- Email: [email protected]
Commentary: Treatment of lichen planopilaris
Commentary: Treatment of lichen planopilaris Some progress, but a long way to go Leonard C. Sperling, MD,a and Jennifer V. Nguyen, MDb Bethesda, Maryland, and Philadelphia, Pennsylvania See related articles on pages 387 and 393 Key words: cicatricial alopecia; hydroxychloroquine; lichen planopilaris; mycophenolate mofetil; treatment.
F
or both patients and clinicians, lichen planopilaris (LPP) is a very challenging disease. Clinically and histologically, we observe active inflammation and disease progression, but our safe and simple anti-inflammatory medications often prove to be woefully inadequate. After topical and intralesional corticosteroids have been tried without good disease control, what are we to do? Unfortunately, the evidence in support of current therapies is questionable, and for some medications, quite weak. The relevant literature is limited to case reports, case series, and expert opinion (level IV or V evidence1), with no randomized, controlled trials performed to date. Most case series studies are difficult to interpret as they are inherently biased, are usually retrospective, lack control groups, and seldom discuss long-term follow-up. Mid- to high-potency topical corticosteroids are generally considered first-line treatment for LPP, usually in conjunction with intralesional corticosteroids. One series of 30 patients treated with topical steroids for 12 weeks showed complete clearing of inflammation and halting of disease progression in 66% of patients, with an additional 20% having mild improvement.2 Similar decreases in signs and symptoms with topical corticosteroids have been From the Departments of Dermatology at Uniformed Services University of the Health Sciences, Bethesda,a and University of Pennsylvania.b Funding sources: None. Conflicts of interest: None declared. Reprints not available from the authors. Correspondence to: Leonard C. Sperling, MD, Department of Dermatology, Uniformed Services University, 4301 Jones Bridge Rd, Bethesda, MD 20814. E-mail: [email protected]. Published online January 11, 2010. J Am Acad Dermatol 2010;62:398-401. 0190-9622/$36.00 ª 2009 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2009.10.025
398
corroborated in other case series,3,4 although one report noted a high rate of relapse after cessation of therapy.5 Although topical calcineurin inhibitors (tacrolimus and pimecrolimus) have shown benefit for cutaneous and mucosal lichen planus,6 there are scarce data on their efficacy in LPP.7,8 Topical cyclosporine has shown improvement in too few reports to be meaningful.2,9 The tetracycline family of antibiotics is popular for LPP because of its favorable side-effect profile, although there is only weak evidence in its favor. A retrospective chart review of 11 patients treated with tetracycline showed a statistically significant improvement in 10 patients (6 with a good response defined as ‘‘stabilization of disease with greater than minimal response to treatment,’’ and 4 with a fair response defined as ‘‘unstable disease with minimal response to treatment’’); however, the results were not based on photographic or hair count data.4 Another retrospective review showed 4 of 15 (27%) patients improving with doxycycline (based on signs, symptoms, and lack of progression), although there was no statistically significant difference compared with hydroxychloroquine.10 Systemic immunomodulators have been used for refractory, rapidly progressing, or extensive disease. A short course of systemic corticosteroids can be effective in halting progression and improving symptoms, but relapse is common after discontinuation.3 Thus, oral corticosteroids are commonly used as a bridge to other systemic agents.11 Hydroxychloroquine is often a preferred secondline agent because it has a relatively good sideeffect profile compared with many other immunomodulatory agents, but results are inconsistent. In one study of 22 patients, 9 patients (41%) had clinical improvement after 6 to 12 months of therapy.10 Conversely, another report showed no effect of hydroxychloroquine in 12 patients, as assessed
