Baseline nail disease in patients with moderate to severe psoriasis and response to treatment with infliximab during 1 year. A therapeutic study of nail psoriasis using electron beams. Psoriasis of the nails treated with grenz rays: a double-blind bilateral trial. Calcipotriol used as monotherapy or combination therapy with betamethasone dipropionate in the treatment of nail psoriasis. Evaluation of the efficacy of methotrexate and cyclosporine therapies on psoriatic nails: a one-blind, randomized study. Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial. Calcipotriol ointment in nail psoriasis: a controlled double-blind comparison with betamethasone dipropionate and salicylic acid. Tazarotene 0.1% gel in the treatment of fingernail psoriasis: a double-blind, randomized, vehicle-controlled study. Treatment of psoriatic nails with tazarotene cream 0.1% vs. clobetasol propionate 0.05% cream: a double-blind study. Low-dose short-term cyclosporine versus etretinate in psoriasis: improvement of skin, nail, and joint involvement. Treatment of psoriatic nails with topical cyclosporin: a prospective, randomized placebo-controlled study. Remission of ordinary psoriasis following a short clearance course of cyclosporin. Dystrophic psoriatic fingernails treated with 1% 5-fluorouracil in a nail penetration-enhancing vehicle: a double-blind study. A double-blind study of superficial radiotherapy in psoriatic nail dystrophy.
Although nail psoriasis occurs frequently in patients with psoriatic skin lesions, effective treatments are limited.
                Occurrence of nail psoriasis by type and incidence of nail clearance using the Nail Psoriasis Severity Index were evaluated.
                This was a 50-week, phase III study in which 378 patients with moderate to severe psoriasis were randomized 4:1 to infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and every 8 weeks through week 46, with placebo crossover to infliximab at week 24.
                Of the 373 evaluated patients, 305 (81.8%) had baseline nail psoriasis. The right thumbnail was most often the worst involved nail, and pitting and onycholysis were the most common lesions. Among patients with baseline nail psoriasis, 6.9%, 26.2%, and 44.7% in the infliximab group had nail disease clearance at weeks 10, 24, and 50, respectively, versus 5.1% in the placebo group at week 24 (P < .001). Mean percent improvements in Nail Psoriasis Severity Index score at weeks 10 and 24 were 26.8% and 57.2%, respectively, in the infliximab group versus -7.7% and -4.1%, respectively, in the placebo group (both P < .001). At week 24, mean percent improvements in nail matrix and nail bed features were 52.9% and 69.2%, respectively (vs -1.9% and 18.4% for placebo; P < .001).
                The study did not evaluate nail response beyond 1 year.
                Patients with psoriasis receiving infliximab experienced marked and sustained nail improvement. nan The effect of grenz ray therapy in the treatment of psoriatic nails was assessed in 22 patients by randomly allocating active treatment to the psoriatic nails of one hand while the other one, which received simulated therapy, served as a control. Five Gy of grenz rays were applied on 10 occasions at intervals of 1 week. There was a significantly better response to active treatment compared with the untreated control. However, the therapeutic response was moderate. It is concluded that grenz ray therapy could be useful only when the psoriatic nails are of normal thickness. nan Treatment of psoriatic nail is difficult.
                The aim of this study was to evaluate and compare the efficacy and safety of methotrexate and cyclosporine in psoriatic nail.
                Thirty-seven psoriatic patients with nail involvement were randomized to treatment with methotrexate (initial dose, 15 mg per week) or cyclosporine (initial dose, 5 mg per kg of bodyweight per day) for 24 weeks. The primary outcome was the Nail Psoriasis Severity Index (NAPSI). The Psoriasis Area and Severity Index (PASI), doctor and patient global score were also measured. The scores were determined by a blinded observer.
