Dermatologic Therapy, Vol. 27, 2014, 365–368 Printed in the United States · All rights reserved
© 2014 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY ISSN 1396-0296
THERAPEUTIC HOTLINE Remarkable improvement of relapsing dyshidrotic eczema after treatment of coexistant hyperhidrosis with oxybutynin Vasiliki Markantoni, Anargyros Kouris, Kalliopi Armyra, Charitomeni Vavouli & George Kontochristopoulos Department of Dermatology and Venereology, Hospital “Andreas Sygros”, Athens, Greece
ABSTRACT: Dyshidrotic hand eczema is a common condition, which can be resistant to various treatments. Although a number of etiologic factors are involved in the pathogenesis of dyshidrotic eczema, hyperhidrosis is assumed to play a significant role. Oxybutynin is an alternative treatment for hyperhidrosis. We present the cases of two patients suffering from hyperhidrosis and dyshidrotic eczema, who were treated with oxybutynin with impressive results. KEYWORDS: dyshidrotic eczema, hyperhidrosis, oxybutynin
Introduction Dyshidrotic eczema, also referred to as pompholyx, is a chronic, recurrent, vesicobullous skin disease affecting the palms and soles symmetrically (1). It is an intensely pruritic and often painful condition that can have a devastating effect on the quality of life (QOL) (1,2). Etiology is unclear, although it is considered to be a reaction, triggered by various endogenous and exogenous factors, such as emotional stress, smoking, seasonal changes, fungal infection, atopy, nickel allergy, hyperhidrosis, and intravenous immunoglobulin therapy (2). We present the cases of two patients suffering from primary focal hyperhidrosis and dyshidrotic eczema, both of whom were successfully treated Address correspondence and reprint requests to: Anargyros Kouris, MD, MSc, Resident, Department of Dermatology and Venereology, Hospital “Andreas Sygros”, Ionos Dragoumi 5, 16121 Athens, Greece, or email: [email protected].
with oxybutynin for their hyperhidrosis. Notably, in both patients, dyshidrotic eczema showed a marked improvement.
Report Two women aged 45 years and 21 years presented with a 30-year and 10-year history, respectively, of primary focal hyperhidrosis involving the palms, axillae, and soles. Clinical examination revealed erythema and intense pruritus with some painful vesicles, followed by erosions and fissures as they resolved (FIG. 1a,b). Both patients experienced frequent relapses during the summertime and when under stress. Moreover, they had not benefited from therapy over the past few years with topical class I or II corticosteroids and oral antihistamines. Patch tests for common allergens associated with hand dermatitis (3) (preservatives, fragrances, metals, rubber, antibiotics) were negative for the
365
Markantoni et al.
a
b
FIG. 2. Remarkable improvement of eczema and regression of hyperhidrosis 10 days after the treatment.
Table 1. Hyperhidrosis Disease Severity Scale (HDSS), Dyshidrotic Eczema Area and Severity Index (DASI), and Dermatology Life Quality Index (DLQI) before treatment with oxybutynin and after 2 months of treatment Patient 1 FIG. 1. Dyshidrotic hand eczema (a) and coexistant hyperhidrosis as depicted by the starch-iodine test (b) at initial examination.
first patient and nickel-positive for the second patient. Both patients displayed IgE antibodies within normal limits. The histological examination of both patients predominantly revealed spongiosis and intraepidermal vesicles that were indicative of dyshidrotic eczema. Our patients followed the same therapeutic protocol with oxybutynin per os for 2 months. They received 5 mg of oxybutynin twice a day for the first month and once a day for the second month. Both patients were assessed before and after the treatment for clinical improvement in palmar hyperhidrosis and dyshidrotic eczema, for any side effects, and the impact of these conditions on QOL. The Hyperhidrosis Disease Severity Scale (HDSS) was chosen to evaluate disease severity, based on the recommendations of the Canadian Hyperhidrosis Advisory Committee (4). Dyshidrotic Eczema Area and Severity Index (DASI) was chosen to evaluate the severity of dyshidrotic eczema (5). Finally, the patients completed the Dermatology Life Quality Index (DLQI) questionnaire (3).
