- Email: [email protected]
Methotrexate for the treatment of generalized lichen planus
164 Letters
J AM ACAD DERMATOL JANUARY 2009
Melanoidins-sunscreens: Dihydroxyacetone with or without naphthoquinones To the Editor: Howe, Reed, and Dellavalle1 noted the use of topical dihydroxyacetone (DHA) to form a melanoidins-sunscreen with ultraviolet A (UVA) protection. The last sentence of their letter, which citied two references (DeLeo2 and Fusaro and Rice3) with respect to sunlight protection from melanoidins, implied that the melanoidins referred to in each reference are functionally protective equivalents. The former2 refers to a DHA Maillard reaction that chemically creates an amorphous melanoidins with some significant UVA protection but with minimal ultraviolet B (sun protection factor 3 or 4)4 protection. The latter3 refers to the naphthoquinone modified DHA Maillard reaction that creates a different amorphous melanoidins-sunscreen that gives total UVA/Soret band protection without any protection failures for photosensitive patients; however, the majority of the patients3 had been exposed to sunlight all day for several months and achieved ultraviolet B protection (a sun protection factor of [18). In vitro light transmission studies using human keratin sheets treated separately with DHA, naphthoquinone, and an instant mixture of both verified that the mixture produced a different melanoidins-sunscreen with superior broad photoprotection across the whole ultraviolet/Soret band spectrum.3
RESEARCH Methotrexate for the treatment of generalized lichen planus To the Editor: Topical treatment is impractical and patient compliance is usually poor for patients with generalized lichen planus (LP). We investigated the efficacy and safety of oral methotrexate (MTX) therapy for generalized LP. The Ethics Committee of the Uludag University Medical Faculty approved this retrospective study. Eleven patients (8 women and 3 men) with clinical and histologically proven generalized LP who had been referred to our department between 2001 and 2005 and received oral MTX therapy were included (Fig 1, A). Clinical data were collected from the medical reports. Previously recorded clinical photographs were also collected. The age of patients ranged from 27 to 55 years (mean, 44.2 yrs). The mean duration of the disease was 6.3 months (range,
Ramon M. Fusaro, MD, PhD Departments of Pharmacy Science and Preventive Medicine and Public Health, Colleges of Pharmacy and Medicine, Creighton University, Omaha, Nebraska Funding sources: None. Conflicts of interest: None declared. Reprint requests: Ramon M. Fusaro, MD, PhD, Departments of Pharmacy Science and Preventive Medicine and Public Health, Colleges of Pharmacy and Medicine, Creighton University, 2500 California Plaza, Omaha, NE 68178 E-mail: [email protected]
REFERENCES 1. Howe W, Reed B, Dellavalle RP. Adding over-the-counter dihydroxyacetone self-tanners to sunscreen regimens to increase ultraviolet A light protection. J Am Acad Dermatol 2008;58:894. 2. DeLeo V. Sunscreen use in photodermatoses. Dermatol Clin 2006;24:27-33. 3. Fusaro RM, Rice EG. The Maillard reaction for sunlight protection. Ann N Y Acad Sci 2005;1043:174-83. 4. Draelos ZD. Self tanning lotions: are they a healthy way to achieve a tan? Am J Clin Dermatol 2002;3:317-8.
doi:10.1016/j.jaad.2008.09.030
LETTERS 2-24 mos). Two patients had typical oral mucosal involvement. There was no scalp, genital, or nail involvement. All patients had a history of topical or systemic corticosteroid therapy that failed to control the disease. Demographic characteristics of the patients are shown in Table I. The patients were screened for hepatitis serology and the other hepatic diseases before initiation of MTX. A ‘‘complete response’’ was considered as the complete resolution of pruritus and the disappearance of cutaneous lesions. A ‘‘partial response’’ was considered as more than 50% improvement, and ‘‘no response’’ was defined as less than 50% clearance of cutaneous lesions and relief of pruritus. MTX was initiated at a single oral dose of 15 mg/week in four patients and 20 mg/week in seven patients. Improvement of mucocutaneous lesions and pruritus was noted within the first month in all patients. Complete response was achieved in
Letters 165
J AM ACAD DERMATOL VOLUME 60, NUMBER 1
Fig 1. Clinical appearance before (A) and after (B) methotrexate therapy.
