Topical Treatment of Primary Focal Hyperhidrosis, Part 1.

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Topical Treatment of Primary Focal Hyperhidrosis, Part 1.

Int J Pharm Compd. 2019 Jan-Feb;23(1):23-31

Authors: Zur E

Abstract
Primary focal hyperhidrosis is idiopathic, localized, uncontrollable, excessive, and unpredictable sweating beyond what is necessary to regulate body temperature. Primary hyperhidrosis is thought to affect approximately 2% to 3% of the population, and its effect on a patient’s quality of life is very significant. Primary focal hyperhidrosis can be managed using various therapeutic options, including drugs (topical and systemic), nonsurgical interventions (e.g., iontophoresis, botulinum toxin injections), and surgery. This article, which is presented in 2 parts, is a comprehensive review of the topical, evidence-based treatments of primary focal hyperhidrosis, and it covers the following active pharmaceutical ingredients: aluminum salts, methenamine, glycopyrronium salts, oxybutynin chloride; the latter 2 ingredients will be discussed in part 2 of this article. This article discusses the evidence-based data that exists from clinical trials that support the use of topical medications to treat the pathology from efficacy and from a safety point of view. This review also discusses compounding considerations for professionally and safely compounding various topical preparations. In addition, a range of relevant formulas are attached to the article and can be used by compounding pharmacists.

PMID: 30668532 [PubMed – in process]

Glycopyrronium tosylate in pediatric primary axillary hyperhidrosis: Post hoc analysis of efficacy and safety findings by age from two phase three randomized controlled trials.

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Glycopyrronium tosylate in pediatric primary axillary hyperhidrosis: Post hoc analysis of efficacy and safety findings by age from two phase three randomized controlled trials.

Pediatr Dermatol. 2018 Nov 19;:

Authors: Hebert AA, Glaser DA, Green L, Werschler WP, Forsha DW, Drew J, Gopalan R, Pariser DM

Abstract
OBJECTIVES: Hyperhidrosis in pediatric patients has been understudied. Post hoc analyses of two phase 3 randomized, vehicle-controlled, 4-week trials (ATMOS-1 [NCT02530281] and ATMOS-2 [NCT02530294]) were performed to assess efficacy and safety of topical anticholinergic glycopyrronium tosylate (GT) in pediatric patients.
METHODS: Patients had primary axillary hyperhidrosis ≥ 6 months, average Axillary Sweating Daily Diary (ASDD/ASDD-Children [ASDD-C]) Item 2 (sweating severity) score ≥ 4, sweat production ≥ 50 mg/5 min (each axilla), and Hyperhidrosis Disease Severity Scale (HDSS) ≥ 3. Coprimary end points were ≥ 4-point improvement on ASDD/ASDD-C Item 2 (a validated patient-reported outcome) and change in gravimetrically measured sweat production at Week 4. Efficacy and safety data are shown through Week 4 for the pediatric (≥ 9 to ≤ 16 years) vs older (> 16 years) subgroups.
RESULTS: Six hundred and ninety-seven patients were randomized in ATMOS-1/ATMOS-2 (GT, N = 463; vehicle, N = 234); 44 were ≥ 9 to ≤ 16 years (GT, n = 25; vehicle, n = 19). Baseline disease characteristics were generally similar across subgroups. GT-treated pediatric vs older patients had comparable improvements in ASDD/ASDD-C Item 2 (sweating severity) responder rate, HDSS responder rate (≥ 2-grade improvement]), sweat production, and quality of life (mean change from Baseline in Dermatology Life Quality Index [DLQI]/children’s DLQI), with greater improvement vs vehicle. Treatment-emergent adverse events were similar between subgroups, and most were mild, transient, and infrequently led to discontinuation.
CONCLUSIONS: Topical, once-daily GT improved disease severity (ASDD/ASDD-C, HDSS), sweat production, and quality of life (DLQI), with similar findings in children, adults, and the pooled population. GT was well tolerated, and treatment-emergent adverse events were qualitatively similar between subgroups and consistent with other anticholinergics.

