psoriasis R. Manhart1, P. Rich2

1Oregon and Research ABSTRACT the appearance of psoriatic arthritis Center, Portland, Oregon, USA; Nail psoriasis affects nearly 80% of by up to 12 years (7, 13). More severe 2 Department of Dermatology, Oregon patients with plaque psoriasis and is plaque psoriasis as well as psoriasis of Health Science University, Portland, even more prevalent in patients with the nails, scalp and intertriginous areas Oregon, USA. psoriatic arthritis. Nail psoriasis is not have been associated with the likeli- Racheal Manhart, BS simply a cosmetic problem but one that hood of developing PsA. The highest Phoebe Rich, MD effects the structure and function of the correlation with PsA appears in pa- Please address correspondence to: nail, resulting in negative psychological Racheal Manhart, tients with nail disease. Oregon Dermatology and Research Center effects. The first level in management of In a large retrospective study from Ger- 2565 NW Lovejoy, Suite 200 nail psoriasis is patient education. The many, 4,146 psoriatic patients were 97210 Portland (OR), USA. hierarchy of nail psoriasis therapy be- analysed for psoriasis history, clinical E-mail: [email protected] gins with topical medication followed findings, PsA, and nail involvement us- Received and accepted on September 2, by devices, intralesional injections, and ing standardised questionnaires to seek 2015. small molecules. For nail psoriasis pa- possible predictive features for psoriat- Clin Exp Rheumatol 2015; 33 (Suppl. 93): tients unresponsive to these treatments, ic arthritis. The strongest predictor for S7-S13. and especially in patients with severe concomitant PsA was nail involvement. © Copyright Clinical and plaque psoriasis, biologics are safe and By contrast, scalp involvement was not Experimental Rheumatology 2015. effective options. a significant predictor of PsA (14).

Key words: psoriatic arthritis, Epidemiology and prevalence Quality of life nail psoriasis, psoriatic , Psoriasis is a chronic inflammatory Psoriasis can have a significant nega- pitting, crumbling, , disorder that affects nearly 2% of the tive impact on a patient’s quality of life NAPSI population and can involve the , (QOL) causing physical impairment scalp, joints, mucous membranes and and pain. Psoriasis of highly visible ar- nails (1, 2). A large study of 1,738 pa- eas of the body (including face, hands, tients with psoriasis showed that 79.2% scalp and nails) affects the patients of patients had involvement of the nails quality of life sometimes more when and estimated lifetime incidence of nail compared to other chronic diseases (8, psoriasis up to 90% (3-5). At the time 15-17). In a series of 1,369 patients with of presentation, psoriasis limited to the nail psoriasis, 90% reported the disease nails is uncommon and estimated to oc- as cosmetically distressing, and had cur in 5% to 10% of patients with pso- restrictions in their activities of daily riasis (6). Many patients who present living due to nail psoriasis (3). A study with psoriasis only in their nails later preformed in the Netherlands, reviewed develop psoriasis of their skin and/or 5,400 patients with psoriasis who com- joints, thus, the absolute number of pleted a self-reported Dermatology Life patients exclusively with nail psoriasis Quality Index (DLQI) and Nail Psoria- is not known. In patients with psoria- sis Quality of life 10 (NPQ10). Patients sis, adults are more likely to have nail with nail psoriasis scored higher on the psoriasis than children. In the pediatric DLQI than patients without nail psoria- population, the prevalence of nail pso- sis. Furthermore, patients with nail bed riasis ranges from 7% to 13% (7-9). psoriasis scored higher on the NPQ10, than patients with only nail matrix Psoriatic arthritis and nail psoriasis psoriasis. Overall NPQ10 scores were The prevalence of psoriatic arthritis higher in females (18). These results (PsA) in psoriatic patients ranges from underscore the negative impacts of nail Competing interests: P. Rich carries out 6% to 42% depending on the study (10, psoriasis in patients’ quality of life. clinical trials for Novartis, Pfizer, Eli Lilly, Celgene, Janssen, Amgen, and AbbVie, 11). The prevalence of nail psoriasis in and also consults for Anacor, Eli Lilly and patients with PsA is high ranging from Clinical features of nail psoriasis Polichem; R. Manhart has declared no 50% to 87% (12, 7). Psoriasis of the The clinical features of nail psoriasis competing interests. skin, scalp and/or nails often precedes depend on the location of the psori-

