Hyperhidrosis: disease aetiology, classification and management in the light of modern treatment modalities

Postepy Dermatol Alergol. 2022 Apr;39(2):251-257. doi: 10.5114/ada.2022.115887. Epub 2022 May 9.

ABSTRACT

Hyperhidrosis is a disorder of sweat glands characterized by overproduction of sweat, which is inadequate to the thermoregulatory needs of the body system. Owing to the heavy social and economic burden of the disproportionate perspiration, current treatment methods still do not seem to be sufficient enough to reach patients’ expectations. Therefore, the researchers continue a robust pursuit of novel therapy modalities such as topical treatment methods, oral agents, minimally-invasive medical approach and surgical techniques. In this review article authors summarise the disease outline with the emphasis on the new era of hyperhidrosis treatment methods.

PMID:35645673 | PMC:PMC9131949 | DOI:10.5114/ada.2022.115887

Open-Label Cohort Study to Evaluate Efficacy and Safety of Application of Glycopyrronium Cloth, 2.4% for Palmar Hyperhidrosis

J Drugs Dermatol. 2022 May 1;21(5):488-495. doi: 10.36849/JDD.6688.

ABSTRACT

BACKGROUND: Hyperhidrosis of the palms has a significant negative impact on quality of life. There is no FDA-approved treatment; however, clinicians often use glycopyrronium cloth off-label for this indication despite the lack of published guidance on optimal method of application for treatment of palms.

OBJECTIVE: To compare the safety and efficacy of 4 different methods of application of glycopyrronium cloth to give clinicians guidance when treating palmar hyperhidrosis.

STUDY DESIGN: This study, conducted completely virtually using live interactive telemedicine, compared application times of 15 minutes, 30 minutes, and overnight without occlusion and 30 minutes under occlusion. The primary endpoint was a decrease in the mean of the Hand Severity Score (HHS) after 4 weeks of once-daily application. Safety data, including local skin reactions and other adverse events, were tabulated by cohort.

RESULTS: Of the application times and methods tested, 30 minutes without occlusion produced the greatest decrease in the HHS with an acceptable safety profile. The most common adverse event was unilateral mydriasis, which presumably occurred from inadvertent introduction of study drug into the eye despite multiple warnings to the subjects to avoid eye contact. A few subjects had adverse events presumably due to systemic absorption of the drug similar to those seen in the pivotal trials for treatment of axillary hyperhidrosis.

CONCLUSION: Glycopyrronium cloth can be used successfully to treat palmar hyperhidrosis. Occlusion for 30 minutes had the poorest response presumably due to the increased sweating causing dilution of the study drug.

CLINICALTRIALS: gov: NCT04906655 J Drugs Dermatol. 2022;21(5):488-494. doi:10.36849/JDD.6688.

PMID:35533035 | DOI:10.36849/JDD.6688

Patient experience and prognostic factors of compensatory hyperhidrosis and recurrence after endoscopic thoracic sympathicotomy

Surg Endosc. 2022 May 9. doi: 10.1007/s00464-022-09284-w. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to investigate compensatory hyperhidrosis (CH) and recurrence based on an online survey of patients who underwent endoscopic thoracic sympathicotomy(ETS) for palmar and/or axillary hyperhidrosis.

METHODS: We enrolled 231 patients who underwent ETS for palmar and/or axillary hyperhidrosis from January 2008 to April 2021. Patients responded to an online questionnaire regarding CH and recurrence, their electronic medical records were reviewed. Logistic regression was performed to find the risk factors related to CH and recurrence.

RESULTS: The median time of survey from surgery was 20 months. Although 94% of patients were satisfied with the surgery, 86.1% experienced CH; of them, it was severe in 30.7%. Three months after surgery, there was no long-term change in the severity of CH. The development of CH showed a close relationship with age of 20 years or more (OR: 2.73). Recurrence occurred in 44(19.0%) patients, and the use of anti-adhesive agents was a significant preventive factor against recurrence after ETS (OR: 0.42).

CONCLUSIONS: We observed that CH and recurrence after ETS for palmar and/or axillary hyperhidrosis were relatively common. Age at the time of surgery was associated with CH, and the use of anti-adhesive agents showed to lower the risk of recurrence after ETS.

PMID:35534737 | DOI:10.1007/s00464-022-09284-w

Transfersomal eosin topical delivery assisted by fractional CO2 laser for photodynamic treatment of palmar hyperhidrosis: case study

Drug Deliv Transl Res. 2022 Apr 20. doi: 10.1007/s13346-022-01164-z. Online ahead of print.

