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Hyperhidrosis: A Central Nervous Dysfunction of Sweat Secretion

Dermatol Ther (Heidelb). 2023 Jan 10. doi: 10.1007/s13555-022-00885-w. Online ahead of print.

ABSTRACT

Hyperhidrosis (HH) is a central nervous dysfunction characterized by abnormally increased sweating due to a central dysregulation of sweat secretion. HH significantly affects the quality of life of patients in their private, social and professional environments. Physiologically, sweating is a mechanism that regulates body temperature, but it may also be triggered by emotional or gustatory stimuli. There are two main types of sweat glands: eccrine and apocrine glands. The central nervous system controls sweat secretion through the release of neurotransmitters into the autonomous nervous system (ANS) that activate the sweat glands. The hypothalamus has two separate neuronal pathways, one for thermoregulation and one for emotions. HH may thus be due to either a neuronal dysfunction of ANS regulation leading to a hyperactivity of the sympathetic nervous system, or to abnormal central processing of emotions. Crucially, there is no dysfunction of the sweat glands themselves. Various pathogenic mechanisms have been proposed to be involved in pathological sweat secretion in HH, ranging from structural changes within the ANS to increased expression of aquaporin 5 and upregulation of activin A receptor type 1 in eccrine sweat glands. Although a genetic predisposition has been demonstrated, it remains unclear exactly which genes are involved. To identify new, potential therapeutic targets and to improve treatment options, a good understanding of the signaling pathways involved, the underlying mechanisms, and the genetic components is essential. In this review we discuss the various aspects of sweat physiology and function that are necessary to explain pathological sweating. Our aim is to raise awareness of the complexity of HH to promote a better understanding of the disorder.

PMID:36627476 | DOI:10.1007/s13555-022-00885-w

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The Impact of Hyperhidrosis on Quality of Life: A Review of the Literature

Am J Clin Dermatol. 2023 Jan 9. doi: 10.1007/s40257-022-00743-7. Online ahead of print.

ABSTRACT

Hyperhidrosis is a condition of excessive sweating, which can have profound physical and mental effects. Hyperhidrosis is a significantly impactful and distressing illness that warrants equal attention as other more well-known dermatologic conditions. However, because of a lack of awareness among the public, stigma, and difficulty with access to treatments (due to cost or insurance coverage), patients are less likely to be diagnosed and treated. In hyperhidrosis, quality-of-life surveys can be useful for determining the magnitude of symptoms and to evaluate treatment outcomes. The purpose of this study was to conduct a narrative literature review to investigate the impact of hyperhidrosis on quality of life. A total of 49 articles investigating the impact of primary hyperhidrosis on quality of life were selected for the review. Hyperhidrosis is a potentially debilitating illness that affects multiple domains of patients’ lives including their psychological, physical, and social functioning. Despite the significant impacts, patients with hyperhidrosis are less likely to seek care. Here, we explore these impacts, and disparities in care, in more detail.

PMID:36622502 | DOI:10.1007/s40257-022-00743-7

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Long-term efficacy and safety of 1% glycopyrronium bromide cream in patients with severe primary axillary hyperhidrosis: results from a Phase 3b trial

J Eur Acad Dermatol Venereol. 2023 Jan 6. doi: 10.1111/jdv.18843. Online ahead of print.

ABSTRACT

BACKGROUND: Primary axillary hyperhidrosis (PAHH) strongly affects the patient’s quality of life. To date, topical treatment options are limited. 1% glycopyrronium bromide (GPB) showed promising efficacy and safety in a pivotal 4-week Phase 3a study.

OBJECTIVES: To assess efficacy and safety of topical 1% GPB cream in patients with severe PAHH in a long-term study of 72 weeks vs. baseline.

METHODS: This was a long-term, open-label, Phase 3b trial for 72 weeks including 518 patients with severe PAHH. Patients were treated with 1% GPB cream once daily for 4 weeks, followed by a flexible dosing scheme (min. twice per week, max. once daily). Primary endpoint was the absolute change in sweat production from baseline to week 12. Further study endpoints included assessment of the severity of PAHH and the impact on quality of life.

RESULTS: Total median sweat production decreased by 119.30 mg (-65.6%, both median) until week 12. Absolute change in sweat production from baseline to week 12 in logarithmic values was statistically significant (p < 0.0001). Patients’ quality of life was improved at all study time points compared to baseline, as assessed by Hyperhidrosis Quality of Life Index and Dermatology Life Quality Index (p < 0.0001). Treatment was safe and locally well-tolerated with only few mild to moderate adverse drug reactions (ADRs). Dry mouth and application site erythema were the most common reported ADRs.

