J AM ACAD DERMATOL
594 Letters
SEPTEMBER 2014
slow disease progression (0.2-2.1 cm/annum) and spontaneous stabilization noted in untreated cases of this scarring alopecia, can the authors be certain that treatment is of significant benefit? A randomized control trial would be required to confirm treatment efficacy and in this context, a validated assessment tool would be of considerable benefit. Susan Holmes, MD, FRCP, and Alison MacDonald, MRCP Alan Lyell Center for Dermatology, Southern General Hospital, Glasgow, United Kingdom Funding sources: None. Conflicts of interest: None declared. Correspondence to: Susan Holmes, MD, FRCP, Alan Lyell Center for Dermatology, Southern General Hospital, 1345 Govan Rd, Glasgow G51 4TF, United Kingdom E-mail: [email protected] REFERENCES 1. Va~ no-Galvan S, Molina-Ruiz AM, Serrano-Falcon C, AriasSantiago S, Rodrigues Barata AR, Garnacho-Saucedo G, et al. Frontal fibrosing alopecia: a multicenter review of 355 patients. J Am Acad Dermatol 2014;70:670-8. 2. MacDonald A, Clark C, Holmes S. Frontal fibrosing alopecia: a review of 60 cases. J Am Acad Dermatol 2012;67:955-61. http://dx.doi.org/10.1016/j.jaad.2014.04.077
Reply to ‘Frontal fibrosing alopecia’ To the Editor: We have read the letter of Holmes and MacDonald and their interesting clarifications. We believe that a point-by-point response will be useful for the reader. Regarding the comment about the high prevalence of nonsmokers between patients with frontal fibrosing alopecia (FFA) in their study,1 it is important to clarify the discussion about this finding because it can lead to misinterpretation, as this comment is included in the ‘‘origin of FFA’’ section.1 Taking into account the findings of their1 and our2 studies, we agree with Holmes and MacDonald that smoking habit does not seem to act as a trigger nor seem to have a protective effect in patients given the diagnosis of FFA. Answering the query of the authors about disease pathogenesis, we suggest that the hormonal imbalance between estrogens and androgens may play an important role as a trigger of the scarring immunologic reaction, based on the high preponderance of postmenopausal women in patients with FFA, the relatively high incidence of early menopause women in our series, and in the apparent good response to
antiandrogenic drugs. However, we agree with the authors that this mechanism does not explain the appearance of FFA in premenopausal women nor in men. So, other yet unknown mechanisms and/or triggers are probable occurring in patients with FFA. Regarding the question about our scale of response to therapy, it is important to explain that in cases of improvement the regrowth of hair was minimal, and always located at the hairline, as we state in our publication. As limitations, our study2 had a retrospective design and it did not pretend to evaluate the response to treatment, only to have a general description of the usefulness of different therapies. In addition, it was difficult to differentiate in some cases between ‘‘stabilization’’ and ‘‘improvement.’’ However, all of these patients did not worsen, so this scale was useful to affirm that in these patients a specific treatment produced at least stabilization. On the other hand, the data of our study suggest that antiandrogenic drugs are useful in the treatment of FFA. In all, 111 of 355 patients (31%) received antiandrogens, with at least stabilization in all of them. Of this cohort of patients (data not shown in our previous article), 28 of 111 patients (25.2%) did not receive other treatment such as topical minoxidil or topical steroids. Stabilization and improvement was observed in 19 and 9 of these patients, respectively. No patients worsened. Therefore, antiandrogens seemed to play a role in at least stabilizing the recession of the hairline (main outcome measure of our study). Spontaneous stabilization of some of these patients could be possible, but its reported frequency is very low (6% in the 79 untreated patients of our series), so it is highly improbable that in all patients the stabilization would have been spontaneous. In addition, although response to antiandrogens was more frequent if androgenetic alopecia was present, it was also observed in patients without