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

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 cotransporter 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 patients with PFH (primary palmar hyperhidrosis, PPH; primary axillary hyperhidrosis, PAH; and 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. Upregulated AQP5 and NKCC1 expression were observed in sweat gland tissues, and AQP5 demonstrated a positive Pearson correlation with NKCC1 in patients with PPH (r = 0.66, P < 0.001), patients with PAH (r = 0.71, P < 0.001), and patients with PCH (r = 0.62, P < 0.001). Upregulated AQP5 and NKCC1 expression were also detected in primary sweat gland cells derived from three subtypes of patients with PFH when compared with primary sweat gland cells derived from healthy control. Acetylcholine stimulation could induce the upregulated 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.NEW & NOTEWORTHY The dependence of ACh-stimulated calcium transients on AQP5 and Na-K-2Cl cotransporter 1 (NKCC1) expression may be involved in the development of primary focal hyperhidrosis (PFH).

Cutaneous findings in patients with acromegaly and its relationship with concomitant endocrinopathies.

OBJECTIVES: Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies. DESIGN, PATIENTS, AND MEASUREMENTS: In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated. RESULTS: The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p: .001), while xerosis cutis was significantly more prevalent in patients remitted (p: .001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p-values: .024, .034 and .027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p: .035). CONCLUSIONS: Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow-up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier.

Subclinical effects of botulinum toxin A and microwave thermolysis for axillary hyperhidrosis: A descriptive study with line-field confocal optical coherence tomography and histology.

Botulinum toxin A (BTX) and microwave thermolysis (MWT) are standard axillary hyperhidrosis treatments, but comparison of their subclinical effects is lacking. Line-field confocal optical coherence tomography (LC-OCT) is a promising non-invasive imaging tool for visualizing tissue-interactions. This study aimed to describe subclinical effects of BTX and MWT for axillary hyperhidrosis with LC-OCT-imaging compared to histology. This study derived from an intra-individual, randomized, controlled trial, treating axillary hyperhidrosis with BTX versus MWT. Subclinical effects based on LC-OCT images from baseline and 6-month follow-up (n = 8 patients) were evaluated and compared to corresponding histological samples. At baseline, LC-OCT visualized eccrine pores at the skin surface and ducts in the upper dermis (500 µm), but not deeper-lying sweat glands. Histology identified entire sweat glands. Six months post-treatment, LC-OCT revealed no detectable morphology changes in any BTX-treated axillae (100%), while recognizing obstructed eccrine pores and atrophy of eccrine ducts in most MWT-treated axillae (75%). Histology corroborated LC-OCT findings, while also showing substantial changes to entire sweat glands. LC-OCT enabled visualization of subclinical alterations of superficial eccrine ducts after MWT and unchanged morphology after BTX. LC-OCT is a promising tool for non-invasive assessment of treatment-specific tissue-interactions that can be complementary to histology.

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

BACKGROUND: The Hyperhidrosis Quality of Life Index (HidroQoL©) is a measure of quality of life (QoL) impacts in hyperhidrosis (HH). 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 (items 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 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 the cut-off value 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), HH 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.

Iatrogenic Shapiro syndrome: a case report.

OBJECTIVES: Shapiro's syndrome (SS) is a rare condition characterized by spontaneous periodic hypothermia. The underlying pathophysiological mechanisms and etiology of this syndrome remain controversial, and fewer than 100 cases have been reported to date. The objective of this case report is to present a unique iatrogenic case of SS and contribute additional insights into the underlying etiology of this rare disorder. METHODS: We conducted an analysis of existing medical literature and described a clinical case of SS secondary to a neurosurgical procedure. RESULTS: To our knowledge, we present the first iatrogenic case of SS in a 53-year-old woman who underwent a partial right parieto-occipital lobectomy in 2003 as a treatment for refractory epilepsy. Several years after the surgical procedure, she began experiencing recurrent episodes of hypothermia. Brain magnetic resonance imaging (MRI) revealed the absence of the splenium of the corpus callosum (CC) and pituitary hyperplasia. After ruling out other potential causes of hypothermia, a diagnosis of SS was made. DISCUSSION: The most plausible mechanism to explain the recurrent hypothermia associated with SS in our patient is a probable disruption of the pathways involved in thermoregulation through the CC as a consequence of the surgical procedure. This case report provides further insights into the etiology of this rare disorder.