366
Patient 2
Pretreatment Posttreatment Pretreatment Posttreatment
HDSS
DASI
DLQI
4 2 3 2
40 16 24 12
22 10 10 2
The patients reported a significant reduction in itch, erythema, vesicles, and hyperhidrosis from the third day of beginning therapy with oxybutynin (FIG. 2). A decrease in hyperhidrosis of approximately 90% was observed, as confirmed by the starch-iodine test. After 4 weeks, follow-up examination found no signs of relapse for either hyperhidrosis or eczema. The clinical improvement of both patients was sustained 2 months later, by which time patients were receiving half the dose of oxybutynin (5 mg once daily). The DLQI, DASI, and HDSS scores before and after 2 months treatment are shown in Table 1. Both patients experienced dry mouth; the first patient also reported mild urine retention. However, these side effects did not cause patients to discontinue the treatment. Moreover, the incidence of side effects was dramatically lower during the second month of treatment when the dose of oxybutynin was halved.
Dyshidrotic eczema treatment with oxybutynin
Discussion Dyshidrotic eczema is a pruritic, recurrent eruption of the hands and feet with unknown etiology. Due to the high density of eccrine sweat glands in the palm and sole, it was initially associated with hyperhidrosis (1). Particularly, dyshidrotic eczema was regarded as emerging from the excessive secretion of sweat and dilatation of the intraepidermal portion of the eccrine sweat ducts (2). This theory was doubted as there were reports describing the development of palmar and plantar vesicles independent of sweat glands. However, secondary pathological alterations, such as rupture of sweat ducts into the spongiotic vesicles, could be driven by inflammation of preexisting vesicles, hence justifying sweat as a possible aggravating factor in patients with pompholyx (6). In addition, a high palmoplantar perspiration rate has been suggested to result in a local concentration of metal salts that may provoke the vesicular reaction. Moreover, methods such as iontophoresis, sympathectomy, and intradermal BTX-A (7) have reduced sweat and also improved dyshidrotic eczema. Oxybutynin is an anticholinergic medication that competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor. It is widely used to relieve urinary and bladder difficulties, as it has a spasmolytic effect on the detrusor muscle of the bladder due to antagonism of the muscarine receptors (8). Although the sweat glands are innervated by sympathetic postganglionic nerve fibers, they use acetylcholine, the neurotransmitter that is generally used exclusively by parasympathetic nerves. Therefore, the anticholinergic properties of oxybutynin may be responsible for its effectiveness against excessive sweating. Different anticholinergic drugs were used to treat hyperhidrosis in the past, but their use did not become routine due to side effects. Patients receiving oxybutynin may experience side effects of variable severity, such as dry mouth (which is the most frequently observed), constipation, headache, and urine retention; however, with lower doses, the frequency and intensity of these side effects decreases (9). Low doses of oxybutynin over a long period of time seem to maintain sudoresis at low levels (10), even under stressful circumstances, and may thus prevent dyshidrotic eczema relapses. Perhaps long-term administration of oxybutynin reduces the secretion of inflammatory agents that contribute to the clinical manifestation of the disease (10). The drawbacks of con-
tinuous treatment with oxybutynin include low compliance of patients, who often refuse the instant use of the medication and possible side effects. Dyshidrotic hand eczema is a common condition, which can provoke resistant to various treatments. Primary focal hyperhidrosis also has high incidence and its debilitating effect on QOL has led to demands for effective treatment. Although a number of etiologic factors are involved in the pathogenesis of dyshidrotic eczema, hyperhidrosis is assumed to play a significant role. To our knowledge, this is the first report to demonstrate the effectiveness of oxybutynin not only in hyperhidrosis but also in pompholyx. Oxybutynin can be effective, safe, and simple treatment with only mild side effects. Consequently, we propose either continuous administration in cases of frequent relapses or occasional use in cases of exacerbation. Undoubtedly, it merits consideration as potential treatment for dyshidrotic eczema although further studies are warranted before definite conclusions can be drawn.
