Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders

Abstract

Abstract-Postural tachycardia syndrome (POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation (MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA (MCAϩPOTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age-matched female controls. MCAϩPOTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79Ϯ4 to 114Ϯ6 bpm), increased systolic blood pressure on standing (from 117Ϯ5 to 126Ϯ7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157Ϯ12 versus 117Ϯ9 in normal controls and 119Ϯ7 mm Hg in POTS; Pϭ0.048), and an exaggerated phase IV blood pressure overshoot (50Ϯ10 versus 17Ϯ3 mm Hg in normal controls; PϽ0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but ␤-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.

Management of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia and Vasovagal Syncope

“…34 Both drugs can cause drowsiness, fatigue and worsen mental clouding. Modafinil might help the fatigue and cognitive dysfunction seen in some patients 35 with only a minimal increase in tachycardia.…”

Selective Response to Omalizumab in a Patient With Concomitant ncMCAS and POTS: What Does it Teach us About the Underlying Disease?

“…Furthermore, there must be a recorded rise in urine or serum levels of mast cell degranulation markers, and the condition must be responsive to antimediator therapy such as histamine 1 and 2 receptor antagonists, leukotriene antagonists, and mast cell stabilizers [1]. A proportion of patients with ncMCAS also have concomitant postural orthostatic tachycardia syndrome (POTS) [2]. POTS is a heterogenous form of orthostatic intolerance characterized by an increase in the heart rate of at least 30 bpm within 10 minutes of assuming an upright posture.…”

“…POTS commonly presents with cardiac symptoms (eg, palpitations, lightheadedness, and dyspnea) and noncardiac symptoms (eg, headache, exercise intolerance, fatigue) [3]. The link between these 2 clinical entities is not entirely clear, although it has been suggested that the vasodilator effect of MCA-related mediators such as histamine, norepinephrine, and neuropeptide Y (NPY) results in increased sympathetic activity, which in turn leads to orthostatic tachycardia [2]. In recent years, a handful of patients with recalcitrant ncMCAS were successfully treated with omalizumab, the monoclonal antibody to IgE [4].…”

“…Indeed, mast cells might contain chemical mediators other than histamine, with physiological effects that could reproduce POTS-related symptoms [2]. It might therefore be expected that agents preventing mast cell degranulation, such as omalizumab, could be effective for both disorders.…”

Orthostatic Hypertension

“…Interestingly, in this "crossover" group of patients, the OHT manifested as either a persistent hypertensive response to upright posture or as a hypertensive crisis with upright BP as high as 240/140. 4 Patients presenting with acute baroreflex failure experience some of the highest blood pressures encountered in contemporary practice, sometimes with surges of Ͼ300 mm Hg. 5 In subsequent days and weeks, the surges moderate, but substantial OHT may continue, although it usually declines somewhat with continued upright posture.…”