J AM ACAD DERMATOL
1016 Letters
Efficacy of oral retinoids in treatment-resistant lichen planopilaris To the Editor: Lichen planopilaris (LPP) is classified as a primary lymphocytic cicatricial alopecia.1 Topical and intralesional corticosteroids, oral tetracyclines, and oral hydroxychloroquine are considered by many as first-line agents in LPP followed by agents such as mycophenolate mofetil and cyclosporine1-3 Current literature suggests oral retinoids may benefit some patients with cutaneous lichen planus. However, the role of oral retinoids in treating LPP is unclear. Ethics board approval was obtained to retrospectively evaluate the effectiveness of oral retinoids in treating patients with LPP who failed or had an incomplete response to 1 or more first-line agents. Patients were from the University of Toronto Hair Clinic over the years 2009 through 2013. Response rates to retinoids were determined; secondary end points included time to response, side-effect profiles, and concomitant treatments. Of 189 patients evaluated with biopsy-proven LPP, 21 patients (17 female, 4 male) were prescribed treatment with oral retinoids after other treatments failed to halt disease progression (ie, incomplete response). Of the 21 patients, the mean age of disease onset was 47.3 years, whereas the mean duration of disease at the time of assessment was 8.8 years. During the course of therapy, 12 patients were treated with acitretin, 8 with isotretinoin, and 1 patient had a period of treatment with each drug (Table I). The vast majority of patients previously received or was receiving treatment with topical or injectable steroids, and other oral immunosuppressives/immunomodulators (Table I). Presence of 1 or more of the following criteria was used as an indicator of treatment response (clinical improvement): (1) improvement in erythema, scaling, or hyperkeratosis; or (2) cessation of hair shedding; or (3) conversion of individuals with a positive pull test result to a negative pull test result. Five of 21 (24%) of patients with treatment-resistant LPP were deemed to benefit from adjunctive oral retinoid therapy with an approximate time of 2 to 4 months to clinical improvement. Other concurrent treatments were maintained at the same dose or decreased after the addition of retinoids, which made it possible to attribute the clinical benefit to the retinoid therapy. Of the responders, 3 received acitretin, and 2 received isotretinoin. Notably, 4 of 5 responders had lichen planus at other body sites (Table I). The most common side effect of oral retinoid therapy reported within the study was dryness of the skin and mucosae (43%). Other side effects included hypercholesterolemia (14.2%), headaches (9.5%), and increased serum transaminases (4.7%).
NOVEMBER 2014
Only 3 of 5 responders ultimately remained on oral retinoids with a 13- to 18-month follow-up interval. The remaining 2 patients had discontinued oral retinoid therapy because of relapse and further progression of the disease. Overall, we found oral retinoid therapy to be a helpful adjunctive treatment in only a small proportion of those with treatment-resistant LPP. Our data series of 21 patients represents one of the largest to date to evaluate the role of oral retinoids in the treatment of LPP. A benefit of retinoid therapy was found in 2 of 3 patients reported by Spencer et al.4 In contrast, 6 patients reported by Assouly and Reygagne2 did not show improvement.2 Our study is limited by its retrospective nature. Furthermore, given that retinoid therapy is not a first-line treatment in our clinic setting, the study group