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by global photographic assessment and hair counts.5 Other negative results have also been published.12 Other orally administered immunosuppressive drugs suggest potential benefit for LPP, but they are less favored because of a history of frequent or serious adverse effects. Cyclosporine has shown efficacy in a few case series,2,7,13 including one prospective study with 10 of 13 patients demonstrating improvement; others have reported no benefit.3 Furthermore, cyclosporine is associated with a high relapse rate.5 Thalidomide also has shown mixed results.14-17 Mycophenolate mofetil is typically well tolerated by patients with few adverse effects compared with other immunomodulators. Various case reports and case series have suggested clinical improvement in LPP after short courses (typically 2-8 months).5,10,18 As the level of evidence for efficacy is low for these immunosuppressive agents, their side-effect profiles and high total costs have precluded their routine use for LPP. Agents that have shown some efficacy in cutaneous lichen planus, such as systemic retinoids and griseofulvin, have been used for LPP with marginal success. Although acitretin might be considered a first-line agent for cutaneous lichen planus, based on a double-blinded, placebo-controlled trial,19 similar studies have not been performed on LPP. Systemic retinoids (oral tretinoin, isotretinoin, and acitretin) have only showed promise in small case series.10,11,20 Eight patients treated with etretinate for 6 months had no improvement in their LPP, and all experienced an iatrogenic telogen effluvium.5 Griseofulvin was effective for symptomatic relief in two case series,3,21 but did not seem to halt progression of alopecia. Other therapies that are relatively safe but have little evidence-based support include low moleculareweight heparin and minoxidil.5,11,22 Minoxidil was reported as effective in preventing further hair loss and stimulating mild to moderate regrowth.5,11 Overall, the literature concerning therapy for LPP does not inspire confidence. In our struggle to define improved strategies for treating LPP, two articles in this month’s edition of the Journal of the American Academy of Dermatology are particularly welcome. Both are authored by Dr Vera Price and colleagues, which is in itself significant. Dr Price is one of the most expert (if not the most expert) authorities on the diagnosis and treatment of hair disease. Her astute observations have helped define new conditions (eg, trichothiodystrophy and loose anagen hair syndrome), and her devotion to the care and study of patients with hair loss is unsurpassed. Dr Price’s University of California, San Francisco, Hair Center is
a mecca for patients with LPP, many of whom have failed treatment elsewhere. LPP is not a common disease, and certainly Dr Price has had ample opportunity to evaluate and treat more patients with LPP than most dermatologists will encounter in an entire career. In the first article, Dr Price and her colleagues document their impression that the use of hydroxychloroquine will lessen clinical severity in most patients.23 The authors enhance their reports with the use of the LPP Activity Index (LPPAI), which is based on a standardized system for recording clinical information at each patient visit. Data generated from this system show reductions in the LPPAI after treatment with hydroxychloroquine in 69% of 38 patients after 6 months, and 83% of 40 patients after 12 months. In a second article, Dr Price and colleagues use the LPPAI system to show the efficacy of mycophenolate mofetil in treating 12 patients with LPP, with 10 of 12 patients exhibiting LPPAI score reductions of at least 25%.24 Although the results are promising, in the world of evidence-based medicine, studies such as these (essentially, retrospective case series) rank near the bottom of the level-of-evidence hierarchy. Surely the results of prospective, randomized, controlled, doubled-blind studies would provide sounder proof of efficacy. However, the reality is that such studies will be difficult to do with LPP. This disease is uncommon, and making the diagnosis with certainty requires