Table I. Demographic characteristics and follow-up data of patients with generalized lichen planus treated with methotrexate Duration of disease before Patient Sex/age, treatment, Extracutaneous mo involvement no. y
1 2 3 4 5
F/54 M/38 F/41 F/41 F/46
2 3 2 24 2
— — — — —
6 7 8
M/55 F/49 M/37
12 8 3
Oral — Oral
9
F/27
3
—
10
F/57
5
—
11
F/42
6
—
Previous treatment
Duration Total of Initial dose of methotrexate, treatment, dosage, mg wk mg/wk
Adverse effects
Relapse after discontinuing treatment
Status at the end of treatment
Topical CS Topical CS Topical CS Topical CS Systemic CS Topical CS Topical CS Systemic CS
15 20 15 15 20
14 8 13 5 10
150 135 110 65 140
— — — — —
— — — — —
Complete Complete Complete Complete Complete
15 20 20
15 9 4
165 120 80
— — —
Complete Complete —
Systemic CS Systemic CS Topical CS
20
6
110
— — Nausea and fatigue —
—
Complete
20
14
175
—
—
Complete
20
8
115
—
2.5 mo
Complete
CS, Corticosteroid; F, female; M, male.
10 patients at the end of the first month, and the dosage of MTX was then decreased gradually (Fig 1, B). One patient discontinued MTX because of intolerable adverse effects (nausea and fatigue) at the fourth week. The therapy was well tolerated without any adverse effects or laboratory abnormalities in 10 patients. Patients received MTX therapy for 5 to 15 weeks (median, 9.6 wks) with a cumulative dose between
65 and 260 mg. During the follow-up period of 6 months, one patient had a recurrence after 2.5 months (Table I). There are no large controlled studies assessing the efficacy and safety of systemic treatment alternatives for generalized LP. Only systemic corticosteroids have been widely used and are usually found to be effective, but prolonged use often results in serious side effects.1
166 Letters
J AM ACAD DERMATOL JANUARY 2009
The efficacy of MTX is mainly related to its effect on epidermal cell proliferation. However, in vitro studies demonstrate that MTX has a more significant effect on lymphoid cells.2 Nylander Lundqvist et al3 treated four patients with erosive LP with MTX (10-15 mg/wk) in combination of topical corticosteroids for 17 months and concluded that MTX was a well tolerated and effective treatment for severe erosive LP. To our knowledge, no clinical trials for MTX in generalized LP have been reported previously. The results of this small retrospective case series suggest that use of weekly oral MTX can be a highly effective and tolerable treatment alternative to systemic corticosteroids. Larger prospective controlled trials are needed to establish the optimal dosage and duration of MTX therapy for generalized LP. Hakan Turan, MD, Emel Bulbul Baskan, MD, Sukran Tunali, MD, Serkan Yazici, MD, and Hayriye Saricaoglu, MD Department of Dermatology, Uludag University Medical Faculty, Bursa, Turkey Funding sources: None. Conflicts of interest: None declared. Correspondence to: Hakan Turan, MD, Department of Dermatology, Uludag University Medical Faculty, Gorukle 16059, Bursa, Turkey E-mail: [email protected] REFERENCES 1. Gallant C, Kenny P. Oral glucocorticoids and their complications. A review. J Am Acad Dermatol 1986;14(2 pt 1):161-77. 2. Jeffes EW 3rd, McCullough JL, Pittelkow MR, McCormick A, Almanzor J, Liu G, et al. Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to cytotoxic and growth inhibitory effects of methotrexate. J Invest Dermatol 1995;104:183-8. 3. Nylander Lundqvist E, Wahlin YB, Hofer PA. Methotrexate supplemented with steroid ointments for the treatment of severe erosive lichen ruber. Acta Derm Venereol 2002;82: 63-64. doi:10.1016/j.jaad.2008.09.054
Adherence to topical hydrocortisone 17-butyrate 0.1% in different vehicles in adults with atopic dermatitis To the Editor: Adherence to topical therapy is poor in pediatric atopic dermatitis (AD) patients but not well characterized in adults.1 Topical medications are available in a variety of vehicles, and patients
have varying preferences among vehicles.2,3 The goal of this study was to assess adherence in adults with AD to a single topical agent in three different vehicles. Methods. Following institutional review board approval, 25 subjects (age $ 18 yrs) with mild to moderate AD (Investigators Global Assessment [IGA], 2 or 3 out of 5; body surface area, 5-30%) were randomized to receive twice daily hydrocortisone 17-butyrate 0.1% (Locoid; Ferndale Laboratories, Ferndale, MI) in one of three vehicles: cream, lipocream, or ointment. Adherence was monitored electronically (MEMS; Aardex Corp, Fremont, CA). Disease severity was evaluated at baseline and week 2 using the Eczema Area Severity Index (EASI), IGA, and target lesion assessments (TLA). Mean change in IGA, EASI, and target lesion scores from baseline to week 2 were compared using t tests. Kruskal-Wallis and analysis of variance tests were performed to compare