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Nail matrix signs The nail matrix is responsible for the formation of the nail plate. When the nail matrix is affected by psoriatic in- flammation, changes in the nail plate include pitting, crumbling, psoriatic leukonychia (white spots), and red mac- ules in the lunula. Occurrence of these features depend on the duration and lo- cation of psoriasis within the distal or proximal matrix (Fig. 1). For example, foci of psoriasis in the proximal matrix cause pitting, whereas the same process in the mid or distal matrix results in pso- riatic leukonychia. The mid and distal areas of leukonychia resemble pitting, but these abnormal cells are trapped in the nail plate resulting in white spots Fig. 1. The location and duration of psoriatic causes the nail matrix psoriasis features. (leukonychia) rather than a pitted sur- These features include: pits, crumbling and psoriatic leukonychia. The proximal matrix which forms the superficial layers of the nail plate is responsible for pitting (1). Crumbling is confluent pitting that face. Crumbling represents confluent results from broad foci of inflammation in the proximal matrix for a longer duration (2). Leukonychia pitting due to a longer duration of nail is caused by psoriasis in the mid and distal nail matrix which forms the deeper layers of the nail plate. psoriasis in the proximal nail matrix. This causes the parakeratotic cells to be trapped within the substance of the nail plate (3). Leukonychia looks like pitting however, the surface of the nail plate is smooth rather than pitted. During the mini- mum time it takes for the nail to grow out, if the smooth surface of the nail plate overlying leukonychia Nail bed signs is worn away, the deeper parakeratotic cells of leukonychia become more superficial and may even The nail bed is responsible for the firm evolve into pitting. Drawing modified from Zaias 1969. Archives Dermatology. attachment of the nail plate. Psoriasis in the nail, and results in changes of atic Inflammation within the nail unit. or all of these structures can be affected oil drop/salmon patch , nail The scientific basis of our current with nail psoriasis. Generally, psoria- bed hyperkeratosis, and splinter haem- knowledge of the clinical features of sis of the nail matrix and nail bed re- orrhages, which disrupts the connection nail psoriasis comes from the research sult in most of the observed pathologic of the nail bed and nail plate resulting of Nardo Zaias done in 1969. He de- changes, whereas psoriasis of the hypo- in onycholysis. scribed the pathophysiology of the nychium and nail folds contribute less clinical features of nail matrix and nail to the pathologic changes (Fig. 2a-b). Assessment and grading of nail bed psoriasis (19, 20). None of the features of nail psoriasis psoriasis The nail unit is composed of four epi- are unique to psoriasis. It is the collec- There are many valid and useful nail thelial structures; the nail bed, nail ma- tion of features that allow us to recog- psoriasis assessment tools, including: trix, hyponychium and nail folds. Any nise a diseased nail as psoriatic. NAPSI, modified NAPSI, Target NAPSI,

A B

Fig. 2. A Psoriasis involving the proximal nail fold results in nail plate surface irregularities similar to forms of ; B Psoriasis of the hyponychium causes hyperkeratosis and distal onycholysis.

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A C

B D

E

Fig. 3. Nail matrix psoriasis features: A. nail pitting B. psoriatic leukonychia C. psoriatic leukonychia D. crumbling E. red dots in lunula

Baran, N-Nail, Cannavo, PNSS, NASS assessment tool published in 2003, and Zaias’ research. His research explains and others (21). None of these tools are has been used in nearly all large phar- the pathogenesis of nail pitting, crum- perfect, and all have benefits and limita- maceutical trials in which nail psoriasis bling, and psoriatic leukonychia in nail tions which, are summarised in an ex- was evaluated (22). This includes more matrix, and of oil drop / salmon patch, cellent review of nail psoriasis assess- than 800 published reports, posters, hyperkeratosis and the resultant onych- ment methods by Kaalssen et al. (21). and abstracts over the past decade. The olysis in the nail bed (20). NAPSI di- NAPSI was the first quantitative nail principles of NAPSI are based firmly in vides the nail into imaginary quadrants

