Category: Hyperhidrosis

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Polydatin ameliorates hyperhidrosis by targeting Aqp5 in a mouse model

Front Pharmacol. 2025 Aug 13;16:1589143. doi: 10.3389/fphar.2025.1589143. eCollection 2025.

ABSTRACT

BACKGROUND: Primary focal hyperhidrosis (PFH) is a neurological dermatological disorder characterized by localized, excessive sweating. Current treatments have limitations, and postoperative compensatory hyperhidrosis remains a concern. Aquaporin 5 (AQP5) and neurologic factors such as Brain-Derived Neurotrophic Factor (BDNF) and Neuregulin-1 (NRG-1) are known to play key roles in sweat regulation. Polydatin, a natural compound with anti-inflammatory and neuroregulatory properties, has shown therapeutic potential in related conditions.

METHODS: This preclinical experimental study investigated the effects of Polydatin in a mouse model of hyperhidrosis. Mice were treated with different doses and durations of Polydatin. Aqp5 knockout mice were used to explore the AQP5-related pathway. Sweat gland function, gene and protein expression (AQP5, BDNF, NRG-1), and cell responses to acetylcholine stimulation were analyzed.

RESULTS: Polydatin at 50 mg/kg/day significantly reduced sweat secretion in hyperhidrotic mice (p < 0.001), while treatment duration showed no significant impact. The therapeutic effect was absent in Aqp5 knockout mice, confirming AQP5 dependence. Polydatin downregulated mRNA and protein expression of AQP5, Na+-K+-Cl– Cotransporter 1 (NKCC1), BDNF, and NRG-1. Additionally, Polydatin inhibited acetylcholine-induced proliferation of sweat gland cells (p < 0.05), an effect abolished by Aqp5 knockdown.

CONCLUSION: Polydatin alleviates hyperhidrosis by targeting AQP5 and suppressing key neurologic factors, supporting its potential as a novel therapeutic approach for PFH.

PMID:40880648 | PMC:PMC12380703 | DOI:10.3389/fphar.2025.1589143

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Efficacy and Safety of Treatments for Primary Palmar Hyperhidrosis: A Systematic Review Assessing Patient-Centric Outcomes

Dermatol Res Pract. 2025 Aug 20;2025:8867838. doi: 10.1155/drp/8867838. eCollection 2025.

ABSTRACT

Background: Primary palmar hyperhidrosis (PH) is a chronic condition characterized by excessive sweating in the palms, significantly affecting the quality of life (QOL) of affected individuals. Despite the availability of various treatment modalities, the long-term efficacy and safety of these interventions remain unclear, warranting a comprehensive evaluation. This systematic review aims to assess the efficacy, safety and patient-reported outcomes of treatments for PH. Methods: A systematic search was conducted in PubMed, Embase and the Cochrane Library from their inception until March 2024, adhering to PRISMA guidelines. Inclusion criteria focused on prospective and retrospective studies examining PH treatments published in English. Data from eligible studies were extracted, analysed qualitatively and reported based on outcomes, including efficacy, QOL improvements and adverse effects. Results: Fourteen studies, including 1733 patients aged 4-77 years, were included in the final review. The treatments assessed included oral and topical oxybutynin, iontophoresis, botulinum toxin A injections, photodynamic therapy (PDT) and endoscopic thoracic sympathectomy (ETS). Oral oxybutynin demonstrated symptomatic relief in 60%-97% of the patients although anticholinergic side effects were frequently reported. ETS, while providing the highest rates of complete sweat cessation, was associated with compensatory hyperhidrosis. Noninvasive treatments like iontophoresis showed moderate efficacy with minimal side effects but required ongoing sessions for maintenance. Conclusion: This review highlights the efficacy of several therapeutic approaches for PH though most treatments are hindered by significant adverse effects or practical limitations. Future research should prioritize long-term studies and standardized outcome measures to guide clinical decision-making more effectively.

PMID:40881604 | PMC:PMC12390518 | DOI:10.1155/drp/8867838

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Imbalance of NKCC1/KCC2 contributes to the pathogenesis of primary focal hyperhidrosis

Neurochem Int. 2025 Aug 27:106043. doi: 10.1016/j.neuint.2025.106043. Online ahead of print.

