Nail psoriasis: a combined treatment with 8% clobetasol nail lacquer and tacalcitol ointment

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1 JEADV ISSN Blackwell Publishing Ltd ORIGINAL ARTICLE Nail psoriasis: a combined treatment with 8% clobetasol nail lacquer and tacalcitol ointment M Sánchez Regaña, G Márquez Balbás, P Umbert Millet Psoriasis and Phototherapy Center, Department of Dermatology, Hospital Universitari Sagrat Cor. Teaching Unit, University of Barcelona, Barcelona, Spain Keywords clobetasol, nail lacquer, nail psoriasis, nail, psoriasis, tacalcitol Correspondence: M. Sánchez Regaña. Department of Dermatology. Hospital Universitari Sagrat Cor. C/Paris th floor Barcelona, Spain, tel ; fax ; ez.reg@terra.es Received: 1 September 2007, accepted 20 December 2007 DOI: /j x Introduction Abstract Background Nail involvement is a common and distressing feature in the course of psoriasis. Although much progress has been made in the treatment of the disease, the presence of psoriasis in the nail continues to pose a challenge. In recent years, vitamin D3 analogs and a new formulation containing 8% clobetasol-17-propionate in a colourless nail lacquer vehicle have produced good results for the control of nail psoriasis. Objective To determine the efficacy and safety of the combined treatment of 8% clobetasol-17-propionate in a lacquer vehicle and tacalcitol ointment in nail psoriasis. Methods Fifteen patients with both nail bed and nail matrix psoriasis were included in the study. They were treated with a colourless nail lacquer containing 8% clobetasol-17-propionate applied at bedtime at the weekend, and with tacalcitol ointment under occlusion on the remaining days, for 6 months. Results All 15 patients responded well to treatment. The therapeutic effect was very fast and directly related to the length of therapy. All nail alterations, including nail pain, were reduced, and the modified target Nail Psoriasis Severity Index fell by an average of 78% compared to baseline levels (±59.6, P < ). Conclusions Combined treatment with tacalcitol ointment and 8% clobetasol- 17-propionate in a nail lacquer is a safe, effective treatment for nail bed and nail matrix psoriasis. Psoriasis is a common skin disorder that may affect the nails. Indeed, nail involvement is a common feature and is found in between 10% and 78% of patients; 1 of the 164 psoriatic patients in a previous study by our group, 53% had nail lesions. 2 Fingernails are more affected than toenails. Nail psoriasis is strongly associated with psoriatic arthritis and also with scalp psoriasis; it is rare in children. In the study by De Jong et al. (n = 1728), 51.8% of patients suffered from nail pain, and 58.9% of these reported a severe impact on their quality of life. 1 A recent study indicated a striking divergence of psoriasis severity depending on the presence or absence of HLA-Cw0602 (on chromosome 6). All types of nail lesions were prevalent in HLA-Cw0606-negative patients, whereas in HLA-Cw0602-positive patients, nail lesions correlated with psoriatic arthritis. 3 The clinical features of nail psoriasis are related to the portion of the nail unit affected by the disease. Nail matrix psoriasis is characterized by pitting, leukonychia, red spots in the lunula and occasionally by nail crumbling. Nail bed psoriasis shows onycholysis, salmon patch, splinter haemorrhages and nail bed hyperkeratosis. These features should be borne in mind in the selection of the treatment. Nail psoriasis is usually diagnosed by clinical findings; only rarely is performance of an ungual biopsy required. Recently, we and others have shown an above-average 2008 The Authors 963