S-9 Nail psoriasis / R. Manhart & P. Rich

A C

D

B

Fig. 4. Nail bed psoriasis features: A. onycholysis, oil drop dyschromia; B. oil drop dyschromia, onycholysis; C. splinter haemorrhages, onycholysis; D. splinter haemorrhages, nail bed hyperkeratosis, onycholysis. and records the number of quadrants in household chores and gardening, and Treatment of nail psoriasis which any of the interchangeable fea- keeping diseased nails short when fin- Physician/provider prescribed thera- tures of nail matrix psoriasis and any gertip activities like typing and piano pies are numerous and are selected of the features of nail bed psoriasis are playing are performed. Patient should based on many individual factors in- seen. The composite score for each nail avoid excessive nail grooming, pick- cluding disease severity, comorbidi- is between 0–8. There are other quality ing, and filing or buffing the surface ties, and the impact of psoriatic nail assessments scales that are scientifical- of the nail plate. Woman can attempt dystrophy on the patient’s QOL due to ly sound, and are listed at the beginning to disguise unsightly psoriatic nails impaired function, pain and aesthetics. of this section (21). However, some by using nail polish (lacquer, enamel), Patient motivation, adherence, and out scales count pits and estimate percent but nail enhancements such as acrylic of pocket cost of medications are ad- of involvement of various features rath- nails are not advised. Patients should be ditional factors. The usual hierarchy er than the binary system of quadrants counseled that nail improvement occurs of treatment of nail psoriasis parallels (21). slowly and clearing often requires 6 or treatment of plaque psoriasis. Topical more months for fingernails, and up therapies such as corticosteroid, calci- Patient education to 12 months for toenails. Few studies potriol, corticosteroids, tazarotene, and The first level in the management of nail show significant nail improvement be- tacrolimus creams and ointments may psoriasis is to instruct patients about fore 12 weeks, and several studies with be helpful in mild or early nail pso- nail care. For example, it is important to infliximab, etanercept, and ustekinum- riasis (Table I). A Chinese botanical, instruct patients on how to avoid activi- ab demonstrate continued improvement Indigo Naturalis (Lindioil) is a newly ties that may result in Koebner (isomor- beyond 6 months (23-25). described topical botanical treatments phic) reaction where localised trauma Approximately 30% of psoriatic - for psoriatic nails (26). Intralesional including minor repetitive trauma to nails have concomitant onychomyco- triamcinolone and light based devic- the skin or nails induces or exacerbates sis. Treating the fungal may es such as excimer and pulse dye are psoriasis at the site of . Simple be helpful in some cases of thick dys- sometimes useful when few nails are advice includes, avoiding minor repeti- trophic psoriatic nails prone to Koebner involved and before systemic medica- tive nail trauma by wearing gloves for reactions. tions are considered.

