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Development of a Nomogram Model for Predicting Anxiety Risk in Patients With Hyperhidrosis: A Study Involving 234 Patients

J Dermatol. 2025 Sep 18. doi: 10.1111/1346-8138.17965. Online ahead of print.

ABSTRACT

Primary focal hyperhidrosis (HH) carries a substantial psychosocial burden, and anxiety is a common but underrecognized comorbidity. We developed and internally validated a nomogram to estimate individualized anxiety risk in primary HH and examined robustness in prespecified sensitivity analyses. We retrospectively analyzed 234 consecutive patients with primary HH at a single center (June 2020-August 2023). Eligibility followed Hornberger criteria; secondary causes were excluded by history/physical examination, medication review, and targeted laboratory tests when indicated. Anxiety was diagnosed clinically according to CCMD-3. After LASSO prescreening with a priori clinical inclusion, the final multivariable logistic model retained 10 readily available predictors: diabetes, intolerance to cold, intolerance to heat, male sex, fatigue, and sweating at the head, hand, foot, chest, and neck. Internal validation used 1000-bootstrap optimism correction to assess discrimination and calibration; clinical utility was quantified with decision-curve analysis (DCA) across threshold probabilities of 0.02-0.36. The nomogram showed good discrimination (optimism-corrected C-index 0.826) and good calibration (bootstrap-corrected MAE 0.033, Brier 0.219). Three prespecified sensitivity analyses yielded consistent conclusions: SA1 (no diabetes) C-index 0.827, Brier 0.221, MAE 0.043; SA2 (craniofacial involvement + number of involved sites) C-index 0.839, Brier 0.220, MAE 0.028; and SA3 (stricter exclusion) C-index 0.811, Brier 0.211, MAE 0.045. Across thresholds of 0.02-0.36, all models demonstrated positive net benefit versus treat-none with largely overlapping curves. This transparent, internally validated tool may help identify HH patients at high risk of anxiety and support timely psychological intervention; external multicenter validation is warranted.

PMID:40964789 | DOI:10.1111/1346-8138.17965

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Atypical Presentations of Levator Ani Syndrome With Perianal Hyperhidrosis: A Case Series

ACG Case Rep J. 2025 Sep 11;12(9):e01826. doi: 10.14309/crj.0000000000001826. eCollection 2025 Sep.

ABSTRACT

Levator ani syndrome (LAS) explains up to 7.4% of anorectal pain cases. Classic symptoms include rectal pain or pressure with sitting. We present 2 patients, ages 32 and 25 years, presenting initially with “diarrhea” and perianal hyperhidrosis. History revealed rectal discomfort, tenesmus, urgency, and sensation of incomplete evacuation. Puborectalis tenderness was present on digital rectal examination. Therapies were tailored to each patient, including pelvic floor physical therapy with biofeedback, bowel regulation, rectal diazepam, and ileostomy. These presentations offer insights into potential pathophysiological mechanisms in LAS and highlight the importance of considering LAS in non-pain presentations.

PMID:40948587 | PMC:PMC12431760 | DOI:10.14309/crj.0000000000001826

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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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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