Tolvaptan-induced remission of primary palmar hyperhidrosis in a patient with ADPKD: a serendipitous finding.

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Tolvaptan-induced remission of primary palmar hyperhidrosis in a patient with ADPKD: a serendipitous finding.

J Nephrol. 2021 Feb 08;:

Authors: Cuka E, Vespa M, Joli G, Manunta P, Sciarrone Alibrandi TM

Abstract
A 37-year old man had suffered palmar hyperhidrosis since he was fifteen years old. In the last year, he has been treated with tolvaptan for autosomic polycystic kidney disease (ADPKD). The start of tolvaptan therapy was associated with a complete resolution of palmar hyperhidrosis and a sensation of relaxation. During the year on which the patient took tolvaptan, he had to suspend the drug twice. The suspension of tolvaptan was associated with the reappearance of palmar hyperhidrosis followed by sudden remission after the drug reintroduction. Palmar sweating also known as ’emotional sweating’ is not related to thermoregulation but allows an adequate adjustment of the frictional force to perform fine hand movements. Palmar hyperhidrosis is a chronic neurologic disorder characterized by excessive sweating of eccrine glands due to overactivity of the sympathetic nervous system. Palmar sweating and emotional processing are controlled by the limbic system. In this case report reduction of palmar sweating was associated with a sense of well-being. Corticotropin releasing factor (CRF) and adrenocorticotropic hormone (ACTH) are the two main hypothalamic hormones that interact with both the limbic system and the peripheral sympathetic nervous system. Tolvaptan is an arginine vasopressin (AVP) antagonist. AVP has effects on the sympathetic nervous system through both central and peripheral actions. Centrally AVP is a well-known ACTH secretagogue. Remission of palmar hyperhidrosis is probably mediated by tolvaptan acting on central ACTH secretion.

PMID: 33555573 [PubMed – as supplied by publisher]

Intercostal Nerve Reconstruction for Severe Compensatory Hyperhidrosis: The “Gebitekin” Technique.

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Intercostal Nerve Reconstruction for Severe Compensatory Hyperhidrosis: The “Gebitekin” Technique.

Ann Thorac Surg. 2021 Jan 30;:

Authors: Gebitekin C, Melek H, Cetinkaya G, Ozer E, Yenturk E, Sevinç TE, Bayram AS

Abstract
Compensatory sweating (CS) is the most common and disabling complication of endoscopic thoracic sympathectomy (ETS) and represents an unmet clinical challenge. Our surgical hypothesis is to generate a parallel pathway to the damaged part of the sympathetic nerve, similar to the Kuntz nerve, by reconstructing the two healthy intercostal nerves, thus treating CS. Here we present a novel videothoracoscopic technique involving bilateral intercostal nerve reconstruction in patients with severe CS after ETS.

PMID: 33529603 [PubMed – as supplied by publisher]

Real-life experience with oral oxybutynin long-term continuous therapy in severe hyperhidrosis and systematic review of the literature.

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Real-life experience with oral oxybutynin long-term continuous therapy in severe hyperhidrosis and systematic review of the literature.

Dermatol Ther. 2021 Feb 02;:

Authors: Briatico G, Pampena R, Fulgione E, Babino G, Giorgio CM, D’Ambra I, Caccavale S, Longo C, Argenziano G

Abstract
BACKGROUND: Hyperhidrosis is a disorder of excessive sweating severely impacting on patient’s quality of life (Qol). Several studies have been published about oral oxybutynin, but no studies focused on the achievement of complete clinical and Qol response.
OBJECTIVES: the aim of this study was to report our real-life experience with oral oxybutynin in patients with severe hyperhidrosis significantly affecting their Qol.
METHODS: In this cohort retrospective study we enrolled, in a 3-year period, patients affected by severe hyperhidrosis with poor Qol, continuously treated with oral oxybutynin. Our outcome was the obtainment of complete clinical and Qol improvement. A systematic review of the literature was also performed reporting efficacy and safety of oral oxybutynin for primary hyperhidrosis.
RESULTS: We enrolled 62 patients, of which 53 (85.5%) received a mean daily dose of 10 mg and 9 (15.5%) of 5 mg. Complete clinical response was achieved in 77.4% (48/62) of cases, while complete Qol improvement occurred in 51.6% (32/62) of cases. Adverse events were only reported as mild, with dry mouth being the most frequently observed (16.1%). Kaplan-Meier survival analysis highlighted that both median clinical and Qol complete responses were reached after 1 year of continuous therapy with oral oxybutynin. The main limitation of our study is the small number of patients enrolled.
CONCLUSIONS: Long-term therapy with oral oxybutynin for severe hyperhidrosis, continuously administered at a mean daily dosage of 5 to 10 mg, allowed the majority of our patients to reach both clinical and Qol complete improvement, without significant adverse events. This article is protected by copyright. All rights reserved.