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Table I. Management of nail psoriasis. When lower level therapy fails or when there is concomitant extensive plaque 1. Patient education a. Avoidance of minor repetitive nail trauma from typing and chores to prevent Koebner psoriasis, systemic treatment may be (isomorphic) reactions that may exacerbate nail psoriasis. employed. For nail psoriasis alone, tra- b. Manage expectations about the time necessary for to nail clearing ditional systemic medications such as c. Discuss nail cosmetics and other factors that may interfere with therapy Cyclosporine A (CsA), methotrexate, d. Discuss prevention and treatment of concomitant fungal infection in psoriatic nails and acetritin appear to be more effective 2. Topical products applied to the involved nails a. Pharmaceutical creams, solutions, ointments: calcipotriol, tazarotene, tacrolimus, etc. in clearing cutaneous plaque psoriasis b. Botanicals Indigo naturalis (Lindioil) than they are in clearing nail psoriasis. c. Treat concomitant fungal nail involvement, if present, with topical and/or systemic Cyclosporine A is associated with mini- as indicated. mal improvement in nail psoriasis (27- 3. Intralesional corticosteroids (when single or few nails are involved) 31). Methotrexate is effective in pso- 4. Devices riasis and psoriatic arthritis but efficacy a. Light energy based devices: excimer laser, PDL, Grenz Ray in nail psoriasis is not compelling (28, 5. Systemic therapy with small molecules 29, 32-34). Acitretin, a retinoid showed a. Traditional small molecule medications- methotrexate, acitretin , cyclosporine A modest effect for improving nail pso- b. Newer small molecules - apremilast, tofacitinib riasis (27, 29, 34, 35). Leflunomide 6. Systemic therapy with biologic agents showed limited efficacy in nail psoriasis a. Adalimumab (ADA), Etanercept ( ETN), Infliximab ( IFN), Certolizumab pegol (CZP), Golimumab, Ustekinumab (UST), Ixekizumab (IXE), Secukinumab (SEC) in a European trial (36). Dozens of clinical trials have been con- ducted of biologic agents for moderate Table II. Therapy of nail psoriasis including references. to severe plaque psoriasis, and many Therapeutic options for nail psoriasis Reference of these trials evaluated efficacy in nail psoriasis as a secondary endpoint Topical agents of treatment. In addition, there have Topial calcipotriol + betamethasone 60, 61 Topical clobetasol lacquer 0.05%, 0.1%, 8% 62 been numerous small trials specifically Tacrolimus ointment 0.1% 63 evaluating efficacy of the investiga- Tazarotene gel .1% daily 64 tional product in nail psoriasis. Some Topical Cyclosporine A 70% in corn oil 65 of the nail-specific trials included small Indigo naturalis lindioil 66 molecules and biologic agents as mono- Topical calcipotriol + betamethasone+ salicylic acid 67 therapy, combination therapy. Some of Devices and Procedural Interventions these aforementioned trials were open- Pulse Dye laser (PDL) 595 nm 68 label, some blinded, and some with Excimer laser 69 Intense pulse light (IPL) 70 comparators. Several excellent recent Photodynamic therapy PDT, PDL plus MAL 71 publications review the data concern- Grenz Ray 72 ing these clinical trials in nail psoriasis Intralesional (IL) corticosteroids 5 mg/cc triamcinolone 73 (Table II). Biologics have been shown with injector monthly x4 to be effective in the treatment of nail IL triamcinolone injection with needleless injector 74 psoriasis in a number of well controlled Combination Therapies studies with the tumour necrosis fac- Phototherapy with psoralen / acitretin 29 PDL + 0.1% tazarotene 75 tor alpha (TNF-α) antagonists, Adali- mumab (29, 31, 34, 37-44), Etanercept Traditional Small Molecule Medications (29, 34, 42-46), Cergtolizumab pegol Methotrexate 28, 29, 32, 33, 34 Cyclosporine A (CsA) 28, 29, 30, 31 (47), and Infliximab (27, 29, 34, 42-44, Acitretin 29, 35 48-53). Ustekinumab is very effective Leflunomide 36 in treating nail psoriasis, with weight Newer Small Molecule Medications based dosing (25, 54-57). Phase 3 data Apremilast 76 with Secukinumab and phase 2 studies Tofacitinib 77 with Ixekizumab showed very good nail Biologic Agents improvement (58, 59, 80, 81). Adalimumab (ADA) 31, 37, 38, 39, 40, 41, 43, 44 Etanercept (ETN) 43, 44, 45, 46 References Infliximab (IFN) 29, 34, 44 1. GELFAND, J, WEINSTEIN R, PORTER SB: Certolizumab pegol (CZP) 47 Prevalence and treatment of psoriasis in the Golimumab 78, 79 UK: a population based study Arch Dermatol Ustekinumab (UST) 54, 55, 56, 25, 57 2005; 141: 1537-4. Ixekizumab (IXE) 80, 58 2. TAN ES, CHONG WS, TEY HL: Nail Psoriasis: Secukinumab (SEC) 81, 59 a review. Am J Clin Dermatol 2012; 13: 375- 88.

