Abstract

Background

Psoriasis is a common skin disease that can also involve the nails. All parts of the nail and surrounding structures can become affected. The incidence of nail involvement increases with duration of psoriasis. Although it is difficult to treat psoriatic nails, the condition may respond to therapy.

Objectives

To assess evidence for the efficacy and safety of the treatments for nail psoriasis.

Search methods

We searched the following databases up to March 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched trials databases and checked the reference lists of retrieved studies for further references to relevant randomised controlled trials (RCTs).

Selection criteria

All RCTs of any design concerning interventions for nail psoriasis.

Data collection and analysis

Two authors independently assessed trial risk of bias and extracted the data. We collected adverse effects from the included studies.  

Main results

We included 18 studies involving 1266 participants. We were not able to pool due to the heterogeneity of many of the studies.

Our primary outcomes were 'Global improvement of nail psoriasis as rated by a clinician', 'Improvement of nail psoriasis scores (NAS, NAPSI)', 'Improvement of nail psoriasis in the participant's opinion'. Our secondary outcomes were 'Adverse effects (and serious adverse effects)'; 'Effects on quality of life'; and 'Improvement in nail features, pain score, nail thickness, thickness of subungual hyperkeratosis, number of affected nails, and nail growth'. We assessed short‐term (3 to 6 months), medium‐term (6 to 12 months), and long‐term (> 12 months) treatments separately if possible.

Two systemic biologic studies and three radiotherapy studies reported significant results for our first two primary outcomes. Infliximab 5 mg/kg showed 57.2% nail score improvement versus ‐4.1% for placebo (P < 0.001); golimumab 50 mg and 100 mg showed 33% and 54% improvement, respectively, versus 0% for placebo (P < 0.001), both after medium‐term treatment. Infliximab and golimumab also showed significant results after short‐term treatment. From the 3 radiotherapy studies, only the superficial radiotherapy (SRT) study showed 20% versus 0% nail score improvement (P = 0.03) after short‐term treatment.

Studies with ciclosporin, methotrexate, and ustekinumab were not significantly better than their respective comparators: etretinate, ciclosporin, and placebo. Nor were studies with topical interventions (5‐fluorouracil 1% in Belanyx® lotion, tazarotene 0.1% cream, calcipotriol 50 ug/g, calcipotriol 0.005%) better than their respective comparators: Belanyx® lotion, clobetasol propionate, betamethasone dipropionate with salicylic acid, or betamethasone dipropionate.

Of our secondary outcomes, not all included studies reported adverse events; those that did only reported mild adverse effects, and there were more in studies with systemic interventions. Only one study reported the effect on quality of life, and two studies reported nail improvement only per feature.

Authors' conclusions

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.

Author(s)

Anna Christa Q de Vries, Nathalie A Bogaards, Lotty Hooft, Marieke Velema, Marcel Pasch, Mark Lebwohl, Phyllis I Spuls

Abstract

Plain language summary

Treatments for nail psoriasis

Psoriasis is a common chronic skin disease with a prevalence in 2% to 3% of the population, according to European studies. Involvement of the nails occurs in about 50%. Nail psoriasis is difficult to treat, but may respond to some treatments. We aimed to review the efficacy and safety of the treatments used for nail psoriasis.

We included 18 randomised controlled clinical trials (RCTs), which involved 1266 participants and were mostly based on a single study per treatment. Ten studies assessed topical treatments, i.e. applied to the surface of the skin (clobetasol, ciclosporin in maize oil, hyaluronic acid with chondroitin sulphates, 5‐fluorouracil, a combination of dithranol with salicylic and UVB, tazarotene, and calcipotriol); 5 studies assessed systemic treatments, i.e. taken orally (golimumab, infliximab, ustekinumab, ciclosporin, and methotrexate); and 3 studies assessed radiotherapy (electron beam, grenz ray, and superficial radiotherapy). With regard to other treatments that are used for nail psoriasis, no RCTs had been carried out.

