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.

Anatomical variations of the thoracic sympathetic ganglions and their effects on sympathicotomy for primary palmar hyperhidrosis.

PURPOSE: The results and side effects of sympathicotomy for primary palmar hyperhidrosis (PPH) can vary due to anatomical variations of the sympathetic ganglions. The aim of our study was to clarify anatomical variations of the sympathetic ganglions by near-infrared (NIR) thoracoscopy and determine their effects on sympathicotomy for PPH. METHODS: The cases of 695 consecutive patients with PPH treated with either R3 or R4 sympathicotomy either by normal thoracoscopy or by NIR fluorescent thoracoscopy between March 2015 and June 2021 were retrospectively reviewed and followed up. RESULTS: The variation rate of third and fourth ganglions was 14.7% and 13.3% on the right side and 8.3% and 11.1% on the left side. Real T3 sympathicotomy (RTS3) was more effective than real T4 sympathicotomy (RTS4) in the short-term and long-term follow-up (p < 0.001 and p < 0.001, respectively). RTS3 was more satisfactory than RTS4 in the long-term follow-up (p = 0.03), but no significant difference was found in the short-term follow-up (p = 0.24). The incidence and severity of compensatory hyperhidrosis (CH) in the areas of the chest and back in the RTS4 group were significantly lower than those in the RTS3 group according to both the short-term results (12.92% vs. 26.19%, p < 0.001; 17.97% vs. 33.33%, p = 0.002, respectively) and the long-term results (19.66% vs. 28.57%, p = 0.017; 21.35% vs. 34.52%, p < 0.001, respectively). CONCLUSIONS: RTS3 may be more effective than RTS4 for PPH. However, RTS4 appears to be associated with a lower incidence and severity of CH in the areas of the chest and back than RTS3. NIR intraoperative imaging of thoracic sympathetic ganglions may improve the quality of sympathicotomy surgeries.

Compensatory Hyperhidrosis After Non-Surgical Treatment of Primary Focal Hyperhidrosis: Two-Year Single-Centered Prospective Study From Jordan.

BACKGROUND: Primary focal hyperhidrosis (PH) can be managed by a wide range of medical and surgical modalities. Compensatory hyperhidrosis (CH) is a well-documented complication of surgical treatment. We aimed to investigate the occurrence of compensatory hyperhidrosis (CH) in PH patients after nonsurgical treatment with botulinum toxin A (BTX- A) or iontophoresis. METHODOLOGY: We carried out a unicentric prospective study on PH patients from King Abdullah University Hospital (KAUH) in Jordan. PH patients were evaluated after 1-month of nonsurgical treatment. Patients who developed CH were re-assessed after 3-6 months through a telephone-based interview. RESULTS: A total of 86 patients with PH who underwent nonsurgical treatment with iontophoresis or botulinum toxin were recruited. Twenty-four (27.9%) patients developed subjective CH. It was mild in (75%), moderate in (21%), and severe in (4%) of patients affected, it was self-limiting within a few months in all patients. Patients with CH did not differ significantly in demographic or clinical variables from patients who did not develop CH except at the site of PH (p value = .05). CONCLUSION: The findings of this study indicate that more than quarter (27.9%) of patients with PH may develop minor compensatory sweating, however this didn't affect satisfaction with treatment.

Comparison of the efficacy of ETS with different segments for palmar, axillary and plantar hyperhidrosis.

BACKGROUND: To compare the near and long-term outcomes of endoscopic thoracic sympathectomy (ETS) for palmar, axillary and plantar hyperhidrosis. METHODS: We retrospectively analyzed the clinical data of 218 patients with hyperhidrosis who were admitted to the Department of Thoracic Surgery of Gansu Provincial People's Hospital for surgical treatment from April 2014 to August 2021. The patients were divided into three groups according to the method of ETS and the perioperative clinical data and postoperative follow-up data were collected to compare the near and long term outcomes of the three groups. RESULTS: There were 197 eligible patients at follow-up, 60 patients in the R4 cut-off group, 95 patients in the R3 + R4 cut-off group and 42 patients in the R4 + R5 cut-off group. There were no statistically significant differences in baseline indicators such as sex, age and positive family history among the three groups (P > 0.05). There was no statistically significant difference between the three groups in terms of operative time (P = 0.148), intraoperative bleeding (P = 0.308) and postoperative hospital stay (P = 0.407). Postoperatively, all three groups showed significant relief of palmar hyperhidrosis symptoms, with the R3 + R4 group having an advantage in terms of relief of axillary hyperhidrosis symptoms, patient satisfaction and quality of life index at 6 months postoperatively and the R4 + R5 group having an advantage in terms of relief of plantar hyperhidrosis symptoms. The difference in compensatory hyperhidrosis at 12 months postoperatively was not statistically significant among the three groups (P = 0.867), but the incidence was higher in the R3 + R4 and R4 + R5 groups than that in the R4 group. CONCLUSION: Patients with simple palmar hyperhidrosis can first consider R4 cut-off treatment; R3 + R4 cut-off is more effective in treating palmar hyperhidrosis combined with axillary hyperhidrosis; R4 + R5 cut-off is more effective in treating palmar hyperhidrosis combined with plantar hyperhidrosis. However, patients need to be informed that R3 + R4 and R4 + R5 dissection may increase the risk of severe compensatory hyperhidrosis after surgery.