outcomes across vehicles. The relationship between adherence and treatment group was tested using a mixed model adjusting for within patient correlation. Results. Twenty subjects 19 to 74 years of age completed the study (Fig 1). Overall adherence across all subjects was 70% (standard deviation 5 0.23). Mean adherence was not statistically different between the three vehicle groups (F test; P 5 .39). Mean IGA, EASI, and target lesion assessment scores significantly improved in all three groups after 2 weeks of treatment (Table I). The ointment group had a larger improvement in IGA, EASI, and TLA than the other vehicles; however, this difference was only significant between ointment and cream for improvement in IGA mean scores (P 5 .05). There were no reported adverse events related to the medication. Discussion. The major finding in this small study is the tremendous variation in use between different individuals. Patients took medications inconsistently, frequently missing doses. Some used the medication more than twice per day. However, nearly all patients reported near perfect usage of the medication. Physicians should expect their patients to misuse topical medications regardless of what they report. Differences in both mean adherence and mean outcomes between vehicle groups were insignificant, perhaps because of the small study size. We had hoped that outcome would not effect adherence over the short study interval, but the rapidity of action of hydrocortisone 17-butyrate 0.1% on AD is so fast that improvement in the disease complicates studies of adherence even over just 2 weeks.
J AM ACAD DERMATOL JANUARY 2009
Melanoidins-sunscreens: Dihydroxyacetone with or without naphthoquinones To the Editor: Howe, Reed, and Dellavalle1 noted the use of topical dihydroxyacetone (DHA) to form a melanoidins-sunscreen with ultraviolet A (UVA) protection. The last sentence of their letter, which citied two references (DeLeo2 and Fusaro and Rice3) with respect to sunlight protection from melanoidins, implied that the melanoidins referred to in each reference are functionally protective equivalents. The former2 refers to a DHA Maillard reaction that chemically creates an amorphous melanoidins with some significant UVA protection but with minimal ultraviolet B (sun protection factor 3 or 4)4 protection. The latter3 refers to the naphthoquinone modified DHA Maillard reaction that creates a different amorphous melanoidins-sunscreen that gives total UVA/Soret band protection without any protection failures for photosensitive patients; however, the majority of the patients3 had been exposed to sunlight all day for several months and achieved ultraviolet B protection (a sun protection factor of [18). In vitro light transmission studies using human keratin sheets treated separately with DHA, naphthoquinone, and an instant mixture of both verified that the mixture produced a different melanoidins-sunscreen with superior broad photoprotection across the whole ultraviolet/Soret band spectrum.3
RESEARCH Methotrexate for the treatment of generalized lichen planus To the Editor: Topical treatment is impractical and patient compliance is usually poor for patients with generalized lichen planus (LP). We investigated the efficacy and safety of oral methotrexate (MTX) therapy for generalized LP. The Ethics Committee of the Uludag University Medical Faculty approved this retrospective study. Eleven patients (8 women and 3 men) with clinical and histologically proven generalized LP who had been referred to our department between 2001 and 2005 and received oral MTX therapy were included (Fig 1, A). Clinical data were collected from the medical reports. Previously recorded clinical photographs were also collected. The age of patients ranged from 27 to 55 years (mean, 44.2 yrs). The mean duration of the disease was 6.3 months (range,
Ramon M. Fusaro, MD, PhD Departments of Pharmacy Science and Preventive Medicine and Public Health, Colleges of Pharmacy and Medicine, Creighton University, Omaha, Nebraska Funding sources: None. Conflicts of interest: None declared. Reprint requests: Ramon M. Fusaro, MD, PhD, Departments of Pharmacy Science and Preventive Medicine and Public Health, Colleges of Pharmacy and Medicine, Creighton University, 2500 California Plaza, Omaha, NE 68178 E-mail: [email protected]
REFERENCES 1. Howe W, Reed B, Dellavalle RP. Adding over-the-counter dihydroxyacetone self-tanners to sunscreen regimens to increase ultraviolet A light protection. J Am Acad Dermatol 2008;58:894. 2. DeLeo V. Sunscreen use in photodermatoses. Dermatol Clin 2006;24:27-33. 3. Fusaro RM, Rice EG. The Maillard reaction for sunlight protection. Ann N Y Acad Sci 2005;1043:174-83. 4. Draelos ZD. Self tanning lotions: are they a healthy way to achieve a tan? Am J Clin Dermatol 2002;3:317-8.