ABSTRACT

BACKGROUND: Primary focal hyperhidrosis (PFH) is characterized by excessive sweating in localized regions, significantly impacting patients’ quality of life. The imbalance between sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) disrupts chloride ion homeostasis, potentially contributing to the pathogenesis of PFH.

METHODS: Sweat gland tissues from 76 healthy controls and 76 PFH patients were collected. Expression levels of NKCC1 and KCC2 were assessed using quantitative real-time PCR and Western blotting. Primary sweat gland cells isolated from PFH patients (PFH-SG) and controls (NPFH-SG) were subjected to NKCC1 knockdown via lentiviral shRNA transfection. A hyperhidrosis mouse model was induced by intraperitoneal injection of pilocarpine hydrochloride, and mice were pretreated with the NKCC1 inhibitor bumetanide for one week. Sweat secretion, serum acetylcholine, and chloride ion concentrations were measured. Expression levels of aquaporin 5 (AQP5), brain-derived neurotrophic factor (BDNF), and neuregulin-1 (NRG-1) proteins were analyzed.

RESULTS: PFH tissues showed significantly elevated NKCC1 and decreased KCC2 expression compared to controls, correlating with lower sweat chloride levels. NKCC1 knockdown in PFH-SG cells reduced elevated AQP5 expression. In vivo, bumetanide treatment markedly reduced sweat secretion, lowered serum acetylcholine, and restored chloride ion concentrations in hyperhidrosis mice. Furthermore, bumetanide treatment significantly decreased expressions of BDNF and NRG-1 in sympathetic ganglia axons, indicating attenuation of sympathetic hyperactivity associated with hyperhidrosis. NKCC1/KCC2 imbalance contributes significantly to PFH pathology.

CONCLUSIONS: Bumetanide effectively improves this imbalance, reducing excessive sweating and modulating related neurotransmitter signaling, offering potential therapeutic avenues for PFH.

PMID:40882919 | DOI:10.1016/j.neuint.2025.106043

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Effect of Radiofrequency Ablation and Comparison With Surgical Sympathectomy in Palmar Hyperhidrosis

Cureus. 2025 Jul 22;17(7):e88543. doi: 10.7759/cureus.88543. eCollection 2025 Jul.

ABSTRACT

BACKGROUND: Palmar hyperhidrosis is a distressing condition characterized by excessive palm sweating that significantly impacts patients’ quality of life (QoL). Radiofrequency ablation (RFA) and surgical sympathectomy are effective treatment modalities. This study aims to evaluate and compare the effectiveness, patient satisfaction, and safety profiles of RFA and surgical sympathectomy in managing palmar hyperhidrosis.

METHODS: This retrospective study included 91 patients diagnosed with primary palmar hyperhidrosis who underwent either RFA or surgical sympathectomy. The primary outcome was the reduction in sweating severity. Statistical analyses were performed to compare treatment outcomes between the two groups.

RESULTS: Both RFA and surgical sympathectomy significantly reduced Hyperhidrosis Disease Severity Scale scores; however, surgical sympathectomy demonstrated greater symptom reduction at six months (p = 0.01) and 12 months (p = 0.002). Patients in the sympathectomy group reported a longer symptom relief duration (11.8 ± 3.1 vs. 9.2 ± 2.5 months, p = 0.003) and greater improvement in QoL scores at 12 months (p = 0.02). The incidence of compensatory sweating was higher in the sympathectomy group (34.0%, n = 16 vs. 18.2%, n = 8, p = 0.08), whereas recurrence of hyperhidrosis was more frequent in the RFA group (27.3%, n = 12 vs. 10.6%, n = 5, p = 0.03).

CONCLUSION: Both RFA and surgical sympathectomy effectively reduce sweating severity in patients with palmar hyperhidrosis. While sympathectomy provides longer-lasting symptom relief and greater QoL improvement, it is associated with a higher incidence of compensatory sweating.

PMID:40851706 | PMC:PMC12370239 | DOI:10.7759/cureus.88543

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Evaluation of Cardiac Autonomic Function in Patients Undergoing Thoracoscopic Sympathetic Chain Clamping for Primary Focal Hyperhidrosis

Med Sci (Basel). 2025 Aug 20;13(3):147. doi: 10.3390/medsci13030147.