Hyperhidrosis treatments in hidradenitis suppurativa: A systematic review.

Hyperhidrosis impairs quality of life (QOL) in hidradenitis suppurativa (HS) patients and may exacerbate HS. However, there is limited literature on whether hyperhidrosis treatments improve HS disease. To systematically review literature on efficacy and tolerability of hyperhidrosis treatments in HS patients. In May 2021, MEDLINE and EMBASE databases were systematically searched by two reviewers per PRISMA guidelines for articles on hyperhidrosis and HS. Sixteen articles met inclusion criteria (2 randomized controlled trials [RCTs], one case-control study, three cross-sectional studies, 10 case-studies/series), encompassing 252 HS patients across studies. They examined botulinum toxin A (BTX-A) (n = 6) and B (BTX-B) (n = 1), suction-curettage (n = 1), diode laser (n = 1), and microwave-based energy device (MED) (n = 3). Overall, BTX treatments improve HS severity, QOL, hyperhidrosis, and were well-tolerated. Suction-curettage did not improve disease. One HS patient tolerated diode laser well, with improvement in sweating and HS. One RCT studying MED was discontinued due to adverse events. Two studies reported MED-induced HS. BTX was overall helpful in HS patients, including in patients without concomitant hyperhidrosis. However, more prospective studies are needed to examine its utility in HS. There is potential harm of MEDs in HS. Most studies examining hyperhidrosis treatments in HS patients are low level of evidence. Larger RCTs should examine the efficacy and tolerability of hyperhidrosis treatments in HS.

Aquagenic Keratoderma: Treatment Update. / La queratodermia acuagénica: actualización terapéutica.

Aquagenic keratoderma is an uncommon acquired dermatosis characterized by edema and whitish-translucent papules triggered by immersion or contact with water. Cases have been described in association with certain medications, hyperhidrosis, and cystic fibrosis. The aim of this review is to evaluate the effectiveness of different treatments for aquagenic keratoderma. We reviewed the literature and analyzed treatments for aquagenic keratoderma described in case series and reports. Aquagenic keratoderma associated with hyperhidrosis can be treated effectively. Tap water iontophoresis, endoscopic thoracic sympathectomy, botulinum toxin injections, and oxybutynin are effective against refractory forms. Topical salicylic acid and aluminum salts are effective, but of little value as maintenance therapy. Oral oxybutynin 5 mg/d is probably the best option for treating aquagenic keratoderma. The reported pathophysiological effects of nonsteroidal anti inflammatory drugs in this setting suggest that the use of prostaglandins might be justified. Additional studies are needed to investigate these hypotheses and resolve other questions.

Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

Control of Diabetic Gustatory Hyperhidrosis With Topical 20% Aluminum Chloride Hexahydrate.

Diabetic gustatory hyperhidrosis is a late sequela of diabetes and can have profound consequences. We report a case of diabetic gustatory hyperhidrosis controlled with topical aluminum chloride hexahydrate and support this as a first-line treatment. Aluminum chloride hexahydrate is a safe, effective, inexpensive and commercially available treatment.

Management of Primary Focal Hyperhidrosis: An Algorithmic Approach.

Hyperhidrosis (HH) is defined as perspiration beyond the level required to maintain temperature regulation. HH affects nearly 4.8% of the population in the United States. It can have a great impact on patient’s quality of life by disturbing daily activity, performance, confidence, social interactions, and mental health. In the majority of patients with HH (93%), the etiology of excess sweating is idiopathic, which classifies it as primary focal HH. Mild HH may be controlled with topical antiperspirants and lifestyle modifications. Based on the location of involvement, iontophoresis and botulinum toxin may be considered if the patient does not respond to topical therapies. Despite minimizing sweating, chronic use of systemic anticholinergics, in particular oxybutynin, may result in detrimental adverse effects such as dementia. Local surgery, radiofrequency, microwave, and lasers are other potential modalities for HH. Sympathectomy can be a last resort for the treatment of focal HH of the palmar, plantar, axillary, and craniofacial areas after failure of less invasive therapeutic options. In this review, we conducted a comprehensive search in the PubMed electronic database to summarize an algorithmic approach for the treatment of HH. This can help broaden options for managing this difficult disease. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5774.