                Seventeen patients completed the study in each group. The mean percentages of reduction of the NAPSI score after methotrexate and cyclosporine treatments were 43.3% and 37.2%, respectively. No significant differences between the treatment groups was found for in the NAPSI, PASI, physician's and patient's global score at the end of the study period. The methotrexate group showed a significant improvement in nail matrix scores and the cyclosporine group in nail bed score.
                Moderate effectiveness on psoriatic nail was found in the two treatment agents and there were no significant differences in efficacy between the groups. A significant improvement was detected in methotrexate group for the nail matrix findings, and in cyclosporine group for the nail bed findings.
                © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology. This phase 2/3, double-blind, placebo-controlled study was designed to assess the safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis. Overall, 158 patients were randomized to receive ustekinumab 45 or 90 mg at weeks 0, 4, and every 12 weeks, or placebo with cross-over to ustekinumab at week 12. The primary end-point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 12. Physician's Global Assessment (PGA), Dermatology Life Quality Index (DLQI), Nail Psoriasis Severity Index and joint pain Visual Analog Scale (VAS) were also measured. At week 12, 59.4% and 67.7% of ustekinumab 45 and 90 mg patients achieved PASI 75, respectively, compared with 6.5% in the placebo group (P < 0.0001 each). PASI 75 responses were maintained through week 64 in 65.0% and 78.6% of the ustekinumab-treated patients, respectively. Placebo cross-over patients had similar responses to ustekinumab-treated patients. Significant improvements in PGA, DLQI and VAS scores were observed at week 12 and generally maintained over time. Adverse events during the placebo-controlled period were similar among groups (45 mg, 65.6%; 90 mg, 59.7%; placebo, 65.6%). Serious adverse events were observed in 0%, 4.8% and 6.3% of patients, respectively. Through week 72, similar rates and types of adverse events and serious adverse events were reported in patients receiving 45 and 90 mg. Rates of injection site reactions and antibodies to ustekinumab were low. Ustekinumab was efficacious and generally well-tolerated in Japanese patients with moderate-to-severe plaque-type psoriasis through 72 weeks. These results are consistent with those reported in the global, phase 3 studies.
                © 2011 Japanese Dermatological Association. This double-blind randomized study was designed to compare the efficacy and safety of calcipotriol ointment (50 microg/g) with betamethasone dipropionate (64 mg/g) and salicylic acid (0.03 g/g) ointment in the treatment of nail bed psoriasis. Fifty-eight patients applied the given drug to the affected nails twice a day for 3-5 months, depending on clinical response. Efficacy was assessed monthly on the basis of nail thickness, measured in millimetres. Photographs of the treated nails were taken at baseline, and after 3 and 5 months. Tolerability was assessed at 3 and 5 months. In patients with fingernail psoriasis, after 3 months of treatment subungual hyperkeratosis was reduced from 2.3 +/- 0.1 mm (mean +/- SEM) to 1.5 +/- 0.1 mm (-26.5%) in the calcipotriol group and from 2.3 +/- 0.1 mm to 1.6 +/- 0.1 mm (-30.4%) in the betamethasone dipropionate and salicylic acid group [not significant (NS) between treatments, analysis of variance (ANOVA)]. After 5 months, responders showed a 49.2% reduction in hyperkeratosis in the calcipotriol group (from 2.8 +/- 0.1 mm to 1.4 +/- 0.2 mm) and 51.7% (from 2.1 +/- 0.1 mm to 1.0 +/- 0.1 mm) in the betamethasone dipropionate and salicylic acid group (P < 0.001 from baseline, NS between treatments, ANOVA). In patients with toenail psoriasis, after 3 months of treatment there was an overall reduction in hyperkeratosis from 2.6 +/- 0.1 mm to 2.1 +/- 0.1 mm (-20.1%) in the calcipotriol group and from 3.0 +/- 0.1 mm to 2.3 +/- 0.1 mm (-22. 