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ORIGINAL ARTICLE
Year : 2022  |  Volume : 67  |  Issue : 3  |  Page : 222-227
Efficacy, safety and quality of life of oxybutynin versus aluminum chloride hexahydrate in treating primary palmar hyperhidrosis


1 Dermatology Department, Faculty of Medicine, Mansoura University, Mansoura, Dakhlia, Egypt
2 Public Health and Preventive Medicine, Faculty of Medicine, Mansoura University, Mansoura, Dakhlia, Egypt
3 Plastic Surgery Department, Faculty of Medicine, Mansoura University, Mansoura, Dakhlia, Egypt

Date of Web Publication22-Sep-2022

Correspondence Address:
Mohamed Elsaid Abdelshaheed
Plastic Surgery Department, Mansoura University Hospitals, Al-Gomhoria Street, Mansoura, Dakhlia; 36 Albostan Street, Talkha, Dakhlia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_799_20

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   Abstract 


Background: Palmar hyperhidrosis is characterized by excessive sweating beyond the physiological needs of the patient's body and the most frequent form is primary or essential. Different treatments protocols have been proposed to control or decrease sweating. Aims and Objectives: This study aimed to compare the efficacy and safety of oral oxybutynin versus topical aluminum chloride hexahydrate (ACH) in treating primary palmar hyperhidrosis. Also, to assess quality of life (QOL) as a measure of improvement of hyperhidrosis state. Materials and Methods: Patients were randomized using the block randomization with sealed envelope method into two treatment groups; oral oxybutynin group and topical ACH group. Hyperhidrosis Disease Severity Scale (HDSS) was used as a primary outcome measure to assess the efficacy of the drug in both groups. Clinical grading and the QOL were used as secondary outcome measures. The safety was evaluated by recording side effects in the follow-up visits. Results: HDSS, clinical grading and QOL score showed a statistically significant improvement in the oral oxybutynin groups. One week after stoppage of treatment, the symptoms recurred again in both groups with return of HDSS and QOL scores to pretreatment levels. The most common side effects were dry mouth (65.8%) and itching (65.0%) for oral oxybutynin group and topical ACH group; respectively. Conclusion: Treatment of primary palmar hyperhidrosis with oxybutynin is a good initial alternative for treatment given that it gives better results and much more improvement in QOL when compared to topical ACH. QOL questionnaire and clinical grading should also be considered as useful tools in the assessment of response to treatment.


Keywords: Efficacy, hyperhidrosis, oxybutynin, palmar, topical ACH


How to cite this article:
Attallah HS, El-Gilany AH, Bayoumy Youssef YE, Abdelshaheed ME, Ahmed Sharaf EF. Efficacy, safety and quality of life of oxybutynin versus aluminum chloride hexahydrate in treating primary palmar hyperhidrosis. Indian J Dermatol 2022;67:222-7

How to cite this URL:
Attallah HS, El-Gilany AH, Bayoumy Youssef YE, Abdelshaheed ME, Ahmed Sharaf EF. Efficacy, safety and quality of life of oxybutynin versus aluminum chloride hexahydrate in treating primary palmar hyperhidrosis. Indian J Dermatol [serial online] 2022 [cited 2022 Sep 30];67:222-7. Available from: https://www.e-ijd.org/text.asp?2022/67/3/222/356761





   Introduction Top


Palmar hyperhidrosis is a well-known clinical condition characterized by excessive sweating beyond the physiological needs of the patient's body and the most frequent form is primary or essential. Sweating is exacerbated by intense emotion or stress with stimulation of the sweat glands by the sympathetic nervous system in which acetylcholine is serving as a neurotransmitter.[1],[2]

The diagnosis of primary palmar hyperhidrosis is mainly clinically based on the patient's subjective statements in combination with his or her family history; laboratory diagnostic tests are typically not needed for the diagnosis.[3],[4] Underdiagnosis may lead to a significant impairment of quality of life (QOL) that could be similar to or greater than that reported for other major dermatologic problems as psoriasis or other chronic diseases.[5]