ABSTRACT

Hyperhidrosis is a condition in which the cholinergic receptors on the eccrine glands are overstimulated, resulting in excessive sweating. It is considered a serious cosmetic and psychological problem that affects the patient’s quality of life. Searching for novel treatment modalities is required to minimize the side effects and to attain better patient satisfaction.Photodynamic therapy (PDT), using eosin as a photosensitizer, is developed as a promising modality of the treatment of palmar and axillary hyperhidrosis. In this study, we treated six cases suffering palmar hyperhidrosis by applying the fractional CO2 laser prior to PDT session. For PDT, a hydrogel of eosin loaded in a transfersomes as a nano-delivery carrier was applied for 5 min, followed by irradiation by intense pulsed light (IPL). The prepared transfersomes loaded by eosin were spherical in shape with encapsulation efficiency of 33 ± 3.5%, particle size 305.5 ± 5.7 nm, average zeta potential of – 54 ± 7.6 mV with 80 ± 4% of the loaded eosin was released after 3 h. Two cases achieved 90% improvement after four sessions, three patients needed six sessions to show 75% improvement, while one patient showed only 25% improvement after six sessions. This resulted in shortening the time of PS application and decreasing the number of sessions required to achieve acceptable improvement. More clinical studies on large number of patients are required to optimize the results.

PMID:35441986 | DOI:10.1007/s13346-022-01164-z

Clinical utility of botulinum toxin type A local injection therapy for head and forehead hyperhidrosis

J Dermatol. 2022 Apr 7. doi: 10.1111/1346-8138.16368. Online ahead of print.

ABSTRACT

Head and forehead hyperhidrosis (HFH) is a disease that causes a large amount of sweating from the head region, and it significantly reduces patients’ quality of life. Only a few reports have shown the effectiveness of botulinum toxin type A (BTX-A) local injection therapy (BTX-A therapy) for HFH. To clarify the benefits of BTX-A for HFH, BTX-A therapy was performed in 15 patients, and its efficacy was evaluated. The amount of sweating was measured by the ventilation capsule method and Minor’s iodine-starch test. Evaluation was also performed using the Hyperhidrosis Disease Severity Scale (HDSS) and the Dermatology Life Quality Index (DLQI). In most cases, a remarkable antiperspirant effect was observed from 2 weeks after the injection, and the effect lasted for approximately 30 weeks. HDSS and DLQI improved along with the decrease in sweating. Two patients (13.3%) complained of transient mild ptosis. There were no serious side-effects. This study showed that BTX-A therapy is a safe and effective treatment for HFH.

PMID:35393718 | DOI:10.1111/1346-8138.16368

Antagonist of Chrna1 prevents the pathogenesis of primary focal hyperhidrosis

Ann Clin Transl Neurol. 2022 Apr 8. doi: 10.1002/acn3.51558. Online ahead of print.

ABSTRACT

BACKGROUND: Primary focal hyperhidrosis (PFH) is an autonomic neurological disease in which exocrine glands are oversecreted due to autonomic dysfunction of the sympathetic nervous system. Chrna1 promotes the pathogenesis of PFH. We aimed to check if downregulating of Chrna1 by cisatracurium could alleviate the symptoms of PFH.

METHODS: The effect of cisatracurium in a hyperhidrosis mice model induced by pilocarpine hydrochloride was monitored for sweat gland secretion, and ultrastructural sweat secretory granules in sweat glands were analyzed. Meanwhile, markers of hyperhidrosis were checked, and release of Bdnf and Nrg1 from sympathetic ganglia axon was tested. Furthermore, the mechanism of cisatracurium function was evaluated in vitro using HEK293 expressing Chrna1. Finally, the effect of cisatracurium was determined in the hyperhidrosis mice model with overexpression or downregulation of Chrna1.

RESULTS: In hyperhidrosis mice, pretreatment with cisatracurium effectively inhibited sweat secretion, along with fewer particle secretion in sweat glands. The molecular markers of hyperhidrosis (Aqp5 and Cacna1c) were inhibited by cisatracurium, acetylcholine (Ach) level in serum was found decreased. Neurotrophic factors (Bdnf and Nrg1) secreted by sympathetic axon activation were also inhibited. At last, it was confirmed that cisatracurium could not alter the gene or protein expression level of Chrna1, but could block the ion channel. Overexpression of Chrna1 abolished the effect of cisatracurium on hyperhidrosis, while cisatracurium could not function more in siChrna1-treated mice.