9%) in the betamethasone dipropionate and salicylic acid group (P < 0.001 from baseline, NS between treatments, ANOVA). By the end of the fifth month there was a 40.7% reduction in hyperkeratosis in the calcipotriol group (from 2.1 +/- 0.1 mm to 1.2 +/- 0.1 mm) and 51.9% in the betamethasone dipropionate and salicylic acid group (from 2.7 +/- 0.1 mm to 1.3 +/- 0.1 mm; P < 0.0001 from baseline, NS between treatments, ANOVA). The results of the study show that calcipotriol is as effective as a combination of a topical steroid with salicylic acid in the treatment of nail psoriasis and represents a safe alternative in the topical treatment of nail psoriasis. A double-blind, randomized, vehicle-controlled, parallel-group trial was performed to compare the efficacy and tolerability of tazarotene 0.1% gel and vehicle gel in 31 patients with fingernail psoriasis. Patients were randomized to receive tazarotene or vehicle gel, which they applied each evening for up to 24 weeks to 2 target fingernails, one under occlusion and one unoccluded. The tazarotene treatment resulted in a significantly greater reduction in onycholysis in occluded nails (P < or = .05 at weeks 4 and 12) and a significantly greater reduction in onycholysis in nonoccluded nails (P < or = .05 at week 24). Tazarotene also resulted in a significantly greater reduction in pitting in occluded nails (P < or = .05 at week 24). There were no other significant between-group differences in pitting, subungual hyperkeratosis, leukonychia, nail plate crumbling/loss, splinter hemorrhage, or nail growth rate. Tazarotene 0.1% gel was well tolerated with only 5 of the 21 tazarotene-treated patients reporting a treatment-related adverse event (all mild or moderate). In conclusion, tazarotene 0.1% gel can significantly reduce onycholysis (in occluded and nonoccluded nails) and pitting (in occluded nails) and is well tolerated in the treatment of nail psoriasis. nan High-dose cyclosporine therapy significantly alleviates psoriasis within 2 to 4 weeks but is associated with a high rate of side effects. Reports are conflicting on the frequency and promptness of relapse after discontinuation of cyclosporine therapy.
                Our purpose was to compare the efficacy and safety of low-dose cyclosporine with that of etretinate and the stability of remission after replacing cyclosporine therapy with topical anthralin during tapering of cyclosporine.
                In a multicenter study 210 patients with moderate to severe chronic plaque-type psoriasis were randomly assigned to treatment with cyclosporine or etretinate. The initial dosages were 2.5 mg/kg/day for cyclosporine and 0.5 mg/kg/day for etretinate, which could be individually adjusted to 5.0 and 0.75 mg/kg/day, respectively. After a treatment phase of 10 weeks (phase 1) patients receiving cyclosporine were again randomly assigned to a group in which cyclosporine was replaced by topical dithranol (anthralin), or to another group in which the drug was tapered during the next 12 weeks (phase 2). All patients treated with etretinate discontinued therapy after 10 weeks and used topical dithranol.
                Mean Psoriasis Area and Severity Index decreased by 71% in the cyclosporine group and by 47% in the etretinate group during phase 1. After 10 weeks of treatment 47% of the patients treated with cyclosporine and 10% of those treated with etretinate showed a reduction of more than 80% in skin involvement. Sixty-four percent of the cyclosporine group and 48% of the etretinate group did not require an increase in the initial dosage, resulting in a mean daily dose of 3.0 and 0.53 mg/kg, respectively. There was significant alleviation of nail involvement and joint complaints in both groups. In phase 2 the increase in mean Psoriasis Area and Severity Index and the incidence of relapse were significantly higher in patients in whom cyclosporine was discontinued and replaced by dithranol than in patients in whom cyclosporine was tapered or who were pretreated with etretinate. During treatment four patients from the cyclosporine group and three patients of the etretinate group discontinued the study because of side effects.
