Immunomodulatory treatment in postural tachycardia syndrome: A case series

Abstract

Background and purpose Postural tachycardia syndrome (POTS) is a form of autonomic dysfunction characterized by symptoms of orthostatic intolerance, often accompanied by sudomotor dysfunction and gastrointestinal dysmotility. Recently, evidence has accumulated that in a subset of patients, the pathogenesis of dysautonomia may be immune‐mediated. The aim of the current report was to evaluate the use of intravenous immunoglobulin (IVIG) treatment in patients with progressive and/or refractory immune‐mediated POTS. Methods We retroactively assessed the effect and tolerance of monthly administered IVIG in six patients using autonomic function testing, standardized symptom questionnaires, and patients' symptom diaries both before and 6 months into IVIG treatment. Objective outcome measures included heart rate increase after 10 min of head‐up tilt as well as duration and anhidrotic area in a thermoregulatory sweat test. Subjective outcome measures were patient reports and symptom ratings from the symptom questionnaire. Results All patients responded to immunomodulatory treatment, regardless of disease duration. After 6 months of IVIG, symptom severity was reduced by nearly 40%. Autonomic function testing showed improved cardiovascular functioning by 50% and a reduction of anhidrotic areas by one third. Overall, tolerance of IVIG treatment was poor, but could be improved by a reduction in infusion rate, premedication with steroids, and additional intravenous hydration. Conclusions Using subjective but also standardized objective measures, the case series describes promising effects of IVIG treatment in POTS patients with immune‐mediated dysautonomia. By reducing the infusion rate, pretreatment with steroids, and intravenous hydration, tolerance could be improved, and no patient had to discontinue the treatment.

Dysautonomia in the Ehlers–Danlos syndromes and hypermobility spectrum disorders—With a focus on the postural tachycardia syndrome

“…Drugs that affect the ANS or cardiovascular organs can also cause dysautonomia in any age group by causing changes in fluid volume or heart rate (HR; diuretics, antihypertensive drugs, cardiac nitrates, sedatives, hypnotics, and antidepressants), or their toxic effects leading to an autonomic neuropathy. A currently relatively small but increasing proportion of cases are those with immune-mediated dysautonomia where immunotherapy is disease modifying (Gunning, Kvale, Kramer, Karabin, & Grubb, 2019), as recently demonstrated in patients with ganglionic antibodies (Koay et al, 2021) and PoTS with autoantibodies against the alpha-1 adrenergic receptor and muscarinic cholinergic receptor (Rodriguez, Hoepner, Salmen, Kamber, & Z'Graggen, 2021).…”

Maintenance therapy with subcutaneous immunoglobulin in a patient with immune‐mediated neuropathic postural tachycardia syndrome

“…This aspect has important implications for medical care, given the widespread availability and proven efficacy of immunotherapies for autoimmune neuropathies. IVIg is increasingly prescribed off-label for autoimmune PoTS and SFN following dosing parameters established in chronic inflammatory demyelinating polyneuropathy (CIDP) trials [ 30 , 36 , 37 ].…”

“…IVIg often causes infusion reactions and rarely causes serious adverse events. Thus, adapted dosing schemes and premedication are suggested in autonomic neuropathies [ 11 , 21 , 37 ]. In light of the novel subcutaneous route of application for immunoglobulin for CIDP [ 19 ], we show that SCIg is an attractive option for autoimmune neuropathic PoTS, due to the improved side-effect profile.…”

“…In light of the novel subcutaneous route of application for immunoglobulin for CIDP [ 19 ], we show that SCIg is an attractive option for autoimmune neuropathic PoTS, due to the improved side-effect profile. Tolerating the medication is probably mostly relevant for patients with autonomic neuropathies, as dysautonomia patients are likely to be more vulnerable to infusion-associated reactions using IVIg standard protocols [ 21 , 37 ].…”

Tolerability of COVID-19 mRNA vaccines in patients with postural tachycardia syndrome: a cross-sectional study

“…15 Immunomodulatory treatment with intravenous immunoglobulins has shown a positive effect on the symptoms of patients with POTS, further supporting an immune-mediated genesis. 23 In the wake of the coronavirus disease 2019 (COVID-19) pandemic, numerous case reports and case series about the occurrence of POTS following an infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have accumulated. [24][25][26][27][28][29][30] Nearly all affected individuals were females without pre-existing conditions who developed symptoms of autonomic dysfunction several days or weeks after an acute COVID-19 infection and there was no association with initial COVID-19 severity.…”