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).

Calidad de vida luego de simpaticotomía toracoscópica por hiperhidrosis focal primaria / Quality of life after thoracoscopic sympathectomy for primary focal hyperhidrosis

RESUMEN Antecedentes: la simpaticotomía toracoscópica demostró ser una cirugía segura para el tratamiento de la hiperhidrosis focal primaria (HFP); sin embargo, la calidad de vida no es totalmente satisfactoria en algunos pacientes, teniendo en cuenta la sudoración compensatoria como principal efecto adverso. Objetivo: evaluar la calidad de vida de los pacientes operados por HFP mediante simpaticotomía toracoscópica utilizando una encuesta anónima posoperatoria. Material y métodos: se incluyó una serie consecutiva de pacientes operados de simpaticotomía toracoscópica entre agosto de 2016 y agosto de 2019. Se excluyeron pacientes que no respondieron a la encuesta de calidad de vida telefónica o cuyo tiempo de seguimiento fue menor de 6 meses. Se evaluaron variables clínicas, quirúrgicas y posoperatorias. Resultados: durante este período se operaron 61 pacientes; del total de la muestra se excluyeron 12 pacientes. El promedio de edad fue 28,9 años. Todos tenían hiperhidrosis primaria palmar y/o axilar moderada o grave, asociadas o no a rubor facial o hiperhidrosis plantar. La encuesta fue respondida por 49 pacientes; de esta observamos una resolución total de la HFP en 32 pacientes (65,3%) y parcial en 17 pacientes (34,6%), con un porcentaje de sudoración compensatoria del 61% (30 pacientes), de los cuales a 4 (8%) la sudoración compensatoria les alteró su calidad de vida, provocando malestar e insatisfacción, la mayoría transitorios. Con un tiempo promedio de 36 meses (6-72), el 97,9% (48 pacientes) sí recomendarían realizar el procedimiento. Conclusión: la simpaticotomía toracoscópica bilateral continúa siendo el tratamiento más eficaz para HFP. El nivel de satisfacción de los pacientes operados fue elevado. Si bien la sudoración compensatoria fue el efecto adverso más frecuente, generalmente se presentó de manera leve y transitoria.

ABSTRACT Background: Thoracoscopic sympathectomy demonstrated to be a safe surgical procedure for the management of primary focal hyperhidrosis (PFH); however, some patients are not completely satisfied with their quality of life as compensatory sweating is the main adverse event. Objective: The aim of this study was to evaluate the quality of life of patients with PFH undergoing thoracoscopic sympathectomy using an anonymous postoperative survey. Material and methods: Consecutive patients undergoing thoracoscopic sympathectomy between August 2016 and August 2019 were included. Patients who did not respond the telephone survey about their quality of life or who had been followed up for < 6 months. Clinical, intraoperative and postoperative variables were analyzed. Results: During this period 61 patients were operated on and 12 of them were excluded. Mean age was 28.9 years. All the patients presented moderate or severe primary palmar and/or axillary hyperhidrosis with or without facial flushing or plantar hyperhidrosis. Forty-nine patients responded the survey. Surgery completely solved PFH in 32 patients (65.3%) while 17 patients (34.6%) achieved a partial relief; 61% (30 patients) developed compensatory sweating affecting the quality of life in 4 (8%) causing transient discomfort and dissatisfaction in most cases. After a mean follow-up of 36 months (6-72), 97.9% (48 patients) recommended the procedure. Conclusion: Bilateral thoracoscopic sympathectomy is still the most efficient treatment for PFH with high level of satisfaction among the patients operated on. Compensatory sweating was the most common adverse effect and is mild and transient in most cases.

Rotura espontánea de quiste hepático simple: éxito del tratamiento conservador / Spontaneous rupture of a simple liver cyst: success of a conservative approach

RESUMEN Los quistes hepáticos simples (QHS) son las lesiones hepáticas más frecuentes. Cursan habitualmente asintomáticas, aunque cuando alcanzan gran tamaño pueden causar síntomas. El objetivo del presente artículo es presentar una complicación excepcional de los QHS. Presentamos a una mujer de 61 años con historia de QHS múltiples que acude a Urgencias por dolor abdominal brusco sin antecedente traumático. Ante la sospecha de rotura quística espontánea, se realiza tomografía computarizada (TC) abdominal que confirma el diagnóstico. Se decide tratamiento conservador con buena evolución. Tras el episodio agudo es intervenida quirúrgicamente realizándose destechamiento de los quistes. a rotura de los QHS es una complicación excepcional que habitualmente cursa con dolor abdominal. Debido a su baja frecuencia no existe un tratamiento estándar. Se acepta que el tratamiento conservador es una buena opción en pacientes sin signos de peritonitis, mientras que la cirugía urgente está indicada en pacientes con abdomen agudo.

