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Involvement of aquaporin 5 and Na-K-2Cl co-transporter 1 in the pathogenesis of primary focal hyperhidrosis: evidence from the primary sweat gland cell culture

Am J Physiol Cell Physiol. 2023 Dec 4. doi: 10.1152/ajpcell.00274.2023. Online ahead of print.

ABSTRACT

People with primary focal hyperhidrosis (PFH) usually have an overactive sympathetic nervous system, which can activate the sweat glands through the chemical messenger of acetylcholine. The role of aquaporin 5 (AQP5) and Na-K-2Cl co-transporter 1 (NKCC1) in PFH is still unknown. The relative mRNA and protein levels of AQP5 and NKCC1 in the sweat gland tissues of three subtypes of PFH patients (primary palmar hyperhidrosis, PPH; primary axillary hyperhidrosis, PAH; primary craniofacial hyperhidrosis, PCH) were detected with Real-Time PCR (qPCR) and Western blot. Primary sweat gland cells from healthy controls (NPFH-SG) were incubated with different concentrations of acetylcholine, and the relative mRNA and protein expression of AQP5 and NKCC1 were also detected. NPFH-SG cells were also transfected with si-AQP5 or shNKCC1, and acetylcholine stimulation-induced calcium transients were assayed with Fluo-3 AM calcium assay. Up-regulated AQP5 and NKCC1 expression were observed in sweat gland tissues, and AQP5 demonstrated a positive Pearson correlation with NKCC1 in PPH patients (r=0.66, p<0.001), PAH patients (r=0.71, p<0.001), and PCH patients (r=0.62, p<0.001). Up-regulated AQP5 and NKCC1 expression were also detected in primary sweat gland cells derived from three subtypes of PFH patients when compared with primary sweat gland cells derived from healthy control. Acetylcholine stimulation could induce the up-regulated AQP5 and NKCC1 expression in NPFH-SG cells, and AQP5 or NKCC1 inhibitions attenuated the calcium transients induced by acetylcholine stimulation in NPFH-SG cells. The dependence of ACh-stimulated calcium transients on AQP5 and NKCC1 expression may be involved in the development of PFH.

PMID:38047298 | DOI:10.1152/ajpcell.00274.2023

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What do Hyperhidrosis Quality of Life Index (HidroQoL ©) scores mean? Transferring science into practice by the establishing of a score banding system

Br J Dermatol. 2023 Nov 28:ljad444. doi: 10.1093/bjd/ljad444. Online ahead of print.

ABSTRACT

BACKGROUND: The Hyperhidrosis Quality of Life Index (HidroQoL ©) is a measure of quality of life (QoL) impacts in hyperhidrosis.

OBJECTIVES: We aimed to establish score banding systems for the HidroQoL total score for specific contexts representing different severity/impact categories by using the Dermatology Life Quality Index (DLQI) and the Hyperhidrosis Disease Severity Scale (HDSS) as anchors, including data from 357 patients from a phase III clinical trial.

METHODS: We used the HDSS, the established DLQI score bands, and two single items (i.e. 5 and 7) of the DLQI as anchors for the creation of banding systems for the HidroQoL. These anchors were chosen via consensus among an expert group according to relevance to patient experience. Due to the distribution of the HDSS and the single DLQI item 7, Receiver Operating Characteristic (ROC) curves were computed, in order to create an optimal cut-off value of the HidroQoL total score. For the DLQI banding system and the single DLQI item 5, we created a banding system for the HidroQoL based on the distribution of their different categories.

RESULTS: A score of 30 and greater is proposed as cut-off for sweating that “always interferes in daily activities”, based on the HDSS as anchor. In terms of overall skin QoL effects, score bands of 0 – 6, 7 – 18, 19 – 25, 26 – 32, and 33 – 36 represent “no effect”, “small effect”, “moderate effect”, “very large effect” and “extremely large effect” on the patient’s life, respectively.

CONCLUSIONS: In this study, we propose different banding systems for four different contexts: skin-specific QoL (DLQI banding), hyperhidrosis severity (HDSS), working and studying (single DLQI item 7), and social and leisure activities (single DLQI item 5). These banding systems and cut-off values can be used in clinical research and practice to place the patients in different severity categories.

CLINICALTRIALS.GOV IDENTIFIER: NCT03658616.

PMID:38015827 | DOI:10.1093/bjd/ljad444

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A multicenter retrospective study of lumbar sympathectomy for plantar hyperhidrosis: satisfaction and postoperative complications

Clin Exp Dermatol. 2023 Nov 15:llad373. doi: 10.1093/ced/llad373. Online ahead of print.