is small despite the relatively large numbers of patients we evaluated with LPP during the study period. Further study is required to determine what factors contribute to the efficacy of retinoids in LPP. Frank Spano, MD,a and Jeff C. Donovan, MD, PhDa,b,c,d Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto,a Division of Dermatology, Department of Medicine, Women’s College Hospital,b Cleveland Clinic Canada,c and University of Toronto,d Ontario, Canada Funding sources: None. Conflicts of interest: None declared. Presented at the 88th Annual Meeting of the Canadian Dermatology Association Meeting, Quebec City, Quebec, Canada. June 27, 2013. Correspondence to: Jeff C. Donovan, MD, PhD, University of Toronto Hair Loss Clinic, Women’s College Hospital, 76 Grenville St, Fifth Floor, Toronto, Ontario, Canada M5S 1B2 E-mail: [email protected] REFERENCES 1. Kang H, Alzolibani AA, Otberg N, Shapiro J. Lichen planopilaris. Dermatol Ther 2008;21:249-56. 2. Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treatment. Semin Cutan Med Surg 2009;28:3-10. 3. Baibergenova A, Donovan J. Lichen planopilaris: update on pathogenesis and treatment. SkinMed 2013;11:161-5. 4. Spencer LA, Hawryluk EB, English JC III. Lichen planopilaris: retrospective study and stepwise therapeutic approach. Arch Dermatol 2009;145:333-4. http://dx.doi.org/10.1016/j.jaad.2014.06.013
J AM ACAD DERMATOL
Letters 1017
VOLUME 71, NUMBER 5
Table I. Summary of demographics, treatment regimen, and response
Patient
Age ( y), sex
Other sites LP
Previously ineffective treatments (duration in months)
1
43, M
None
HCQ (25) MMF (8) DOXY (7) CLOB (16) None
2
52, F
R hand, R shoulder, L leg
3
50, F
Nails
PIO (7)
4
58, F
Ears, nose, lip, nails
5
67, F
Axilla, legs, pubic
HCQ (21) DOXY (6) CsA (7) None
6
40, F
None
7
43, F
None
8
45, F
None
9
49, M
None
10
50, F
Oral, nail, legs
11
68, F
Oral
12
68, F
None
13
36, M
None
14
53, F
Vulvar
HCQ (17) DOXY (13) CLOB (19) DOXY (7) HCQ (24) CLOB (13) ILK (3) CLOB (13) ILK (3) DOXY (9) HCQ (22) MMF (4) TAC (7) DOXY (4) PRED (3) CLOB (22) ILK (13) DOXY (4) HCQ (15) MMF (7) ILK (11) HCQ (8) CLOB (22) ILK (15) DOXY (2) HCQ (16) MMF (3) CsA (4) ILK (2) DOXY (6) HCQ (16) CLOB (4) TAC (13) ILK (14) DOXY (8) HCQ (17) MMF (3)
Concurrent treatment before addition of retinoid (duration in months)
Specific retinoid added
Response to retinoid
PRED (5)
ISO
Clinical improvement at 2 mo; response maintained to 8 mo followed by relapse
CLOB (18) HCQ (16)
ISO
CLOB (22) TAC (12) HCQ (19) ILK (14) CLOB (25) Finasteride (54) HCQ (19) CLOB (24) MINOX (13) ILK (16) ILK (11) OCP (3 years)
ACI
Clinical improvement at 3.5 mo; response maintained to 15-mo follow-up Clinical improvement at 4 mo; response maintained to 18-mo follow-up Clinical improvement at 4 mo; response maintained to 6 mo followed by relapse Clinical improvement at 4 mo; response maintained to 13-mo follow-up
ACI
ACI
ISO
No response after 6 mo
OCP (3 years) TAC (8)
ISO
No response after 8 mo
None
ISO
No response after 5 mo
HCQ (23) ILK (9) CLOB (18) None
ISO
No response after 9 mo
ISO
No response after 6 mo
CLOB (14)
ISO
No response after 5 mo
None
ACI (3 mo) ISO (5 mo)
ACI not well tolerated and stopped at 3 mo No response after 5 mo ISO
CLOB (21)
ACI
No response after 7 mo
None
ACI
No response after 5 mo
Continued
J AM ACAD DERMATOL
1018 Letters
NOVEMBER 2014
Table I. Cont’d
Patient
Age ( y), sex
Other sites LP
Previously ineffective treatments (duration in months)
15
56, F
Oral, nails
CLOB (2) PRED (5)
16
59, F
None
17
61, F
L buccal mucosa
18
62, F
Arm, legs, oral
19
72, F
None
20
73, F
None