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3. JIARAVUTHISAN MM, SASSEVILLE D, psoriasis. J Am Acad Dermatol 2004; 50: 37. SOLA-ORTIGOSA J, SANCHEZ-REGANA M, VENDER RB, URPHY F, MUHN CY: Psoria- 289-92. UMBERT-MILLET P: Efficacy of adalimumab sis of the nail: anatomy, pathology, clinical 23. ORTONNE JP, PAUL C, BERARDESCA E et al.: in the treatment of psoriasis: A retrospective presentation,and a review of the literature on A 24-week randomized clinical trial investi- study of 15 patients in daily practice. J Der- therapy. J Am Acad Dermatol 2007; 57: 1-27. gating the efficacy and safety of two doses matolog Treat 2012; 23: 203-7. 4. COHEN MR, REDA DJ, CLEGG DO: Baselne of etanercept in nail psoriasis. Br J Dermatol 38. LEONARDI C, LANGLEY RG, PAPP K et al.: Relationship between psoriasis and psoriatic 2013; 168: 1080-7. Adalimumab for treatment of moderate to arthritis, analysis of 221 pts Department of 24. REICH K, ORTONNE JP, KERKMANN U et severe chronic plaque psoriasis of the hands VA Cooperative Study Group. J Rheumatol- al.: Skin and nail responses after 1 year of and feet: Efficacy and safety results from ogy 1999 26: 1752. infliximab therapy in patients with moderate- REACH, a randomized, placebo-controlled, 5. SAMMAN PD, FENTON: The nails in Disea- to-severe psoriasis: a retrospective analysis double-blind trial. Arch Dermatol 2011; 147: se5th Ed Butterworth Heinenman1994. of the EXPRESS Trial. Dermatology 2010; 429-36. 6. GLADMAN DD, ANTONI C, MEASE P: Psori- 221: 172-8. 39. RIGOPOULOS D, GREGORIOU S, LAZARIDOU atic arthritis, epidemiology clinical features, 25. IGARASHI A, KATO T, KATO M, SONG M, NA- E et al.: Treatment of nail psoriasis with adali- course and outcomes Ann Rheum Disease KAGAWA H; Japanese Ustekinumab Study mumab: An open label unblinded study. J Eur 2005; 64 (Suppl 2): 14-7. Group: Efficacy and safety of ustekinumab Acad Dermatol Venereol 2010; 24: 530-4. 7. NESTLE FO, KAPLAN DH, BARKER J: Psoria- in Japanese patients with moderate-to-severe 40. Van den BOSCH F, MANGER B, GOUPILLE P sis. N Engl J Med 2009; 361: 496-509. plaque-type psoriasis: long-term results from et al.: Effectiveness of adalimumab in treat- 8. THAM SN, LIM JJ, TAY SH et al.: Clinical ob- a phase 2/3 clinical trial. J Dermatol 2012; ing patients with active psoriatic arthritis and servations on nail changes in psoriasis. Ann 39: 242-52. predictors of good clinical responses for ar- Acad Med Singapore 1988; 17: 482-5. 26. LIN Y, CHANG Y, HUI R et al.: A Chinese herb, thritis, skin and nail lesions. Ann Rheum Dis 9. LAVARONI G, KOKELJ F, PAULUZZI P, TRE- indigo naturalis, extracted in oil (lindioil) 2010; 69: 394-9. VISAN G: The nails in psoriatic arthritis. Acta used topically to treat psoriatic nails: a ran- 41. RUDWALEIT M, Van den BOSCH F, KRON M, Derm Venereol Suppl (Stockh) 1994; 186: domized clinical trial. JAMA Dermatol 2015; KARY S, KUPPER H: Effectiveness and safety 113. 151: 672-4. of adalimumab in patients with ankylosing 10. ZACHARIAE H: Prevalence of joint disease 27. CASSELL S, KAVANAUGH AF: Therapies for spondylitis or psoriatic arthritis and history in patients with psoriasis: implications for psoriatic nail disease. A systematic review. of anti-tumor necrosis factor therapy. Arthri- therapy. Am J Clin Dermatol 2003; 4: 441-7. J Rheumatol 2006; 33: 1452-6. tis Res Ther 2010; 12: R117. 11. GISONDI P, GIROLOMONI G, SAMPOGNA F, 28. GUMUSEL M, OZDEMIR M, MEVLITOGLU 42. OZMEN I, ERBIL AH, KOC E, TUNCA M: Treat- TABOLLI S, ABENI D: Prevalance of psori- I, BODUR S: Evaluation of the efficacy of ment of nail psoriasis with tumor necrosis atic arthritis and joint complaints in a large methotrexate and cyclosporine therapies factor-alpha blocker agents: An open-label, population of Italian patients hospitalized for on psoriatic nails: A one-blind, randomized unblinded, comparative study. J Dermatol psoriasis. Eur J Dermatol 2005; 15: 279-83. study. J Eur Acad Dermatol Venereol 2011; 2013; 40: 755-6. 12. WILSON FC, ICEN M, CROWSON CS, McE- 25: 1080-4. 