[Palmar Hyperhidrosis Associated with the Azygos Lobe].

A 66-year-old man visited our department because of palmar hyperhidrosis. Computed tomography had revealed division of the right upper lobe by a fissure and the azygos vein, and the presence of an azygos lobe had been diagnosed. Endoscopic thoracic sympathectomy (resection of T3 ganglion) was performed. Adhesion between the azygos lobe and parietal pleura was dissected to pulling out the azygos lobe and the sympathectomy was safely performed.

[Hyperhidrosis: treatment, results, problems]. / Gipergidroz: lechenie, rezul'taty, problemy.

OBJECTIVE: To analyze the results of thoracic sympathectomy for hyperhidrosis. MATERIAL AND METHODS: The study included 166 patients aged from 15-51 years. There were 118 women and 48 men. Isolated palmar hyperhidrosis was observed in 46 patients, axillary - 46 patients, palmar-axillary - 74 cases. Video-assisted thoracic bilateral sympathectomy was performed. In patients with palmar hyperhidrosis, sympathetic chain was transected between the ribs II and III, axillary and palmar-axillary hyperhidrosis - between the ribs III and IV. RESULTS: Intraoperative injury of intercostal artery occurred in 1 case. Cautery was effective. Postoperative complications occurred in 4 (2.4%) patients (pneumothorax followed by drainage for up to 2-3 days). Symptoms of hyperhidrosis disappeared early after surgery in all cases. Long-term results were followed in 47 patients. Persistent positive effect and patient satisfaction with postoperative outcome were noted in 44 (93.6%) cases. Recurrences occurred in 2 patients with palmar hyperhidrosis and 1 patient with axillary hyperhidrosis for the period from 2 weeks to 6 months. Compensatory sweating developed in 26 (55.3%) patients (within several weeks up to 6 months). Mild compensatory sweating occurred in 17 patients, moderate - 8 patients, severe - 1 patient. Compensatory sweating was more common in patients with axillary and palmar-axillary hyperhidrosis compared to those with isolated palmar hyperhidrosis (p<0.05). We found no significant difference in the incidence of compensatory sweating depending on the level of sympathetic chain intersection (p>0.05). CONCLUSION: An effectiveness of thoracic sympathectomy for hyperhidrosis is obvious. Compensatory sweating is the main undesirable consequence of this surgery. Prediction and prevention of compensatory sweating are not possible. It is imperative to warn the patient about possible compensatory sweating.

Sudomotor Dysfunction.

Disorders of sudomotor function are common and diverse in their presentations. Hyperhidrosis or hypohidrosis in generalized or regional neuroanatomical patterns can provide clues to neurologic localization and inform neurologic diagnosis. Conditions that impair sudomotor function include small fiber peripheral neuropathy, sudomotor neuropathy, myelopathy, α-synucleinopathies, autoimmune autonomic ganglionopathy, antibody-mediated hyperexcitability syndromes, and a host of medications. Particularly relevant to neurologic practice is the detection of postganglionic sudomotor deficits as a diagnostic marker of small fiber neuropathies. Extensive anhidrosis is important to recognize, as it not only correlates with symptoms of heat intolerance but may also place the patient at risk for heat stroke when under conditions of heat stress. Methods for assessing sudomotor dysfunction include the thermoregulatory sweat test, the quantitative sudomotor axon reflex test, silicone impressions, and the sympathetic skin response.

Botulinum toxin: Pharmacology and injectable administration for the treatment of primary hyperhidrosis.

Hyperhidrosis is a dermatological condition defined by excessive sweating beyond thermoregulatory needs with significant effects on patients' quality of life. Hyperhidrosis is categorized as primary or secondary: primary hyperhidrosis is mostly focal and idiopathic, whereas secondary hyperhidrosis is commonly generalized and caused by an underlying medical condition or use of medications. Various surgical and nonsurgical therapies exist for primary hyperhidrosis. Although botulinum toxin is one of the deadliest toxins known, when used in small doses, it is one of the most effective therapies for primary hyperhidrosis. Botulinum toxin injections are widely used as a second-line primary hyperhidrosis treatment option once topical treatment strategies have failed. This article provides an overview of the commercially available botulinum toxin formulations and their applications in the treatment of primary hyperhidrosis.