CLOB (3) ILK (15) DOXY (8) HCQ (22) CsA (4) CLOB (13) DOXY (1) HCQ (6) DOXY (13) HCQ (17) ILK (4) HCQ (16) MMF (7) HCQ (14)
21
74, F
None
DOXY (8) CLOB (24)
Concurrent treatment before addition of retinoid (duration in months)
Specific retinoid added
Response to retinoid
ACI
No response after 10 mo
ACI
No response after 4 mo; stopped because of increased lipids
ILK (33) PIO (6)
ACI
No response after 7 mo
ILK (22) CLOB (12) CLOB (26)
ACI
No response after 6 mo
ACI
No response after 9 mo
ACI
No response after 5 mo
ACI
No response after 8 mo
ILK (18) HCQ (16) FLUO (22) None
CLOB (17) ILK (9) ILK (31) HCQ (12)
ACI, Acitretin (25-50 mg orally daily); CLOB, topical clobetasol; CsA, cyclosporine (5 mg/kg); DOXY, doxycycline (100 mg orally twice a day); F, female; FLUO, topical fluocinolone acetonide oil; HCQ, hydroxychloroquine (400 mg orally daily, to maximum 6.5 mg/kg); ILK, intralesional triamcinolone acetonide (5 mg/mL) every 3-4 mo; ISO, isotretinoin (1 mg/kg); L, left; LP, lichen planus; M, male; MINOX, minoxidil 5% topical; MMF, mycophenolate mofetil (1000 mg orally twice a day); OCP, oral contraceptive; PIO, pioglitazone (15-30 mg orally daily); PRED, oral prednisone (0.5-1 mg/kg); R, right; TAC, topical tacrolimus.
Treatment of bullous pemphigoid with adjuvant immunoadsorption: A case series To the Editor: Immunoadsorption (IA) has been used as a rational, effective, and relatively safe treatment in different case series of patients with pemphigus, but has only been reported in individual patients with bullous pemphigoid (BP) so far.1 Because BP autoantibodies to the immunodominant domain of BP180 (BP180 NC16A) are known to correlate with disease severity, and pathogenicity of anti-BP180 autoantibodies has been clearly shown in different in vitro and in vivo models,2 autoantibody depletion by IA represents an attractive novel therapeutic principle for this disease. In this investigator-initiated, open-label pilot study, 7 patients (6 female, 1 male) with BP (based on both detection of linear deposits of IgG and/or C3 at the dermoepidermal junction along with circulating IgG autoantibodies against BP180 NC16A by direct immunofluorescence microscopy and enzyme-linked immunosorbent assay, respectively) aged between 75 and 94 (mean 82) years were enrolled. All had skin blistering covering more than 30% of body surface area and disease duration of 1 to 24 (mean 6) months.
Before study enrollment, 4 patients had failed to respond to standard treatment with prednisolone (20-90 mg/d) and topical clobetasol propionate partly in combination with dapsone or mycophenolate mofetil for 1 to 24 (mean 6) months. IA was chosen as first-line therapy in the remaining 3 patients as they showed a particularly high disease activity (ie, more widespread skin lesions). Protein A IA (Immunosorba, Fresenius Medical Care, Bad Homburg, Germany) was performed as described previously.3 Following a previously published protocol for the treatment of pemphigus,1,3 patients were treated by 3 IA on consecutive days. In each therapy session, a mean plasma volume of 203 mL/kg 1 body weight, representing 1.7 to 2.2 plasma volumes, was processed over approximately 4 hours. In addition, all patients received prednisolone 0.25 mg/kg/d, dapsone 1.0 to 1.5 mg/kg/d, and clobetasol propionate 0.05% ointment twice daily restricted to skin lesions, all of which was gradually tapered depending on disease activity. Although IA slightly changed plasma volume as a result of applied anticoagulant solutions, it did not require substitution of plasma components and therefore had no impact on dosages of any concomitant medication used.