CONCLUSIONS: Treatment with 1% GPB cream over 72 weeks significantly reduces sweat production and improves quality of life in patients with severe PAHH. 1% GPB cream is well-tolerated and provides an effective treatment option for long-term use in patients with severe PAHH.

PMID:36606529 | DOI:10.1111/jdv.18843

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Efficacy, Safety and Quality of Life of Oxybutynin versus Aluminum Chloride Hexahydrate in Treating Primary Palmar Hyperhidrosis

Indian J Dermatol. 2022 May-Jun;67(3):222-227. doi: 10.4103/ijd.IJD_799_20.

ABSTRACT

BACKGROUND: Palmar hyperhidrosis is characterized by excessive sweating beyond the physiological needs of the patient’s body and the most frequent form is primary or essential. Different treatments protocols have been proposed to control or decrease sweating.

AIMS AND OBJECTIVES: This study aimed to compare the efficacy and safety of oral oxybutynin versus topical aluminum chloride hexahydrate (ACH) in treating primary palmar hyperhidrosis. Also, to assess quality of life (QOL) as a measure of improvement of hyperhidrosis state.

MATERIALS AND METHODS: Patients were randomized using the block randomization with sealed envelope method into two treatment groups; oral oxybutynin group and topical ACH group. Hyperhidrosis Disease Severity Scale (HDSS) was used as a primary outcome measure to assess the efficacy of the drug in both groups. Clinical grading and the QOL were used as secondary outcome measures. The safety was evaluated by recording side effects in the follow-up visits.

RESULTS: HDSS, clinical grading and QOL score showed a statistically significant improvement in the oral oxybutynin groups. One week after stoppage of treatment, the symptoms recurred again in both groups with return of HDSS and QOL scores to pretreatment levels. The most common side effects were dry mouth (65.8%) and itching (65.0%) for oral oxybutynin group and topical ACH group; respectively.

CONCLUSION: Treatment of primary palmar hyperhidrosis with oxybutynin is a good initial alternative for treatment given that it gives better results and much more improvement in QOL when compared to topical ACH. QOL questionnaire and clinical grading should also be considered as useful tools in the assessment of response to treatment.

PMID:36386101 | PMC:PMC9644765 | DOI:10.4103/ijd.IJD_799_20

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Risk Factors Affecting the Outcomes of CT-Guided Radiofrequency Thermocoagulation of Thoracic Sympathetic Nerve in the Treatment of Primary Palm Hyperhidrosis

Pain Physician. 2022 Nov;25(8):E1219-E1228.

ABSTRACT

BACKGROUND: Primary palm hyperhidrosis (PPH) is a chronic disease characterized by uncontrolled palm-sweating exceeding physiological needs. It negatively impacts the quality of life of the patients and can lead to different degrees of psychological problems. Currently, there are a variety of treatment options for PPH, of which thoracotomy is a first-line treatment that has shown good efficacy. However, since it is an invasive procedure requiring general anesthesia and is often associated with high costs and serious complications, better alternatives should be explored. Computed tomography (CT)-guided percutaneous puncture of radiofrequency thermocoagulation (RF-TC) of the thoracic sympathetic nerve is a promising alternative treatment. It is a minimally invasive procedure that can be performed under local anesthesia and is associated with rapid recovery. However, the factors affecting the duration of the surgery-related benefits and outcomes of CT-guided percutaneous RF-TC of the thoracic sympathetic nerve are unclear.

OBJECTIVES: To investigate the factors influencing the outcomes of CT-guided percutaneous RF-TC of the thoracic sympathetic nerve in patients with PPH.

STUDY DESIGN: A retrospective study.

SETTING: This study was conducted at the Pain Department of Jiaxing University Affiliated Hospital (Jiaxing, China).

METHODS: After approval by the Ethics Committee of the Affiliated Hospital of Jiaxing College, the data of 232 corresponding patients were assessed. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to identify factors associated with PPH and to construct a nomogram for predicting postoperative recurrence. Time-independent receiver operating characteristic (ROC) curve analyses were performed to assess the nomogram’s predictive capacity.