doi:10.1016/j.jaad.2008.09.030
LETTERS 2-24 mos). Two patients had typical oral mucosal involvement. There was no scalp, genital, or nail involvement. All patients had a history of topical or systemic corticosteroid therapy that failed to control the disease. Demographic characteristics of the patients are shown in Table I. The patients were screened for hepatitis serology and the other hepatic diseases before initiation of MTX. A ‘‘complete response’’ was considered as the complete resolution of pruritus and the disappearance of cutaneous lesions. A ‘‘partial response’’ was considered as more than 50% improvement, and ‘‘no response’’ was defined as less than 50% clearance of cutaneous lesions and relief of pruritus. MTX was initiated at a single oral dose of 15 mg/week in four patients and 20 mg/week in seven patients. Improvement of mucocutaneous lesions and pruritus was noted within the first month in all patients. Complete response was achieved in
Letters 165
J AM ACAD DERMATOL VOLUME 60, NUMBER 1
Fig 1. Clinical appearance before (A) and after (B) methotrexate therapy.
Table I. Demographic characteristics and follow-up data of patients with generalized lichen planus treated with methotrexate Duration of disease before Patient Sex/age, treatment, Extracutaneous mo involvement no. y
1 2 3 4 5
F/54 M/38 F/41 F/41 F/46
2 3 2 24 2
— — — — —
6 7 8
M/55 F/49 M/37
12 8 3
Oral — Oral
9
F/27
3
—
10
F/57
5
—
11
F/42
6
—
Previous treatment
Duration Total of Initial dose of methotrexate, treatment, dosage, mg wk mg/wk
Adverse effects
Relapse after discontinuing treatment
Status at the end of treatment
Topical CS Topical CS Topical CS Topical CS Systemic CS Topical CS Topical CS Systemic CS
15 20 15 15 20
14 8 13 5 10
150 135 110 65 140
— — — — —
— — — — —
Complete Complete Complete Complete Complete
15 20 20
15 9 4
165 120 80
— — —
Complete Complete —
Systemic CS Systemic CS Topical CS
20
6
110
— — Nausea and fatigue —
—
Complete
20
14
175
—
—
Complete
20
8
115
—
2.5 mo
Complete
CS, Corticosteroid; F, female; M, male.