                Low-dose short-term cyclosporine therapy for psoriasis is, in comparison with etretinate, highly effective and well tolerated. Individually adjusted cyclosporine therapy allows the majority of patients to continue the low dosage of 2.5 mg/kg/day and still achieve a good clinical response. Remission can be better preserved by tapering the drug than by discontinuing treatment abruptly. Nail involvement is a frequent event in the course of psoriasis causing severe distress. While systemic cyclosporin (CsA) represents a well-established therapy of psoriasis, its topical use is limited by the difficult penetration of the molecule through the skin and the nail because of its highly lipophilic nature.
                We carried out a prospective randomized placebo-controlled study in order to analyze the effectiveness and tolerability of topical oil-dissolved 70% CsA solution in nail psoriasis.
                Sixteen adult patients with nail psoriasis, divided randomly into two groups of 8 patients (group A and group B), were treated respectively with a 70% maize-oil-dissolved oral CsA solution and maize oil alone. To compare the therapeutic effectiveness, all patients were evaluated, before starting the treatment and after 12 weeks of therapy, by the same dermatologists. The patients were also asked to assess the severity of their nail involvement at baseline and at the end of the treatment.
                In group A, 3 patients came to a complete resolution of nail lesions and 5 showed a substantial improvement of the overall severity score. In group B, a slight improvement was noted in only 1 patient. All the patients of group A judged positively the results of the therapy, while in group B only 1 patient reported a moderate improvement.
                Our results show that topical therapy with oral CsA solution is a safe, effective and cosmetically highly acceptable treatment modality for nail psoriasis. The ability of CsA to influence keratinocyte proliferation and T-cell lymphokine release, reducing the cornification of the upper layers of the epidermis, may prevent the typical alterations observed in nail psoriasis.
                Copyright 2003 S. Karger AG, Basel We set out to show that the assumption is incorrect that continuous treatment with cyclosporin is necessary in psoriasis, as this tenet forms a basis for current recommended treatment regimens. Sixty patients with mild to moderate plaque psoriasis were allocated at random to treatment with oral cyclosporin 5 mg/kg/day (30 patients) or topical dithranol and ultraviolet B therapy (30 patients) for up to 16 weeks until clear (median time 6 weeks cyclosporin and 8 dithranol), and the times to relapse compared. The patients were seen monthly for up to 8 months, and the severity and the extent of psoriasis were assessed. Relapse, defined as return of psoriasis to 50% of the area at the start of the trial or patient demand for further treatment, was not significantly different between the groups (hazard ratio 1.11, 95% CI 0.55-2.32). No patients suffered a rebound of severe disease and none relapsed in the first 8 weeks after stopping treatment. The relapse rate was higher following cyclosporin from 8 to 28 weeks after treatment and following dithranol from 28 to 34 weeks. The patients with arthritis had a higher median joint severity score at relapse than prior to treatment with cyclosporin. At the end of 8 months, 5 patients treated with dithranol and 8 patients with cyclosporin remained clear, 75% and 67% having relapsed. We conclude that rapid relapse does not occur after clearance of mild to moderate plaque psoriasis with cyclosporin and the relapse rate was no different from dithranol treatment. Topically applied nail therapeutics need to permeate the nail plate to reach the nail bed or nail matrix and exert their potential beneficial effect at these locations to obtain a therapeutic benefit. So far only topically applied 5-fluorouracil on affected nails of psoriatic patients has been shown to produce a notable clearance. Vehicle formulations enhancing nail permeation processes are thought to increase the concentration of the active agent and therefore therapeutic efficacy, possibly enabling the use of a low concentration of the active agent thereby lowering the incidence of adverse effects.
                This study was designed to verify whether a recently developed nail penetration enhancer in a lotion formulation, Belanyx((R)) (urea, propylene glycol), improves the efficacy of a low concentration of 5-fluorouracil (1%) in psoriatic fingernail lesions.