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

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.

A novel pathogenic variant in TDP2 causes spinocerebellar ataxia autosomal recessive 23 accompanied by pituitary tumor and hyperhidrosis: a case report.

TDP2 gene encodes tyrosyl DNA phosphodiesterase 2, an enzyme required for effective repair of the DNA double-strand breaks (DSBs). Spinocerebellar ataxia autosomal recessive 23 (SCAR23) is a rare disease caused by the pathogenic mutation of TDP2 gene and characterized by intellectual disability, progressive ataxia and refractory epilepsy. Thus far, merely nine patients harboring five different variants (c.425 + 1G > A; c.413_414delinsAA, p. Ser138*; c.400C > T, p. Arg134*; c.636 + 3_ 636 + 6 del; c.4G > T, p. Glu2*) in TDP2 gene have been reported. Here, we describe the tenth patient with a novel variant (c.650del, p. Gly217GlufsTer7) and new phenotype (pituitary tumor and hyperhidrosis).

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

BACKGROUND: 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. OBJECTIVES: To report the satisfaction of patients with primary plantar hyperhidrosis treated with mechanical lumbar sympathectomy as well as their postoperative complications. METHODS: This was a multicentre retrospective observational study of 16 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. RESULTS: Lumbar sympathectomy was performed on 16 patients, 14 were women and 2 were men with a total of 31 procedures. Fourteen (88%) patients were satisfied and would recommend the surgery to other patients. Compensatory hyperhidrosis occurred in 75% of patients, recurrence of hyperhidrosis in 31% and sexual dysfunction in 19%. CONCLUSIONS: Lumbar sympathectomy provides satisfying results for plantar hyperhidrosis with acceptable postoperative complications, regardless of sex. Compensatory hyperhidrosis was the most frequent complication but had no impact on patient satisfaction. In the literature, data on the risk of sexual dysfunction are reassuring and in our study only one of two men experienced transient ejaculation disorder.

Advances in the treatment of axillary bromhidrosis.

BACKGROUND: Bromhidrosis, characterized by foul-smelling sweat, is a prevalent condition that significantly affects patients' social and psychological well-being. METHODS: This review presents novel treatment approaches and discusses the pros and cons of various treatment options for axillary bromhidrosis. RESULTS: Extensive research has explored numerous treatment modalities for bromhidrosis. This article systematically reviews both surgical and nonsurgical interventions utilized in clinical practice. CONCLUSION: By synthesizing available evidence, this review aims to offer evidence-based recommendations for effectively managing bromhidrosis, considering factors such as treatment efficacy, safety profiles, patient preferences, and clinical outcomes.

A novel SERPINA12 variant and first European patients with diffuse palmoplantar keratoderma.

BACKGROUND: Hereditary palmoplantar keratodermas (hPPKs) comprise a heterogeneous group of skin disorders characterized by persistent palmoplantar hyperkeratosis. Loss-of-function variants in a serine peptidase inhibitor, SERPINA12, have recently been implicated in autosomal recessive diffuse hPPK. The disorder appears to share similarities with another hPPK associated with protease overactivity, namely Nagashima-type PPK (NPPK) caused by biallelic variants in SERPINB7. OBJECTIVES: The aim of this study was to enhance the understanding of the clinical and genetic characteristics of serine protease-related hPPKs caused by variants in SERPINA12 and SERPINB7. METHODS: Whole-exome sequencing (WES) was performed for hPPK patients. Haplotype analysis was completed for the patients with identified recessive SERPINA12 variants and their available family members. In addition, the current literature of SERPINA12- and SERPINB7-related hPPKs was summarized. RESULTS: The phenotype of SERPINA12-related hPPK was confirmed by reporting three new SERPINA12 patients, the first of European origin. A novel SERPINA12 c.1100G>A p.(Gly367Glu) missense variant was identified confirming that the variant spectrum of SERPINA12 include both truncating and missense variants. The previously reported SERPINA12 c.631C>T p.(Arg211*) was indicated enriched in the Finnish population due to a plausible founder effect. In addition, SERPINA12 hPPK patients were shown to share a similar phenotype to patients with recessive variants in SERPINB7. The shared phenotype included diffuse transgradient PPK since birth or early childhood and frequent palmoplantar hyperhidrosis, aquagenic whitening and additional hyperkeratotic lesions in non-palmoplantar areas. SERPINA12 and SERPINB7 hPPK patients cannot be distinguished without genetic analysis. CONCLUSIONS: Recessive variants in SERPINA12 and SERPINB7 leading to protease overactivity and hPPK produce a similar phenotype, indistinguishable without genetic analysis. SERPINA12 variants should be assessed also in non-Asian patients with diffuse transgradient PPK. Understanding the role of serine protease inhibitors will provide insights into the complex proteolytic network in epidermal homeostasis.