Different treatments protocols have been proposed to control or decrease the sweating of primary palmar hyperhidrosis.[6],[7],[8],[9] According to the Canadian Hyperhidrosis Advisory Committee, topical treatment with aluminum chloride hexahydrate (ACH) is recommended as a first-line therapy while the systemic anticholinergic oxybutynin is considered the second-line.[10]

To date, most treatment protocols; in spite of few studies on topical ACH therapy, recommend it as a first line treatment of primary palmar hyperhidrosis but no study was conducted to evaluate its effect on QOL compared to oxybutynin therapy. To fill this knowledge gap, we designed this study to compare the efficacy and safety of oral oxybutynin versus topical ACH in the treatment of primary palmar hyperhidrosis. Also, to assess QOL as a measure of improvement of hyperhidrosis state.


   Materials and Methods Top


This is a randomized controlled study carried out in Mansoura University Hospital, Egypt during the period from the start of June 2017 to the end of July 2020. The study was approved by IRB, Faculty of Medicine, Mansoura University [IRB code: MS/16.04.71] and was registered in Pan African Clinical Trial Registry [identification number: PACTR202006915898923]. Study participants or their legal guardians gave a written informed consent after assurance of data confidentiality.

The study included patients with primary palmar hyperhidrosis aged nine years or more with Hyperhidrosis Disease Severity Scale (HDSS) of at least 2 and agreed to keep on follow-up. Pregnant and lactating women, hypersensitive patients to any of the active ingredients or have a history of hypersensitivity, patients with known closed-angle glaucoma, prostatic disorders, intestinal obstruction, toxic megacolon, intestinal atony, severe ulcerative colitis, and myasthenia were excluded from the study.

Sample size calculation was based on the percentage of HDSS improvement at least one point in 60% of patients receiving oxybutynin versus 27% in placebo group retrieved from previous research.[11] Using G*power version 3.0.10 to calculate difference between two proportions, 2-tailed, with α error = 0.05 and power = 80.0%. The calculated sample size is 35 in each group and 10% was added to compensate for drop out then the total calculated sample size was 80 (40 in each group).

Patients were randomized using the block randomization with sealed envelope method into two treatment groups; oral oxybutynin group and topical ACH group.

A full medical history was taken from each patient. Ophthalmological examination was done to exclude closed-angle glaucoma. HDSS,[12] Clinical severity grading of palmar hyperhidrosis[13] and QOL questionnaire[14] were also reported.

Oral Oxybutynin (5 mg tab and syrup 5 mg/5 ml) was used for 12 weeks according to the standardized protocol of Wolosker and his colleges.[15] Treatment was started with 2·5 mg per day and increased gradually until it reached an effective dose, without exceeding 10 mg per day. Patients weighing ≥ 40 kg received 2.5 mg of oxybutynin (once daily in the evening) for 7 days, then the dose was increased to 2.5 mg twice daily from day 7–21 and then to 5 mg twice daily from day 22 to the end of week 12. Patients weighing < 40 kg received the same treatment regimen for the first 3 weeks, but the dose was not increased after day 21. When there was severe side effects (especially dry mouth), the final dose was decreased by 2.5 mg.

Topical ACH (20% solution) was applied to a completely dry palm skin at night (when sweating is diminished) for six to eight hours before being washed off and was repeated every 24 to 48 hours until anhidrosis is attained. Occlusion with gloves or plastic film enhances penetration of the drug. Application was repeated for three to five consecutive nights, then one to two times a week as needed to control sweating.

HDSS was used as a primary outcome measure to assess the efficacy of the drug in both groups. A 1-point HDSS score improvement has been shown to correlate with a 50% sweat reduction. An improvement of 2 points corresponds to an 80% sweat reduction.[12] Clinical grading and the QOL were used as secondary outcome measures. The safety was evaluated by recording side effects in the follow-up visits.

