Pediatric Dermatology Vol. 31 No. 1 e28–e30, 2014
Oral Glycopyrrolate for Refractory Pediatric and Adolescent Hyperhidrosis Abstract: Primary hyperhidrosis is a common disorder affecting children and adolescents, and it can have a significant negative psychosocial effect. Treatment for pediatric hyperhidrosis tends to be limited by low efficacy, low adherence, and poor tolerance. Oral glycopyrrolate is emerging as a potential second-line treatment option, but experience with safety, efficacy, and dosing is especially limited in children. We present an institutional review of 12 children with severe, refractory hyperhidrosis treated with oral glycopyrrolate; 11 (92%) noted improvement and 9 (75%) would recommend oral glycopyrrolate to their friends. No significant side effects were noted. Our retrospective analysis suggests that oral glycopyrrolate is safe and effective in children with hyperhidrosis.
Primary hyperhidrosis affects 1.6% of adolescents and 0.6% of prepubertal children (1). Hyperhidrosis can severely affect quality of life and increase the risk of cutaneous infection (1–3). Conventional therapies, including topical aluminum chloride, iontophoresis, and botulinum toxin, may be irritating, painful, inconvenient, or ineffective. Recent reports suggest that oral glycopyrrolate, an anticholinergic agent, may be a second-line treatment for pediatric hyperhidrosis (3,4), but there have been few studies of oral glycopyrrolate for pediatric hyperhidrosis, and optimal dosing has not been established. We present an institutional review of children with hyperhidrosis treated with oral glycopyrrolate. RESULTS We performed a retrospective analysis of the efficacy and side effects of oral glycopyrrolate used for hyperhidrosis at a single pediatric center. After Institutional Review Board approval, patients were identified for the study. Those selected were younger
DOI: 10.1111/pde.12236
e28
than 18, had been identified by a board-certified pediatric dermatologist, and had an International Classification of Diseases, Ninth Revision, code for hyperhidrosis. Eighteen patients were prescribed oral glycopyrrolate from July 2009 to January 2012. All 18 patients met the criteria for primary hyperhidrosis and had failed topical aluminum chloride. Thirteen of the 18 patients completed a telephone interview and questionnaire. One of these patients never filled the prescription for glycopyrrolate because of fear of side effects. Eight girls and four boys completed the telephone questionnaire (Table 1). One or more of the palms, soles, and axillae were affected in the cohort. The average age at the time of therapy commencement was 14 years (range 11–17 yrs), and the average length of therapy was 18 months (range 1 wk–42 mos). The most common dosing regimen was 1 mg/day, although this varied as families adjusted the dose based on results and side effects. Overall, 11 patients (92%) had improvement, with 4 claiming major improvement. Patients who stopped treatment had limited benefit. Seven patients noted side effects, including dry mouth (n = 6), constipation (n = 1), dizziness (n = 1), and facial swelling (n = 1). Six patients (50%) were still taking oral glycopyrrolate at the time of the interview. Nine patients (75%) would recommend glycopyrrolate to others. DISCUSSION Therapeutic options are limited for hyperhidrosis in children and adolescents. Topical aluminum chloride is considered the first-line treatment, but is limited by local irritation and low adherence. Recently oral glycopyrrolate has been suggested as a second-line treatment based on 90% improvement in a series of 31 children, but evidence remains limited. Our study suggests high efficacy of oral glycopyrrolate in children (92%), similar to the study by Paller et al (3). Only one patient claimed no improvement after taking 0.5 mg nightly for 1 week. He stopped after 1 week because of dry mouth. Because the halflife of glycopyrrolate is 7 yrs
Lifelong
Daily
Daily
Daily
Daily
Daily
Daily
Frequency of HH
14 yrs
5–8 yrs
4 yrs
Lifelong
Years
2–3 yrs
Duration of HH (years)
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed; oxybutyninimprovement decreased with time AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
Previous treatment of HH
11
14
15
15
14
15
13
17
14
15
11
17
No
Yes
Yes
Yes
Yes
No
Yes
No
No
Yes
No
No
Still using oral glycopyrrolate
1/2 mg qd night
1 mg bid
1 mg qd
2 mg qd morning, 1 mg qd night 1 mg bid to tid
1 mg qd
1 mg qd to bid
1 mg qd
1 mg qd
1 mg qd
1 mg qd
1 mg qd to bid
Dose regimine
HH, hyperhidrosis; AlCl, aluminum chloride; qd, daily; bid, twice a day; tid, three times a day.