ABSTRACT Simple liver cysts (SLC) are the most common liver tumors. They are usually asymptomatic but large cysts may produce symptoms. The aim of this article is to report a rare complication of SLC. We report the case of a 61-year-old woman with a history of multiple SLCs who sought medical care due to sudden abdominal pain not associated with trauma. A probable diagnosis of spontaneous rupture was made, and the patient underwent computed tomography (CT) scan of the abdomen which confirmed the suspicion. Conservative treatment was decided, with favorable outcome. After the acute episode the patient underwent surgery and the cysts were unroofed. Rupture of SLC is a rare complication that usually presents with abdominal pain. There is no standard of care due to the low incidence of this complication. The conservative approach is a good option in patients without signs of peritonitis, while emergency surgery is indicated in patients with acute abdomen.

CHRNA1 promotes the pathogenesis of primary focal hyperhidrosis.

The aim of the study was to elucidate the involvement of cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in the pathogenesis of primary focal hyperhidrosis (PFH). The hyperhidrosis mouse model was constructed using pilocarpine injection. The expression levels of CHRNA1 in sweat gland tissues of PFH patients and hyperhidrosis mice were compared using Western blots and quantitative real-time PCR (qRT-PCR) analyses. Sweat secretion in hyperhidrosis mice treated with small-interfering RNA (siRNA) targeting CHRNA1 (si-CHRNA1) or non-specific siRNA were compared. Sweat secretory granules in the sweat gland cells of hyperhidrosis mice were examined using transmission electron microscopy. The serum level of acetylcholine was measured using enzyme-linked immunosorbent assay, while markers associated with PFH, including Aquaporin 5 (AQP5) and Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), were assessed using immunohistochemical assay and Western blots. Brain-derived neurotrophic factor (BDNF) and Neuregulin 1 (NRG-1) in sympathetic ganglia axons of hyperhidrosis mice were quantified using Western blots. CHRNA1 up-regulation is a characteristic of the sweat glands of PFH patients and Hyperhidrosis mice. Silencing CHRNA1 decreased sweat secretion and the number of sweat secretory granules of hyperhidrosis mice. Serum acetylcholine, as well as AQP5 and CACNA1C expression in the sweat glands, was reduced by siCHRNA1. BDNF1 and NRG-1 levels in the sympathetic ganglia axons were also attenuated by siCHRNA1 treatment. CHRNA1 up-regulation is a potential biomarker of PFH and downregulating CHRNA1 could alleviate the symptoms of PFH through inactivating the sympathetic system.

Efficacy and tolerability of 20% aluminum sesquichlorohydrate vs 20% aluminum chloride for the treatment of axillary hyperhidrosis: A randomized controlled trial.

This study evaluated the efficacy and tolerability of topical aluminum sesquichlorohydrate (AS) when compared to aluminum chloride (AC) as a treatment for primary axillary hyperhidrosis (PAH). Twenty subjects were included in this randomized, controlled, split-side 8-week study. All participants applied 20% AS and 20% AC lotions in their axillae (one treatment per axilla) every night for 2 weeks; next, the application was reduced to three times a week for 4 weeks. The assessment was performed using the sweating intensity visual scale (SIVS), hyperhidrosis disease severity score (HDSS), patient satisfaction score, and the appearance of adverse effects on weeks 0, 1, 2, 4, 6, and 8. Both AS as well as AC application showed positive results, significantly differing from the baseline, as assessed using SIVS, HDSS, and patient satisfaction score at every follow-up visit; however, no significant difference was observed between the AS and AC groups at any follow-up visit. The mean time of response was 1.14 weeks for both treatments. A side effect was observed in one subject (5%), who reported itching on the AC axilla. The therapeutic effects persisted even after reducing the frequency of application and lasted for at least 2 weeks after cessation of use. In conclusion, topical 20% AS demonstrated similar efficacy to topical 20% AC in the treatment of PAH, with a high safety profile.