CONCLUSION: Our results suggested that pretreatment of cisatracurium could alleviate hyperhidrosis in mice, probably through blocking the ion channel function of Chrna1.

PMID:35393764 | DOI:10.1002/acn3.51558

Two-week prospective observational study of 5% sofpironium bromide gel in Japanese patients with primary axillary hyperhidrosis

J Dermatol. 2022 Apr 8. doi: 10.1111/1346-8138.16384. Online ahead of print.

ABSTRACT

In 2020, 5% sofpironium bromide (ECCLOCK® ) gel (hereinafter referred to as sofpironium) was approved in Japan for the topical treatment of primary axillary hyperhidrosis. A phase III study of sofpironium demonstrated the efficacy and safety of sofpironium; however, no study has assessed its early efficacy at <6 weeks after starting treatment. Therefore, to assess the earlier effectiveness of sofpironium, we conducted a 2-week, single-center, exploratory, prospective, observational study in Japanese patients with primary axillary hyperhidrosis. Patients aged ≥20 years and satisfying with a Hyperhidrosis Disease Severity Scale (HDSS) score of 3 or 4 at baseline were eligible for the study. The primary endpoint for the effectiveness was change in the proportion of patients with a HDSS score of 1, 2, 3, or 4 during the 2-week study period. In 80 patients included in the full analysis set (FAS), there were more women than men (93.8% vs. 6.3%), and the mean age (±standard deviation [SD]) was 33.3 ± 9.4 years. In the FAS, the proportion of patients with a HDSS score of 1 or 2 was 55.0% on day 7, and statistically significant changes were observed after day 3 compared to baseline (p < 0.05). Mean HDSS scores (±SD) were significantly decreased from baseline value of 3.5 ± 0.5 to 2.4 ± 0.9 on day 7 (p < 0.001). The median period for sofpironium treatment to achieve a HDSS score of 1 or 2 for a continuous 2 days was 6 days (95% confidence interval, 4-8). Safety was evaluated in 92 patients in the safety analysis set, and no adverse events were reported during the study period of 2 weeks. These results suggest that after 1-week treatment with sofpironium for patients with a HDSS score of 3 or 4, approximately 50% of the patients can achieve a HDSS score of 1 or 2, which is a clinically significant improvement for the patients.

PMID:35394087 | DOI:10.1111/1346-8138.16384

Hyperhidrosis in Parkinson’s disease: a 3-year prospective cohort study

J Eur Acad Dermatol Venereol. 2022 Mar 13. doi: 10.1111/jdv.18072. Online ahead of print.

ABSTRACT

BACKGROUND: Although hyperhidrosis is a common symptom in patients with Parkinson’s disease (PD), no study has yet examined it longitudinally.

OBJECTIVES: We conducted a 3-year prospective cohort study to investigate the development, evolution, and correlates of hyperhidrosis in patients with PD.

METHODS: A total of 224 patients with early-stage PD were enrolled at baseline and followed up annually for three consecutive years. Hyperhidrosis was assessed using hyperhidrosis question (item 30) of the Non-Motor Symptoms Scale (NMSS). The generalized estimating equations model was applied to investigate the correlates of both presence and severity of hyperhidrosis.

RESULTS: The frequency of hyperhidrosis in PD had an overall increasing tendency from 24.1% at baseline to 34.4% after 3 years, although hyperhidrosis was not always persistent in all patients over the 3-year study period. The presence of hyperhidrosis was found to be associated with dyskinesia (OR 2.27 [1.02-5.04], p = 0.045), the sexual function domain subscore of the NMSS (OR 1.04 [1.01-1.07], p = 0.016), the Hamilton Anxiety Rating Scale (HARS) score (OR 1.08 [1.03-1.13], p = 0.001) and the Unified Parkinson’s Disease Rating Scale part III score (OR 1.02 [1.00-1.04], p = 0.036). Only the HARS score was associated with the severity of hyperhidrosis (B 0.08 [0.03-0.12], p = 0.001).

CONCLUSIONS: Hyperhidrosis is common in PD, and its frequency increases along with disease duration. Hyperhidrosis in PD is not only associated with motor severity and motor complication such as dyskinesia, but may be also with non-motor symptoms such as sexual dysfunction and anxiety.

PMID:35279891 | DOI:10.1111/jdv.18072