1016 Letters
Efficacy of oral retinoids in treatment-resistant lichen planopilaris To the Editor: Lichen planopilaris (LPP) is classified as a primary lymphocytic cicatricial alopecia.1 Topical and intralesional corticosteroids, oral tetracyclines, and oral hydroxychloroquine are considered by many as first-line agents in LPP followed by agents such as mycophenolate mofetil and cyclosporine1-3 Current literature suggests oral retinoids may benefit some patients with cutaneous lichen planus. However, the role of oral retinoids in treating LPP is unclear. Ethics board approval was obtained to retrospectively evaluate the effectiveness of oral retinoids in treating patients with LPP who failed or had an incomplete response to 1 or more first-line agents. Patients were from the University of Toronto Hair Clinic over the years 2009 through 2013. Response rates to retinoids were determined; secondary end points included time to response, side-effect profiles, and concomitant treatments. Of 189 patients evaluated with biopsy-proven LPP, 21 patients (17 female, 4 male) were prescribed treatment with oral retinoids after other treatments failed to halt disease progression (ie, incomplete response). Of the 21 patients, the mean age of disease onset was 47.3 years, whereas the mean duration of disease at the time of assessment was 8.8 years. During the course of therapy, 12 patients were treated with acitretin, 8 with isotretinoin, and 1 patient had a period of treatment with each drug (Table I). The vast majority of patients previously received or was receiving treatment with topical or injectable steroids, and other oral immunosuppressives/immunomodulators (Table I). Presence of 1 or more of the following criteria was used as an indicator of treatment response (clinical improvement): (1) improvement in erythema, scaling, or hyperkeratosis; or (2) cessation of hair shedding; or (3) conversion of individuals with a positive pull test result to a negative pull test result. Five of 21 (24%) of patients with treatment-resistant LPP were deemed to benefit from adjunctive oral retinoid therapy with an approximate time of 2 to 4 months to clinical improvement. Other concurrent treatments were maintained at the same dose or decreased after the addition of retinoids, which made it possible to attribute the clinical benefit to the retinoid therapy. Of the responders, 3 received acitretin, and 2 received isotretinoin. Notably, 4 of 5 responders had lichen planus at other body sites (Table I). The most common side effect of oral retinoid therapy reported within the study was dryness of the skin and mucosae (43%). Other side effects included hypercholesterolemia (14.2%), headaches (9.5%), and increased serum transaminases (4.7%).
NOVEMBER 2014
Only 3 of 5 responders ultimately remained on oral retinoids with a 13- to 18-month follow-up interval. The remaining 2 patients had discontinued oral retinoid therapy because of relapse and further progression of the disease. Overall, we found oral retinoid therapy to be a helpful adjunctive treatment in only a small proportion of those with treatment-resistant LPP. Our data series of 21 patients represents one of the largest to date to evaluate the role of oral retinoids in the treatment of LPP. A benefit of retinoid therapy was found in 2 of 3 patients reported by Spencer et al.4 In contrast, 6 patients reported by Assouly and Reygagne2 did not show improvement.2 Our study is limited by its retrospective nature. Furthermore, given that retinoid therapy is not a first-line treatment in our clinic setting, the study group is small