Conflict of interest Authors declare no conflict of interest.
References 1. Wollina U. Pompholyx: a review of clinical features, differential diagnosis, and management. Am J Clin Dermatol 2010: 11: 305–314. 2. Lodi A, Betti R, Chiarelli G, et al. Epidemiological, clinical and allergological observations on pompholyx. Contact Dermatitis 1992: 26: 17–21. 3. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical measure for routine clinical use. Clin Exp Dermatol 1994: 19: 210–216. 4. Solish N, Bertucci V, Dansereau A, et al. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. Dermatol Surg 2007: 33: 908–923. 5. Vocks E, Plotz SG, Ring S. The Dyshidrotic Eczema Area and Severity Index – a score developed for the assessment of dyshidrotic eczema. Dermatology 1999: 198: 265– 269. 6. Lee WJ, Lee DW, Kim CH, et al. Pompholyx with bilecoloured vesicles in a patient with jaundice: are sweat ducts involved in the development of pompholyx? J Eur Acad Dermatol Venereol 2010: 24: 235–236. 7. Kontochristopoulos G, Gregoriou S, Agiasofitou E, et al. Regression of relapsing dyshidrotic eczema after treatment of concomitant hyperhidrosis with botulinum toxin-A. Dermatol Surg 2007: 33: 1289–1290. 8. Arisco AM, Brantly EK, Kraus SR. Oxybutynin extended release for the management of overactive bladder:
367
Markantoni et al. a clinical review. Drug Des Devel Ther 2009: 3: 151– 161. 9. Wolosker N, Campos JR, Kauffman P, et al. The use of oxybutynin for treating facial hyperhidrosis. An Bras Dermatol 2011: 86: 451–456.
368
10. Maillard H, Fenot M, Bara C, Celerier P. Therapeutic value of moderate-dose oxybutynin in extensive hyperhidrosis. Ann Dermatol Venereol 2011: 138: 652–656.
© 2014 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY ISSN 1396-0296
THERAPEUTIC HOTLINE Remarkable improvement of relapsing dyshidrotic eczema after treatment of coexistant hyperhidrosis with oxybutynin Vasiliki Markantoni, Anargyros Kouris, Kalliopi Armyra, Charitomeni Vavouli & George Kontochristopoulos Department of Dermatology and Venereology, Hospital “Andreas Sygros”, Athens, Greece
ABSTRACT: Dyshidrotic hand eczema is a common condition, which can be resistant to various treatments. Although a number of etiologic factors are involved in the pathogenesis of dyshidrotic eczema, hyperhidrosis is assumed to play a significant role. Oxybutynin is an alternative treatment for hyperhidrosis. We present the cases of two patients suffering from hyperhidrosis and dyshidrotic eczema, who were treated with oxybutynin with impressive results. KEYWORDS: dyshidrotic eczema, hyperhidrosis, oxybutynin
Introduction Dyshidrotic eczema, also referred to as pompholyx, is a chronic, recurrent, vesicobullous skin disease affecting the palms and soles symmetrically (1). It is an intensely pruritic and often painful condition that can have a devastating effect on the quality of life (QOL) (1,2). Etiology is unclear, although it is considered to be a reaction, triggered by various endogenous and exogenous factors, such as emotional stress, smoking, seasonal changes, fungal infection, atopy, nickel allergy, hyperhidrosis, and intravenous immunoglobulin therapy (2). We present the cases of two patients suffering from primary focal hyperhidrosis and dyshidrotic eczema, both of whom were successfully treated Address correspondence and reprint requests to: Anargyros Kouris, MD, MSc, Resident, Department of Dermatology and Venereology, Hospital “Andreas Sygros”, Ionos Dragoumi 5, 16121 Athens, Greece, or email: [email protected].
with oxybutynin for their hyperhidrosis. Notably, in both patients, dyshidrotic eczema showed a marked improvement.