2 Nail psoriasis: clobetasol 8% plus tacalcitol Regaña et al. prevalence of onychomycosis in patients with psoriasis. 4,5 In view of these results, it is mandatory to rule out concurrent mycosis when we are evaluating nail psoriasis patients prior to treatment. In recent years, the Nail Psoriasis Severity Index (NAPSI) has established itself as a reproducible, objective numerical tool for the evaluation of nail psoriasis. 7 Nevertheless, some authors have proposed a modified version of this scale for the evaluation of a target nail. 8 Finally, the scoring system proposed by Baran 9 evaluates several signs of nail psoriasis separately. Although the treatment of nail psoriasis has generally been considered unsatisfactory by patients and dermatologists, we believe that these new therapeutic options are extremely promising. To date, tests with topical treatments (for instance, topical and intralesional steroids and 1% 5- flurouracil) have produced poor results and are associated with major side effects such as pain, atrophy and discoloration. However, promising results have been reported in recent years with four topical treatments for nail psoriasis: calcipotriol, 8% clobetasol nail lacquer, topical cyclosporin and tazarotene. The therapeutic potential of calcipotriol ointment in occlusion has been tested in several studies that have also produced positive results. In our open study, patients completed 3 months of treatment and presented good response in all ungual lesions (especially onycholysis and subungual hyperkeratosis), with the exception of nail pitting. In a controlled study, Tosti et al. 11 showed that calcipotriol was as effective as a combination of betamethasone dipropionate and salicylic acid. Another series of 24 cases 12 confirmed that calcipotriol was particularly effective for treating subungual hyperkeratosis, onycholysis and discoloration when applied twice daily without occlusion for 3 months. In all these studies, calcipotriol proved to be safe and well tolerated, and we believe that this molecule has great potential in the treatment of nail psoriasis. However, with the exception of a single case report of a patient with nail psoriasis treated with calcitriol, 13 no data on other vitamin D3 analogs are currently available. To our knowledge, no studies of the effectiveness of tacalcitol ointment in nail psoriasis have been published to date. In 1999, Baran and Tosti 14 reported a major breakthrough in nail psoriasis treatment, using a new formulation containing 8% clobetasol-17-propionate in a colourless nail lacquer vehicle. Patients were divided into two groups: A and B. Group A patients (n = 26) were treated with the nail lacquer once daily until the end of treatment (average 2.5 months), whereas group B patients (n = 15) applied the nail lacquer once daily during the first week and two or three times per week from the second week onwards (average time, 7 months). Sixty-nine per cent of group A patients and 80% of group B patients showed a clear improvement after therapy. The signs that responded best to therapy were onycholysis and pitting, indicating action on the nail matrix. No side effects were reported. Later, our group performed an open study of 10 patients treated with 8% clobetasol nail lacquer 15 applied once daily for 21 days and then twice weekly for 9 months. Within 4 weeks of therapy, all nail alterations had improved, including nail pain. The response was directly related to the length of therapy. The nail parameters that responded best to therapy were onycholysis, pitting and salmon patches. However, subungual hyperkeratosis improved only moderately and splinter haemorrhages hardly at all. The treatment was well tolerated and highly acceptable from the cosmetic point of view; furthermore, no local and or systemic side effects were observed. In a recent prospective, randomized, placebo-controlled study, Cannavò et al. 16 reported the effectiveness of topical oil-dissolved 70% cyclosporin solution in nail psoriasis. In recent years, tazarotene has emerged as another promising option for this challenging form of psoriasis. Tazarotene s therapeutic potential has been evaluated in one open-label study 17 and in one placebo-controlled study 18 with good results. Rigopoulos et al. 19 conducted an interesting double-blind study comparing the efficacy of tazarotene 0.1% cream with clobetasol propionate 0.05% cream in nail psoriasis, concluding