ABSTRACT

Background/Objectives. Heart rate variability (HRV) is the variability in the beat-by-beat heart period. Primary focal hyperhidrosis (PFHH) is a disease characterized by excessive sweat production, strongly affecting social life. Several authors define this condition as a dysautonomic disorder, mainly driven by exaggerated sympathetic activity. The aim of the study was to demonstrate a possible cardiac involvement in the disease. Other outcomes were the occurrence of dysautonomic disorders after surgery and its possible correlation with baseline characteristics. Methods. This observational, controlled trial enrolled patients with a confirmed clinical diagnosis of severe PFHH candidates to thoracoscopic sympathetic chain clamping. Before and after surgery, ECG was obtained using KardiaMobile 6L (AliveCor®, Mountain View, CA, USA) device with a five-minute recording and HRV was analyzed using Kubios HRV Premium (Kubios©) software. Results. 111 patients were compared to 222 healthy control subjects. No differences were seen in HRV analysis between the two groups at baseline (time-domain p > 0.05, frequency-domain p > 0.05, autonomic indexes p > 0.05). When comparing autonomic function indexes in patients before and after the surgical procedure, no differences were seen in frequency-domain HRV analysis, but a blunted increase in SNS index (0.2 vs. 1.38, p 0.02). No development of systemic dysautonomic disorders nor significant compensatory hyperhidrosis were seen after the surgery. Conclusions. This study shows that PFHH is a peripheral autonomic nervous system derangement, rather than central. Sympathetic chain clamping resulted safe and effective in improving patients’ conditions, with no risks of dysautonomic disorders.

PMID:40843769 | DOI:10.3390/medsci13030147

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20-Year Efficacy of Endoscopic Thoracic Sympathectomy for Primary Hyperhidrosis: A Cohort Study

J Clin Med. 2025 Jul 8;14(14):4831. doi: 10.3390/jcm14144831.

ABSTRACT

Background: Primary focal hyperhidrosis, characterized by excessive sweating primarily affecting the hands and axillae, can significantly impact quality of life. Bilateral thoracic sympathectomy is the gold standard treatment, providing permanent resolution of palmar hyperhidrosis. Most studies evaluating outcomes and patient satisfaction after sympathectomy focus on short- to medium-term follow-up, typically up to 5 years. This study aimed to assess anxiety, satisfaction, and sweat redistribution 20 years after bilateral endoscopic thoracic sympathectomy. Methods: Between January 2002 and December 2003, 106 patients with primary hyperhidrosis underwent bilateral endoscopic thoracic sympathectomy targeting ganglia T2-T3 at our center. The patients were contacted via telephone in 2023 and asked to complete the same survey they had filled out preoperatively and 12 months postoperatively. The survey evaluated sweat redistribution, anxiety, hyperhidrosis-related symptoms, and satisfaction. Anxiety, satisfaction, and perceived sweating were rated using a 5-point visual analog scale (VAS) ranging from 0 (unsatisfied/no symptoms) to 4 (very satisfied/severe symptoms). Results: Of the 106 eligible patients, 24 (22.6%) completed the survey. Most reported persistent anhidrosis (palmar or palmar-axillary) 20 years post-surgery. The survey results remained consistent with those at the 1-year follow-up. Significant sweat redistribution to the abdomen and back was observed. Patient satisfaction remained high, with no significant differences between the 1-year and 20-year assessments. Anxiety significantly decreased compared to preoperative levels (p < 0.001). Conclusions: Bilateral endoscopic thoracic sympathectomy is an effective long-term treatment for reducing excessive sweating. Patient satisfaction remains high over time, despite the persistence of compensatory sweating.

PMID:40725520 | DOI:10.3390/jcm14144831

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[[Translated article]]Hyperhidrosis, Anticholinergics, and Dementia

Actas Dermosifiliogr. 2025 Jul 19:S0001-7310(25)00502-2. doi: 10.1016/j.ad.2025.07.007. Online ahead of print.

