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

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

Eur Neurol. 2020 Jun 17;:1-8

Authors: Niwa ASM, Gregório ML, Leão LEV, de Godoy MF

Abstract
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.

PMID: 32554973 [PubMed – as supplied by publisher]

Video-assisted thoracoscopic sympathectomy versus modified Wittmoser method in surgical management of primary hyperhidrosis.

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Video-assisted thoracoscopic sympathectomy versus modified Wittmoser method in surgical management of primary hyperhidrosis.

J Cardiothorac Surg. 2020 Jun 10;15(1):133

Authors: Divisi D, Zaccagna G, Imbriglio G, Di Francescantonio W, De Vico A, Barone M, Crisci R

Abstract
PURPOSES: We compared two different surgical methods evaluating the effectiveness of procedures and the quality of life (QoL) of patients.
METHODS: From January 2010 to November 2017 we carried out 476 biportal video-assisted thoracoscopic surgery (VATS) approaches of sympathetic chain in 238 patients. One hundred and twenty-nine (54%) patients underwent conventional sympathectomy (CS) while 109 (46%) patients underwent sympathicotomy associated with the division of the rami communicantes (MWT). Quality of Life (QoL) was classified as follows: from 20 to 35 excellent; from 36 to 51 very good; from 52 to 68 good; from 69 to 84 poor; and > 84 very poor.
RESULTS: We noticed statistical significant reduction of complications comparing CS with MWT approaches (chest pain from 36.4 to 4.5%; paresthesias from 8.5 to 3.6%; bradycardia from 28.6 to 10%, respectively). The preoperative and postoperative QoL index evaluation revealed a statistically significant improvement after surgery (CS: 86 ± 2 versus 35 ± 1, p = 0.00001; MWT: 85 ± 1 versus 33 ± 2, p = 0.00001), with general satisfaction of the two techniques.
CONCLUSION: Modified Wittmoser method seems to be a valid alternative to conventional sympathectomy, minimizing the percentage rate of complications and showing significant effectiveness in the quality of life improvement.

PMID: 32522214 [PubMed – in process]

Electronic Pneumatic Injection‐Assisted Dermal Drug Delivery Visualized by Ex Vivo Confocal Microscopy

Background and Objectives
Electronic pneumatic injection (EPI) is a technique for dermal drug delivery, which is increasingly being used in clinical practice. However, only few studies have been reported on cutaneous drug distribution and related clinical endpoints. We aimed to visualize the immediate cutaneous drug distribution, changes in skin architecture, and related clinical endpoint of EPI.

Study Design/Materials and Methods
Acridine orange (AO) solution was administered to ex vivo porcine skin by EPI at pressure levels from 4 to 6 bar with a fixed injection volume of 50 µl and nozzle size of 200 µm. Immediate cutaneous distribution was visualized using ex vivo confocal microscopy (EVCM). Changes in skin architecture were visualized using both EVCM and hematoxylin and eosin‐stained cryosections.

Results
The defined immediate endpoint was a clinically visible papule formation on the skin. The pressure threshold to consistently induce a papule was 4 bar, achieving delivery of AO to the deep dermis (2319 µm axial and 5944 µm lateral distribution). Increasing the pressure level to 6 bar did not lead to significant differences in axial and lateral dispersion (P = 0.842, P = 0.905; respectively). A distinctively hemispherical distribution pattern was identified. Disruption of skin architecture occurred independently of pressure level, and consisted of subepidermal clefts, dermal vacuoles, and fragmented collagen.

Conclusions
This is the first study to relate a reproducible clinical endpoint to EPI‐assisted immediate drug delivery using EVCM. An EPI‐induced skin papule indicates dermal drug delivery throughout all layers of the dermis, independent of pressure level settings. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC

Hyperhidrosis Quality of Life Index (HidroQoL©): further validation and clinical application in patients with axillary hyperhidrosis using data from a phase III RCT

Summary

Background
The Hyperhidrosis Quality of Life Index (HidroQoL©) is a validated patient‐reported outcome measure capturing the quality of life of people affected by hyperhidrosis. We aimed to extend the validity evidence to physician‐confirmed diagnosis of primary axillary hyperhidrosis.

Methods
Data from a phase 3 randomized placebo‐controlled clinical trial were used (n = 171). Confirmatory factor analysis was carried out to confirm a priori two‐factor structure of the HidroQoL. Internal consistency was assessed using Cronbach’s alpha. Intraclass correlation coefficients (ICCs) were calculated to evaluate test‐retest reliability after 4 to 7 days. Convergent validity was assessed using correlations with the Dermatology Life Quality Index (DLQI), the Hyperhidrosis Disease Severity Scale (HDSS) and gravimetric sweat production. Known groups were analyzed to evaluate discriminative validity. Responsiveness after 29 days was assessed and minimal important difference (MID) values were calculated using both anchor‐ and distribution‐based approaches. All analyses were carried out for total HidroQoL and its two domains.