Eccrine mucinous nevus: clinical and histopathological description in an adult Nevus mucinoso ecrino en el adulto: descripción clínicohistológica.

Eccrine mucinous nevus is an uncommon hamartoma whose histological diagnosis is simple because of its peculiar morphological features, which include an increase in the number and/or size of the glands and eccrine ducts accompanied by abundant mucin deposits. When it presents with the typical symptom, focal hyperhidrosis, clinical suspicion is possible. El nevus mucinoso ecrino (NME) es un hamartoma escasamente reportado en la literatura cuyo diagnóstico histológico es sencillo debido a sus peculiares rasgos morfológicos, que incluye un aumento del número y/o tamaño de las glándulas ductos ecrinos acompañado de abundante depósito de mucina. Cuando presenta los hallazgos típicos, como la hiperhidrosis focal, es posible su sospecha clínica.

The etiology, diagnosis, and management of hyperhidrosis: A comprehensive review: Etiology and clinical work-up.

Hyperhidrosis (HH) is a dermatologic disorder defined by sweat production exceeding thermoregulatory needs. Clinically, HH is diagnosed when excess sweating creates significant emotional, physical, or social discomfort, causing a negative impact on the patient's quality of life. Existing data imply that this condition may affect at least 4.8% of the US population. The etiology of HH may stem from a complex autonomic nervous system dysfunction, resulting in neurogenic overactivity of otherwise normal eccrine sweat glands. Alternatively, HH may be a result of aberrant central control of emotions. This condition is categorized as primary or secondary HH. Approximately 93% of patients with HH have primary HH, of whom >90% have a typical focal and bilateral distribution affecting the axillae, palms, soles, and craniofacial areas. Secondary HH presents in a more generalized and asymmetric distribution and is generated by various underlying diseases or medications. Secondary causes of HH need to be excluded before diagnosing primary HH.

The etiology, diagnosis, and management of hyperhidrosis: A comprehensive review: Therapeutic options.

Hyperhidrosis (HH) is a chronic disorder of excess sweat production that may have a significant adverse effect on quality of life. A variety of treatment modalities currently exist to manage HH. Initial treatment includes lifestyle and behavioral recommendations. Antiperspirants are regarded as the first-line therapy for primary focal HH and can provide significant benefit. Iontophoresis is the primary remedy for palmar and plantar HH. Botulinum toxin injections are administered at the dermal-subcutaneous junction and serve as a safe and effective treatment option for focal HH. Oral systemic agents are reserved for treatment-resistant cases or for generalized HH. Energy-delivering devices such as lasers, ultrasound technology, microwave thermolysis, and fractional microneedle radiofrequency may also be utilized to reduce focal sweating. Surgery may be considered when more conservative treatments have failed. Local surgical techniques, particularly for axillary HH, include excision, curettage, liposuction, or a combination of these techniques. Sympathectomy is the treatment of last resort when conservative treatments are unsuccessful or intolerable, and after accepting secondary compensatory HH as a potential complication. A review of treatment modalities for HH and a sequenced approach are presented.

Hyperhidrotic Macrodactylism Caused by Osteoid Osteoma: A Case Report and Review of the Literature.

Macrodactylism or macrodactyly is referred to as congenital deformity of fingers or toes, and the corresponding incidence rate is relatively low. In this article, we describe a young male with macrodactylism of the second toe of his right foot. He was suffering from persistent pain, overgrowth, and hyperhidrosis ofthe involved toe. Radiographic examination of the right foot showed a small translucent area surrounded by hyperplasia and sclerotic bone in the second distal phalanx, in addition to increased soft tissue density and volume. Surgical resection of the bone lesion and reduction of the soft tissue bulk were performed. Pathological findings showed osteoblast hyperplasia, which was diagnosed as osteoid osteoma, and noabnormal findings were seen in the skin. Symptoms of pain and hyperhidrosis disappeared postsurgery and did not recur over the subsequent 2-year follow-up. As far as we know, this was a rare case of osteoid osteoma occurring in the toe that resulted in macrodactylism, which was also associated with localized hyperhidrosis.

Unilateral hyperhidrosis secondary to brainstem meningioma producing mass effect.

Unilateral hyperhidrosis of neurological origin has been associated with head trauma, cerebral palsy, spinal cord injury, peripheral neuropathy, lesions of the hypothalamus, and cerebral or brainstem strokes. In this report, we describe a 61-year-old man with isolated sweating on the left side of his entire body. A right-sided brainstem meningioma producing mass effect is suspected as the underlying etiology.