PMID: 30451318 [PubMed – as supplied by publisher]

Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Patient-Reported Outcomes from the ATMOS-1 and ATMOS-2 Phase III Randomized Controlled Trials.

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Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Patient-Reported Outcomes from the ATMOS-1 and ATMOS-2 Phase III Randomized Controlled Trials.

Am J Clin Dermatol. 2018 Oct 30;:

Authors: Pariser DM, Hebert AA, Drew J, Quiring J, Gopalan R, Glaser DA

Abstract
BACKGROUND: Glycopyrronium tosylate (GT) is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged ≥ 9 years. GT was evaluated for primary axillary hyperhidrosis in replicate, randomized, double-blind, vehicle-controlled, phase III trials. GT reduced sweating severity and production versus vehicle and was generally well tolerated.
OBJECTIVE: Our objective was to evaluate patient-reported outcomes (PROs) from these trials.
METHODS: Patients aged ≥ 9 years with primary axillary hyperhidrosis ≥ 6 months, gravimetrically measured sweat production ≥ 50 mg/5 min in each axilla, Axillary Sweating Daily Diary (ASDD) Item 2 severity score ≥ 4, and Hyperhidrosis Disease Severity Scale (HDSS) score ≥ 3 were randomized 2:1 to GT 3.75% or vehicle applied once daily to each axilla for 4 weeks. The 4-item ASDD, 6 Weekly Impact (WI) items, Patient Global Impression of Change (PGIC), HDSS, and Dermatology Life Quality Index (DLQI) were utilized.
RESULTS: In the pooled population, 463 patients were randomized to GT and 234 to vehicle; 426 (92.0%) and 225 (96.2%) completed the trials. At baseline, most patients considered their axillary sweating to be at least moderate in severity, impact, and bothersomeness (ASDD items 2, 3, and 4, respectively). Improvement was substantially greater for GT than for vehicle at every study week, and, at week 4, ASDD scores improved from baseline by 62.6 versus 34.0% (severity), 65.5 versus 40.3% (impact), and 65.4 versus 39.0% (bothersomeness). Improvements favoring GT versus vehicle also occurred for WI items, PGIC, HDSS, and DLQI.
CONCLUSIONS: PRO results demonstrated that GT reduced the disease burden of primary axillary hyperhidrosis.
TRIAL REGISTRATION: Clinicaltrials.gov; ATMOS-1 (NCT02530281), ATMOS-2 (NCT02530294).

PMID: 30378087 [PubMed – as supplied by publisher]

[Hyperhidrosis-aetiopathogenesis, diagnosis, clinical symptoms and treatment].

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[Hyperhidrosis-aetiopathogenesis, diagnosis, clinical symptoms and treatment].

Hautarzt. 2018 Oct;69(10):857-869

Authors: Wohlrab J, Kreft B

Abstract
Although primary hyperhidrosis is a common disease, secondary symptomatic hyperhidrosis is rather rare. Primary hyperhidrosis is a complex neuropathic dysregulation with a genetic predisposition and is diagnosed when patients show pathologic sweating patterns and excessive sweating for at least 6 months and fulfill at least four of the following criteria: affected areas are axillae and/or palms and/or soles and/or forehead; symmetry; no night sweating; at least once a week; onset before the age of 25; positive family history; negative impact on daily activities. Frequently used therapies are topical aluminum salts and anticholinergics, iontophoresis in water, and intracutaneous botulinum toxin. Anticholinergics are also used as systemic treatment. Surgical procedures are used as a last result. Furthermore procedures using thermolysis have been developed.

PMID: 30218113 [PubMed – in process]

Sweaty feet in adolescents-Early use of botulinum type A toxin in juvenile plantar hyperhidrosis.

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Sweaty feet in adolescents-Early use of botulinum type A toxin in juvenile plantar hyperhidrosis.