concomitant androgenetic alopecia (30 of 111 patients). Of these patients, finasteride or dutasteride was the only treatment in 10 (33%) of them. FFA is a fascinating entity with many yet unknown points, such as the exact pathogenesis or best treatment for all patients. We agree with Holmes and MacDonald that randomized controlled trials using a validated assessment tool would be the best evidenced-based way to confirm treatment efficacy. Meanwhile, the combination of antiandrogens and intralesional steroids seems to be the strategy that achieves higher proportions of stabilization in the published series.2-4 Sergio Va~ no-Galv an, MD, PhD,a Salvador AriasSantiago, MD, PhD,b and Francisco Camacho, MD, PhDc
J AM ACAD DERMATOL
Letters 595
VOLUME 71, NUMBER 3
Departments of Dermatology at Ram on y Cajal University Hospital, Madrida; Virgen de las Nieves University Hospital, Granadab; and Virgen Macarena University Hospital, Sevilla,c Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Salvador Arias-Santiago, MD, PhD, Dermatology Department, Virgen de las Nieves University Hospital, Av Fuerzas Armadas, Granada, Spain
REFERENCES 1. MacDonald A, Clark C, Holmes S. Frontal fibrosing alopecia: a review of 60 cases. J Am Acad Dermatol 2012;67:955-61. 2. Vano-Galvan S, Molina-Ruiz AM, Serrano-Falcon C, AriasSantiago S, Rodrigues Barata AR, Garnacho-Saucedo G, et al. Frontal fibrosing alopecia: a multicenter review of 355 patients. J Am Acad Dermatol 2014;70:670-8. 3. Ladizinski B, Bazakas A, Selim MA, Olsen EA. Frontal fibrosing alopecia: a retrospective review of 19 patients seen at Duke University. J Am Acad Dermatol 2013;68:749-55. 4. Banka N, Mubki T, Bunagan MJ, McElwee K, Shapiro J. Frontal fibrosing alopecia: a retrospective clinical review of 62 patients with treatment outcome and long-term follow-up. Int J Dermatol doi: 10.1111/ijd.12479. Published online April 16, 2014.
E-mail: [email protected]
http://dx.doi.org/10.1016/j.jaad.2014.05.049
RESEARCH
LETTERS
Clinical efficacy of diphenylcyclopropenone in alopecia areata: Retrospective data analysis of 50 patients
Table I. Demographic data and clinical characteristics
To the Editor: Topical immunomodulators hold promise for treatment of recalcitrant and extensive alopecia areata (AA).1 Diphenylcyclopropenone (DPCP) is the most common contact immunotherapeutic agent, but its use is currently limited by the need for in-office administration and lack of therapeutic dosing and duration guidelines. Also, there is a need to better characterize which patients will respond to DPCP.2,3 To explore these questions, we conducted an institutional review board-approved retrospective study of 50 randomly chosen AA patients who underwent DPCP therapy at the Cleveland Clinic Foundation from 1997 to 2012 (Table I). Patients were categorized into alopecia subtypes: patchy, ophiasis, alopecia totalis (AT), and alopecia universalis (AU). All patients had failed previous therapy with topical, intralesional, or oral steroids for at least 2 months. Minoxidil therapy initiated before DPCP therapy was continued (46% patients). Extent of hair loss was documented. The primary response goal was terminal hair regrowth of 50% or more. In our study, therapy was initiated in office by a nurse-administered challenge with 2% DPCP solution to a quarter-size area on the occipital scalp. Patients subsequently applied DPCP to the scalp twice weekly at home at increasing concentrations (0.001%, 0.01%, 0.02%, and so on), until a mild eczematous reaction was reached. Once cosmetically acceptable regrowth of scalp hair was achieved, DPCP therapy was not discontinued, but application frequency was decreased to once weekly and then twice monthly.
Patients Anergic patients (not assessed in further analysis) Gender (M/F) Race Caucasian Black Asian Age at disease onset ( years) Median Range Age at initiation of DPCP ( years) Median Range Disease duration before DPCP treatment ( years) Median Range DPCP treatment duration ( years) Median Range Alopecia areata subtype Patchy Totalis Universalis Ophiasis Comorbidities Thyroid dysfunction Atopy Anemia Polycystic ovarian syndrome Nail changes Body hair loss Family history Alopecia areata Autoimmune disease
Demographic data
DPCP, Diphenylcyclopropenone.