43. SARACENO R, PIETROLEONARDO L, MAZ- VOY MT, GABRIEL SE, KREMERS HM: 29. SANCHEZ-REGANA M, SOLA-ORTIGOSA J, ZOTTA A, ZANGRILLI A, BIANCHI L, CHI- Incidence and clinical predictors of psoriatic ALSINA-GIBERT M, VIDAL-FERNANDEZ MENTI S: TNF-alpha antagonists and nail arthritis in patients with psoriasis: a popula- M, UMBERT-MILLET P: Nail psoriasis: A psoriasis: An open, 24-week, prospective tion-based study. Arthritis Rheum 2009; 61: retrospective study on the effectiveness of cohort study in adult patients with psoriasis. 233-9. systemic treatments (classical and biologi- Expert Opin Biol Ther 2013; 13: 469-73. 13. BOEHNCKE WH, QURESHI A, MEROLA JF et cal therapy). J Eur Acad Dermatol Venereol 44. KYRIAKOU A, PATSATSI A, SOTIRIADIS D: al.: Diagnosing and treating psoriatic arthri- 2011; 25: 579-86. Anti-TNF agents and nail psoriasis: A single- tis-an update. Br J Dermatol 2014; 170: 772- 30. SYUTO T, ABE M, ISHIBUCHI H, ISHIKAWA O: center, retrospective, comparative study. 86. Successful treatment of psoriatic nails with J Dermatolog Treat 2013; 24: 162-8. 14. LANGENBRUCH A, RADTKE MA, KRENSEL low-dose cyclosporine administration. Eur J 45. ORTONNE JP, PAUL C, BERARDESCA E et al.: M, JACOBI A, REICH K, AUGUSTIN M: Nail Dermatol 2007; 17: 248-9. A 24-week randomized clinical trial investi- involvement as a predictor of concomitant 31. KARANIKOLAS GN, KOUKLI EM, KATSA- gating the efficacy and safety of two doses psoriatic arthritis in patients with psoriasis. LIRA A et al.: Adalimumab or cyclosporine of etanercept in nail psoriasis. Br J Dermatol Br J Dermatol 2014; 171: 1123-8. as monotherapy and in combination in severe 2013; 168: 1080-7. 15. BARAN RL DR: Diseases of the nail and their psoriatic arthritis: Results from a prospective 46. LUGER TA, BARKER J, LAMBERT J et al.: management. 4th ed: Wiley-Blackwell; 2012. 12-month nonrandomized unblinded clinical Sustained improvement in joint pain and nail 16. PURI KJ: Nail Atlas: a clinical approach. New trial. J Rheumatol 2011; 38: 2466-74. symptoms with etanercept therapy in patients Delhi: Jaypee; 2008. 32. KINGSLEY GH, KOWALCZYK A, TAYLOR H with moderate-to-severe psoriasis. J Eur 17. HEYDENDAEL VM, de BORGIE CA, SPULS PI, et al.: A randomized placebo-controlled trial Acad Dermatol Venereol 2009; 23: 896-904. BOSSUYT PM, BOS JD, de RIE MA: The bur- of methotrexate in psoriatic arthritis. Rheu- 47. MEASE PJ, FLEISCHMANN R, DEODHAR AA den of psoriasis is not determined by disease matology 2012; 51: 1368-77. et al.: Effect of certolizumab pegol on signs severity only. J Investig Dermatol Symp Proc 33. REICH K, LANGLEY RG, PAPP KA et al.: and symptoms in patients with psoriatic ar- 2004; 9: 131-5. A 52-week trial comparing briakinumab thritis: 24-week results of a Phase 3 double- 18. KLAASSEN KM, van de KERKHOF PC, PASCH with methotrexate in patients with psoriasis. blind randomised placebo-controlled study MC: Nail Psoriasis, the unknown burden of N Engl J Med 2011; 365: 1586-96. (RAPID-PsA). Ann Rheum Dis 2014; 73: 48- disease. J Eur Acad Dermatol Venereol 2014; 34. DEMIRSOY EO, KIRAN R, SALMAN S et al.: 55. 28: 1690-50 Effectiveness of systemic treatment agents 48. FABRONI C, GORI A, TROIANO M, PRIGNA- 19. ZAIAS N: Psoriasis of the nail. A clinical- on psoriatic nails: A comparative study. NO F, LOTTI T: Infliximab efficacy in nail pathologic study. Arch Dermatol 1969; 99: J Dermatol 2013; 12: 1039-43. psoriasis. A retrospective study in 48 pa- 567-79. 35. TOSTI A, RICOTTI C, ROMANELLI P, CAMELI tients. J Eur Acad Dermatol Venereol 2011; 20. ZAIAS N: Embryology of the human nail. N, PIRACCINI BM: Evaluation of the efficacy 25: 549-53. Arch Dermatol 1963; 87: 37-53. of acitretin therapy for nail psoriasis. Arch 49. TORII H, NAKAGAWA H: Japanese Infliximab 21. KLAASSEN KM, van de KERKHOF PC, BAS- Dermatol 2009; 145: 269-71. Study I. Long-term study of infliximab in TIAENS MT, PLUSJÉ LG, BARAN RL PASCH 36. BEHRENS F, FINKENWIRTH C, PAVELKA K et Japanese patients with plaque psoriasis, pso- MCJ: Scoring nail psoriasis. Am Acad Der- al.: Leflunomide in psoriatic arthritis: Results riatic arthritis, pustular psoriasis and psoriatic matol 2014; 70: 1061-6. from a large European prospective observa- erythroderma. J Dermatol 2011; 38: 321-34. 22. RICH P, SCHER RK: Nail Psoriasis Severity tional study. Arthritis Care Res 2013; 65: 50. REICH K, ORTONNE JP, KERKMANN U et al.: Index: a useful tool for evaluation of nail 464-70. Skin and nail responses after 1 year of inf-