ABSTRACT

Primary plantar hyperhidrosis has a severe impact on quality of life and conservative treatments are only effective in the short-term. Thoracic sympathectomy has proven its effectiveness in the treatment of palmar hyperhidrosis, but lumbar sympathectomy for plantar hyperhidrosis remains poorly described. The objective of this study is to report the satisfaction of treated patients as well as the postoperative complications. This was a multicenter retrospective observational study of sixteen patients with primary plantar hyperhidrosis, treated with mechanical lumbar sympathectomy from December 2012 to October 2022. Patients’ characteristics were collected from medical records. Quality of life, postoperative satisfaction and complications were evaluated using a standardized questionnaire. Lumbar sympathectomy was performed on 16 patients, fourteen were women and two were men with a total of thirty-one procedures. 87.5% of patients were satisfied and would recommend the surgery to other patients. Compensatory hyperhidrosis occured in 75% of patients, recurrence of hyperhidrosis in 31.3% and sexual dysfunction in 18.8%. Lumbar sympathectomy provides satisfying results for plantar hyperhidrosis with acceptable postoperative complications, regardless of gender. Compensatory hyperhidrosis was the most frequent complication but had no impact on patient satisfaction. Data on the risk of sexual dysfunction are reassuring, with only one case of transient ejaculation disorder.

PMID:37966306 | DOI:10.1093/ced/llad373

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Management of primary plantar hyperhidrosis with botulinum toxin type A: A retrospective case series of 129 patients

Australas J Dermatol. 2023 Nov 14. doi: 10.1111/ajd.14188. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: To date, scientific data on the efficacy of botulinum toxin type A (BoNT-A) for primary plantar hyperhidrosis (PPH) are mainly derived from case reports and small case series. Herein, we sought to assess the efficacy and safety of BoNT-A for PPH on a large series of patients.

METHODS: Medical records of patients who were referred to the outpatient department for hyperhidrosis of a tertiary care hospital and received BoNT-A for PPH from March 2003 until December 2022 were reviewed.

RESULTS: A total of 129 patients [12 males, 117 females; median age 32 years (range, 16-72)] were included in the study, after excluding 24 patients with insufficient documented follow-up data. Most patients [115 (89.1%)] received onabotulinumtoxin-A, nine (7.0%) abobotulinumtoxin-A and five (3.9%) both in subsequent sessions. The mean number of sessions was 2.02 [standard deviation (SD), 2.29] and the mean duration of response 6.16 months (SD, 4.01). The percentage of response, as evaluated by Minor’s test, was 71.67%, 63.44%, 47.78% and 34.13% after 1, 3, 6 and 9 months, respectively. Most patients were satisfied (21.7%) or very satisfied (58.9%) with the treatment. No serious side effects were reported.

CONCLUSIONS: The results of this retrospective study suggest that BoNT-A is an effective and safe treatment option for PPH.

PMID:37964488 | DOI:10.1111/ajd.14188

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Ultrasound-guided percutaneous puncturing technique: novel radiofrequency ablation technique for thoracic sympathectomy in treatment of palmar hyperhidrosis

Eur J Cardiothorac Surg. 2023 Nov 8:ezad372. doi: 10.1093/ejcts/ezad372. Online ahead of print.

ABSTRACT

Radiofrequency thoracic sympathectomy is routinely conducted under computed tomography or fluoroscopy in treatment of palmar hyperhidrosis. However, it remains a great challenge to perform thoracic paravertebral puncture precisely and safely, that is associated with repeated exposure of radiation and risk of pneumothorax. Alternatively, ultrasound-guided technique can provide high-resolution and real-time needle tracking during percutaneous procedure. Here, we provided our experience of ultrasonic guidance in radiofrequency sympathectomy for treatment of primary palmar hyperhidrosis.

PMID:37947326 | DOI:10.1093/ejcts/ezad372

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Botulinum toxin A dissolving microneedles for hyperhidrosis treatment: design, formulation and in vivo evaluation

Biomater Sci. 2023 Oct 31. doi: 10.1039/d3bm01301d. Online ahead of print.