despite the relatively large numbers of patients we evaluated with LPP during the study period. Further study is required to determine what factors contribute to the efficacy of retinoids in LPP. Frank Spano, MD,a and Jeff C. Donovan, MD, PhDa,b,c,d Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto,a Division of Dermatology, Department of Medicine, Women’s College Hospital,b Cleveland Clinic Canada,c and University of Toronto,d Ontario, Canada Funding sources: None. Conflicts of interest: None declared. Presented at the 88th Annual Meeting of the Canadian Dermatology Association Meeting, Quebec City, Quebec, Canada. June 27, 2013. Correspondence to: Jeff C. Donovan, MD, PhD, University of Toronto Hair Loss Clinic, Women’s College Hospital, 76 Grenville St, Fifth Floor, Toronto, Ontario, Canada M5S 1B2 E-mail: [email protected] REFERENCES 1. Kang H, Alzolibani AA, Otberg N, Shapiro J. Lichen planopilaris. Dermatol Ther 2008;21:249-56. 2. Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treatment. Semin Cutan Med Surg 2009;28:3-10. 3. Baibergenova A, Donovan J. Lichen planopilaris: update on pathogenesis and treatment. SkinMed 2013;11:161-5. 4. Spencer LA, Hawryluk EB, English JC III. Lichen planopilaris: retrospective study and stepwise therapeutic approach. Arch Dermatol 2009;145:333-4. http://dx.doi.org/10.1016/j.jaad.2014.06.013
J AM ACAD DERMATOL
Letters 1017
VOLUME 71, NUMBER 5
Table I. Summary of demographics, treatment regimen, and response
Patient
Age ( y), sex
Other sites LP
Previously ineffective treatments (duration in months)
1
43, M
None
HCQ (25) MMF (8) DOXY (7) CLOB (16) None
2
52, F
R hand, R shoulder, L leg
3
50, F
Nails
PIO (7)
4
58, F
Ears, nose, lip, nails
5
67, F
Axilla, legs, pubic
HCQ (21) DOXY (6) CsA (7) None
6
40, F
None
7
43, F
None
8
45, F
None
9
49, M
None
10
50, F
Oral, nail, legs
11
68, F
Oral
12
68, F
None
13
36, M
None
14
53, F
Vulvar
HCQ (17) DOXY (13) CLOB (19) DOXY (7) HCQ (24) CLOB (13) ILK (3) CLOB (13) ILK (3) DOXY (9) HCQ (22) MMF (4) TAC (7) DOXY (4) PRED (3) CLOB (22) ILK (13) DOXY (4) HCQ (15) MMF (7) ILK (11) HCQ (8) CLOB (22) ILK (15) DOXY (2) HCQ (16) MMF (3) CsA (4) ILK (2) DOXY (6) HCQ (16) CLOB (4) TAC (13) ILK (14) DOXY (8) HCQ (17) MMF (3)
Concurrent treatment before addition of retinoid (duration in months)
Specific retinoid added
Response to retinoid
PRED (5)
ISO
Clinical improvement at 2 mo; response maintained to 8 mo followed by relapse
CLOB (18) HCQ (16)
ISO
CLOB (22) TAC (12) HCQ (19) ILK (14) CLOB (25) Finasteride (54) HCQ (19) CLOB (24) MINOX (13) ILK (16) ILK (11) OCP (3 years)
ACI
Clinical improvement at 3.5 mo; response maintained to 15-mo follow-up Clinical improvement at 4 mo; response maintained to 18-mo follow-up Clinical improvement at 4 mo; response maintained to 6 mo followed by relapse Clinical improvement at 4 mo; response maintained to 13-mo follow-up
ACI
ACI
ISO
No response after 6 mo
OCP (3 years) TAC (8)
ISO
No response after 8 mo
None
ISO
No response after 5 mo
HCQ (23) ILK (9) CLOB (18) None
ISO
No response after 9 mo
ISO
No response after 6 mo
CLOB (14)
ISO
No response after 5 mo
None
ACI (3 mo) ISO (5 mo)
ACI not well tolerated and stopped at 3 mo No response after 5 mo ISO
CLOB (21)
ACI
No response after 7 mo
None
ACI
No response after 5 mo
Continued
J AM ACAD DERMATOL
1018 Letters
NOVEMBER 2014
Table I. Cont’d
Patient
Age ( y), sex
Other sites LP
Previously ineffective treatments (duration in months)
15
56, F
Oral, nails
CLOB (2) PRED (5)
16
59, F
None
17
61, F
L buccal mucosa
18
62, F
Arm, legs, oral
19
72, F
None
20
73, F
None