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liximab therapy in patients with moderate-to- combination therapy with betamethasone di- Acad Dermatol Venereol 2009; 23: 891-5. severe psoriasis: A retrospective analysis of propionate in the treatment of nail psoriasis. 72. LINDEL.F B: Psoriasis of the nails treated the EXPRESS Trial. Dermatology 2010; 22: Acta Derm Venereol 2008; 88: 279-80. with grenz rays: a double-blind bilateral trial. 172-8. 62. NAKAMURA RC, ABREU LD, DUQUE- Acta Derm Venereol 1989; 69: 80-2. 51. TORII H, NAKAGAWA H: Japanese Infliximab ESTRADA B, TAMLER C, LEVERONE AP: 73. BLEEKER JJ: Intralesional triamcinolone ace- Study I. Infliximab monotherapy in Japanese Comparison of nail lacquer clobetasol ef- tonide using the Port-O-Jet and needle injec- patients with moderate-to-severe plaque pso- ficacy at 0.05%, 1%and 8%in nail psoriasis tions in localized dermatoses. Br J Dermatol. riasis and psoriatic arthritis. A randomized, treatment: prospective, controlled and rand- 1974; 91: 97-101. double-blind, placebo-controlled multicenter omized pilot study. An Bras Dermatol 2012; 74. NANTEL-BATTISTA M, RICHER V, MARCIL I, trial. J Dermatol Sci 2010; 59: 40-9. 87: 203-11. BENOHANIAN A: Treatment of nail psoriasis 52. RICH P, GRIFFITHS CE, REICH K et al.: Base- 63. De SIMONE C, MAIORINO A, TASSONE F, with intralesional triamcinolone acetonide line nail disease in patients with moderate to D’AGOSTINO M, CALDAROLA G: Tacroli- using a needle-free jet injector: a prospective severe psoriasis and response to treatment mus 0.1% ointment in nail psoriasis: A ran- trial. J Cutan Med Surg 2014; 18: 38-42. with infliximab during 1 year. J Am Acad domized controlled open-label study. J Eur 75. HUANG YC, CHOU CL, CHIANG YY: Efficacy Dermatol 2008; 58: 224-31. Acad Dermatol Venereol 2013; 27: 1003-6. of pulsed dye laser plus topical tazarotene 53. RIGOPOULOS D, GREGORIOU S, STRATIGOS 64. FISCHER-LEVANCINI C, SANCHEZ-REGANA versus topical tazarotene alone in psoriatic A et al.: Evaluation of the efficacy and safety M, LLAMBI F, COLLGROS H, EXPOSITO-SER- nail disease: A single-blind, intrapatient left- of infliximab on psoriatic nails: An unblind- RANO V, UMBERT-MILLET P: Nail psoriasis: to-right controlled study. Lasers Surg Med ed, nonrandomized, open-label study. Br J Treatment with tazarotene 0.1% hydrophilic 2013; 45: 102-7. Dermatol 2008; 159: 453-6. ointment. Actas Dermosifiliogr 2012; 103: 76. PAPP K, REICH K, LEONARDI C et al.: 54. PATSATSI A, KYRIAKOU A, SOTIRIADIS D: 725-8. Apremilast, and oral phosphodiesterase 4 in- Ustekinumab in nail psoriasis: An open- 65. CANNAVO SP, GUARNERI F, VACCARO M, hibitor, in nail, and scalp psoriasis: 52-week label, uncontrolled, nonrandomized study. BORGIA F, GUARNERI B: Treatment of psori- results from the ESTEEM 1 study [abstract J Dermatolog Treat 2013; 24: 96-100. atic nails with topical cyclosporin: a prospec- 203]. Paper presented at: European Academy 55. RICH P, BOURCIER M, SOFEN H et al.: tive, randomized placebo-controlled study. of Dermatology & Venereology; October Ustekinumab improves nail disease in pa- Dermatology 2003; 206: 153-6. 