure.

Some medications used at baseline to manage mast cell activation can provide some relief for respiratory symptoms, including antihistamines, like cetirizine, and leukotriene receptor antagonists, like montelukast. [vii]

Shortness of breath, increased respiratory rate, and difficulty breathing are sometimes seen in COVID-19. These symptoms can cause tachycardia, rapid heartbeat. Beta blockers are commonly used in the general population to treat tachycardia. Beta blockers are a hard contraindication for mast cell patients due to their increased risk of anaphylaxis. Beta blockers interfere with the action of epinephrine and taking them is a huge risk factor for fatal anaphylaxis worldwide in all populations. [xi] There are a variety of alternatives available.

While many COX inhibitors are widely available, the most common are non-steroidal anti-inflammatories (NSAIDs). Many mast cell patients take NSAIDs like aspirin or ibuprofen for daily management of mast cell disease. [vi] COX inhibitors stop the production of prostaglandins, including PGD2, and its derivative 9a,11b-PGF2, both significantly active mast cell mediators; and PGE2, a minor mast cell activator and mediator, but critically important in fever response. Prostaglandin E2, elevated during fevers, can also downregulate or promote mast cell degranulation. [x]

In the past week, there have been multiple reports that ibuprofen could lead to additional complications when used in patients with COVID-19. There is no indication at this time that other NSAIDs, such as aspirin, are similarly problematic in this scenario. There is also nothing to indicate that COX inhibitors in other drug classes could cause similar issues.

It is too soon to know definitely if there is a risk associated with ibuprofen use in COVID-19 patients. However, I feel that it is reasonable to ask your provider if you should abstain from using ibuprofen during this time, particularly since patients can be asymptomatic despite active infection. If mast cell patients routinely use ibuprofen, they should speak to their provider about whether or not they should discontinue this medication, and which medication they should use to replace it.

References:

[i] Cruse G, Bradding P. (2016). Mast cells in airway diseases and interstitial lung disease. European Journal of Pharmacology 778, 125-138.

[ii] Zhang D, et al. (2012). Mast-cell degranulation induced by physical stimuli involves the activation of transient receptor-potential channel TRPV2. Physiol Res, 61(1):113-124.

[iii] Chatterjea D, Martinov T. (2015). Mast cells: versatile gatekeepers of pain. Mol Immunol, 63(1),38-44.

[iv] Dewachter P, et al. (2014). Perioperative management of patients with mastocytosis. Anesthesiology, 120, 753-759.

[v] Brockow K, Bonadonna P. (2012). Drug allergy in mast cell disease. Curr Opin Allergy Clin Immunol, 12, 354-360.

[vi] Molderings GJ, et al. (2016). Pharmacological treatment options for mast cell activation disease. Naunyn-Schmiedeberg’s Arch Pharmol, 389:671.

[vii] Molderings GJ, et al. Mast cell activation disease: a concise, practical guide to diagnostic workup and therapeutic options. J Hematol Oncol 2011; 4 (10).

[viii] Walsh P, et al. (2008). Comparison of nebulized epinephrine to albuterol in bronchiolitis. Acad Emerg Med, 15(4):305-313.

[ix] Afrin LB. (2013). Diagnosis, presentation and management of mast cell activation syndrome. Mast cells.

[x] Theoharides TC, et al. (2012). Mast cells and inflammation. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1822(1), 21-33.

[xi] Simons FER, et al. (2015). 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines. World Allergy Organization Journal, 8(32).