CLOB (3) ILK (15) DOXY (8) HCQ (22) CsA (4) CLOB (13) DOXY (1) HCQ (6) DOXY (13) HCQ (17) ILK (4) HCQ (16) MMF (7) HCQ (14)
21
74, F
None
DOXY (8) CLOB (24)
Concurrent treatment before addition of retinoid (duration in months)
Specific retinoid added
Response to retinoid
ACI
No response after 10 mo
ACI
No response after 4 mo; stopped because of increased lipids
ILK (33) PIO (6)
ACI
No response after 7 mo
ILK (22) CLOB (12) CLOB (26)
ACI
No response after 6 mo
ACI
No response after 9 mo
ACI
No response after 5 mo
ACI
No response after 8 mo
ILK (18) HCQ (16) FLUO (22) None
CLOB (17) ILK (9) ILK (31) HCQ (12)
ACI, Acitretin (25-50 mg orally daily); CLOB, topical clobetasol; CsA, cyclosporine (5 mg/kg); DOXY, doxycycline (100 mg orally twice a day); F, female; FLUO, topical fluocinolone acetonide oil; HCQ, hydroxychloroquine (400 mg orally daily, to maximum 6.5 mg/kg); ILK, intralesional triamcinolone acetonide (5 mg/mL) every 3-4 mo; ISO, isotretinoin (1 mg/kg); L, left; LP, lichen planus; M, male; MINOX, minoxidil 5% topical; MMF, mycophenolate mofetil (1000 mg orally twice a day); OCP, oral contraceptive; PIO, pioglitazone (15-30 mg orally daily); PRED, oral prednisone (0.5-1 mg/kg); R, right; TAC, topical tacrolimus.
Treatment of bullous pemphigoid with adjuvant immunoadsorption: A case series To the Editor: Immunoadsorption (IA) has been used as a rational, effective, and relatively safe treatment in different case series of patients with pemphigus, but has only been reported in individual patients with bullous pemphigoid (BP) so far.1 Because BP autoantibodies to the immunodominant domain of BP180 (BP180 NC16A) are known to correlate with disease severity, and pathogenicity of anti-BP180 autoantibodies has been clearly shown in different in vitro and in vivo models,2 autoantibody depletion by IA represents an attractive novel therapeutic principle for this disease. In this investigator-initiated, open-label pilot study, 7 patients (6 female, 1 male) with BP (based on both detection of linear deposits of IgG and/or C3 at the dermoepidermal junction along with circulating IgG autoantibodies against BP180 NC16A by direct immunofluorescence microscopy and enzyme-linked immunosorbent assay, respectively) aged between 75 and 94 (mean 82) years were enrolled. All had skin blistering covering more than 30% of body surface area and disease duration of 1 to 24 (mean 6) months.
Before study enrollment, 4 patients had failed to respond to standard treatment with prednisolone (20-90 mg/d) and topical clobetasol propionate partly in combination with dapsone or mycophenolate mofetil for 1 to 24 (mean 6) months. IA was chosen as first-line therapy in the remaining 3 patients as they showed a particularly high disease activity (ie, more widespread skin lesions). Protein A IA (Immunosorba, Fresenius Medical Care, Bad Homburg, Germany) was performed as described previously.3 Following a previously published protocol for the treatment of pemphigus,1,3 patients were treated by 3 IA on consecutive days. In each therapy session, a mean plasma volume of 203 mL/kg 1 body weight, representing 1.7 to 2.2 plasma volumes, was processed over approximately 4 hours. In addition, all patients received prednisolone 0.25 mg/kg/d, dapsone 1.0 to 1.5 mg/kg/d, and clobetasol propionate 0.05% ointment twice daily restricted to skin lesions, all of which was gradually tapered depending on disease activity. Although IA slightly changed plasma volume as a result of applied anticoagulant solutions, it did not require substitution of plasma components and therefore had no impact on dosages of any concomitant medication used.