It was not possible to pool and compare the results because the studies were all so different.

In 5 studies, we found significant improvement of nail psoriasis compared to placebo: with infliximab (5 mg/kg), golimumab (50 mg and 100 mg), superficial radiotherapy, electron beam, and grenz rays.

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 a candidate for these systemic treatments because of skin psoriasis or psoriatic arthritis. 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. Topical treatment options could be beneficial and need to be further investigated.

Clinical trials on nail psoriasis need to be rigorous in design, with clear reporting to enable readers to better interpret the results. Trials should accurately describe the participants' characteristics and diagnostic features of nail psoriasis; use standard validated nail scores and patient‐reported outcomes; be long enough to report efficacy and safety; and include more details of effects on nail features.

Author(s)

Anna Christa Q de Vries, Nathalie A Bogaards, Lotty Hooft, Marieke Velema, Marcel Pasch, Mark Lebwohl, Phyllis I Spuls

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

The included studies in this review often showed a lot of heterogeneity and very limited evidence per treatment type (often only one study per treatment), so meta‐analysis of the data was not possible. The quality of studies was low.

Clinical decision‐making on the choice of intervention for nail psoriasis should be based on high‐level evidence if it is available. In the absence of such high‐level evidence for use of an intervention, decisions should be based on the best available evidence. This is sometimes clinical experience and may be based on an individual person's characteristics and preferences.

The studies on the biologicals infliximab 5 mg/kg (Rich 2008), golimumab 50 mg, and golimumab 100 mg (Kavanaugh 2009) reported significant results compared to placebo with regard to the primary outcome 'Improvement of nail psoriasis'. This was after short‐ (until 12 weeks) and medium‐term (12 to 24 weeks) treatment. After 24 weeks of treatment, infliximab 5 mg/kg and golimumab 100 mg reported greater than 50% nail score improvement compared to placebo, which was significant. Electron beam (Kwang 1995), grenz rays (Lindelof 1989), and superficial radiotherapy (Yu 1992) reported significant results compared to placebo with regard to the primary outcome 'Improvement of nail psoriasis' after short‐term treatment.

The studies with topical ciclosporin 70% in maize oil (applied twice daily for 12 weeks, Cannavo 2003) and tazarotene cream compared to clobetasol (once daily under occlusion for 12 weeks, Rigopoulos 2007) showed > 75% nail improvement compared to baseline after short‐term treatment. These data were all based on one study per treatment. These studies did not use standard outcome measures to assess nail psoriasis.

Unfortunately, the medium‐term studies (12 to 24 weeks of treatment) (e.g. systemic therapy) had no measure points on the short‐term (up to 12 weeks of treatment), which made comparison with the short‐term studies impossible. The treatments for psoriasis nail features were also difficult to compare because the included trials often did not assess the same nail features during treatment. Furthermore, trials with systemic interventions were primarily for cutaneous psoriasis trials, where nail features were mostly not specified.

Eleven studies reported separate data on nail features (our secondary outcome parameter), of which 3 of the 4 studies discussed here showed significant results. After 90 days' treatment with hyaluronic acid and chondroitin sulphate, there was a significant improvement in onychorrhexis (P = 0.039), onycholysis (P = 0.041), and hyperkeratosis (P = 0.041) in the participants (Flori 1994). After treatment with tazarotene gel, there was a significant improvement in those with onycholysis and pitting. Onycholysis improved after treatment under occlusion at weeks 4 and 12 (P < 0.05), and at week 24 without occlusion (P < 0.05). Pitting improved under occlusion at week 24 (P < 0.05) (Scher 2001). Oil drop discolourations significantly improved after 12 weeks' treatment with calcipotriol 0.005% (P < 0.039) (Tzung 2008). One study (infliximab (Rich 2008)) showed a significant decrease in the occurrence of individual features over time.