Pediatr Dermatol. 2018 Nov;35(6):784-786

Authors: Bernhard MK, Krause M, Syrbe S

Abstract
BACKGROUND/OBJECTIVES: Plantar hyperhidrosis can have severe social effects on children and adolescents. Therapeutic options include antiperspirants and surgical interventions (eg, sympathectomy). Botulinum type A toxin is approved for axillary hyperhidrosis in adults only. The aim of the study was the determination of effect and safety of botulinum type A toxin in plantar hyperhidrosis in juvenile patients.
METHODS: Children and adolescents with idiopathic focal plantar hyperhidrosis were treated with 50-100 U of botulinum type A toxin per sole. Local anesthesia was provided using topical eutectic mixture of local anesthetics cream and ice, in combination with midazolam as an anxiolytic.
RESULTS: Fifteen patients (aged 12-17) were included in the study. Best results were achieved with a dose of 75-100 U of botulinum type A toxin per sole. Two patients did not benefit from the therapy, and 11 (73%) were satisfied with the results. Nine patients (60%) experienced pain at the injection site for a maximum duration of 3 days. One patient reported transient focal weakness for 4 weeks.
CONCLUSION: Botulinum type A toxin seems to be a safe secondary treatment option for plantar hyperhidrosis in adolescents aged 12 and older. A dose of 75-100 U per sole resulted in a good therapeutic effect of variable duration in most patients. There were no severe side effects.

PMID: 30178509 [PubMed – indexed for MEDLINE]

Hyperhidrosis: Management Options.

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Hyperhidrosis: Management Options.

Am Fam Physician. 2018 Jun 01;97(11):729-734

Authors: McConaghy JR, Fosselman D

Abstract
Hyperhidrosis is excessive sweating that affects patients’ quality of life, resulting in social and work impairment and emotional distress. Primary hyperhidrosis is bilaterally symmetric, focal, excessive sweating of the axillae, palms, soles, or craniofacial region not caused by other underlying conditions. Secondary hyperhidrosis may be focal or generalized, and is caused by an underlying medical condition or medication use. The Hyperhidrosis Disease Severity Scale is a validated survey used to grade the tolerability of sweating and its impact on quality of life. The score can be used to guide treatment. Topical aluminum chloride solution is the initial treatment in most cases of primary focal hyperhidrosis. Topical glycopyrrolate is first-line treatment for craniofacial sweating. Botulinum toxin injection (onabotulinumtoxinA) is considered first- or second-line treatment for axillary, palmar, plantar, or craniofacial hyperhidrosis. Iontophoresis should be considered for treating hyperhidrosis of the palms and soles. Oral anticholinergics are useful adjuncts in severe cases of hyperhidrosis when other treatments fail. Local microwave therapy is a newer treatment option for axillary hyperhidrosis. Local surgery and endoscopic thoracic sympathectomy should be considered in severe cases of hyperhidrosis that have not responded to topical or medical therapies.

PMID: 30215934 [PubMed – in process]

Tatami Mats: A Source of Pitted Keratolysis in a Martial Arts Athlete?

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Tatami Mats: A Source of Pitted Keratolysis in a Martial Arts Athlete?