                In a randomised, double-blind, left-right study the efficacy of 1% 5-fluorouracil in the Belanyx vehicle was compared to the vehicle preparation Belanyx in dystrophic fingernails of 57 psoriatic patients. Both preparations were applied in a once daily regimen for 12 weeks. Responses and adverse effects of one selected target nail were recorded at screening, at baseline and at weeks 2, 4, 8 and 12 of treatment with a final assessment at week 16: 4 weeks after the end of treatment. As parameter of efficacy was chosen the total nail area severity (NAS) score, consisting of the separate parameters nail pitting area, number of nail pits, subungual keratosis, onycholysis, oil spots and the various scores of overall improvement.
                The efficacy of 1% 5-fluorouracil in lotion and that of the vehicle in suppressing the parameters of dystrophy were shown to be similar at the end of treatment (p = 0.063) or follow-up (p = 0.130). Both preparations produced statistically significant improvements (p </= 0.05) for almost all assessed parameters after 12 weeks of treatment and after the 4 weeks of follow-up. For Belanyx lotion this applied to the nail pitting area, the number of nail pits, subungual keratosis, onycholysis and oil spots. The investigators' and patients' opinion of overall improvement of severity as well as the total NAS score of one target nail likewise showed a statistically significant improvement at the end of treatment and at the end of the observation period (p </= 0.05). With the 1% 5-fluorouracil lotion the same statistically significant improvements were obtained in all of the assessed symptoms with the exception of the number of pits and onycholysis at week 12 and week 16. Possible treatment-related adverse effects were established in 6 patients showing inflammation and infection (3 patients) or discoloration (5 patients); 3 patients on 5-fluorouracil lotion showed onycholysis.
                Addition of 1% 5-fluorouracil to the nail permeation enhancer Belanyx does not increase the efficacy of the active agent in psoriatic nail dystrophy of this study population. The obtained results also suggest that Belanyx lotion can be used in this indication since it has shown a favourable efficacy-safety ratio.
                Copyright (R) 2000 S. Karger AG, Basel In a double-blind controlled study, superficial radiotherapy (SRT) was given to psoriatic fingernails as three fractionated doses of 150 cGy (90 kV, 5 mA, 1.00 mm aluminium filter). The treated nails demonstrated a significant fall in scoring on a clinical rating scale 10 and 15 weeks after therapy (mean scores = 4.4 and 4.6 respectively) when compared with a mean pretreatment score of 5.5 at week 0 (p less than 0.0001 and p less than 0.05 respectively); the treated nails also showed significant clinical improvement when compared with the sham-treated nails at weeks 10 and 15 (p less than 0.05). Mean nail thickness in treated nails 15 weeks after therapy was significantly thinner (mean thickness = 0.75 mm) than that of sham-treated nails (0.88 mm, p = 0.005), but the difference was not significant at week 20. The rate of linear nail growth was unaffected. SRT appears to confer a definite albeit temporary benefit on psoriasis of the nails at this dosage.
Infliximab, golimumab, SRT, grenz rays, and electron beam caused significant nail improvement compared to the comparative treatment. Although the quality of trials was generally poor, this review may have some implications for clinical practice.
Although powerful systemic treatments have been shown to be beneficial, they may have serious adverse effects. So they are not a realistic option for people troubled with nail psoriasis, unless the patient is prescribed these systemic treatments because of cutaneous psoriasis or psoriatic arthritis or the nail psoriasis is severe, refractory to other treatments, or has a major impact on the person's quality of life. Because of their design and timescale, RCTs generally do not pick up serious side-effects. This review reported only mild adverse effects, recorded mainly for systemic treatments. Radiotherapy for psoriasis is not used in common practice. The evidence for the use of topical treatments is inconclusive and of poor quality; however, this does not imply that they do not work.
Future trials need to be rigorous in design, with adequate reporting. Trials should correctly describe the participants' characteristics and diagnostic features, use standard validated nail scores and participant-reported outcomes, be long enough to report efficacy and safety, and include details of effects on nail features.