PMID: 33527699 [PubMed – as supplied by publisher]

Transareolar single-port endoscopic thoracic sympathectomy with a flexible endoscope for primary palmar hyperhidrosis: a prospective randomized controlled trial.

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Transareolar single-port endoscopic thoracic sympathectomy with a flexible endoscope for primary palmar hyperhidrosis: a prospective randomized controlled trial.

Ann Transl Med. 2020 Dec;8(24):1659

Authors: Lin JB, Kang MQ, Chen JF, Du Q, Li X, Lai FC, Tu YR

Abstract
Background: Transareolar single-port endoscopic thoracic sympathectomy (ETS) with a flexible endoscope has rarely been reported. This study assessed the performance of this novel minimally invasive technique for primary palmar hyperhidrosis (PPH).
Methods: From January 2019 to September 2019, 118 males with severe PPH requiring single-port and bilateral ETS were randomly allocated to undergo transareolar ETS using a flexible endoscope (group A, n=58) or transaxillary ETS using a 5 mm thoracoscope (group B, n=60).
Results: Both groups had similar patient characteristics. All procedures were performed successfully, with no mortality or conversion to open surgery. All patients had dry and warm palms immediately after surgery. Compared with group B, group A had a significantly shorter median incision length [5.1 (5.0-5.2) vs. 10.9 (10.8-11.9) mm; P<0.001], and significantly lower median postoperative pain score [1 (1.0-2.0) vs. 3 (3.0-4.0); P<0.001]. There were no differences between the two groups in operative time, palmar temperature increase, and transient postoperative sweating. After complete follow-up, group A had a significantly higher median cosmetic score than group B [4.0 (3.0-4.0) vs. 3.0 (3.0-3.0); P<0.001]. There were no differences between the two groups regarding symptom resolution, compensatory hyperhidrosis, and satisfaction score. No patient reported residual pain or symptom recurrence.
Conclusions: Transareolar single-port ETS with a flexible endoscope is safe, effective, and minimally invasive with a small incision, minimal pain, and excellent cosmetic results. This novel procedure is suitable for routine treatment of PPH in males.

PMID: 33490171 [PubMed]

A systematic evidence-based review of treatments for primary hyperhidrosis.

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A systematic evidence-based review of treatments for primary hyperhidrosis.

J Drug Assess. 2020 Dec 24;10(1):35-50

Authors: Stuart ME, Strite SA, Gillard KK

Abstract
Objective: Hyperhidrosis (excessive sweating) is associated with significant quality-of-life burden yet is often undertreated. With limited FDA-approved treatments, health care providers must determine optimal treatment among approved and off-label options. Key objectives of this review were to reassess, update, and expand a previous systematic review of commonly used treatment options for primary hyperhidrosis, including consideration of aluminum and zirconium compounds.
Methods: We performed a qualitative systematic review of efficacy, health-related quality of life, satisfaction, and safety of interventions, replicating and expanding the strategy outlined in a previous systematic review, with the addition of studies utilizing a within-patient design. We performed a critical appraisal of identified studies to determine risk of bias (RoB) and strength of evidence (SOE).
Results: A total of 32 studies were eligible for critical appraisal. Only three studies – two clinical trials of glycopyrronium cloth (2.4%) and one trial of botulinum toxin A injections in axillary hyperhidrosis were rated as “low” RoB; both had SOE ratings of “moderate” for use in axillary hyperhidrosis – the highest rating included in this review.
Conclusions: Optimal treatment choice depends on several factors, including understanding the quality of evidence regarding each treatment’s efficacy and safety (considerations of convenience and cost are beyond the scope of this review). In hyperhidrosis, as in other clinical conditions, treatment decisions should be patient centered. At this time, because of the quality of evidence, only imprecise estimates of effect are possible for hyperhidrosis treatments included in this review, and statements about comparative effectiveness are not possible.

PMID: 33489435 [PubMed]

CHRNA1 promotes the pathogenesis of primary focal hyperhidrosis.

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CHRNA1 promotes the pathogenesis of primary focal hyperhidrosis.