some sophistication. Thus, large numbers of patients will be difficult to recruit. Even if patients were available, there is little industry or government interest in funding a serious clinical trial for an uncommon hair disorder. Meaningful, objective end points are needed to confidently determine the efficacy and safety of current treatments. Most studies on LPP focus on subjective features (symptoms, signs of activity, and progression of hair loss). However, Dr Price and colleagues attempt to apply a more rigorous analysis to a field dominated by relatively noncritical studies. In the authors’ own words, ‘‘as current treatments for LPP are largely based on case reports or case series, this study represents a significant step forward in level-of-evidence’’ because of their use of a standardized scoring system.24 This system, the LPPAI, is an attempt to quantify various clinical parameters (both signs and symptoms) used to assess treatment efficacy from one visit to the next. The simple fact that such an attempt is being made is indeed a step forward. The strength of the LPPAI is that it is fairly comprehensive, using several different signs and symptoms to provide an overall snapshot of patient
400 Sperling and Nguyen
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progress. Furthermore, the scoring system imparts statistical data that could facilitate comparative studies. The weakness of this tool is that it is based on entirely subjective dataenamely the clinician’s impression of the severity of signs (eg, erythema, scale, amount of hair loss); the patient’s impression of symptom severity (eg, pruritus, pain); and a measure of disease activity, the so-called ‘‘anagen pull test.’’ The anagen pull test (the number of anagen hairs that can be easily extracted with gentle pulling) is an important indicator of disease activity because anagen hairs cannot be easily extracted from normal scalps. However, the technique for performing the test is not standardized, and the results of the test have never been critically evaluated. The test is almost certainly user dependenteDr Price might extract two hairs; an overly zealous colleague, 4; and a timid investigator, none. Interobserver studies are needed to clarify this. To determine a LPPAI score, the various subjective impressions of doctor and patient are converted into numeric values. For example, is this disease spreading? ‘‘No’’ is graded as 0, ‘‘not sure’’ as 1, and ‘‘yes’’ as 2. Once converted, these numbers are plugged into a formula. Discussing the formula is unnecessary, because it is an arbitrary invention of the authors. However, it is weighted to reflect the expert opinion of a seasoned clinician as to what constitutes ‘‘getting better,’’ ‘‘getting worse,’’ or ‘‘staying about the same.’’ Similarly, the classification of the scores into stratifications (‘‘complete response’’ for an LPPAI reduction [ 85%, ‘‘partial response’’ for 25%-85% reduction) seems to be based on arbitrary cut-offs whose clinical and therapeutic meaning is as yet untested. The LPPAI, with or without refinements, will need to be validated for reliability. Would different clinicians rating the same set of patients arrive at similar LPPAI values? Are these values properly weighted so that the different observers can agree that a favorable score reflects a favorable outcome? Clearly, further analysis of the scoring system’s clinical significance is required before its routine use. Although the LPPAI is imperfect, we should not ignore it. The LPPAI offers us a framework on which to build and improve. Can some of the subjectivity of this grading system be reduced or eliminated? For example, a well-designed system for using digital photography to document clinical signs is probably a must. It is impossible for those of us without photographic memories to recall exactly what a patient looked like at a previous visit. A photograph always remembers, down to the pixel. Photographs would also allow for a panel of investigators to grade clinical signs in a blinded fashion. Good clinical photography, especially when used for clinical