Acta Dermatovenerol Croat. 2018 Apr;26(1):68-70

Authors: Balić A, Bukvić Mokos Z, Marinović B, Ledić Drvar D

Abstract
Dear Editor, Pitted keratolysis (PK), also known as keratosis plantaris sulcatum, is a non-inflammatory, bacterial, superficial cutaneous infection, characterized by many discrete superficial crateriform ”pits” and erosions in the thickly keratinized skin of the weight-bearing regions of the soles of the feet (1). The disease often goes unnoticed by the patient, but when it is noticed it is because of the unbearable malodor and hyperhidrosis of the feet, which are socially unacceptable and cause great anxiety to many of the patients. PK occurs worldwide, with the incidence rates varying based on the environment and occupation. The prevalence of this condition does not differ significantly based on age, sex, or race. People who sweat profusely or wash excessively, who wear occlusive footwear, or are barefoot especially in hot and humid weather are extremely prone to this condition (2). Physicians commonly misdiagnose it as tinea pedis or plantar warts. Treatment is quite simple and straightforward, with an excellent expected outcome if treated properly. We report a case of a 32-year-old male patient with skin changes of approximately one-year duration diagnosed as plantar verrucae, who was referred to our Department for cryotherapy. The patient presented with asymptomatic, malodorous punched-out pits and erosions along with hyperkeratotic skin on the heel and metatarsal region of the plantar aspect of both feet. The arches, toes, and sides of the feet were spared (Figure 1). Except for these skin changes, the patient was healthy and denied any other medical issues. He was an athlete active in martial arts and had a history of sweating of feet and training barefoot on the tatami mat for extended periods of time. The diagnosis of PK was established based on the clinical findings (crateriform pitting and malodor), negative KOH test for hyphae, and a history of prolonged sweating in addition to contact of the skin with tatami mats, which are often a source of infection if hygiene measures are not adequately implemented. Swabs could have been helpful to identify causative organisms, but they were not crucial for the diagnosis and treatment. The patient was prescribed with general measures to prevent excessive sweating (cotton socks, open footwear, and proper hygiene), antiseptic potassium permanganate foot soaks followed by clindamycin 1% and benzoyl peroxide 5% in a gel vehicle twice daily. At the one-month follow-up visit, the skin changes, hyperhidrosis, and malodor were entirely resolved (Figure 2). Pitted keratolysis is common among athletes (3,4). The manifestations of PK are due to a superficial cutaneous infection caused by several bacterial Gram-positive species including Corynebacterium species, Kytococcus sedentarius, Dermatophilus congolensis, Actynomices keratolytica, and Streptomyces that proliferate and produce proteinase and sulfur-compound by-products under appropriate moist conditions (5-7). Proteinases digest the keratin and destroy the stratum corneum, producing the characteristic skin findings, while sulfur compounds (sulfides, thiols, and thioesters) are responsible for the malodor. Athletes and soldiers who wear occlusive footwear for prolonged periods of time or even barefooted people that sweat extensively and spend time on wet surfaces such as laborers, farmers, and marine workers are more prone to this problem (3,4,8-11). Martial arts athletes are at greater risk of skin infections due to the constant physical contact that can lead to transmission of viral, bacterial, and fungal pathogens directly but also indirectly through contact with the mat and the skin flora of an another infected individual. A national survey of the epidemiology of skin infections among US high school athletes conducted by Ashack et al. supported the prevalent theory that contact sports are associated with an increased risk of skin infections. In this study, wrestling had the highest skin infection rate of predominantly bacterial origin (53.8%), followed by tinea (35.7%) and herpetic lesions (6.7%), which is consistent with other literature reporting (12). Being barefoot on the tatami mat in combination with excessive sweating and non-compliance with hygiene measures makes martial arts athletes more susceptible to skin infections, including PK. The diagnosis is clinical, by means of visual examination and recognition of the characteristic odor. Dermoscopy can be useful, revealing abundant pits with well-marked walls that sometimes show the bacterial colonies (13). Cultures, if taken, show Gram-positive bacilli or coccobacilli. Because of the ease of diagnosis on clinical findings, biopsy of pitted keratolysis is rarely performed. Skin scraping is often performed to exclude tinea pedis, which is one of the main differential diagnosis, the others including verrucae, punctate palmoplantar keratoderma, keratolysis exfoliativa, circumscribed palmoplantar hypokeratosis, and basal cell nevus syndrome. If unrecognized and left untreated, skin findings and smelly feet can last for many years. Sometimes, if unrecognized, PK can be mistreated with antifungals, or even with aggressive treatment modalities such as cryotherapy. Appropriate treatment includes keeping feet dry with adequate treatment of hyperhidrosis, preventive measures, and topical antibiotic therapy. Topical forms of salicylic acid, sulfur, antibacterial soaps, neomycin, erythromycin, mupirocin, clindamycin and benzoyl peroxide, clotrimazole, imidazoles, and injectable botulinum toxin are all successful in treatment and prevention of PK (14,15). Topical antibiotics are the first line of medical treatment, among which fusidic acid, erythromycin 1% (solution or gel), mupirocin 2%, or clindamycin are the most recommended (14). As in our case, a fixed combination of two approved topical drugs – clindamycin 1%-benzoyl peroxide 5% gel, had been already demonstrated by Vlahovich et al. as an excellent treatment option with high adherence and no side-effect (16). The combined effect of this combination showed significantly greater effect due to the bactericidal and keratolytic properties of benzoyl peroxide. Additionally, this combination also lowers the risk of resistance of causative microorganisms to clindamycin. Skin infections are an important aspect of sports-related adverse events. Due to the interdisciplinary nature, dermatologists are not the only ones who should be aware of the disease, but also family medicine doctors, sports medicine specialists, and occupational health doctors who should educate patients about the etiology of the skin disorder, adequate prevention, and treatment. Athletes must enforce the disinfecting and sanitary cleaning of the tatami mats and other practice areas. Keeping up with these measures could significantly limit the spread of skin infections that can infect athletes indirectly, leading to significant morbidity, time loss from competition, and social anxiety as well.

