Category: Treatment

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Altered Th17/Treg balance and therapeutic targeting of RORgamma in primary focal hyperhidrosis

Front Immunol. 2025 Oct 17;16:1656632. doi: 10.3389/fimmu.2025.1656632. eCollection 2025.

ABSTRACT

BACKGROUND: Primary focal hyperhidrosis (PFH) significantly impacts patients’ physical and mental health, yet its underlying mechanisms remain unclear.

METHODS: This study involved 80 healthy controls and 60 patients each with primary palmar (PPH), craniofacial (PCH), or axillary hyperhidrosis (PAH). Peripheral blood mononuclear cells (PBMCs) were analyzed via flow cytometry to assess Th17 and Treg cell populations. Cytokine levels were measured in patient serum using ELISA, while sweat gland tissue from PAH patients underwent gene expression analysis. A pilocarpine-induced mouse model of hyperhidrosis was used to test SR2211, a RORγ inverse agonist.

RESULTS: PFH patients exhibited a disrupted Th17/Treg balance, with increased Th17 and decreased Treg cells across all subtypes compared to controls. Elevated IL-17 and IL-6 and reduced IL-10 and TGF-β1 levels were observed in PFH serum. Sweat glands showed increased RORγt and decreased FOXP3 expression. In mice, SR2211 treatment reduced sweat secretion, secretory granules, and serum acetylcholine. It also lowered Th17 infiltration, serum IL-17/IL-6, and IL-17A expression in sweat glands.

DISCUSSION: PFH is associated with a Th17/Treg immune imbalance. SR2211 alleviated hyperhidrosis and Th17-related inflammation in mice, highlighting the potential of targeting the RORγ-Th17 axis as a therapeutic strategy for PFH.

PMID:41181099 | PMC:PMC12575253 | DOI:10.3389/fimmu.2025.1656632

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Development and validation of a model for predicting depression risk in primary palmar hyperhidrosis: a cross-sectional retrospective observational study

BMJ Open. 2025 Oct 10;15(10):e101212. doi: 10.1136/bmjopen-2025-101212.

ABSTRACT

OBJECTIVE: Primary palmar hyperhidrosis (PPH), characterised by excessive palm sweating, significantly impacts patients’ physiology, psychology, self-esteem, work, life and social interactions. The incidence of depression is higher among PPH patients. Timely detection of key predictive factors and the development of risk prediction models are crucial for effective intervention and treatment in this patient group.

DESIGN: We conducted an in-depth analysis of clinical data from 926 PPH patients treated at the Thoracic Surgery Department of Beijing Haidian Hospital between 2016 and 2021. We used the Boruta algorithm alongside the Backward Elimination strategy to select predictive factors and constructed five machine-learning models. By evaluating these models’ performance, we determined the optimal one. Additionally, we introduced the Shapley Additive exPlanations method to enhance the interpretability of this optimal model.

RESULTS: The Personality Diagnostic Questionnaire-4 score, Self-Rating Anxiety Scale score, family history, quality of life excluding PPH, onset age and the age when PPH begins to impact life (Impact age) are six predictive factors for depression in PPH patients. The support vector machine (SVM) model performs more comprehensively through model validation. In the validation set, the area under the curve is 0.798 (95% CI: 0.737 to 0.859), with a Brier score of 0.1451 (95% CI: 0.1233 to 0.1716), accuracy of 0.7184, sensitivity of 0.775, specificity of 0.699 and F1 score of 0.585.

CONCLUSIONS: These findings can enhance our understanding of depression in PPH patients, and the SVM model is a valuable screening tool for assessing the risk of depression in PPH patients.

PMID:41073115 | DOI:10.1136/bmjopen-2025-101212

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Hyperhidrosis: Diagnosis and management strategies

Nurse Pract. 2025 Oct 1;50(10):31-36. doi: 10.1097/01.NPR.0000000000000354. Epub 2025 Sep 25.

ABSTRACT

Hyperhidrosis, a condition characterized by an overactive cooling system that produces four to five times the normal amount of sweat, can profoundly impact a person’s physical, psychological, and social well-being. It can be classified as primary or secondary, and the location and severity determine treatment options. These options include topical agents, systemic agents, and nonsurgical and surgical procedures. Nurse practitioners play a crucial role in managing this condition, and their awareness and understanding are vital in designing effective treatment options for their patients. This article aims to enhance knowledge by discussing hyperhidrosis, its impact on a patient’s physical and psychological well-being, and recommended treatment modalities.

PMID:40996843 | DOI:10.1097/01.NPR.0000000000000354

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Unilateral versus Bilateral T3 Ganglionectomy in Primary Palmar Hyperhidrosis Patients

Thorac Cardiovasc Surg. 2025 Sep 11. doi: 10.1055/a-2699-8163. Online ahead of print.

ABSTRACT

BACKGROUND: Primary palmar hyperhidrosis (PPH) is a distressing condition that significantly impairs quality of life. Endoscopic thoracic sympathectomy (ETS) is an effective treatment, but compensatory hyperhidrosis (CH) remains a common and problematic complication. The optimal extent of surgical interruption, particularly the choice between unilateral and bilateral ganglionectomy, remains uncertain.

METHODS: We conducted a retrospective analysis of 118 patients who underwent unilateral (n=41) or bilateral (n=77) T3 ganglionectomy via video-assisted thoracoscopic surgery (VATS) between November 2023 and January 2025. Patient-reported outcomes, including CH and postoperative satisfaction, were assessed three months postoperatively using standardized questionnaires. Comparisons between the two groups were performed using t-tests and chi-square tests.

RESULTS: Baseline demographics were comparable between groups. The unilateral group reported significantly higher satisfaction, with 93% “very satisfied” compared to 61% in the bilateral group (p<0.001). CH was less prevalent in the unilateral group (20% vs. 48%, p=0.007), and when present, was generally mild and limited to a single body region. In contrast, bilateral ganglionectomy was associated with more frequent and multi-regional CH. Among unilateral ETS patients, only 22% later underwent contralateral surgery, indicating that unilateral intervention was sufficient in most cases.

CONCLUSIONS: Unilateral T3 ganglionectomy offers a favorable balance of efficacy and safety, yielding higher satisfaction and significantly reduced CH compared to bilateral procedures. These findings support the use of unilateral ETS as a first-line surgical strategy for PPH, particularly in patients sensitive to CH. A tailored, staged approach may enhance long-term outcomes and patient satisfaction.

PMID:40935159 | DOI:10.1055/a-2699-8163

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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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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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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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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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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