10 patients at the end of the first month, and the dosage of MTX was then decreased gradually (Fig 1, B). One patient discontinued MTX because of intolerable adverse effects (nausea and fatigue) at the fourth week. The therapy was well tolerated without any adverse effects or laboratory abnormalities in 10 patients. Patients received MTX therapy for 5 to 15 weeks (median, 9.6 wks) with a cumulative dose between
65 and 260 mg. During the follow-up period of 6 months, one patient had a recurrence after 2.5 months (Table I). There are no large controlled studies assessing the efficacy and safety of systemic treatment alternatives for generalized LP. Only systemic corticosteroids have been widely used and are usually found to be effective, but prolonged use often results in serious side effects.1
166 Letters
J AM ACAD DERMATOL JANUARY 2009
The efficacy of MTX is mainly related to its effect on epidermal cell proliferation. However, in vitro studies demonstrate that MTX has a more significant effect on lymphoid cells.2 Nylander Lundqvist et al3 treated four patients with erosive LP with MTX (10-15 mg/wk) in combination of topical corticosteroids for 17 months and concluded that MTX was a well tolerated and effective treatment for severe erosive LP. To our knowledge, no clinical trials for MTX in generalized LP have been reported previously. The results of this small retrospective case series suggest that use of weekly oral MTX can be a highly effective and tolerable treatment alternative to systemic corticosteroids. Larger prospective controlled trials are needed to establish the optimal dosage and duration of MTX therapy for generalized LP. Hakan Turan, MD, Emel Bulbul Baskan, MD, Sukran Tunali, MD, Serkan Yazici, MD, and Hayriye Saricaoglu, MD Department of Dermatology, Uludag University Medical Faculty, Bursa, Turkey Funding sources: None. Conflicts of interest: None declared. Correspondence to: Hakan Turan, MD, Department of Dermatology, Uludag University Medical Faculty, Gorukle 16059, Bursa, Turkey E-mail: [email protected] REFERENCES 1. Gallant C, Kenny P. Oral glucocorticoids and their complications. A review. J Am Acad Dermatol 1986;14(2 pt 1):161-77. 2. Jeffes EW 3rd, McCullough JL, Pittelkow MR, McCormick A, Almanzor J, Liu G, et al. Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to cytotoxic and growth inhibitory effects of methotrexate. J Invest Dermatol 1995;104:183-8. 3. Nylander Lundqvist E, Wahlin YB, Hofer PA. Methotrexate supplemented with steroid ointments for the treatment of severe erosive lichen ruber. Acta Derm Venereol 2002;82: 63-64. doi:10.1016/j.jaad.2008.09.054
Adherence to topical hydrocortisone 17-butyrate 0.1% in different vehicles in adults with atopic dermatitis To the Editor: Adherence to topical therapy is poor in pediatric atopic dermatitis (AD) patients but not well characterized in adults.1 Topical medications are available in a variety of vehicles, and patients
have varying preferences among vehicles.2,3 The goal of this study was to assess adherence in adults with AD to a single topical agent in three different vehicles. Methods. Following institutional review board approval, 25 subjects (age $ 18 yrs) with mild to moderate AD (Investigators Global Assessment [IGA], 2 or 3 out of 5; body surface area, 5-30%) were randomized to receive twice daily hydrocortisone 17-butyrate 0.1% (Locoid; Ferndale Laboratories, Ferndale, MI) in one of three vehicles: cream, lipocream, or ointment. Adherence was monitored electronically (MEMS; Aardex Corp, Fremont, CA). Disease severity was evaluated at baseline and week 2 using the Eczema Area Severity Index (EASI), IGA, and target lesion assessments (TLA). Mean change in IGA, EASI, and target lesion scores from baseline to week 2 were compared using t tests. Kruskal-Wallis and analysis of variance tests were performed to compare outcomes across vehicles. The relationship between adherence and treatment group was tested using a mixed model adjusting for within patient correlation. Results. Twenty subjects 19 to 74 years of age completed the study (Fig 1). Overall adherence across all subjects was 70% (standard deviation 5 0.23). Mean adherence was not statistically different between the three vehicle groups (F test; P 5 .39). Mean IGA, EASI, and target lesion assessment scores significantly improved in all three groups after 2 weeks of treatment (Table I). The ointment group had a larger improvement in IGA, EASI, and TLA than the other vehicles; however, this difference was only significant between ointment and cream for improvement in IGA mean scores (P 5 .05). There were no reported adverse events related to the medication. Discussion. The major finding in this small study is the tremendous variation in use between different individuals. Patients took medications inconsistently, frequently missing doses. Some used the medication more than twice per day. However, nearly all patients reported near perfect usage of the medication. Physicians should expect their patients to misuse topical medications regardless of what they report. Differences in both mean adherence and mean outcomes between vehicle groups were insignificant, perhaps because of the small study size. We had hoped that outcome would not effect adherence over the short study interval, but the rapidity of action of hydrocortisone 17-butyrate 0.1% on AD is so fast that improvement in the disease complicates studies of adherence even over just 2 weeks.