research, is more cumbersome than a simple lookand-touch examination, but it allows for more objectivity. Unquestionably, LPP is a difficult disorder to diagnose and study, and we applaud the efforts of Dr Price and colleagues. As we await prospective and well-controlled studies, we must rely on the extant literature. Large case series (consisting of 2030 patients) report the use of topical and intralesional corticosteroids, but even these show variable, although positive, results. Given their favorable sideeffect profile, they remain useful first-line agents. A few smaller case series (10-20 patients) have been performed on tetracyclines and hydroxychloroquine, with some patients showing a good response. Although the data are weak, given their minimal adverse effects, they are reasonable second choices. Cyclosporine has shown some benefit in several small case series (\3 patients), and in one prospective study of 13 patients. The side-effect profile, however, is less favorable, and it will probably not find widespread use. The evidence in support of other systemic drugs, such as mycophenolate mofetil, thalidomide, and oral retinoids, is limited to scattered case reports and small case series (\10 patients), and the results are mixed. Nevertheless, for patients with refractory or rapidly progressive disease, the risk of adverse effects associated with these agents may be preferable to the possibility of severe and permanent hair loss. The case series reported in this issue provide additional evidence in support of two promising treatments for LPP. The authors’ creation of the LPPAI provides a platform for further research. Once validated, the tool would be useful for assessing treatment response in future therapeutic trials. REFERENCES 1. Oxford Center for Evidence-based Medicine (2009). Oxford Centre for Evidence-based Medicine - Levels of Evidence. Available from: http://www.cebm.net. Accessed September 29, 2009. 2. Chieregato C, Zini A, Barba A, Magnanini M, Rosina P. Lichen planopilaris: report of 30 cases and review of the literature. Int J Dermatol 2003;42:342-5. 3. Mehregan DA, van Hale HM, Muller SA. Lichen planopilaris: clinical and pathologic study of forty-five patients. J Am Acad Dermatol 1992;27:935-42. 4. Cevasco NC, Bergfeld WF, Remzi BK, de Knott HR. A case-series of 29 patients with lichen planopilaris: the Cleveland Clinic Foundation experience on evaluation, diagnosis, and treatment. J Am Acad Dermatol 2007;57:47-53. 5. Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treatment. Semin Cutan Med Surg 2009;28:3-10. 6. Volz T, Caroli U, Lu¨dtke H, Bra¨utigam M, Kohler-Spa¨th H, Ro¨cken M, et al. Pimecrolimus cream 1% in erosive oral lichen planusea prospective randomized double-blind vehicle-controlled study. Br J Dermatol 2008;159:936-41.
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7. Mirmirani P, Willey A, Price VH. Short course of oral cyclosporine in lichen planopilaris. J Am Acad Dermatol 2003;49: 667-71. 8. Blazek C, Megahed M. Lichen planopilaris: successful treatment with tacrolimus [German]. Hautarzt 2008;59:874-7. 9. Scalvenzi M, De Natale F, Forgione P, Russo N, Delfino M. Topical cyclosporin A in the treatment of lichen planopilaris. Ann Ital Dermatol Clin Sper 1998;52:37-40. 10. Spencer LA, Hawryluk EB, English JC III. Lichen planopilaris: retrospective study and stepwise therapeutic approach. Arch Dermatol 2009;145:333-4. 11. Tan E, Martinka M, Ball N, Shapiro J. Primary cicatricial alopecias: clinicopathology of 112 cases. J Am Acad Dermatol 2004;50:25-32. 12. Jouanique C, Reygagne P, Assouly P, Matard B, Marechal E, Bachelez H, et al. Hydroxychloroquine sulphate’s ineffectiveness in the treatment of lichen planopilaris and idiopathic pseudopelade. Research abstract presented at: Third Intercontinental Meeting of Hair Research Societies; June 13-15, 2001; Tokyo, Japan. 13. Bianchi L, Paro Vidolin A, Piemonte P, Carboni I, Chimenti S. Graham Little-Piccardi-Lassueur syndrome: effective treatment with cyclosporin A. Clin Exp Dermatol 2001;26:518-20. 14. Boyd AS, King LE Jr. Thalidomide-induced remission of lichen planopilaris. J Am Acad Dermatol 2002;47:967-8. 15. Doherty SD, Hsu S. A case series of 48 patients treated with thalidomide. J Drugs Dermatol 2008;7:769-73.