Report Two women aged 45 years and 21 years presented with a 30-year and 10-year history, respectively, of primary focal hyperhidrosis involving the palms, axillae, and soles. Clinical examination revealed erythema and intense pruritus with some painful vesicles, followed by erosions and fissures as they resolved (FIG. 1a,b). Both patients experienced frequent relapses during the summertime and when under stress. Moreover, they had not benefited from therapy over the past few years with topical class I or II corticosteroids and oral antihistamines. Patch tests for common allergens associated with hand dermatitis (3) (preservatives, fragrances, metals, rubber, antibiotics) were negative for the
365
Markantoni et al.
a
b
FIG. 2. Remarkable improvement of eczema and regression of hyperhidrosis 10 days after the treatment.
Table 1. Hyperhidrosis Disease Severity Scale (HDSS), Dyshidrotic Eczema Area and Severity Index (DASI), and Dermatology Life Quality Index (DLQI) before treatment with oxybutynin and after 2 months of treatment Patient 1 FIG. 1. Dyshidrotic hand eczema (a) and coexistant hyperhidrosis as depicted by the starch-iodine test (b) at initial examination.
first patient and nickel-positive for the second patient. Both patients displayed IgE antibodies within normal limits. The histological examination of both patients predominantly revealed spongiosis and intraepidermal vesicles that were indicative of dyshidrotic eczema. Our patients followed the same therapeutic protocol with oxybutynin per os for 2 months. They received 5 mg of oxybutynin twice a day for the first month and once a day for the second month. Both patients were assessed before and after the treatment for clinical improvement in palmar hyperhidrosis and dyshidrotic eczema, for any side effects, and the impact of these conditions on QOL. The Hyperhidrosis Disease Severity Scale (HDSS) was chosen to evaluate disease severity, based on the recommendations of the Canadian Hyperhidrosis Advisory Committee (4). Dyshidrotic Eczema Area and Severity Index (DASI) was chosen to evaluate the severity of dyshidrotic eczema (5). Finally, the patients completed the Dermatology Life Quality Index (DLQI) questionnaire (3).
366
Patient 2
Pretreatment Posttreatment Pretreatment Posttreatment
HDSS
DASI
DLQI
4 2 3 2
40 16 24 12
22 10 10 2
The patients reported a significant reduction in itch, erythema, vesicles, and hyperhidrosis from the third day of beginning therapy with oxybutynin (FIG. 2). A decrease in hyperhidrosis of approximately 90% was observed, as confirmed by the starch-iodine test. After 4 weeks, follow-up examination found no signs of relapse for either hyperhidrosis or eczema. The clinical improvement of both patients was sustained 2 months later, by which time patients were receiving half the dose of oxybutynin (5 mg once daily). The DLQI, DASI, and HDSS scores before and after 2 months treatment are shown in Table 1. Both patients experienced dry mouth; the first patient also reported mild urine retention. However, these side effects did not cause patients to discontinue the treatment. Moreover, the incidence of side effects was dramatically lower during the second month of treatment when the dose of oxybutynin was halved.