The benefits of systemic interventions should be balanced against their possible harms. Powerful systemic treatments have been shown to be beneficial, but they may often not be a realistic option for people troubled with nail psoriasis because of side‐effects, unless they are candidates for these systemic treatments because of their cutaneous psoriasis. Current RCTs generally do not pick up serious side‐effects because of their timescale and design, which is probably why this review was only able to report mild adverse effects for systemic treatment. Some topical therapies were shown to be beneficial and seemed to cause fewer adverse effects. Radiotherapy treatments for psoriasis are not generally used in common practice.

Randomised controlled trials for psoriasis treatments that include the assessment of nail psoriasis are lacking, for example, other topical corticosteroids, acitretin, UV therapy, laser, and biologics like adalimumab and etanercept that need further research. The lack of evidence for these interventions does not mean the treatments don't improve nail psoriasis. In particular, evidence for topical treatment should be further investigated as these play a major role in common prescribing practice. Also, treatments with conflicting results need further research.

Implications for research 

More RCTs on nail psoriasis are needed, assessing the efficacy and safety of possible treatments, e.g. topical treatments compared to each other, topical versus systemic therapy, conventional systemic therapy compared to biologics, biologics head‐to‐head.

The quality of studies should be improved. To compare studies, clinical homogeneity should be reached by clear descriptions of the populations, e.g. isolated nail psoriasis or with skin involvement, type of nail psoriasis (nail matrix and nail bed psoriasis), disease severity, treatment dosage and frequency, durations of treatment (long enough), outcome measurements (like point scales and nail scores (NAPSI, NAS); participants' reported outcomes, such as quality of life; and adverse effects), and time points of assessments, including long enough follow up to be meaningful.

Participants with nail psoriasis could have a solitary nail psoriasis problem or have psoriasis of the skin, joints with nail involvement, or both. Studies dealing with the overall impact of systemic treatments for psoriasis may report on nail psoriasis as a secondary outcome. In the future, separate trials including participants with only nail psoriasis would be welcome. These studies should describe participants' characteristics, results (with validated nail scores), adverse effects, and separate information on dropouts for those with nail psoriasis. Patient‐reported outcomes, such as 'quality of life', are important outcomes because of the great impact nail psoriasis can have on daily life.

The RCTs in our review included treatment durations of 12 to 64 weeks. The duration of treatment in the included studies was often short. To regrow a nail completely takes at least six months (de Jong 1999), so to obtain clear evidence for the efficacy of an intervention, a trial with a duration of at least six months is necessary. These studies may have obtained better results if the duration had been appropriate. As shown by Igarashi 2012 and Rich 2008, at 64 weeks and 46 weeks of treatment, respectively, the nail score improvement was considerably increased compared to the short‐term measure point, and it was maintained compared to the medium‐term measurement. Therefore, future trials must be performed with sufficient duration to report the efficacy of the intervention. In addition, the follow up must be long enough, because follow up and the rate of relapse after treatment discontinuation is also of clinical importance.

Harmonised and validated outcome measures are necessary for evaluating nail psoriasis. There are some validation studies for the NAPSI. Aktan 2007 investigated the interobserver reliability of the NAPSI, graded by 3 dermatologists looking at 25 participants. They found a moderate to good scoring agreement with the NAPSI. Cassell 2007 showed in participants with psoriatic arthritis, a modified NAPSI (mNAPSI), with an inter‐rater reliability and construct validity. A nail score (like NAPSI, mNAPSI, or NAS) is required to assess and compare the improvements of different trials. For quality criteria for outcome measures, the COSMIN (consensus‐based standards for the selection of health measurement instruments) checklist can be used (Mokkink 2010).

Also, studies reported methodological heterogeneity, e.g. incomplete data about the internal validity. Future trials need to be rigorous in design, which reduces bias. High‐quality descriptions of all aspects of methodology will improve the interpretation of results. This could be achieved by following the Consolidated Standards of Reporting Trials (CONSORT) statement checklist in future trials (Schulz 2010). For internally‐controlled trials with topical treatments, one should be aware of the systemic impact of the carry‐over effect on the compared finger or toenail.

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