Mol Cell Neurosci. 2021 Jan 18;:103598

Authors: Lin JB, Kang MQ, Huang LP, Zhuo Y, Li X, Lai FC

Abstract
The aim of the study was to elucidate the involvement of cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in the pathogenesis of primary focal hyperhidrosis (PFH). The hyperhidrosis mouse model was constructed using pilocarpine injection. The expression levels of CHRNA1 in sweat gland tissues of PFH patients and hyperhidrosis mice were compared using Western blots and quantitative real-time PCR (qRT-PCR) analyses. Sweat secretion in hyperhidrosis mice treated with small-interfering RNA (siRNA) targeting CHRNA1 (si-CHRNA1) or non-specific siRNA were compared. Sweat secretory granules in the sweat gland cells of hyperhidrosis mice were examined using transmission electron microscopy. The serum level of acetylcholine was measured using enzyme-linked immunosorbent assay, while markers associated with PFH, including Aquaporin 5 (AQP5) and Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), were assessed using immunohistochemical assay and Western blots. Brain-derived neurotrophic factor (BDNF) and Neuregulin 1 (NRG-1) in sympathetic ganglia axons of hyperhidrosis mice were quantified using Western blots. CHRNA1 up-regulation is a characteristic of the sweat glands of PFH patients and Hyperhidrosis mice. Silencing CHRNA1 decreased sweat secretion and the number of sweat secretory granules of hyperhidrosis mice. Serum acetylcholine, as well as AQP5 and CACNA1C expression in the sweat glands, was reduced by siCHRNA1. BDNF1 and NRG-1 levels in the sympathetic ganglia axons were also attenuated by siCHRNA1 treatment. CHRNA1 up-regulation is a potential biomarker of PFH and downregulating CHRNA1 could alleviate the symptoms of PFH through inactivating the sympathetic system.

PMID: 33476802 [PubMed – as supplied by publisher]

A 1% glycopyrronium bromide cream for the topical treatment of primary axillary hyperhidrosis: Efficacy and Safety Results from a Phase 3a Randomised Controlled Study.

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A 1% glycopyrronium bromide cream for the topical treatment of primary axillary hyperhidrosis: Efficacy and Safety Results from a Phase 3a Randomised Controlled Study.

Br J Dermatol. 2021 Jan 14;:

Authors: Abels C, Soeberdt M, Kilic A, Reich H, Knie U, Jourdan C, Schramm K, Heimstaedt-Muskett S, Masur C, Szeimies RM

Abstract
BACKGROUND: Effective topical treatment options for patients with primary axillary hyperhidrosis are limited. Recent phase 1 trial showed promising results regarding efficacy and safety for topical cream containing glycopyrronium bromide (GPB).
OBJECTIVE: To assess efficacy, safety and tolerability of a 4-week topical treatment with 1% GPB cream in subjects with primary axillary hyperhidrosis compared to placebo.
METHODS: 171 patients (84 placebo; 87 1% GPB) with primary axillary hyperhidrosis were included in this 4 week, multicenter, randomised, double-blind, placebo-controlled Phase 3a part of the pivotal study. Sweat production was measured by gravimetry. Patients rated disease impact using the Hyperhidrosis Disease Severity Scale (HDSS) and Hyperhidrosis Quality of Life Index (HidroQoL© ).
RESULTS: Absolute change in sweat production from baseline to day 29 in logarithmic values was significantly larger in the 1% GPB group than in the placebo group (p=0.0038). The improvement in HidroQoL© exceeded minimal clinically important difference of 4. The proportion of responders was two-fold higher than for placebo for sweat reduction, HDSS and HidroQoL© (-197.08 mg GPB vs. -83.49 mg placebo; 23% GPB vs 11.9% placebo and 59.8% GPB vs. 26.2% placebo respectively). Treatment was safe, most TEAEs were mild or moderate and transient. Local tolerability was very good with 9.2% of patients having only mild or moderate application site reactions. The most reported ADR was dry mouth (16.1%), an expected anticholinergic effect of the treatment.
CONCLUSION: 1% GPB cream may provide an effective new treatment option exhibiting a good safety profile for patients with primary axillary hyperhidrosis. The long-term open-label part (Phase 3b) is ongoing.

PMID: 33445205 [PubMed – as supplied by publisher]

Lumbar Sympathetic Nerve Modulation Using Absolute Ethanol for the Treatment of Primary Lower-Extremity Hyperhidrosis: A Dose-Effect Pilot Study.