Data were analyzed using IBM SPSS software package version 22.0. Categorical variables were presented as number and percent. Chi-square or Fisher's exact was used for significance testing; as appropriate. Quantitative variables were tested for normality using Shapiro test. Non-parametric variables were presented as median (minimum-maximum) and Mann–Whitney test was used for significance testing. Normally distributed variables were presented as mean ± SD and unpaired t test was used for testing significance between the two groups. A value of P ≤ 0.001 was considered statistically significant.


   Results Top


[Table 1] shows that the two groups were matched in age, sex, occupation, disease duration and the clinical grades before treatment [Figure 1]a, [Figure 1]b, [Figure 2]a, [Figure 3]a, [Figure 4]a, [Figure 5]a. However after treatment [Figure 1]c, [Figure 1]d, [Figure 2]b, [Figure 3]b, [Figure 4]b, [Figure 5]b, the minimal moisture grade was statistically significant in the oral oxybutynin group than topical ACH group (52.5 vs. 17.5, P = 0.002).
Figure 1: Case 5, a 17-year-old female with grade III/severe hyperhidrosis with formation of visible sweat droplets on the palmar (a) and dorsal (b) surfaces of the hand. Three months after oxybutynin therapy with minimal moisture on the palmar (c) and dorsal (d) surfaces

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Figure 2: Case 9, a 15-year-old female with grade II/moderate hyperhidrosis with formation of visible sweat droplets on the palmar surface only (a). Three months after topical treatment with aluminum chloride hexahydrate (ACH) with mild hyperhidrosis and significantly increased skin moisture (b)

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Figure 3: Case 14, a 14-year-old female with grade II/moderate hyperhidrosis with formation of visible sweat droplets which is limited to palmar surface only (a). Three months after oxybutynin therapy with minimal moisture (b)

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Figure 4: Case 31, a 14-year-old female with grade II/moderate hyperhidrosis with formation of visible sweat droplets which is limited to palmar surface only (a). Three months after oxybutynin therapy with mild hyperhidrosis and significantly increased skin moisture (b)

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Figure 5: Case 36, a 16-year-old female with grade II/moderate hyperhidrosis with formation of visible sweat droplets which is limited to palmar surface only (a). Three months after topical treatment with aluminum chloride hexahydrate (ACH) with mild hyperhidrosis (b)

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Table 1: Demographic and clinical data of both groups

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[Table 2] shows that both groups were matched in HDSS and QOL at the start of treatment. However, both of them showed a statistically significant improvement in the oral oxybutynin groups. One week after stoppage of treatment, the symptoms recurred again in both groups with return of HDSS and QOL scores to their pretreatment levels with no statistically significant difference between both groups.
Table 2: HDSS, improvement and quality of life in both groups

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The most common side effects with oral oxybutynin were dry mouth (65.8%), nausea (27.5%), headache (20.0%) and dizziness (2.5%) while in topical ACH group, there were itching (65.0%), burning sensation (56.5%) and skin irritation (32.5%).


   Discussion Top


Primary palmar hyperhidrosis symptoms most frequently start during childhood and most patients who seek treatment are young adults.[16] In 2013, Wolosker and his colleges[17] reported in their study that most of their patients were in the initial twenties. In this study, the mean age of patients was 15.37 ± 4.04 and 14.70 ± 3.49 years for oral oxybutynin and topical ACH groups; respectively.

Females represented 56.7% of patients indicating a slight female predominance and this agrees with previous studies.[11],[18],[19],[20] The predominance of females in the different studies, including our study, could be possibly explained as this type of excessive sweating represents a significant problem in a girl's daily life, motivating a search for a treatment.[21]

In practice, the challenge remains to evaluate the severity of hyperhidrosis to achieve the best therapeutic outcome[12] and many studies stated that this can be done most effectively using the HDSS and QOL questionnaire scores.[15],[22] We evaluated our patients using both scores. In addition, we used the clinical grading as an outcome measure in which we considered the minimal moisture as a near-normal state and also all patients showed an improvement.