Results
The two‐factor structure of the HidroQoL could be confirmed. Internal consistency and test‐retest reliability were strong (Cronbach’s α: 0.81‐0.90; ICCs: 0.89‐0.93). Correlations with other outcome measures were in line with a priori hypotheses. The HidroQoL discriminated between different severity groups (p ≤ .001) and showed sensitivity to change towards improvement (p

Something to Sweat About: Two Cases of Dupilumab-Induced Hyperhidrosis and Bromhidrosis.

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Something to Sweat About: Two Cases of Dupilumab-Induced Hyperhidrosis and Bromhidrosis.

Allergy Rhinol (Providence). 2020 Jan-Dec;11:2152656720927703

Authors: Rowane M, Valencia R, Schend J, Jhaveri D, Hostoffer R

Abstract
Introduction: Atopic dermatitis (AD, eczema) is familial chronic inflammatory skin disease of complex etiology and increasing prevalence. Dupilumab is an IL-4 receptor subunit alpha (IL-4Rα) antagonist that is the first Food and Drug Administration-approved biological therapy for moderate-to-severe adult AD inadequately controlled with topical therapies. Adverse effects reported in the literature include injection site reactions, conjunctivitis, headache, and nasopharyngitis.
Objective: We report the first cases of hyperhidrosis and bromhidrosis as side effects from dupilumab (Dupixent®) for the treatment of AD.
Case Reports: Case 1 is a 20-year-old woman with controlled allergic rhinitis and severe AD reported axillary hyperhidrosis with bromhidrosis, comparable to sweat from high-intensity exercise, with no relief from several different over-the-counter antiperspirants. Case 2 is a 61-year-old woman with history of chronic asthma, allergic contact dermatitis, allergic rhinitis, and AD noticed markedly increased sweating with bromhidrosis that was reminiscent of her menopausal symptomology, about 3 months after initiating dupilimab.
Discussion: Traditional immunosuppressive agents and corticosteroids have limited efficacy, numerous side effects, and increased risk of infection. The safety profile and efficacy of the newly approved IL-4Rα antagonist dupilumab may be favorable to oral immunosuppressants, but its use remains limited to severe recalcitrant cases, due to financial implications and lack of long-term safety data and comparative head-to-head trials.
Conclusion: We report improved outcomes with dupilumab, in addition to unpublished cases of bromhidrosis and hyperhidrosis in 2 patients with AD. This report of additional complications may inspire further clinical research and assist clinicians in considering the option of dupilumab for uncontrolled AD, despite aggressive traditional treatment.

PMID: 32489715 [PubMed]

Involvement of activin a receptor type 1 (ACVR1) in the pathogenesis of primary focal hyperhidrosis.

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Involvement of activin a receptor type 1 (ACVR1) in the pathogenesis of primary focal hyperhidrosis.

Biochem Biophys Res Commun. 2020 May 27;:

Authors: Lin JB, Chen JF, Lai FC, Li X, Xie JB, Tu YR, Kang MQ

Abstract
The pathogenesis of primary focal hyperhidrosis (PFH) is still not clear. PFH is thought to be a genetic disease. Whether activin A receptor type 1 (ACVR1) is involved in the pathogenesis of PFH is unknown. In this study, the expression of ACVR1 in sweat glands of patients with PAH was detected by western blot and immunofluorescence. The primary sweat gland cells obtained from primary axillary hyperhidrosis (PAH) patients were transfected with acvr1 vector. Cell proliferation, apoptosis and cell cycling of gland cells were measured after transfection with acvr1 vector. The mRNA and protein expression of aquaporin 5 (AQP5) and Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) were detected. Our data showed that ACVR1 expression in axillary sweat gland tissue of PAH patients was significantly higher than that of normal control group. The function of ACVR1 was further investigated in the gland cells obtained from PAH patients. Compared with NC group, ACVR1 overexpression significantly promoted the proliferation of sweat gland cells and inhibited the apoptosis of sweat gland cells. Meanwhile, ACVR1 overexpression significantly reduced the percentage of cells in G0/G1 and G2/M phases, and increased the percentage of cells in S phase. In addition, ACVR1 overexpression significantly promoted the expression of AQP5 and NKCC1 at both mRNA and protein levels. Together, ACVR1 expression is related to PFH and ACVR1 overexpression can promote the proliferation of sweat gland cells and inhibit apoptosis by promoting the expression of AQP5 and NKCC1.

PMID: 32473755 [PubMed – as supplied by publisher]

Transdermal theranostics

Skin offers an easily accessible site for drug administration as well as for health signal monitoring, with non‐noninvasiveness or minimal‐invasiveness, convenience, and good patient compliance. Transdermal theranostics promises for personalized, home‐based, long‐term management of chronic diseases.

Abstract
Skin offers an easily accessible site for drug administration as well as for health signal monitoring, with non‐invasiveness or minimal‐invasiveness, convenience, and good patient compliance. Transdermal theranostics promises for personalized, home‐based, and long‐term management of chronic diseases, and is expected to change the landscape of healthcare profoundly. In this article, we review the recent advances in transdermal drug delivery, diagnosis based on sweat and skin interstitial fluid, and wearable devices. The advantages, limitations, and commercialization of these emerging techniques are comparatively discussed.