Treatment of Palmar Hyperhidrosis With Radiofrequency Microneedling-Based on Ultrasound Measurements.

This study addresses the treatment of palmar hyperhidrosis, which has been difficult to manage. A new treatment has been developed using radiofrequency microneedling to reduce sweating non-surgically by ablating sweat glands. Based on ultrasound measurements of the dermis and precise microneedling damage, effective energy was applied to locate the sweat glands and disabled their function. Radiofrequency microneedling with ultrasound can safely and effectively treat hyperhidrosis in a minimally invasive way.

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

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.

Self-reported clinical features and treatment effectiveness of Papillon-Lefèvre syndrome patients from five Latin American countries: A cross-sectional online survey study.

BACKGROUND/OBJECTIVES: Most studies about Papillon-Lefèvre syndrome (PLS) are limited to case reports and patients of the same nationality. This study aimed to determine the self-reported prevalence of signs, symptoms and treatment effectiveness in PLS patients from five Latin American countries. METHODS: An online survey was conducted among adult and paediatric patients from Mexico, Argentina, Colombia and Brazil. Data were collected using multiple-choice, open-ended and image-chooser questions on demographics, signs and symptoms, perceived treatment effectiveness and quality of life. RESULTS: Seventeen patients (10 males and 7 females) aged 4-47 years were surveyed. All had palmoplantar hyperkeratosis. Other affected sites were the feet and hand dorsum (82.35%), Achilles tendon (88.24%), forearms (58.82%), legs (29.41%) and glutes (23.53%). They frequently presented hyperhidrosis and nail pitting. Four had a history of delayed umbilical cord separation. All used topical treatments, with moderate effectiveness; half used oral retinoids, perceived as highly effective. Most reported decreased quality of life and walking difficulties. CONCLUSIONS: The study's results align with prior research on PLS, but reveal new insights, including the impact on patients' quality of life and a history of delayed umbilical cord separation. These findings warrant consideration in future research and patient care.

Long-term efficacy of fractional microneedle radiofrequency versus botulinum toxin-A in primary axillary hyperhidrosis: a randomized controlled trial.

Primary axillary hyperhidrosis is an idiopathic disorder that creates severe psycho-social burden due to excessive uncontrolled sweating. Various therapeutic agents have been described, but each has its own limitations. The use of fractional microneedling radiofrequency has emerged lately with promising results. This study aimed to determine the efficacy and safety of fractional microneedle radiofrequency in comparison to Botulinum toxin-A (BT-A) in patients with primary axillary hyperhidrosis. In this randomized controlled clinical trial, 20 patients (40 sides) were randomized to either fractional microneedle radiofrequency (4 sessions at 3-week intervals) or BT-A (single session), where each side received one of the treatment modalities. Efficacy was measured at 3, 6 and 12 months using Minor's starch iodine test, HDSS score, Hqol questionnaire, and patient satisfaction. Fractional microneedle radiofrequency, although showed moderate efficacy, is inferior to BT-A regarding longitudinal efficacy at 12 months, as well as patients' satisfaction. Both treatment modalities showed to be equally safe, but fractional microneedle radiofrequency procedure was substantially more painful. In conclusion, fractional microneedle radiofrequency does not offer a better substitute to BT-A in primary axillary hyperhidrosis. BT-A shows higher efficacy, is less painful, less expensive, and needs a smaller number of sessions.

Comparison of Microwave-Based Therapy and Negative-Pressure Suction-Curettage for Axillary Hyperhidrosis and Bromhidrosis: A Retrospective Analysis.