2-6, 2013; Istanbul, Turkey. tients with moderate-to-severe psoriasis: Re- 66. LIN YK, SEE LC, HUANG YH et al.: Efficacy 77. PAPP KA, MENTER A, ABE M et al.: Tofacitin- sults from PHOENIX 1. Br J Dermatol 2014; and safety of Indigo naturalis extract in oil ib, an oral Janus Kinase inhibitor, for treat- 170: 398-407. (Lindioil) in treating nail psoriasis: a rand- ment of Chronic plaque psoriasis: results 56. VITIELLO M, TOSTI A, ABUCHAR A, ZAIAC omized, observer-blind, vehicle-controlled from 2 phase three trials. Br J Dermatol M, KERDEL FA: Ustekinumab for the treat- trial. Phytomedicine 2014; 21: 1015-20. 2015 Jul 7 [Epub ahead of print]. ment of nail psoriasis in heavily treated pso- 67. TOSTI A, PIRACCINI BM, CAMELI N et al.: 78. KAVANAUGH A, McINNES I, MEASE P et al.: riatic patients. Int J Dermatol 2013; 52: 358- Calcipotriol ointment in nail psoriasis: a con- Golimumab, a new human tumor necrosis 62. trolled double-blind comparison with beta- factor alpha antibody, administered every 57. RIGOPOULOS D, GREGORIOU S, MAKRIS M, methasone dipropionate and salicylic acid. four weeks as a subcutaneous injection in IOANNIDES D: Efficacy of ustekinumab in Br J Dermatol 1998; 139: 655-9. psoriatic arthritis: Twenty-four-week efficacy nail psoriasis and improvement in nail-asso- 68. TREEWITTAYAPOOM C, SINGVAHANONT and safety results of a randomized, placebo- ciated quality of life in a population treated P, CHANPRAPAPH K, HANEKE E: The effect controlled study. Arthritis Rheum 2009; 60: with ustekinumab for cutaneous psoriasis: of different pulse durations in the treatment 976-86. An open prospective unblinded study. Der- of nail psoriasis with 595-nm pulsed dye 79. KAVANAUGH A, van der HEIJDE D, McINNES matology 2011; 223: 325-9. laser: A randomized, double-blind, intrapa- IB et al.: Golimumab in psoriatic arthritis: 58. LANGLEY R, RICH P, MENTER A et al.: tient left-to-right study. J Am Acad Dermatol One-year clinical efficacy, radiographic, and Improvement of scalp and nail lesions with 2012; 66: 807-12. safety results from a phase III, randomized, ixekizumab in a phase 2 trial in patients with 69. NAWAF Al-MUTAIRI, NOOR T, AL-HADDAD placebo-controlled trial. Arthritis Rheum chronic plaque psoriasis. J Eur Acad Derma- A: Single blinded left-to-right comparison 2012; 64: 2504-17. tol Venereol 2015; 29: 1763-70. study of excimer laser versus pulsed dye la- 80. LEONARDI C, MATHESON R, ZACHARIAE C 59. GARNOCK-JONES KP: Secukinumab: a re- ser for the treatment of nail psoriasis. Der- et al.: Anti-interleukin-17 monoclonal anti- view in moderate to severe plaque psoriasis. matol Ther (Heidelb) 2014; 4: 197-205. body ixekizumab in chronic plaque psoriasis. Am J Clin Dermatol 2015; 16: 323-30. 70. TAWFIK AA: Novel treatment of nail psoria- N Engl J Med 2012; 366: 1190-9. 60. RIGOPOULOS D, GREGORIOU S, DANIEL CR sis using the intense pulsed light: a 1-year 81. PAUL C, REICH K, GOTTLIEB AB et al.: III et al.: Treatment of nail psoriasis with a follow-up study. Dermatol Surg. 2014. Secukinumab improves hand, foot and nail two-compound formulation of calcipotriol 71. FERNANDEZ-GUARINO M, HARTO A, lesions in moderate-to-severe plaque pso- plus betamethasone dipropionate ointment. SANCHEZ-RONCO M, GARCIA-MORALES I, riasis: subanalysis of a randomized, double- Dermatology 2009; 218: 338-41. JA.N P: Pulsed dye laser vs. photodynamic blind, placebo-controlled, regimen-finding 61. TZUNG TY, CHEN CY, YANG CY, LO PY, CHEN therapy in the treatment of refractory nail phase 2 trial [published online January 7, YH: Calcipotriol used as monotherapy or psoriasis: a comparative pilot study. J Eur 2014]. J Eur Acad Dermatol Venereol.

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