16. George SJ, Hsu S. Lichen planopilaris treated with thalidomide. J Am Acad Dermatol 2001;45:965-6. 17. Jouanique C, Reygagne P, Bachelez H, Dubertret L. Thalidomide is ineffective in the treatment of lichen planopilaris. J Am Acad Dermatol 2004;51:480-1. 18. Tursen U, Api H, Kaya T, Ikizoglu G. Treatment of lichen planopilaris with mycophenolate mofetil. Dermatol Online J 2004;10:24. 19. Laurberg G, Geiger JM, Hjorth N, Holm P, Hou-Jensen K, Jacobsen KU, et al. Treatment of lichen planus with acitretin: a double-blind, placebo-controlled study in 65 patients. J Am Acad Dermatol 1991;24:434-7. 20. Ott F, Bollag W, Geiger JM. Efficacy of oral low-dose tretinoin (all- trans-retinoic acid) in lichen planus. Dermatology 1996; 192:334-6. 21. Massa MC, Rogers RS III. Griseofulvin therapy of lichen planus. Acta Derm Venereol 1981;61:547-50. 22. Stefanidou MP, Ioannidou DJ, Panayiotides JG, Tosca AD. Low molecular weight heparin; a novel alternative therapeutic approach for lichen planus. Br J Dermatol 1999;141:1040-5. 23. Chiang C, Sah D, Cho BK, Ochoa BE, Price VH. Hydroxychloroquine and lichen planopilaris: efficacy and introduction of Lichen Planopilaris Activity Index scoring system. J Am Acad Dermatol 2010;62:387-92. 24. Cho BK, Sah D, Chwalek J, Roseborough I, Ochoa BE, Chiang C, et al. Efficacy and safety of mycophenolate mofetil for lichen planopilaris. J Am Acad Dermatol 2010;62:393-7.
F
or both patients and clinicians, lichen planopilaris (LPP) is a very challenging disease. Clinically and histologically, we observe active inflammation and disease progression, but our safe and simple anti-inflammatory medications often prove to be woefully inadequate. After topical and intralesional corticosteroids have been tried without good disease control, what are we to do? Unfortunately, the evidence in support of current therapies is questionable, and for some medications, quite weak. The relevant literature is limited to case reports, case series, and expert opinion (level IV or V evidence1), with no randomized, controlled trials performed to date. Most case series studies are difficult to interpret as they are inherently biased, are usually retrospective, lack control groups, and seldom discuss long-term follow-up. Mid- to high-potency topical corticosteroids are generally considered first-line treatment for LPP, usually in conjunction with intralesional corticosteroids. One series of 30 patients treated with topical steroids for 12 weeks showed complete clearing of inflammation and halting of disease progression in 66% of patients, with an additional 20% having mild improvement.2 Similar decreases in signs and symptoms with topical corticosteroids have been From the Departments of Dermatology at Uniformed Services University of the Health Sciences, Bethesda,a and University of Pennsylvania.b Funding sources: None. Conflicts of interest: None declared. Reprints not available from the authors. Correspondence to: Leonard C. Sperling, MD, Department of Dermatology, Uniformed Services University, 4301 Jones Bridge Rd, Bethesda, MD 20814. E-mail: [email protected]. Published online January 11, 2010. J Am Acad Dermatol 2010;62:398-401. 0190-9622/$36.00 ª 2009 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2009.10.025
398
corroborated in other case series,3,4 although one report noted a high rate of relapse after cessation of therapy.5 Although topical calcineurin inhibitors (tacrolimus and pimecrolimus) have shown benefit for cutaneous and mucosal lichen planus,6 there are scarce data on their efficacy in LPP.7,8 Topical cyclosporine has shown improvement in too few reports to be meaningful.2,9 The tetracycline family of antibiotics is popular for LPP because of its favorable side-effect profile, although there is only weak evidence in its favor. A retrospective chart review of 11 patients treated with tetracycline showed a statistically significant improvement in 10 patients (6 with a good response defined as ‘‘stabilization of disease with greater than minimal response to treatment,’’ and 4 with a fair response defined as ‘‘unstable disease with minimal response to treatment’’); however, the results were not based on photographic or hair count data.4 Another retrospective review showed 4 of 15 (27%) patients improving with doxycycline (based on signs, symptoms, and lack of progression), although there was no statistically significant difference compared with hydroxychloroquine.10 Systemic