Thoracoscopic sympathicotomy for the treatment of intolerable palmar and axillary hyperhidrosis in children is associated with high recurrence rates.

BACKGROUND: Treatment of palmar and axillary primary focal hyperhidrosis (PFH) in children up to 16 years using thoracoscopic sympathicotomy is supported by scarce evidence. Therefore, this study aimed to summarize the results of our standardized bilateral, one-stage, single-port sympathicotomy (BOSS) in children up to 16 years of age. METHODS: Consecutive children (n = 14) up to 16 years of age undergoing BOSS between October 2011 and June 2015 in our institution were included in this retrospective study. RESULTS: Recurrence of primary hyperhidrosis was noted in seven patients (50.0%), of whom five patients (35.7%) underwent reoperation. Reoperations were associated with placement of additional thoracoscopic ports (n = 1; 12.5%), intraoperative placement of pleural drains (n = 2; 25%), and prolonged air leak (n = 1; 12.5%). Despite the high recurrence and reoperation rates, overall patient satisfaction was high with a median satisfaction score of 7.5 (interquartile range of 1.75; range: 4-9). CONCLUSION: Although the overall patient satisfaction score in our cohort was good, BOSS for the treatment of intolerable palmar and axillary PFH in children up to 16 years of age is associated with a high recurrence and reoperation rate.

Heart Rate Variability Assessment and Its Application for Autonomic Function Evaluation in Patients with Hyperhidrosis.

BACKGROUND: Pathophysiology mechanism of primary focal hyperhidrosis (PFHH) is controversial. Heart rate variability (HRV) could explain if there is a systemic component present. We aimed to investigate the functions of the autonomic nervous system in patients diagnosed with PFHH compared to controls using the analysis of HRV in the domains of time, frequency, and nonlinearity, as well as analysis of the recurrence plots (RPs). METHODS: We selected 34 patients with PFHH (29.4 ± 10.2 years) and 34 controls (29.2 ± 9.6 years) for HRV analysis. Heart beats were recorded with Polar RS800CX monitor (20 min, at rest, in supine position), and RR intervals were analyzed with Kubios Premium HRV software. RPs were constructed with Visual Recurrence Analysis software. Statistical analysis included unpaired t test (p < 0.05). RESULTS: Our results showed that HRV parameters in the 3 domains evaluated did not show any differences between the groups. The same was observed with RPs. CONCLUSIONS: The findings suggest that PFHH, from the pathophysiological point of view, may be caused by peripheral involvement of the sympathetic nervous system (glandular level or nerve terminals), as there was no difference between the groups studied. More specific studies should help elucidate this issue.

Correlation between benign joint hypermobility syndrome and primary focal hyperhidrosis in children: a novel concept.

BACKGROUND: Benign joint hypermobility syndrome (BJHS) is one of the most common hereditary connective tissue disorders in children in which autonomic nervous system involvement has been reported. This study aimed to evaluate the frequency of primary focal hyperhidrosis in children with BJHS. METHODS: This observational-analytical study was conducted in a case-control setting on children aged 3 to 15 years in 2018 at Mofid Children's Hospital, Tehran, Iran. Benign joint hypermobility syndrome was diagnosed according to the Brighton criteria; then, the patients referred to a dermatologist for evaluation of hyperhidrosis. RESULTS: In total, 130 eligible patients with confirmed BJHS and 160 age- and sex-matched healthy subjects were enrolled in this study. Primary focal hyperhidrosis (PFH) was seen in 56.2 and 16.3% of the cases and controls, respectively, indicating a significant difference (P < 0.05). The severity of hyperhidrosis did not differ between the two groups. CONCLUSION: Although the results of the study showed a significant correlation between BJHS and PFH, more comprehensive studies are needed to confirm these findings.

Incorporating diagnosis and treatment of hyperhidrosis into clinical practice.

Proper billing and coding are essential to document the diagnosis of hyperhidrosis and to assure proper reimbursement for treatment. Providers should become familiar with the payment policies of local health plans to streamline the preauthorization process that is often needed for many treatments commonly used for hyperhidrosis. Having a preprinted letter of medical necessity and patient intake forms that record the necessary historical information about the disease, previous treatments, and other pertinent information will help increase the speed of the office flow. This article presents algorithms for treatment of the various forms of primary focal hyperhidrosis.