ABSTRACT

In recent decades, the use of certain oral anticholinergics for the treatment of hyperhidrosis has become widespread, often off-label but supported by multiple studies, including clinical trials, demonstrating their effectiveness and an apparently good safety profile. Similarly, various studies published in recent years have associated the use of anticholinergics to the development of dementia, particularly in elderly patients. Additionally, other studies have suggested that hyperhidrosis itself may be an early symptom of developing dementia. However, to date, no research has specifically linked the use of oral anticholinergics for hyperhidrosis treatment with the development of dementia. We present the currently available data on this controversial topic.

PMID:40691936 | DOI:10.1016/j.ad.2025.07.007

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Autonomic seizures and hyperhidrosis due to glioblastoma in a middle-aged man: a case report

J Med Case Rep. 2025 Jul 1;19(1):296. doi: 10.1186/s13256-025-05375-z.

ABSTRACT

BACKGROUND: Hyperhidrosis is common. History, physical examination, and simple investigations are often sufficient to confirm the diagnosis. However, hyperhidrosis can result from focal autonomic seizures. Diagnosing focal autonomic seizures is challenging, and there is a high rate of misdiagnosis.

CASE PRESENTATION: A 59-year-old Emirati man presented with intermittent sweating episodes and fatigue of 3 weeks duration. Initial differential diagnoses included poorly controlled diabetes, hyperthyroidism, and cardiac arrhythmia. A focal autonomic seizure was suspected after visits to five different specialities. A diagnosis of temporal glioblastoma was confirmed on an magnetic resonance imaging scan. The patient had surgical removal of the tumor, and his symptoms resolved after treatment with levetiracetam and dexamethasone.

CONCLUSION: Hyperhidrosis is common and can be easy to treat. However, hyperhidrosis may be a manifestation of focal autonomic seizure resulting from life-threatening conditions such as glioblastoma. Clinicians need to have a high index of suspicion when managing patients with excessive recurrent sweating.

PMID:40598620 | DOI:10.1186/s13256-025-05375-z

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Primary hyperhidrosis: an updated review

Drugs Context. 2025 Jun 16;14:2025-3-2. doi: 10.7573/dic.2025-3-2. eCollection 2025.

ABSTRACT

BACKGROUND: Hyperhidrosis (HH) is a condition characterized by excessive sweating beyond the physiological needs of thermoregulation. HH can be classified as primary (idiopathic) hyperhidrosis (PHH) or secondary hyperhidrosis (SHH), which is associated with underlying medical conditions, medications or systemic disorders. This narrative review provides an updated overview of PHH, with a focus on epidemiology, aetiopathogenesis, clinical manifestations, diagnostic approaches and current management strategies, particularly highlighting pharmacological and procedural treatment options.

METHODS: A literature search was conducted in February 2025 across Ovid Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) using the key term “hyperhidrosis”. The review included observational studies, clinical trials, narrative reviews, guidelines and meta-analyses published in the past 10 years. Additional references were identified through manual searches of relevant bibliographies.

RESULTS: The global prevalence of PHH is estimated to range between 0.072% and 9%, with PHH accounting for 93% of all HH cases. Whilst the precise pathophysiology remains unclear, PHH is believed to result from sympathetic overactivity, whereas SHH is associated with endocrine, neurological, infectious, malignant and medication-induced causes. PHH is diagnosed clinically and distinguishing between primary and secondary forms is essential. Management options vary based on severity, ranging from topical therapies (antiperspirants, anticholinergics), systemic medications (oral anticholinergics, adrenergic modulators), device-based interventions (iontophoresis, microwave thermolysis), injectable therapies (botulinum toxin) and surgical approaches (sympathectomy, excision, liposuction/curettage). Whilst these interventions can significantly improve symptoms and quality of life, long-term efficacy, recurrence and adverse effects remain concerns.

CONCLUSION: PHH significantly impacts the quality life of patients contributing to both physical discomfort and psychosocial distress. An individualized, multi-modal approach is crucial to optimizing management. Further research is warranted to refine existing therapies and evaluate emerging treatment modalities for improved long-term outcomes.

PMID:40575073 | PMC:PMC12201942 | DOI:10.7573/dic.2025-3-2