BACKGROUND: Axillary hyperhidrosis and bromhidrosis are common clinical diseases, affecting the patients' work and life. Negative-pressure suction-curettage is the most popular treatment now, but challenged by a new microwave-based therapy (MiraDry). We intend to compare the safety and efficiency of the 2 treatments. METHODS: A retrospective analysis of 39 female patients with both primary hyperhidrosis and bromhidrosis was conducted. Seventeen patients were treated with MiraDry, and 22 underwent negative-pressure suction-curettage. The postoperative follow-up program included sweat and odor assessments, satisfaction measurement, safety evaluation, and recurrence assessment at different time points until 12 months. RESULTS: Both treatments showed a significant reduction (P < 0.05) in HDSS score and odor level at 6 and 12 months compared with the baseline. No significant difference in relative reduction was observed between the 2 groups. The satisfaction score of the microwave-based therapy group was higher than that of the negative-pressure suction-curettage group, but no statistical difference was found. The difference in the recurrence rate and complication rate between the groups did not reach significance. CONCLUSIONS: Microwave-based therapy is a noninvasive treatment with durable effects, low risks, shorter downtime, good appearance, and high satisfaction for axillary hyperhidrosis and bromhidrosis.

Revealing the Antiperspirant Components of Floating Wheat and Their Mechanisms of Action through Metabolomics and Network Pharmacology.

Floating wheat is a classical herbal with potential efficacy in the treatment of hyperhidrosis. Aiming at revealing the main components and potential mechanisms of floating wheat, a comprehensive and unique phytopharmacology profile study was carried out. First, common wheat was used as a control to look for chemical markers of floating wheat. In the screening analysis, a total of 180 shared compounds were characterized in common wheat and floating wheat, respectively. The results showed that floating wheat and common wheat contain similar types of compounds. In addition, in non-targeted metabolomic analysis, when taking the contents of the constituents into account, it was found that there indeed existed quite a difference between floating wheat and common wheat and 17 potential biomarkers for floating wheat. Meanwhile, a total of seven components targeted for hyperhidrosis were screened out based on network pharmacology. Seven key differential components were screened, among which kaempferol, asiatic acid, sclareol, enoxolone, and secoisolariciresinol had higher degree values than the others. The analysis of interacting genes revealed three key genes, namely, MAP2K1, ESR1, and ESR2. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses showed that various signaling pathways were involved. Prolactin signaling, thyroid cancer, endocrine resistance, gonadotropin secretion, and estrogen signaling pathways were the main pathways of the intervention of floating wheat in excessive sweating, which was associated with the estrogenic response, hormone receptor binding, androgen metabolism, apoptosis, cancer, and many other biological processes. Molecular docking showed that the screened key components could form good bindings with the target proteins through intermolecular forces. This study reveals the active ingredients and potential molecular mechanism of floating wheat in the treatment of hyperhidrosis and provides a reference for subsequent basic research.

Comparative Study of 1444 nm Laser Monotherapy versus Integrated Liposuction in the Treatment of Axillary Osmidrosis.

Background and Objectives: The 1444 nm wavelength Neodymium:Yttrium-Aluminum-Garnet (Nd:YAG) laser treatment is an efficient method for treating axillary osmidrosis (AO); however, it has a relatively low treatment persistence. To address this issue, we performed integrated liposuction surgery with a laser to treat AO and compared the results with those of a group treated only with a laser. Materials and Methods: This study compared the outcomes of AO treatment between the two groups up to six months postoperatively. The first group of 18 patients underwent laser treatment alone, and the second group of 12 patients underwent integrated liposuction surgery in addition to laser treatment. Outcomes were assessed using the following variables: degree of malodor (DOM), sweating area, patient satisfaction, pain levels, and complications, such as burns, swelling, and contractures. Results: Compared to the laser-only group, the integrated liposuction group demonstrated significantly superior outcomes in terms of DOM (p = 0.002) and patient satisfaction (p = 0.006), as well as a reduction in the sweating area (p = 0.012). The pain rating was higher in the liposuction group, but the difference was not statistically significant (p = 0.054). Compared with the patients in the integrated liposuction treatment group, those in the laser treatment group exhibited a significantly higher number of burns under the axillae (p = 0.025). However, no significant differences were observed in the swelling or contracture between the groups. Conclusions: Integrated liposuction with laser therapy significantly improved treatment outcomes, including malodor, patient satisfaction, sweat test results, and decreased complication rates.