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Lumbar Sympathetic Nerve Modulation Using Absolute Ethanol for the Treatment of Primary Lower-Extremity Hyperhidrosis: A Dose-Effect Pilot Study.

Med Sci Monit. 2021 Jan 12;27:e928209

Authors: Liu M, Ni H, Tao J, Xie K

Abstract
BACKGROUND Primary lower-extremity hyperhidrosis (PLEH) can be treated by CT-guided lumbar sympathetic nerve modulation using absolute ethanol. However, doses of ethanol that are too high can cause nerve injury, and doses that are too low have suboptimal results. The present study aimed to investigate the dose-effect relationship of CT-guided lumbar sympathetic nerve modulation with absolute ethanol for PLEH. MATERIAL AND METHODS The study was conducted at the First Affiliated Hospital of Jiaxing University between 07/2014 and 02/2017. Twenty participants were enrolled in each group. The doses of absolute ethanol were 2.0 ml in the R₁ group, 2.5 ml in the R₂ group, 3.0 ml in the R₃ group, 3.5 ml in the R₄ group, and 4.0 ml in the R₅ group. Treatment effectiveness was assessed according to the time to complete hyperhidrosis relief: <10 min, effective; ≥10 min, non-effective. RESULTS The patient characteristics among the 5 groups were not statistically different (P>0.05). The onset time and time to complete hyperhidrosis relief decreased significantly with increasing dose of absolute ethanol (P<0.05). The effective rates in the 5 groups were 15.0%, 35.0%, 60.0%, 90.0%, and 100.0%, respectively. The ED₅₀ and ED₉₅ were 2.306 ml (95% CI: 2.003-2.512 ml) and 3.343 ml (95% CI: 3.051-3.962 ml), respectively. CONCLUSIONS This was the first dose-effect pilot study of consecutive PLEH patients treated by CT-guided lumbar sympathetic nerve modulation. CT-guided lumbar sympathetic nerve modulation with 2.306 ml (ED₅₀) and 3.343 ml (ED₉₅) of absolute ethanol showed treatment efficacy for PLEH. No complications were seen.

PMID: 33434188 [PubMed – in process]

Limited Systemic Exposure with Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis.

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Limited Systemic Exposure with Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis.

Clin Pharmacokinet. 2021 Jan 12;:

Authors: Pariser DM, Lain EL, Mamelok RD, Drew J, Mould DR

Abstract
BACKGROUND: Glycopyrronium tosylate (GT; Qbrexza® [glycopyrronium] cloth, 2.4%) is a topical anticholinergic approved (USA) for primary axillary hyperhidrosis in patients aged ≥ 9 years.
OBJECTIVE: The objective of this study was to compare the pharmacokinetics and safety of GT to oral glycopyrrolate (phase I study) and assess the relationship between glycopyrronium pharmacokinetics and anticholinergic-related adverse events or efficacy with population pharmacokinetics using data from two phase II studies.
METHODS: In the phase I study, study staff applied GT to axillae of patients with primary axillary hyperhidrosis (aged 9-65 years) once daily (5 days); oral glycopyrrolate was administered to healthy adults (aged 18-65 years) every 8 hours (15 days). In the phase II studies (NCT02016885 [20 December, 2013], NCT02129660 [2 May, 2014]), adults with primary axillary hyperhidrosis applied topical glycopyrronium (0.8-3.2%) or vehicle to axillae once daily (4 weeks). Pharmacokinetic and adverse event data were collected in all studies.
RESULTS: Glycopyrronium pharmacokinetic parameters were similar between adult and pediatric patients treated with GT; there was no evidence of accumulation. Systemic absorption of glycopyrronium was lower with GT vs oral glycopyrrolate. No anticholinergic-related adverse events occurred with GT in the phase I study, while dry mouth and nasal dryness occurred with oral glycopyrrolate; anticholinergic adverse events occurred in the phase II studies. In the population pharmacokinetic analysis, frequency/severity of anticholinergic-related adverse events increased with higher glycopyrronium concentration; no relationship was observed between efficacy and pharmacokinetic measures.
CONCLUSIONS: These studies indicate limited absorption of GT compared to oral glycopyrrolate and a low risk of anticholinergic adverse events with proper GT administration when following instructions for use (wipe each underarm once with same cloth, wash hands, avoid ocular contact).

PMID: 33433785 [PubMed – as supplied by publisher]