M
Gender
1
Patient
Location of HH
Age started oral glyco pyrrolate (years)
TABLE 1. Patient Demographics and Hyperhidrosis Treatment Profile
0.25
36
12
42
30
3
3
36
12
36
3
6
Length of therapy (mos)
None
Major
Major
Major
Major
Minor
Minor
Minor
Minor
Minor
Minor
Minor
Improvement
None
1/2 hour
Few hours
Unsure
1 hour
Hours
1–2 hour
45 minutes
1 hour
1–2 hour
1 hour
Hours
Time to improvement
Dry mouth
Dry mouth
None
None
None
Face swelling
None
Dry mouth
Dry mouth, dizzy for sports
Dry mouth, constipation Dry mouth
None
Side effects
No
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
No
Recommend to friend
Actually recommended to his friend
Noted decrease in sweating while on seroquel for schizoaffective disorder, but increased sweating after stopping that medication; sweating through clothes
Interfering with school work and social function Oxybutynin worked at first, but then minimal improvement Increasingly socially bothersome Sweat soaks through clothing regularly, embarrassing at school Bothersome with volleyball
Concomittantly on accutane for acne
Additional information
Brief Report e29
e30 Pediatric Dermatology Vol. 31 No. 1 January/February 2014
REFERENCES 1. Strutton DR, Kowalski JW, Glaser DA et al. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: results from a national survey. J Am Acad Dermatol 2004;51:241–248. 2. Walling HW. Primary hyperhidrosis increases the risk of cutaneous infection: a case-controlled study of 387 patients. J Am Acad Dermatol 2009;61:242–246. 3. Paller AS, Shah PR, Silverio AM et al. Oral glycopyrrolate as second-line treatment for primary pediatric hyperhidrosis. J Am Acad Dermatol 2012;67:918–923. 4. Walling HW. Systemic therapy for primary hyperhidrosis: a retrospective study of 59 patients treated with
glycopyrrolate or clonidine. J Am Acad Dermatol 2012;66:387–392. Monique G. Kumar, M.D. Rebecca S. Foreman, M.D. David R. Berk, M.D. Susan J. Bayliss, M.D. Division of Dermatology, Departments of Internal Medicine and Pediatrics, School of Medicine, Washington University and St. Louis Children’s Hospital, St. Louis, Missouri Address correspondence to Monique G. Kumar, M.D., Campus Box 8123, 4921 Parkview Place, St. Louis, MO 63110, or e-mail: [email protected].
Oral Glycopyrrolate for Refractory Pediatric and Adolescent Hyperhidrosis Abstract: Primary hyperhidrosis is a common disorder affecting children and adolescents, and it can have a significant negative psychosocial effect. Treatment for pediatric hyperhidrosis tends to be limited by low efficacy, low adherence, and poor tolerance. Oral glycopyrrolate is emerging as a potential second-line treatment option, but experience with safety, efficacy, and dosing is especially limited in children. We present an institutional review of 12 children with severe, refractory hyperhidrosis treated with oral glycopyrrolate; 11 (92%) noted improvement and 9 (75%) would recommend oral glycopyrrolate to their friends. No significant side effects were noted. Our retrospective analysis suggests that oral glycopyrrolate is safe and effective in children with hyperhidrosis.
Primary hyperhidrosis affects 1.6% of adolescents and 0.6% of prepubertal children (1). Hyperhidrosis can severely affect quality of life and increase the risk of cutaneous infection (1–3). Conventional therapies, including topical aluminum chloride, iontophoresis, and botulinum toxin, may be irritating, painful, inconvenient, or ineffective. Recent reports suggest that oral glycopyrrolate, an anticholinergic agent, may be a second-line treatment for pediatric hyperhidrosis (3,4), but there have been few studies of oral glycopyrrolate for pediatric hyperhidrosis, and optimal dosing has not been established. We present an institutional review of children with hyperhidrosis treated with oral glycopyrrolate. RESULTS We performed a retrospective analysis of the efficacy and side effects of oral glycopyrrolate used for hyperhidrosis at a single pediatric center. After Institutional Review Board approval, patients were identified for the study. Those selected were younger
DOI: 10.1111/pde.12236
e28