Topical Anticholinergics in the Management of Focal Hyperhidrosis in Adults and Children. A Narrative Review. / Anticolinérgicos tópicos en el manejo de la hiperhidrosis focal en adultos y niños. Una revisión narrativa.

Hyperhidrosis, or excessive sweating, is characterized by overactivity of the eccrine sweat glands, usually associated with dysfunction of the autonomic nervous system. Primary focal hyperhidrosis is the most common form and can affect the axillae, palms, soles, and/or face, often leading to significantly impaired quality of life and social functioning. Treatment is complex. Topical antiperspirants are normally recommended as the first-line treatment for mild hyperhidrosis. Multiple clinical trials and prospective studies support the efficacy and tolerability of oral and topical anticholinergics in the management of hyperhidrosis. Topical glycopyrronium, which has been investigated in at least 8 clinical trials enrolling more than 2000 patients, is probably the first-line pharmacological treatment for axillary hyperhidrosis in patients with moderate to severe disease poorly controlled with topical antiperspirants. Second-line treatments include botulinum toxin injections, microwave treatment, and oral anticholinergics. We review the use of topical anticholinergics in the management of focal hyperhidrosis in adults and children.

Nationwide Cross-sectional Analysis of Endoscopic Thoracic Sympathectomy to Treat Hyperhidrosis Over 12 years in Brazil: Epidemiology, Costs, and Mortality.

OBJECTIVE: To analyze the number of endoscopic thoracic sympathectomies performed to treat hyperhidrosis in the Universal Public Health System of Brazil, the government reimbursements, and the in-hospital mortality rates. BACKGROUND: Even though endoscopic thoracic sympathectomy has been widely performed for the definitive treatment of hyperhidrosis, no series reported mortality and there are no population-based studies evaluating its costs or its mortality rate. METHODS: Data referring to endoscopic thoracic sympathectomy to treat hyperhidrosis between 2008 and 2019 were extracted from the database of the Brazilian Public Health System, which insures more than 160 million inhabitants. RESULTS: Thirteen thousand two hundred one endoscopic thoracic sympathectomies to treat hyperhidrosis were performed from 2008 to 2019, with a rate of 68.44 procedures per 10 million inhabitants per year. There were 6 in-hospital deaths during the whole period, representing a mortality rate of 0.045%. The total expended throughout the years was U$ 6,767,825.14, with an average of U$ 512.68 per patient. CONCLUSIONS: We observed a rate of 68.44 thoracoscopic sympathectomies for hyperhidrosis' treatment per 10 million inhabitants per year. The inhospital mortality rate was very low, 0.045%, though not nil. To our knowledge, no published series is larger than ours and we are the first authors to formally report deaths after endoscopic thoracic sympathectomies to treat hyperhidrosis. Moreover, there is no other population-based study addressing costs and mortality rates of every endoscopic thoracic sympathectomy for the treatment of any site of hyperhidrosis in a given period.

Design and validation of neuronal exocytosis blocking peptides as potential novel antiperspirants.

Thermoregulation and heat dissipation by sweat production and evaporation are vital for human survival. However, hyperhidrosis or excessive perspiration might affect people's quality of life by causing discomfort and stress. The prolonged use of classical antiperspirants, anticholinergic medications or botulinum toxin injections for persistent hyperhidrosis might produce diverse side effects that limit their clinical use. Inspired by botox molecular mode of action, we used an in silico molecular modelling approach to design novel peptides to target neuronal acetylcholine exocytosis by interfering with the Snapin-SNARE complex formation. Our exhaustive design rendered the selection of 11 peptides that decreased calcium-dependent vesicle exocytosis in rat DRG neurons, reducing αCGRP release and TRPV1 inflammatory sensitization. The most potent peptides were palmitoylated peptides SPSR38-4.1 and SPSR98-9.1 that significantly suppressed acetylcholine release in vitro in human LAN-2 neuroblastoma cells. Noteworthy, local acute and chronic administration of SPSR38-4.1 peptide significantly decreased, in a dose-dependent manner, pilocarpine-induced sweating in an in vivo mouse model. Taken together, our in silico approach lead to the identification of active peptides able to attenuate excessive sweating by modulating neuronal acetylcholine exocytosis, and identified peptide SPSR38-4.1 as a promising new antihyperhidrosis candidate for clinical development.