Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association

Abstract

Background Recently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS. Methods and Results Data were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with <4 months symptom duration, evident ongoing inflammatory disease, suspected volume depletion, or declined consent were excluded. All patients had typical POTS symptoms; some, however, had additional nonorthostatic complaints not usually associated with POTS. The latter patients underwent additional testing for known MCA biochemical mediators including prostaglandins, histamine, methylhistamine, and plasma tryptase. The study comprised 69 patients who met POTS diagnostic criteria. In 44 patients (44/69, 64%) additional nonorthostatic symptoms included migraine, allergic complaints, skin rash, or gastrointestinal symptoms. Of these 44 patients, 29 (66%) exhibited at least 1 laboratory abnormality suggesting MCA disorder, and 11/29 patients had 2 or more such abnormalities. Elevated prostaglandins (n=16) or plasma histamine markers (n=23) were the most frequent findings. Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder. Conclusions Laboratory findings suggesting MCA disorder were relatively common in patients diagnosed with POTS and who present with additional nonorthostatic gastrointestinal, cutaneous, and allergic symptoms. While solitary abnormal laboratory findings are not definitive, they favor MCA disorder being considered in such cases.

Comparative Cohort Study of Post-Acute Covid-19 Infection with a Nested, Randomized Controlled Trial of Ivabradine for Those With Postural Orthostatic Tachycardia Syndrome (The COVIVA Study)

“…One of the possible mechanisms underlying POTS is activation of basophils and mast cells by parasympathetic neurons. This hypothesis is supported by a recent study where two thirds of individuals with POTS demonstrated increased histamine or other mast cell mediators in the blood in the setting of postural tachycardia (15). The present study will investigate whether this also occurs in post COVID-19 POTS.…”

Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?

“…In mast cell activation disorder, the inappropriate release of histamine and other mast cell mediators in response to physical activity or orthostatic stress may lead to orthostatic tachycardia [49]. Flushing, headaches, and gastrointestinal symptoms are more prevalent in these individuals, and a recent study showed markedly elevated prostaglandins and histamine markers in patients with gastrointestinal complaints, reinforcing the case for a mast cell activation disorder in a subset of POTS patients [78]. A case of mast cell activation syndrome was described in a 50-year-old female with previous COVID-19 with signs and symptoms of POTS [52].…”

Impact of Comorbidities on the Prognosis of Pediatric Postural Tachycardia Syndrome

“… 16 Furthermore, mast cell activation disorder (MCAD), a condition in which mast cells increase in number or excessively release inflammatory mediators, 31 was considered to be a comorbidity of adult POTS, and some of which might be secondary to allergic disorders. 32 , 33 A previous study on adults reported that patients with POTS were complicated with abnormal mast cell activation and significant increases in methylhistamine, leukotriene, and prostaglandin D 2 in their urine. 34 These inflammatory vasoactive substances may aggravate the dilation of peripheral blood vessels and increase vasopermeability, which can theoretically facilitate the occurrence of OI.…”