ABSTRACT

Multiple periodic injections of botulinum toxin A (BTX-A) are the standard treatment of hyperhidrosis which causes excessive sweating. However, BTX-A injections can create problems, including incorrect and painful injections, the risk of drug entry into the bloodstream, the need for medical expertise, and waste disposal problems. New drug delivery systems can substantially reduce these problems. Transdermal delivery is an effective alternative to conventional BTX-A injections. However, BTX-A’s large molecular size and susceptibility to degradation complicate transdermal delivery. Dissolving microneedle patches (DMNPs) encapsulated with BTX-A (BTX-A/DMNPs) are a promising solution that can penetrate the dermis painlessly and provide localized translocation of BTX-A. In this study, using high-precision 3D laser lithography and subsequent molding, DMNPs were prepared based on a combination of biocompatible polyvinylpyrrolidone and hyaluronic acid polymers to deliver BTX-A with ultra-sharp needle tips of 1.5 ± 0.5 μm. Mechanical, morphological and histological assessments of the prepared DMNPs were performed to optimize their physicochemical properties. Furthermore, the BTX-A release and diffusion kinetics across the skin layers were investigated. A COMSOL simulation was conducted to study the diffusion process. The primary stability analysis reported significant stability for three months. Finally, the functionality of the BTX-A/DMNPs for the suppression of sweat glands was confirmed on the hyperhidrosis mouse footpad, which drastically reduced sweat gland activity. The results demonstrate that these engineered DMNPs can be an effective, painless, inexpensive alternative to hypodermic injections when treating hyperhidrosis.

PMID:37905676 | DOI:10.1039/d3bm01301d

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Hyperhidrosis as the initial symptom in FUS mutation-associated amyotrophic lateral sclerosis: a case report and comprehensive literature review

Neurol Sci. 2023 Oct 31. doi: 10.1007/s10072-023-07141-9. Online ahead of print.

ABSTRACT

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is now recognized to involve autonomic dysfunction. The burden of autonomic dysfunction is an important factor in the quality of life and prognosis of ALS patients. This article presents the clinical characteristics of a young female ALS patient with a fused in sarcoma (FUS) gene mutation and notable hyperhidrosis.

METHOD: Detailed clinical characteristics of the patients were collected, and comprehensive examinations such as electrophysiological assessment, neuro-ultrasound, genetic testing, and relevant blood tests were conducted.

RESULT: A 24-year-old female experienced progressive weakness in both lower limbs for over 5 months, along with excessive sweating on both palms and feet. A positive skin iodine-starch test was observed. Electromyography revealed extensive neurogenic damage and prolonged sympathetic skin response (SSR) latency in both lower limbs. Full exon gene sequencing showed a heterozygous mutation c.1574C>T (p.Pro525Leu) in the FUS gene.

CONCLUSION: The pathogenesis of ALS remains unclear at present. This case underscores the presence of autonomic nervous symptoms in ALS associated with FUS mutation and highlights the importance of early diagnosis and timely treatment intervention to enhance patient prognosis.

PMID:37904013 | DOI:10.1007/s10072-023-07141-9

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The success rate and associated risk factors of CT-guided percutaneous radiofrequency sympathectomy in the treatment of primary hyperhidrosis: A retrospective observational trial

J Clin Neurosci. 2023 Oct 25;118:81-89. doi: 10.1016/j.jocn.2023.10.010. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to investigate the success rate of surgical technique and associated risk factors based on the follow-up of patients who underwent CT-guided percutaneous radiofrequency sympathectomy (RFS) to treat primary hyperhidrosis (PH).

METHODS: 370 patients who underwent RFS for PH treatment between January 2018 and April 2022 were enrolled. Patients responded to a questionnaire and telephone follow-up on the effects of treatment and their electronic medical records and imaging findings were reviewed. Logistic regression was performed to identify risk factors related to the success rate of surgical technique.

RESULTS: A temperature difference ≥2 °C before and after procedure was defined as a successful surgical technique. Among the 370 patients (740 sides), 637 sides had successful RFS, and the technical success rate was 86.1 %. Immediately after procedure, 636 sides (85.9 %) were completely dry, 64 (8.7 %) were partially dry, and 40 (5.4 %) were still wet. During the longest follow-up period (54 months), 103 patients relapsed. The median hyperhidrosis disease severity scale score on both sides decreased from 4 to 1 after RFS. According to logistic regression analysis, only the pre-post pulse index was associated with the success rate of surgical technique (odds ratio, 1.14; 95 % confidence interval, 1.06-1.23; p = 0.0004).

CONCLUSIONS: We observed that the immediate efficiency and success rate of surgical technique after RFS for PH treatment were relatively high, although there is a possibility of recurrence in the long term. In general, RFS is a safe and effective procedure for alleviating the symptoms of patients with hyperhidrosis.

PMID:37890198 | DOI:10.1016/j.jocn.2023.10.010