Dyshidrotic eczema treatment with oxybutynin
Discussion Dyshidrotic eczema is a pruritic, recurrent eruption of the hands and feet with unknown etiology. Due to the high density of eccrine sweat glands in the palm and sole, it was initially associated with hyperhidrosis (1). Particularly, dyshidrotic eczema was regarded as emerging from the excessive secretion of sweat and dilatation of the intraepidermal portion of the eccrine sweat ducts (2). This theory was doubted as there were reports describing the development of palmar and plantar vesicles independent of sweat glands. However, secondary pathological alterations, such as rupture of sweat ducts into the spongiotic vesicles, could be driven by inflammation of preexisting vesicles, hence justifying sweat as a possible aggravating factor in patients with pompholyx (6). In addition, a high palmoplantar perspiration rate has been suggested to result in a local concentration of metal salts that may provoke the vesicular reaction. Moreover, methods such as iontophoresis, sympathectomy, and intradermal BTX-A (7) have reduced sweat and also improved dyshidrotic eczema. Oxybutynin is an anticholinergic medication that competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor. It is widely used to relieve urinary and bladder difficulties, as it has a spasmolytic effect on the detrusor muscle of the bladder due to antagonism of the muscarine receptors (8). Although the sweat glands are innervated by sympathetic postganglionic nerve fibers, they use acetylcholine, the neurotransmitter that is generally used exclusively by parasympathetic nerves. Therefore, the anticholinergic properties of oxybutynin may be responsible for its effectiveness against excessive sweating. Different anticholinergic drugs were used to treat hyperhidrosis in the past, but their use did not become routine due to side effects. Patients receiving oxybutynin may experience side effects of variable severity, such as dry mouth (which is the most frequently observed), constipation, headache, and urine retention; however, with lower doses, the frequency and intensity of these side effects decreases (9). Low doses of oxybutynin over a long period of time seem to maintain sudoresis at low levels (10), even under stressful circumstances, and may thus prevent dyshidrotic eczema relapses. Perhaps long-term administration of oxybutynin reduces the secretion of inflammatory agents that contribute to the clinical manifestation of the disease (10). The drawbacks of con-
tinuous treatment with oxybutynin include low compliance of patients, who often refuse the instant use of the medication and possible side effects. Dyshidrotic hand eczema is a common condition, which can provoke resistant to various treatments. Primary focal hyperhidrosis also has high incidence and its debilitating effect on QOL has led to demands for effective treatment. Although a number of etiologic factors are involved in the pathogenesis of dyshidrotic eczema, hyperhidrosis is assumed to play a significant role. To our knowledge, this is the first report to demonstrate the effectiveness of oxybutynin not only in hyperhidrosis but also in pompholyx. Oxybutynin can be effective, safe, and simple treatment with only mild side effects. Consequently, we propose either continuous administration in cases of frequent relapses or occasional use in cases of exacerbation. Undoubtedly, it merits consideration as potential treatment for dyshidrotic eczema although further studies are warranted before definite conclusions can be drawn.
Conflict of interest Authors declare no conflict of interest.
References 1. Wollina U. Pompholyx: a review of clinical features, differential diagnosis, and management. Am J Clin Dermatol 2010: 11: 305–314. 2. Lodi A, Betti R, Chiarelli G, et al. Epidemiological, clinical and allergological observations on pompholyx. Contact Dermatitis 1992: 26: 17–21. 3. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical measure for routine clinical use. Clin Exp Dermatol 1994: 19: 210–216. 4. Solish N, Bertucci V, Dansereau A, et al. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. Dermatol Surg 2007: 33: 908–923. 5. Vocks E, Plotz SG, Ring S. The Dyshidrotic Eczema Area and Severity Index – a score developed for the assessment of dyshidrotic eczema. Dermatology 1999: 198: 265– 269. 6. Lee WJ, Lee DW, Kim CH, et al. Pompholyx with bilecoloured vesicles in a patient with jaundice: are sweat ducts involved in the development of pompholyx? J Eur Acad Dermatol Venereol 2010: 24: 235–236. 7. Kontochristopoulos G, Gregoriou S, Agiasofitou E, et al. Regression of relapsing dyshidrotic eczema after treatment of concomitant hyperhidrosis with botulinum toxin-A. Dermatol Surg 2007: 33: 1289–1290. 8. Arisco AM, Brantly EK, Kraus SR. Oxybutynin extended release for the management of overactive bladder:
367
Markantoni et al. a clinical review. Drug Des Devel Ther 2009: 3: 151– 161. 9. Wolosker N, Campos JR, Kauffman P, et al. The use of oxybutynin for treating facial hyperhidrosis. An Bras Dermatol 2011: 86: 451–456.
368
10. Maillard H, Fenot M, Bara C, Celerier P. Therapeutic value of moderate-dose oxybutynin in extensive hyperhidrosis. Ann Dermatol Venereol 2011: 138: 652–656.