immunomodulators have been used for refractory, rapidly progressing, or extensive disease. A short course of systemic corticosteroids can be effective in halting progression and improving symptoms, but relapse is common after discontinuation.3 Thus, oral corticosteroids are commonly used as a bridge to other systemic agents.11 Hydroxychloroquine is often a preferred secondline agent because it has a relatively good sideeffect profile compared with many other immunomodulatory agents, but results are inconsistent. In one study of 22 patients, 9 patients (41%) had clinical improvement after 6 to 12 months of therapy.10 Conversely, another report showed no effect of hydroxychloroquine in 12 patients, as assessed
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by global photographic assessment and hair counts.5 Other negative results have also been published.12 Other orally administered immunosuppressive drugs suggest potential benefit for LPP, but they are less favored because of a history of frequent or serious adverse effects. Cyclosporine has shown efficacy in a few case series,2,7,13 including one prospective study with 10 of 13 patients demonstrating improvement; others have reported no benefit.3 Furthermore, cyclosporine is associated with a high relapse rate.5 Thalidomide also has shown mixed results.14-17 Mycophenolate mofetil is typically well tolerated by patients with few adverse effects compared with other immunomodulators. Various case reports and case series have suggested clinical improvement in LPP after short courses (typically 2-8 months).5,10,18 As the level of evidence for efficacy is low for these immunosuppressive agents, their side-effect profiles and high total costs have precluded their routine use for LPP. Agents that have shown some efficacy in cutaneous lichen planus, such as systemic retinoids and griseofulvin, have been used for LPP with marginal success. Although acitretin might be considered a first-line agent for cutaneous lichen planus, based on a double-blinded, placebo-controlled trial,19 similar studies have not been performed on LPP. Systemic retinoids (oral tretinoin, isotretinoin, and acitretin) have only showed promise in small case series.10,11,20 Eight patients treated with etretinate for 6 months had no improvement in their LPP, and all experienced an iatrogenic telogen effluvium.5 Griseofulvin was effective for symptomatic relief in two case series,3,21 but did not seem to halt progression of alopecia. Other therapies that are relatively safe but have little evidence-based support include low moleculareweight heparin and minoxidil.5,11,22 Minoxidil was reported as effective in preventing further hair loss and stimulating mild to moderate regrowth.5,11 Overall, the literature concerning therapy for LPP does not inspire confidence. In our struggle to define improved strategies for treating LPP, two articles in this month’s edition of the Journal of the American Academy of Dermatology are particularly welcome. Both are authored by Dr Vera Price and colleagues, which is in itself significant. Dr Price is one of the most expert (if not the most expert) authorities on the diagnosis and treatment of hair disease. Her astute observations have helped define new conditions (eg, trichothiodystrophy and loose anagen hair syndrome), and her devotion to the care and study of patients with hair loss is unsurpassed. Dr Price’s University of California, San Francisco, Hair Center is
a mecca for patients with LPP, many of whom have failed treatment elsewhere. LPP is not a common disease, and certainly Dr Price has had ample opportunity to evaluate and treat more patients with LPP than most dermatologists will encounter in an entire career. In the first article, Dr Price and her colleagues document their impression that the use of hydroxychloroquine will lessen clinical severity in most patients.23 The authors enhance their reports with the use of the LPP Activity Index (LPPAI), which is based on a standardized system for recording clinical information at each patient visit. Data generated from this system show reductions in the LPPAI after treatment with hydroxychloroquine in 69% of 38 patients after 6 months, and 83% of 40 patients after 12 months. In a second article, Dr Price and colleagues use the LPPAI system to show the efficacy of mycophenolate mofetil in treating 12 patients with LPP, with 10 of 12 patients exhibiting LPPAI score reductions of at least 