than 18, had been identified by a board-certified pediatric dermatologist, and had an International Classification of Diseases, Ninth Revision, code for hyperhidrosis. Eighteen patients were prescribed oral glycopyrrolate from July 2009 to January 2012. All 18 patients met the criteria for primary hyperhidrosis and had failed topical aluminum chloride. Thirteen of the 18 patients completed a telephone interview and questionnaire. One of these patients never filled the prescription for glycopyrrolate because of fear of side effects. Eight girls and four boys completed the telephone questionnaire (Table 1). One or more of the palms, soles, and axillae were affected in the cohort. The average age at the time of therapy commencement was 14 years (range 11–17 yrs), and the average length of therapy was 18 months (range 1 wk–42 mos). The most common dosing regimen was 1 mg/day, although this varied as families adjusted the dose based on results and side effects. Overall, 11 patients (92%) had improvement, with 4 claiming major improvement. Patients who stopped treatment had limited benefit. Seven patients noted side effects, including dry mouth (n = 6), constipation (n = 1), dizziness (n = 1), and facial swelling (n = 1). Six patients (50%) were still taking oral glycopyrrolate at the time of the interview. Nine patients (75%) would recommend glycopyrrolate to others. DISCUSSION Therapeutic options are limited for hyperhidrosis in children and adolescents. Topical aluminum chloride is considered the first-line treatment, but is limited by local irritation and low adherence. Recently oral glycopyrrolate has been suggested as a second-line treatment based on 90% improvement in a series of 31 children, but evidence remains limited. Our study suggests high efficacy of oral glycopyrrolate in children (92%), similar to the study by Paller et al (3). Only one patient claimed no improvement after taking 0.5 mg nightly for 1 week. He stopped after 1 week because of dry mouth. Because the halflife of glycopyrrolate is 7 yrs
Lifelong
Daily
Daily
Daily
Daily
Daily
Daily
Frequency of HH
14 yrs
5–8 yrs
4 yrs
Lifelong
Years
2–3 yrs
Duration of HH (years)
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed; oxybutyninimprovement decreased with time AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
AlCl, failed
Previous treatment of HH
11
14
15
15
14
15
13
17
14
15
11
17
No
Yes
Yes
Yes
Yes
No
Yes
No
No
Yes
No
No
Still using oral glycopyrrolate
1/2 mg qd night
1 mg bid
1 mg qd
2 mg qd morning, 1 mg qd night 1 mg bid to tid
1 mg qd
1 mg qd to bid
1 mg qd
1 mg qd
1 mg qd
1 mg qd
1 mg qd to bid
Dose regimine
HH, hyperhidrosis; AlCl, aluminum chloride; qd, daily; bid, twice a day; tid, three times a day.
M
Gender
1
Patient
Location of HH
Age started oral glyco pyrrolate (years)
TABLE 1. Patient Demographics and Hyperhidrosis Treatment Profile
0.25
36
12
42
30
3
3
36
12
36
3
6
Length of therapy (mos)
None
Major
Major
Major
Major
Minor
Minor
Minor
Minor
Minor
Minor
Minor
Improvement
None
1/2 hour
Few hours
Unsure
1 hour
Hours
1–2 hour
45 minutes
1 hour
1–2 hour
1 hour
Hours
Time to improvement
Dry mouth
Dry mouth
None
None
None
Face swelling
None
Dry mouth
Dry mouth, dizzy for sports
Dry mouth, constipation Dry mouth
None
Side effects
No
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
No
Recommend to friend
Actually recommended to his friend
Noted decrease in sweating while on seroquel for schizoaffective disorder, but increased sweating after stopping that medication; sweating through clothes
Interfering with school work and social function Oxybutynin worked at first, but then minimal improvement Increasingly socially bothersome Sweat soaks through clothing regularly, embarrassing at school Bothersome with volleyball
Concomittantly on accutane for acne
Additional information
Brief Report e29
e30 Pediatric Dermatology Vol. 31 No. 1 January/February 2014
REFERENCES 1. Strutton DR, Kowalski JW, Glaser DA et al. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: results from a national survey. J Am Acad Dermatol 2004;51:241–248. 2. Walling HW. Primary hyperhidrosis increases the risk of cutaneous infection: a case-controlled study of 387 patients. J Am Acad Dermatol 2009;61:242–246. 3. Paller AS, Shah PR, Silverio AM et al. Oral glycopyrrolate as second-line treatment for primary pediatric hyperhidrosis. J Am Acad Dermatol 2012;67:918–923. 4. Walling HW. Systemic therapy for primary hyperhidrosis: a retrospective study of 59 patients treated with
glycopyrrolate or clonidine. J Am Acad Dermatol 2012;66:387–392. Monique G. Kumar, M.D. Rebecca S. Foreman, M.D. David R. Berk, M.D. Susan J. Bayliss, M.D. Division of Dermatology, Departments of Internal Medicine and Pediatrics, School of Medicine, Washington University and St. Louis Children’s Hospital, St. Louis, Missouri Address correspondence to Monique G. Kumar, M.D., Campus Box 8123, 4921 Parkview Place, St. Louis, MO 63110, or e-mail: [email protected].