n (%)
50 1 14 (28)/36 (72) 46 (92) 3 (6) 1 (2) 21 3 to 59 37.5 10 to 61
5 2 months to 45 years 3 0.5-15 9 14 25 1
(18) (29) (51) (2)
25 27 14 3 10 35
(51) (55) (29) (6) (20) (71)
11 (22) 31 (63)
594 Letters
SEPTEMBER 2014
slow disease progression (0.2-2.1 cm/annum) and spontaneous stabilization noted in untreated cases of this scarring alopecia, can the authors be certain that treatment is of significant benefit? A randomized control trial would be required to confirm treatment efficacy and in this context, a validated assessment tool would be of considerable benefit. Susan Holmes, MD, FRCP, and Alison MacDonald, MRCP Alan Lyell Center for Dermatology, Southern General Hospital, Glasgow, United Kingdom Funding sources: None. Conflicts of interest: None declared. Correspondence to: Susan Holmes, MD, FRCP, Alan Lyell Center for Dermatology, Southern General Hospital, 1345 Govan Rd, Glasgow G51 4TF, United Kingdom E-mail: [email protected] REFERENCES 1. Va~ no-Galvan S, Molina-Ruiz AM, Serrano-Falcon C, AriasSantiago S, Rodrigues Barata AR, Garnacho-Saucedo G, et al. Frontal fibrosing alopecia: a multicenter review of 355 patients. J Am Acad Dermatol 2014;70:670-8. 2. MacDonald A, Clark C, Holmes S. Frontal fibrosing alopecia: a review of 60 cases. J Am Acad Dermatol 2012;67:955-61. http://dx.doi.org/10.1016/j.jaad.2014.04.077
Reply to ‘Frontal fibrosing alopecia’ To the Editor: We have read the letter of Holmes and MacDonald and their interesting clarifications. We believe that a point-by-point response will be useful for the reader. Regarding the comment about the high prevalence of nonsmokers between patients with frontal fibrosing alopecia (FFA) in their study,1 it is important to clarify the discussion about this finding because it can lead to misinterpretation, as this comment is included in the ‘‘origin of FFA’’ section.1 Taking into account the findings of their1 and our2 studies, we agree with Holmes and MacDonald that smoking habit does not seem to act as a trigger nor seem to have a protective effect in patients given the diagnosis of FFA. Answering the query of the authors about disease pathogenesis, we suggest that the hormonal imbalance between estrogens and androgens may play an important role as a trigger of the scarring immunologic reaction, based on the high preponderance of postmenopausal women in patients with FFA, the relatively high incidence of early menopause women in our series, and in the apparent good response to
antiandrogenic drugs. However, we agree with the authors that this mechanism does not explain the appearance of FFA in premenopausal women nor in men. So, other yet unknown mechanisms and/or triggers are probable occurring in patients with FFA. Regarding the question about our scale of response to therapy, it is important to explain that in cases of improvement the regrowth of hair was minimal, and always located at the hairline, as we state in our publication. As limitations, our study2 had a retrospective design and it did not pretend to evaluate the response to treatment, only to have a general description of the usefulness of different therapies. In addition, it was difficult to differentiate in some cases between ‘‘stabilization’’ and ‘‘improvement.’’ However, all of these patients did not worsen, so this scale was useful to affirm that in these patients a specific treatment produced at least stabilization. On the other hand, the data of our study suggest that antiandrogenic drugs are useful in the treatment of FFA. In all, 111 of 355 patients (31%) received antiandrogens, with at least stabilization in all of them. Of this cohort of patients (data not shown in our previous article), 28 of 111 patients (25.2%) did not receive other treatment such as topical minoxidil or topical steroids. Stabilization and improvement was observed in 19 and 9 of these patients, respectively. No patients worsened. Therefore, antiandrogens seemed to play a role in at least stabilizing the recession of the hairline (main outcome measure of our study). Spontaneous stabilization of some of these patients could be possible, but its reported frequency is very low (6% in the 79 untreated patients of our series), so it is highly improbable that in all patients the stabilization would have been spontaneous. In addition, although response to antiandrogens was more frequent if androgenetic alopecia was present, it was also observed in patients without concomitant