25%.24 Although the results are promising, in the world of evidence-based medicine, studies such as these (essentially, retrospective case series) rank near the bottom of the level-of-evidence hierarchy. Surely the results of prospective, randomized, controlled, doubled-blind studies would provide sounder proof of efficacy. However, the reality is that such studies will be difficult to do with LPP. This disease is uncommon, and making the diagnosis with certainty requires some sophistication. Thus, large numbers of patients will be difficult to recruit. Even if patients were available, there is little industry or government interest in funding a serious clinical trial for an uncommon hair disorder. Meaningful, objective end points are needed to confidently determine the efficacy and safety of current treatments. Most studies on LPP focus on subjective features (symptoms, signs of activity, and progression of hair loss). However, Dr Price and colleagues attempt to apply a more rigorous analysis to a field dominated by relatively noncritical studies. In the authors’ own words, ‘‘as current treatments for LPP are largely based on case reports or case series, this study represents a significant step forward in level-of-evidence’’ because of their use of a standardized scoring system.24 This system, the LPPAI, is an attempt to quantify various clinical parameters (both signs and symptoms) used to assess treatment efficacy from one visit to the next. The simple fact that such an attempt is being made is indeed a step forward. The strength of the LPPAI is that it is fairly comprehensive, using several different signs and symptoms to provide an overall snapshot of patient
400 Sperling and Nguyen
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progress. Furthermore, the scoring system imparts statistical data that could facilitate comparative studies. The weakness of this tool is that it is based on entirely subjective dataenamely the clinician’s impression of the severity of signs (eg, erythema, scale, amount of hair loss); the patient’s impression of symptom severity (eg, pruritus, pain); and a measure of disease activity, the so-called ‘‘anagen pull test.’’ The anagen pull test (the number of anagen hairs that can be easily extracted with gentle pulling) is an important indicator of disease activity because anagen hairs cannot be easily extracted from normal scalps. However, the technique for performing the test is not standardized, and the results of the test have never been critically evaluated. The test is almost certainly user dependenteDr Price might extract two hairs; an overly zealous colleague, 4; and a timid investigator, none. Interobserver studies are needed to clarify this. To determine a LPPAI score, the various subjective impressions of doctor and patient are converted into numeric values. For example, is this disease spreading? ‘‘No’’ is graded as 0, ‘‘not sure’’ as 1, and ‘‘yes’’ as 2. Once converted, these numbers are plugged into a formula. Discussing the formula is unnecessary, because it is an arbitrary invention of the authors. However, it is weighted to reflect the expert opinion of a seasoned clinician as to what constitutes ‘‘getting better,’’ ‘‘getting worse,’’ or ‘‘staying about the same.’’ Similarly, the classification of the scores into stratifications (‘‘complete response’’ for an LPPAI reduction [ 85%, ‘‘partial response’’ for 25%-85% reduction) seems to be based on arbitrary cut-offs whose clinical and therapeutic meaning is as yet untested. The LPPAI, with or without refinements, will need to be validated for reliability. Would different clinicians rating the same set of patients arrive at similar LPPAI values? Are these values properly weighted so that the different observers can agree that a favorable score reflects a favorable outcome? Clearly, further analysis of the scoring system’s clinical significance is required before its routine use. Although the LPPAI is imperfect, we should not ignore it. The LPPAI offers us a framework on which to build and improve. Can some of the subjectivity of this grading system be reduced or eliminated? For example, a well-designed system for using digital photography to document clinical signs is probably a must. It is impossible for those of us without photographic memories to recall exactly what a patient looked like at a previous visit. A photograph always remembers, down to the pixel. Photographs would also allow for a panel of investigators to grade clinical signs in a blinded fashion. Good clinical photography, especially when used for clinical