In this study, HDSS improved at least one point in all patients received oxybutynin and this is considered much more better than the results of other studies which reported improvement in more than 80% of individuals in one study[23] and 60% in another study.[20] HDSS improvement with oxybutynin therapy was documented also in special population groups such as children,[23] obese[17] and postmenopausal women.[24]

QOL improved in 97.5% of patients received oxybutynin and this is also considered much more better than the results of other studies which reported improvement in more than 74.1%,[23] 70%[25] and more than 85%[22] of individuals. Similar improvement in QOL was reported by other investigators using oral oxybutynin in treatment of focal or generalized hyperhidrosis.[14],[20],[26],[27]

Topical ACH showed inferior results to those of oxybutynin; five cases (12.5%) showed no improvement in HDSS score and 10 cases (25%) with “no difference” of QOL than before treatment. However, many studies recommend it as a first line treatment for all mild forms of primary focal hyperhidrosis because of its efficacy, low cost and convenience.[28],[29],[30]

HDSS and QOL scores deteriorated in both groups after stoppage of treatment and returned back to their pre-treatment levels. This may be related to the frustration felt by the patient due to recurrence of symptoms after stoppage of treatment. This is why palmar hyperhidrosis should be considered as a chronic disease and patients should continue and adhere to the treatment regimens.

The reported side effects in oxybutynin group were consistent with the results of many studies.[11],[20],[24],[31] Similar to our study, several studies also reported that patients continue treatment with oxybutynin in spite of these side effects.[20],[24],[31],[32] However, in their study, Cruddas and Baker reported that 10% of patients stopped taking oxybutynin because of adverse effects.[33]

As most treatment recommendations are based on expert consensus, because the evidence is poor (e.g., few study participants, nonrandomized trials, often not based on prospective trials),[10] we recommend treatment of primary palmar hyperhidrosis with oxybutynin as a good initial alternative for treatment given that it gives good results and improves QOL with minimal side effects and a relatively low cost and this was also recommended by many authors.[23],[25] Topical treatment can be considered as a first line treatment for mild cases who do not wish any systemic treatments.

Oral oxybutynin should also be considered as a possible first-line occasional or episodic treatment (instead of topical treatment) for patients with primary palmar hyperhidrosis, for example when hyperhidrosis may be less tolerable, such as before a social or work event, before exams, or at certain times of the year.

One limitation of this study is the inevitable unblinding in both groups, due to the obvious side effects of the medications.


   Conclusion Top


Treatment of primary palmar hyperhidrosis with oxybutynin is a good initial alternative for treatment given that it gives better results and much more improvement in QOL when compared to topical ACH. QOL questionnaire and clinical grading should also be considered as useful tools in the assessment of response to treatment.

Ethical approval

Our institutional review board (IRB) approved the study [IRB code: MS/16.04.71].

Informed consent

Informed consent was obtained from all the patients or their legal guardians.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Wolosker N, Teivelis MP, Krutman M, de Paula RP, Kauffman P, de Campos JR, et al. Long-term results of the use of oxybutynin for the treatment of plantar hyperhidrosis. Int J Dermatol 2015;54:605-11.  Back to cited text no. 15
    
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Kalantari KK, Zeinalzade A, Kobarfard F, Nazary Moghadam S. The effect and persistency of 1% aluminum chloride hexahydrate iontophoresis in the treatment of primary palmar hyperhidrosis. Iran J Pharm Res 2011;10:641-5.  Back to cited text no. 28
    
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32.
Costa Ads S Jr, Leão LE, Succi JE, Perfeito JA, Filho Castelo A, Rymkiewicz E, et al. Randomized trial-Oxybutynin for treatment of persistent plantar hyperhidrosis in women after sympathectomy. Clinics 2014;69:101-5.  Back to cited text no. 32
    
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Cruddas L, Baker DM. Treatment of primary hyperhidrosis with oral anticholinergic medications: A systematic review. J Eur Acad Dermatol Venereol 2017;31:952-63.  Back to cited text no. 33
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

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