Postural tachycardia syndrome (POTS) is a common cause of orthostatic intolerance that is characterized by an excessive increase in heart rate (HR) upon standing.1,2 POTS not only causes the well-recognized symptoms of dizziness and palpitation, but also various other symptoms including headache, fatigue, profuse perspiration, blurred vision, difficulty concentrating, and gastrointestinal discomfort.3,4 The clinical significance of POTS has recently increased with findings of associations with depression,5,6 sleep disturbance,7 chronic fatigue syndrome,8-10 and diminished quality of life (QOL).7,11 Despite the increased prevalence of POTS reported over the past 2 decades due to the increased awareness of this syndrome,1 it is still considered an underdiagnosed disease and deserves more attention from clinicians.4,12

POTS can be diagnosed in patients with orthostatic intolerance symptoms when the following criteria are fulfilled: HR increment of ≥ 30 beats/min (or ≥ 40 beats/min in individuals aged 12-19 years) within 10 minutes of standing or head-up tilting, and in the absence of orthostatic hypotension (a decrease in systolic blood pressure [BP] of ≥ 20 mmHg and/or decrease in diastolic BP of ≥ 10 mmHg) and other causes of tachycardia.13,14 However, there are challenges associated with diagnosing POTS. For example, patients often present with various symptoms other than the typical ones of dizziness and palpitations, which may obscure an accurate diagnosis.1 Many POTS patients complain of headache, depression, fatigue, difficulty concentrating, and gastrointestinal disturbances such as abdominal pain and irregular bowel movements.12,15 Therefore, an accurate POTS diagnosis requires a detailed knowledge of the history of the patient’s symptoms.

Many patients also complain of worsening of symptoms in the morning with subsequent improvement throughout the course of the day, which may be explained by the diurnal variability of hemodynamic parameters.16 It has been demonstrated that orthostatic HR increments are greater in the morning than in the afternoon, and so some patients may fulfill the criteria for POTS in the morning but not later in the day.17 This discrepancy is probably due to the physiological changes that occur during sleep associated with being supine for a prolonged period without any fluid intake.1 Therefore, when there is clinical suspicion of POTS, repeated orthostatic vital-sign tests should be conducted, including one in the early morning.

Orthostatic intolerance is the main characteristic of POTS,15 and can manifest as a variety of symptoms such as headache, dizziness, nausea, lightheadedness, blurred vision, palpitations, tremors, and difficulty concentrating.4,15 It has been reported that the degree of orthostatic HR increment is not directly correlated with clinical symptoms, probably due to the diurnal variability of orthostatic tachycardia.3 However, the severity of orthostatic intolerance symptoms is significantly correlated with depression and QOL. In particular, chest discomfort and difficulty concentrating are strongly associated with depression, and nausea and difficulty concentrating are associated with diminished QOL.3

The exact pathogenesis underlying POTS remains unknown. Several clinical characteristics support the possibility that POTS is an autoimmune disorder, such as female predominance, preceding viral illness, prior vaccination history, and coexistence of other autoimmune disorders, characteristics that are frequently reported in other autoimmune diseases.18

There have been many reports describing patients who developed POTS after receiving a polyvalent human papilloma virus (HPV) vaccine.19-24 However, the American Autonomic Society recently issued a statement concluding that the available evidence was insufficient to confirm a causal relationship between receipt of an HPV vaccination and development of POTS.25

The presence of various types of autoantibody in patients with POTS and their effects on cholinergic and adrenergic receptors has been found in numerous studies.26,27 While the presence of antibodies to ganglionic acetylcholine receptors (AChRs) has both low sensitivity and specificity for a POTS diagnosis, antibodies to adrenergic receptors are likely to be involved in the pathogenesis and can be used as a potential diagnostic biomarker.28 One group found that most patients with POTS harbored antibodies that activate the β1 adrenergic receptor, while a smaller proportion of patients had antibodies that activate the β2 adrenergic receptor and also act as partial agonists/antagonists to α1 receptors.18,27 Moreover, patients with POTS have a higher positive rate of antinuclear antibodies than general population,29 as well as a higher incidence of systemic autoimmune disease, including Hashimoto’s thyroiditis, Sjögren’s syndrome, lupus, and rheumatoid arthritis.28 Therefore, it has been suggested that POTS should be considered a novel member of the family of autoimmune disorders.25

An association with human leukocyte antigen allele status was recently reported in Korean patients with severe POTS, defined as an orthostatic HR increment of ≥ 50 beats/min or experiencing syncope/near-syncope during orthostatic vital-signs measurement.30 Seven of 17 patients (41%) harbored DQB1*06:09 and six (35%) had the A*33:03-B*58:01-C*03:02-DRB1*13:02-DQB1*06:09 haplotype, a significantly higher proportion than was found among healthy Koreans (Table 1).30

Based on these findings, at least a proportion of POTS cases should be considered autoimmune in nature. The development of the first animal model of POTS, achieved by immunization of rabbits with adrenergic receptor peptides,31 promises to be useful for future mechanistic studies. These animals exhibit POTS-like phenotypes in vivo, such as orthostatic tachycardia.32

POTS is a heterogeneous clinical syndrome that causes chronic orthostatic intolerance and is accompanied by other medical conditions. It is important to understand that diurnal variability of hemodynamic parameters exists and that the symptoms of orthostatic intolerance are associated with depression and diminished QOL. The pathophysiology of POTS is not fully understood, but an autoimmune component has recently been proposed. An integrative approach combining nonpharmacological and pharmacological treatments is important for the management of this condition.