research, is more cumbersome than a simple lookand-touch examination, but it allows for more objectivity. Unquestionably, LPP is a difficult disorder to diagnose and study, and we applaud the efforts of Dr Price and colleagues. As we await prospective and well-controlled studies, we must rely on the extant literature. Large case series (consisting of 2030 patients) report the use of topical and intralesional corticosteroids, but even these show variable, although positive, results. Given their favorable sideeffect profile, they remain useful first-line agents. A few smaller case series (10-20 patients) have been performed on tetracyclines and hydroxychloroquine, with some patients showing a good response. Although the data are weak, given their minimal adverse effects, they are reasonable second choices. Cyclosporine has shown some benefit in several small case series (\3 patients), and in one prospective study of 13 patients. The side-effect profile, however, is less favorable, and it will probably not find widespread use. The evidence in support of other systemic drugs, such as mycophenolate mofetil, thalidomide, and oral retinoids, is limited to scattered case reports and small case series (\10 patients), and the results are mixed. Nevertheless, for patients with refractory or rapidly progressive disease, the risk of adverse effects associated with these agents may be preferable to the possibility of severe and permanent hair loss. The case series reported in this issue provide additional evidence in support of two promising treatments for LPP. The authors’ creation of the LPPAI provides a platform for further research. Once validated, the tool would be useful for assessing treatment response in future therapeutic trials. REFERENCES 1. Oxford Center for Evidence-based Medicine (2009). Oxford Centre for Evidence-based Medicine - Levels of Evidence. Available from: http://www.cebm.net. Accessed September 29, 2009. 2. Chieregato C, Zini A, Barba A, Magnanini M, Rosina P. Lichen planopilaris: report of 30 cases and review of the literature. Int J Dermatol 2003;42:342-5. 3. Mehregan DA, van Hale HM, Muller SA. Lichen planopilaris: clinical and pathologic study of forty-five patients. J Am Acad Dermatol 1992;27:935-42. 4. Cevasco NC, Bergfeld WF, Remzi BK, de Knott HR. A case-series of 29 patients with lichen planopilaris: the Cleveland Clinic Foundation experience on evaluation, diagnosis, and treatment. J Am Acad Dermatol 2007;57:47-53. 5. Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treatment. Semin Cutan Med Surg 2009;28:3-10. 6. Volz T, Caroli U, Lu¨dtke H, Bra¨utigam M, Kohler-Spa¨th H, Ro¨cken M, et al. Pimecrolimus cream 1% in erosive oral lichen planusea prospective randomized double-blind vehicle-controlled study. Br J Dermatol 2008;159:936-41.
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7. Mirmirani P, Willey A, Price VH. Short course of oral cyclosporine in lichen planopilaris. J Am Acad Dermatol 2003;49: 667-71. 8. Blazek C, Megahed M. Lichen planopilaris: successful treatment with tacrolimus [German]. Hautarzt 2008;59:874-7. 9. Scalvenzi M, De Natale F, Forgione P, Russo N, Delfino M. Topical cyclosporin A in the treatment of lichen planopilaris. Ann Ital Dermatol Clin Sper 1998;52:37-40. 10. Spencer LA, Hawryluk EB, English JC III. Lichen planopilaris: retrospective study and stepwise therapeutic approach. Arch Dermatol 2009;145:333-4. 11. Tan E, Martinka M, Ball N, Shapiro J. Primary cicatricial alopecias: clinicopathology of 112 cases. J Am Acad Dermatol 2004;50:25-32. 12. Jouanique C, Reygagne P, Assouly P, Matard B, Marechal E, Bachelez H, et al. Hydroxychloroquine sulphate’s ineffectiveness in the treatment of lichen planopilaris and idiopathic pseudopelade. Research abstract presented at: Third Intercontinental Meeting of Hair Research Societies; June 13-15, 2001; Tokyo, Japan. 13. Bianchi L, Paro Vidolin A, Piemonte P, Carboni I, Chimenti S. Graham Little-Piccardi-Lassueur syndrome: effective treatment with cyclosporin A. Clin Exp Dermatol 2001;26:518-20. 14. Boyd AS, King LE Jr. Thalidomide-induced remission of lichen planopilaris. J Am Acad Dermatol 2002;47:967-8. 15. Doherty SD, Hsu S. A case series of 48 patients treated with thalidomide. J Drugs Dermatol 2008;7:769-73.
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