PMID: 29782305 [PubMed – indexed for MEDLINE]

Plantar Hyperhidrosis: An Overview.

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Plantar Hyperhidrosis: An Overview.

Clin Podiatr Med Surg. 2016 Jul;33(3):441-51

Authors: Vlahovic TC

Abstract
Plantar hyperhidrosis, excessive sweating on the soles of feet, can have a significant impact on patients’ quality of life and emotional well-being. Hyperhidrosis is divided into primary and secondary categories, depending on the cause of the sweating, with plantar hyperhidrosis typically being primary and idiopathic. There is an overall increased risk of cutaneous infection in the presence of hyperhidrosis, including fungal, bacterial, and viral infections. This article discusses a range of treatment options including topical aluminum chloride, iontophoresis, injectable botulinum toxin A, glycopyrrolate, oxybutynin, laser, and endoscopic lumbar sympathectomy. Lifestyle changes regarding hygiene, shoe gear, insoles, and socks are also discussed.

PMID: 27215162 [PubMed – indexed for MEDLINE]

Iontophoresis for palmar and plantar hyperhidrosis.

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Iontophoresis for palmar and plantar hyperhidrosis.

Dermatol Clin. 2014 Oct;32(4):491-4

Authors: Pariser DM, Ballard A

Abstract
Iontophoresis is a safe, efficacious, and cost-effective primary treatment of palmar and plantar hyperhidrosis. Decades of clinical experience and research show significant reduction in palmoplantar excessive sweating with minimal side effects. To get the best results from iontophoresis, health care professionals need to provide education on the mechanism of action and benefits, evidence of its use, and creation of a future patient-specific plan of care for continued treatments at home or in the physician’s office. Iontophoresis may be combined with other hyperhidrosis treatments, such as topical antiperspirants and botulinum toxin injections.

PMID: 25152342 [PubMed – indexed for MEDLINE]

Pitted keratolysis, erythromycin, and hyperhidrosis.

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Pitted keratolysis, erythromycin, and hyperhidrosis.

Dermatol Ther. 2014 Mar-Apr;27(2):101-4

Authors: Pranteda G, Carlesimo M, Pranteda G, Abruzzese C, Grimaldi M, De Micco S, Muscianese M, Bottoni U

Abstract
Pitted keratolysis (PK) is a plantar skin disorder mainly caused by coryneform bacteria. A common treatment consists of the topical use of erythromycin. Hyperhidrosis is considered a predisposing factor for bacterial proliferation and, consequently, for the onset of PK. The aim of this study was to evaluate the relationship between PK erythromycin and hyperhidrosis. All patients with PK seen in Sant’Andrea Hospital, between January 2009 and December 2011, were collected. PK was clinically and microscopically diagnosed. All patients underwent only topical treatment with erythromycin 3% gel twice daily. At the beginning of the study and after 5 and 10 days of treatment, a clinical evaluation and a gravimetric measurement of plantar sweating were assessed. A total of 97 patients were diagnosed as PK and were included in the study. Gravimetric measurements showed that in 94 of 97 examined patients (96.90%) at the time of the diagnosis, there was a bilateral excessive sweating occurring specifically in the areas affected by PK. After 10 days of antibiotic therapy, hyperhidrosis regressed together with the clinical manifestations. According to these data, we hypothesize that hyperhidrosis is due to an eccrine sweat gland hyperfunction, probably secondary to bacterial infection.

PMID: 24703267 [PubMed – indexed for MEDLINE]