androgenetic alopecia (30 of 111 patients). Of these patients, finasteride or dutasteride was the only treatment in 10 (33%) of them. FFA is a fascinating entity with many yet unknown points, such as the exact pathogenesis or best treatment for all patients. We agree with Holmes and MacDonald that randomized controlled trials using a validated assessment tool would be the best evidenced-based way to confirm treatment efficacy. Meanwhile, the combination of antiandrogens and intralesional steroids seems to be the strategy that achieves higher proportions of stabilization in the published series.2-4 Sergio Va~ no-Galv an, MD, PhD,a Salvador AriasSantiago, MD, PhD,b and Francisco Camacho, MD, PhDc
J AM ACAD DERMATOL
Letters 595
VOLUME 71, NUMBER 3
Departments of Dermatology at Ram on y Cajal University Hospital, Madrida; Virgen de las Nieves University Hospital, Granadab; and Virgen Macarena University Hospital, Sevilla,c Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Salvador Arias-Santiago, MD, PhD, Dermatology Department, Virgen de las Nieves University Hospital, Av Fuerzas Armadas, Granada, Spain
REFERENCES 1. MacDonald A, Clark C, Holmes S. Frontal fibrosing alopecia: a review of 60 cases. J Am Acad Dermatol 2012;67:955-61. 2. Vano-Galvan S, Molina-Ruiz AM, Serrano-Falcon C, AriasSantiago S, Rodrigues Barata AR, Garnacho-Saucedo G, et al. Frontal fibrosing alopecia: a multicenter review of 355 patients. J Am Acad Dermatol 2014;70:670-8. 3. Ladizinski B, Bazakas A, Selim MA, Olsen EA. Frontal fibrosing alopecia: a retrospective review of 19 patients seen at Duke University. J Am Acad Dermatol 2013;68:749-55. 4. Banka N, Mubki T, Bunagan MJ, McElwee K, Shapiro J. Frontal fibrosing alopecia: a retrospective clinical review of 62 patients with treatment outcome and long-term follow-up. Int J Dermatol doi: 10.1111/ijd.12479. Published online April 16, 2014.
E-mail: [email protected]
http://dx.doi.org/10.1016/j.jaad.2014.05.049
RESEARCH
LETTERS
Clinical efficacy of diphenylcyclopropenone in alopecia areata: Retrospective data analysis of 50 patients
Table I. Demographic data and clinical characteristics
To the Editor: Topical immunomodulators hold promise for treatment of recalcitrant and extensive alopecia areata (AA).1 Diphenylcyclopropenone (DPCP) is the most common contact immunotherapeutic agent, but its use is currently limited by the need for in-office administration and lack of therapeutic dosing and duration guidelines. Also, there is a need to better characterize which patients will respond to DPCP.2,3 To explore these questions, we conducted an institutional review board-approved retrospective study of 50 randomly chosen AA patients who underwent DPCP therapy at the Cleveland Clinic Foundation from 1997 to 2012 (Table I). Patients were categorized into alopecia subtypes: patchy, ophiasis, alopecia totalis (AT), and alopecia universalis (AU). All patients had failed previous therapy with topical, intralesional, or oral steroids for at least 2 months. Minoxidil therapy initiated before DPCP therapy was continued (46% patients). Extent of hair loss was documented. The primary response goal was terminal hair regrowth of 50% or more. In our study, therapy was initiated in office by a nurse-administered challenge with 2% DPCP solution to a quarter-size area on the occipital scalp. Patients subsequently applied DPCP to the scalp twice weekly at home at increasing concentrations (0.001%, 0.01%, 0.02%, and so on), until a mild eczematous reaction was reached. Once cosmetically acceptable regrowth of scalp hair was achieved, DPCP therapy was not discontinued, but application frequency was decreased to once weekly and then twice monthly.
Patients Anergic patients (not assessed in further analysis) Gender (M/F) Race Caucasian Black Asian Age at disease onset ( years) Median Range Age at initiation of DPCP ( years) Median Range Disease duration before DPCP treatment ( years) Median Range DPCP treatment duration ( years) Median Range Alopecia areata subtype Patchy Totalis Universalis Ophiasis Comorbidities Thyroid dysfunction Atopy Anemia Polycystic ovarian syndrome Nail changes Body hair loss Family history Alopecia areata Autoimmune disease
Demographic data
DPCP, Diphenylcyclopropenone.
n (%)
50 1 14 (28)/36 (72) 46 (92) 3 (6) 1 (2) 21 3 to 59 37.5 10 to 61
5 2 months to 45 years 3 0.5-15 9 14 25 1
(18) (29) (51) (2)
25 27 14 3 10 35
(51) (55) (29) (6) (20) (71)
11 (22) 31 (63)