that tazarotene is a safe and effective therapy. Here, we report an open study conducted to evaluate the efficacy, tolerability and safety of a combination of a nail lacquer containing 8% clobetasol and tacalcitol ointment for the treatment of nail psoriasis. Patients and methods Patients Fifteen patients (6 men and 9 women, aged years) with nail psoriasis were included in the study. Informed consent was obtained from all subjects. The nail features of each patient at baseline are shown in Table 1. Inclusion criteria Involvement of the fingernail units (bed and matrix) with psoriasis resulting in any one of the following clinical findings: onycholysis, pitting, subungual hyperkeratosis, salmon patches, splinter haemorrhages and pain. Exclusion criteria Onychomycosis and bacterial infection were ruled out by direct microscopy (KOH) and cultures before and during the treatment. Other exclusion criteria were pregnancy or The Authors

3 Regaña et al. Nail psoriasis: clobetasol 8% plus tacalcitol Table 1 Clinical characteristics of our 15 patients at the beginning of the study n Sex (years) Age Type of psoriasis Subungual hyperkeratosis Onycholysis Salmon patches Splinter haemorrhages Pitting Pain NAPSI 1 M 40 Plaque-type M 56 Plaque-type M 34 Plaque-type F 65 Plaque-type M 58 Arthropathic F 48 Plaque-type M 53 Plaque-type F 79 Plaque-type F 71 Arthropathic F 62 Plaque-type M 44 Plaque-type F 53 Plaque-type F 33 Plaque-type F 31 Plaque-type F 49 Plaque-type M, male; F, female. +, mild; ++, moderate; +++, severe;, absent, 1 = yes; 2 = no. breast-feeding, age under 18, severe renal or hepatic insufficiency and intake of any systemic agent for psoriasis that might have affected the nail lesions during the past 6 weeks. Clinical assessment of efficacy All patients were evaluated at baseline, and after 3 and 6 months by the same dermatologist (Dr Sánchez Regaña). The severity of each nail psoriatic feature was scored from 0 (absent) to +++ (severe). An average of all nails involved was calculated. We also assessed the NAPSI at the same times using the modified target NAPSI for the target nail, as previously reported. 8 Briefly, the nail is divided into quadrants, and each quadrant is given a score of 0 to 3 to reflect zero, mild, moderate, or severe involvement for each parameter of nail matrix or bed psoriasis. The highest possible score is 96. Photographs were also taken, before and after treatment. Blood and urine cortisol and serum adrenocorticotropic hormone (ACTH) were assessed in all patients. Study design For 6 months, all patients applied tacalcitol monohydrate ointment 4 μg/g under occlusion five nights a week (Monday to Friday) and, at the week-end, a colourless nail lacquer containing 8% clobetasol-17-propionate, also at night. The nail lacquer was removed with a nail varnish remover before a new application, and nail occlusion was performed using cotton gloves. The times visits were 0, 12 and 24 weeks. fig. 1 Evolution of onycholysis during treatment. Statistical analysis The Wilcoxon signed ranks test was performed using the SPSS software (version 10.0; SPSS Inc, Chicago, IL), P < 0.05 was considered significant. Results All 15 patients showed good, progressive response to treatment. The results were noticeable after 4 weeks and were more marked at the end of treatment (6 months). All clinical signs of nail psoriasis showed a marked, maintained improvement (figs 1 10). Nail pain disappeared completely after 4 weeks in the 10 patients who had reported this symptom at baseline. At baseline, modified target NAPSI scores ranged from 8 to 49 (mean 20.87; ±10.41). At week 12, the modified 2008 The Authors 965