RESULTS: In the one-year survival analysis model, gender (HR = 1.573, 95%CI: 0.844 to 2.934), age (HR = 0.965, 95%CI: 0.915 to 1.018), disease course (HR = 0.960, 95%CI: 0.908 to 1.015), palm temperature difference (HR = 0.377, 95%CI: 0.287 to 0.495), perfusion index difference (HR = 0.590, 95%CI: 0.513 to 0.680) and hyperhidrosis disease severity scale (HR = 1.963, 95%CI: 0.769 to 5.011) were identified as statistically significant factors in univariate analysis, while palm temperature difference (HR = 0.589, 95%CI: 0.369 to 0.941) and perfusion index difference (HR = 0.357, 95%CI: 0.588 to 0.968) were the independent factors in the multivariate Cox proportional hazards risk model. In the 2-year survival analysis model, palm temperature difference (HR = 0.353, 95%CI: 0.261 to 0.478), perfusion index difference (HR = 0.589, 95%CI: 0.510 to 0.680) and hyperhidrosis disease severity scale (HR = 1.964, 95%CI: 0.771 to 5.006) were the statistically significant factors while palm temperature difference (HR = 0.507, 95%CI: 0.321 to 0.799) and perfusion index difference (HR = 0.789, 95%CI: 0.625 to 0.995) were the independent factors.

LIMITATIONS: This single-center retrospective study was limited by its small sample size, short follow-up time, and the possibility of bias resulting from the non-random patient selection.

CONCLUSION: Palm temperature difference and perfusion index difference were independent risk factors associated with prolonging the surgical benefits and reducing postoperative recurrence of CT-guided RF-TC of the sympathetic nerves in patients with PPH.

PMID:36375194

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Case Reports of Transdermal Fentanyl Patch Administration Difficulties in Cancer Patients with Excess Sweating

J Pain Palliat Care Pharmacother. 2022 Nov 15:1-6. doi: 10.1080/15360288.2022.2141413. Online ahead of print.

ABSTRACT

(Case 1) A 45-year-old male was diagnosed with prostate cancer. Treatment was administered using bicalutamide and leuprorelin acetate, while a transdermal fentanyl (TDF) was applied for pain relief. However, TDF continued to peel off owing to excessive sweating, even when reinforced by a protective layer. As such, TDF was discontinued and pain control was initiated using other medicines. Sweating occurred irregularly because of hot flashes, approximately four to five times per day. (Case 2) A 37-year-old male was diagnosed with a malignant thymoma and sacral metastasis. For analgesic control, etodolac tablets, carbamazepine tablets, and TDF were administered. Subsequently, the dose of the TDF was gradually increased, but the analgesic effect was low; thus, fentanyl blood concentration was measured. The measurements showed that even higher TDF doses did not increase fentanyl blood levels. During this period, full body sweating began to occur to a large extent due to unknown causes, and it was thought that the absorption of fentanyl decreased. When using a TDF, it is necessary to monitor patients for any sweating during treatment, while also considering changes in medication in some cases. This should promote the maintenance and improvement of the quality of life of the affected patients.

PMID:36378038 | DOI:10.1080/15360288.2022.2141413

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Long-term outcomes of bilateral thoracoscopic T3 sympathectomy for primary focal hyperhidrosis in children

J Pediatr Surg. 2022 Sep 24:S0022-3468(22)00604-2. doi: 10.1016/j.jpedsurg.2022.09.014. Online ahead of print.

ABSTRACT

BACKGROUND: Thoracoscopic bilateral T3 sympathectomy for primary focal palmar hyperhidrosis in children has excellent short-term outcomes. However, data in the literature, on the long-term outcomes of the operation are scarce.

METHODS: We conducted a retrospective institutional review of all children and adolescents undergoing T3 bilateral thoracoscopic sympathectomy for primary focal palmar hyperhidrosis between June 2013 and October 2020. We composed a quality of life (QoL) questionnaire evaluating the patient’s perception of how much the hyperhidrosis affected their daily life in multiple domains. The questionnaire was completed before the operation and at every postoperative follow-up visit.

RESULTS: We operated on 58 patients with a median age of 15 (6-25) years. There were no intraoperative or postoperative complications, and all patients had immediate complete postoperative resolution of their palmar hyperhidrosis. Fifty-three patients (91.4%) had long-term follow-up data available with a median of 2.5 (range 0.1-7.5) years. Two patients (3.4%) experienced recurrence of their palmar hyperhidrosis. Nine patients (15.5%) experienced compensatory hyperhidrosis and required occasional medical management with oral anticholinergics. Two patients reported regretting having undergone the operation. Overall, the mean QoL score improved remarkably, from 42/100 before the operation to 92/100 at 1 month, 89/100 at six months to a year, 97/100 between two and four years, and 80/100 ≥ 5 years after the operation.

CONCLUSION: Thoracoscopic bilateral T3 sympathectomy has a high success rate for primary palmar hyperhidrosis in children in the mid- to long-term. Compensatory sweating and recurrence can occur years after the operation, so long-term follow up is mandatory.

LEVEL OF EVIDENCE: IV.

PMID:36344285 | DOI:10.1016/j.jpedsurg.2022.09.014