Abstract
Nail involvement in psoriatic diseases causes significant physical and functional disabilities. Evaluating, measuring, and treating nail involvement is important in improving the health outcomes and quality of life among patients with psoriasis and psoriatic arthritis (PsA). We performed a systematic analysis of the literature on nail psoriasis to help inform an update of treatment recommendations by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
We performed 2 independent comprehensive literature searches of English-language human studies, published in the Medline database between January 1, 2006, and March 1, 2014, using the following search terms: psoriasis, psoriatic arthritis (PsA), nail, and treatment. Articles from the 2 searches were combined, and reference lists from articles from the database search were manually reviewed for additional relevant publications. Inclusion criteria were the following: adults (studies with > 5 patients) with psoriasis or PsA and psoriatic nail involvement, and clinical trials, case series, or observational studies of therapies for psoriatic nail disease. Authors independently extracted the data, and any disagreements were adjudicated by consensus. Results are summarized below and presented fully in Tables 1A–1E.
Topical therapies for nail psoriasis.
Topical Therapies1,2,3,4,5 (Table 1A)
Topical therapies, an initial option for patients with mild nail involvement without significant functional impairment, include calcipotriol, a synthetic analog of vitamin D3 (50 µg/g), alone or in combination with betamethasone diproprionate. Limited evidence supports modest efficacy in psoriasis limited to < 2 nails when used for ≥ 12 weeks1,2,3. Moreover, twice daily calcipotriol monotherapy may have modest efficacy similar to daily calcipotriol and betamethasone diproprionate combination therapy.
Tacrolimus, a nonsteroidal topical calcineurin inhibitor that downregulates antigen-specific T cell activity and proinflammatory cytokine production, may have modest efficacy when applied once daily for ≥ 12 weeks4.
Tazarotene, a third-generation topical retinoid available as a cream or gel, may have a modest effect when used once daily in patients with nail bed and nail matrix lesions of moderate severity affecting > 2 nails1,5.
5-fluorouracil (5-FU), an antimetabolite that inhibits pyrimidine synthesis, has been used to treat actinic keratosis and squamous cell carcinoma in situ. However, topical 5-FU 1% lotion was no more effective than vehicle lotion when used daily for 12 weeks in patients with severe psoriatic nail dystrophy in ≥ 1 nail1.
Procedural Therapies1,2,6,7 (Table 1B)
Procedural therapies for nail psoriasis.
The 595-nanometer pulsed dye laser (PDL) has been used to treat moderate-to-severe psoriatic nails monthly for ≥ 6 months with limited efficacy6,7. Longer pulse durations (e.g., 6 ms vs 0.45 ms) do not appear to result in greater efficacy and may cause greater side effects, such as pain6,7.
Limited evidence suggests that intralesional corticosteroid injections may be moderately effective in treating psoriatic nail dystrophies, particularly abnormalities of the nail matrix. However, studies vary on dosing and frequency, and many lack sufficient patient characteristics, e.g., severity and type of psoriatic disease1. Typically, 0.05–0.3 ml of triamcinolone acetonide 2.5–10 mg/ml is injected at multiple sites in the proximal nailfold at weekly intervals for ≤ 5 months2.
Traditional Oral Systemic Therapies1,8-16 (Table 1C)
Traditional oral systemic therapies for nail psoriasis.
Although traditional systemic therapies have not been rigorously tested, oral cyclosporine, an immunosuppressant drug that interferes with activity and growth of T cells, has modest efficacy in nail psoriasis1,8,9,10,11. Oral methotrexate (MTX, ≤ 15 mg weekly), an antimetabolite and antifolate drug commonly used to treat psoriasis and inflammatory arthritis, has been tested rigorously, but is unlikely to result in significant improvement in psoriatic nail disease8,9,12,13,14. Briakinumab [an interleukin 12/23 (IL-12/23) inhibitor no longer in development] was superior to MTX in 1 study13. Acitretin, a second-generation retinoid and a metabolite of etretinate, had modest efficacy at doses of 0.2–0.3 mg/kg/day for 6 months1,9,14,15. Leflunomide, an oral pyrimidine synthesis inhibitor, also had modest efficacy in psoriatic nail dystrophy when dosed at 100 mg/day for 3 days, then 20 mg/day for 24 weeks16.
Biologic Therapies1,9,11,14,17-41 (Table 1D)
Biologic therapies for nail psoriasis.
Tumor necrosis factor-α (TNF-α) plays a key role in the pathogenesis of psoriasis and PsA, and can interrupt TNF signaling, thereby leading to improvements in nail dystrophy. In several controlled studies, adalimumab (ADM)9,11,14,17,18,19,20,21,22,23,24, certolizumab pegol25, etanercept9,14,22,23,24,26,27, golimumab28,29, and infliximab1,9,14,22,23,24,30,31,32,33,34,35 were highly efficacious in treating psoriatic nail disease. Larger studies are necessary to determine comparative effectiveness of these agents9,14,22,23,24.
Ustekinumab, an anti-IL-12/23 monoclonal antibody, was highly effective in treating nail psoriasis, when weight-based dosing was used36,37,38,39,40. Limited data show that IL-17 blockade with ixekinumab (> 75 mg subcutaneously) also appears to be effective41.
Combination Therapies11,42 (Table IE)
Combination therapies for nail psoriasis.
Literature on combination therapies for nail psoriasis is limited. In 1 single-blind, within-patient trial of PDL (595 nm, 1.5 ms pulse duration) plus topical 0.1% tazarotene cream compared to topical tazarotene alone, a significantly greater mean decrease in nail matrix modified NAPSI score was observed with PDL-tazarotene compared to tazarotene alone42.
In a nonrandomized, unblinded study of ADM plus cyclosporine (CSA) compared to ADM monotherapy and CSA monotherapy, 100% of patients receiving combination therapy reported > 50% improvement in mean NAPSI score at week 12 compared to patients receiving either CSA (44%) or ADM (56%) alone11.
In conclusion, nail psoriasis results in significant morbidity and warrants adequate treatment. Topical therapies may be an initial option, but their efficacy is modest. Procedural therapies require more investigation to determine their efficacy. Traditional oral therapies, e.g., MTX or CSA, may be helpful at high doses. The most rigorously studied therapies are biologic agents, with evidence suggesting that TNF-α inhibitors and IL-12/23 inhibitors are highly efficacious in treating nail psoriasis.
REFERENCES
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