4 Nail psoriasis: clobetasol 8% plus tacalcitol Regaña et al. In the population under study, treatment with tacalcitol ointment five times a week, combined with 8% clobetasolfig. 2 Evolution of salmon patches during treatment. fig. 4 Evolution of subungual hyperkeratosis during treatment. fig. 3 Evolution of pitting during treatment. target NAPSI had fallen to a range of 0 to 26 (mean, 10.33; ±6.24), and finally at week 24 to a range of 0 to 11 (±3.33, P = 0.001; fig. 6). This represents a mean reduction of 78% from baseline levels (±59.6, P < ). The tolerability of both treatments (tacalcitol and nail lacquer) was excellent. None of the 15 patients presented atrophy at the end of the study. Repeated cultures fig. 5 Evolution of splinter haemorrhages during treatment. remained negative throughout. Laboratory tests (cortisol and ACTH) were also within normal ranges. Discussion fig. 6 Change in the modified target NAPSI during the study The Authors

5 Regaña et al. Nail psoriasis: clobetasol 8% plus tacalcitol fig. 7 Nail psoriasis with predominant onycholysis at the beginning of the study. fig. 8 Onycholysis after 12 weeks of treatment. 17-propionate in a colourless nail lacquer, effected a substantial improvement in all signs of nail psoriasis (both bed and matrix) at the end of the 6-month study. At week 24, all 15 patients presented improvement compared to baseline and achieved a mean reduction of 78% in the modified target NAPSI. These excellent results using 8% clobetasol nail lacquer in nail psoriasis have already been reported, by Baran and Tosti 14 and by our group. 15 The high concentration of clobetasol propionate (8%) did not cause skin atrophy or secondary infections in the present study and or in the two just mentioned. Furthermore, serum levels of cortisol and ACTH were within normal limits at the end of the study. In our previous study, 15 we observed that the parameters that responded best to therapy were onycholysis, pitting and salmon patches, whereas subungual hyperkeratosis and splinter haemorrhages presented moderate and poor improvement, fig. 9 Pitting before treatment. fig. 10 Pitting after 24 weeks of therapy. respectively. In the present study, all nail parameters showed a marked improvement, indicating a synergistic action between 8% clobetasol nail lacquer and tacalcitol. Clobetasol propionate and other topical steroids have been used in nail psoriasis for decades, but at the concentrations presently available on the market (0.05%), their control of the disease is poor because drug penetration is very limited. High concentrations (8%) and the lacquer vehicle optimize penetration. In contrast, intralesional injection of steroids may cause pain and atrophy. Recently, our group and others have reported the positive results obtained with calcipotriol in the treatment of nail psoriasis Another study has also shown the efficacy of calcitriol. 13 To date, tacalcitol has not been assessed. In this study, we used tacalcitol because it causes little irritation and also because only one application is needed The Authors 967

6 Nail psoriasis: clobetasol 8% plus tacalcitol Regaña et al. No standard therapeutic regimens exist for the use of topical steroids or vitamin D3 analogs in nail psoriasis. However, in clinical practice, physicians prescribe high potent steroids in occlusion when there is a predominance of nail matrix psoriasis. In nail bed psoriasis, an application of vitamin D3 can achieve optimal benefits. 21 Patients often present both nail bed and matrix psoriasis, and in this case, the combination of topical steroids and vitamin D3 analogs is synergistic. The good clinical results of this combination were observed by Rigopoulos et al. who used a combined treatment with calcipotriol cream and clobetasol cream. 22 We believe that the results obtained with this combination can be optimized by using a nail lacquer with a higher steroid concentration in order to increase the drug penetration into the nail. Although spontaneous remission in the course of nail psoriasis cannot be ruled out, we believe that the timing of the clinical responses observed in our study was suggestive of a synergistic effect of 8% clobetasol nail lacquer and tacalcitol ointment in the treatment of the disease. Although there is a strong evidence that cyclosporin 23 and biologics 6 are effective in nail psoriasis, in clinical practice, they are only rarely indicated when nail psoriasis is isolated. In conclusion, we believe that the combined treatment of 8% clobetasol nail lacquer and tacalcitol ointment is a safe, effective and cosmetically acceptable treatment for nail bed and matrix psoriasis. However, as our patient sample was small, further double-blind studies are necessary to confirm our results. Acknowledgement The authors are grateful to Dra Núria Parra for statistical analysis and Dra Teresa Serra Porta for her help with the figures. References 1 De Jong EMGJ, Seegers BA, Gulinck MK et al. Psoriasis of the nails associated with disability in a large number of patients: results of a recent interview with 1728 patients. Dermatology 1996; 193: Sánchez Regaña M, Iglesias M, Creus L et al. Prevalencia de enfermedades hepáticas crónicas en pacientes con psoriasis. Actas Dermosifiliogr 2000; 91: Gudjonsson JE, Karason A, Runarsdottir EH et al. Distinct clinical differences between HAL-Cw*0602 positive and negative psoriasis patients an analysis of 1019 HLA-C- and HLA-B-typed patients. J Invest Dermatol 2006; 126: Sánchez Regaña M, Videla S, Villoria J et al. Report on the prevalence of fungal involvement in a series of patients with nail psoriasis. Clin Exp Dermatol 2007; 33: Gupta AK, Lynde CW, Jain HC et al. A higher prevalence of onychomycosis in psoriatics compared with nonpsoriatics: a multicentre study. Br J Dermatol 1997; 136: Lawry M. Biological therapy and nail psoriasis. Dermatologic Ther 2007; 20: Rich PH, Scher RK. Nail psoriasis severity index: a useful tool for evaluation of nail psoriasis. J Am Acad Dermatol 2003; 49: Parrish CA, Sobera JO, Elewski BE. Modification of the nail psoriasis severity index. J Am Acad Dermatol 2005; 53: Baran RL. A nail psoriasis severity index. Br J Dermatol 2004; 150: Sánchez Regaña M, Ojeda R, Umbert P. Empleo de calcipotriol tópico en la psoriasis ungueal. Piel 2002; 17: Tosti A, Piraccini BM, Cameli N et al. Calcipotriol ointment in nail psoriasis: a controlled double-blind comparison with betamethasone dipropionate and salicylic acid. Br J Dermatol 1998; 139: Zakeri M, Valikhani M, Mortazavi H, Barzegari M. Topical calcipotriol therapy in nail psoriasis: a study of 24 cases. Dermatol Online J 2005; 11: Usmani N, Wilson C. A case of nail psoriasis treated with topical calcitriol. Clin Exp Dermatol 2006; 31: Baran R, Tosti A. Topical treatment of nail psoriasis with a new corticoid-containing nail lacquer formulation. J Dermatol Treat 1999; 10: Sánchez Regaña M, Martin G, Umbert P. Treatment of nail psoriasis with 8% clobetasol nail lacquer: positive experience in 10 patients. J Eur Acad Derm Venereol 2005; 19: Cannavò SP, Guarneri F, Vaccaro M, Borgia F, Guarneri B. Treatment of psoriatic nails with topical cyclosporin: a prospective, randomized placebo-controlled study. Dermatology 2003; 206: Bianchi L, Soda R, Diluvio L, Chimenti S. Tazarotene 0.1% gel for psoriasis of the fingernails and toenails: an open prospective study. Br J Dermatol 2003; 149: Scher RK, Stiller M, Zhu YI. Tazarotene 0.1% gel in the treatment of fingernail psoriasis: a double-blind, randomized, vehicle-controlled study. Cutis 2001; 68: Rigopoulos D, Gregoriou S, Katsambas A. Treatment of psoriatic nails with tazarotene cream 0.1% vs. Clobetasol propionate 0.05% cream: a double-blind study. Acta Derm Venereol 2007; 87: Lecha M, Mirada A, López S, Artes M. T.O.P. Research Group. Tacalcitol in treatment of psoriasis vulgaris: the Spanish experience. J Eur Acad Derm Venereol 2005; 19: The Authors

7 Regaña et al. Nail psoriasis: clobetasol 8% plus tacalcitol 21 Jiaravuthisan MM, Sasseville D, Vender RB et al. Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy. J Am Acad Dermatol 2007; 57: Rigopoulos D, Ioannides D, Prastitis N, Katsambas A. Nail psoriasis: a combined treatment using calcipotriol cream and clobetasol propionate cream. Acta Derm Venereol 2002; 82: Ojeda R, Sánchez Regaña M, Massana J, Oliete R, Umbert P. Clinical experience with the use of cyclosporin A in psoriasis. Results of a retrospective study. J Dermatol Treat 2005; 16: The Authors 969