Nail Psoriasis: Treatment Options and Management Strategies in Special Patient P

Xu-Yue Zhou, Jia-An Zhang, Kun Chen∗

Department of Physical Therapy, Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, Jiangsu 210042, China.

Abstract Nail involvement is common in psoriasis and is considered a risk factor for and a predictor of the development of psoriatic arthritis.The treatment of nail psoriasis is challenging because of the unique anatomical structure of nails and the absence of standardized treatment protocols.Herein,we provide an up-to-date overview of the treatment options for nail psoriasis,including topical drugs and penetration enhancement strategies,traditional and novel oral drugs,and biologic agents. In addition, we highlight the available individualized management strategies in special patient populations such as pediatric patients, geriatric patients, women of childbearing age, and patients with concomitant onychomycosis or psoriatic arthritis.

Keywords: nail psoriasis, onychomycosis, psoriatic arthritis, treatment

Introduction

Psoriasis is a chronic inflammatory skin disease mediated by T-cells.In addition to the classical skin manifestations,nail involvement is common in psoriasis, with a documented prevalence of 10%to 80%and an estimated lifetime incidence of 80% to 90%, while isolated nail psoriasis is present in only 5% to 10% of patients.1

The nail structure protects the fingertips from traumatic injuries and enhances the ability of the fingers to make precise movements when manipulating small objects.Although the affected surface area is small, nail psoriasis may seriously decrease quality of life because of the great psychosocial, aesthetic, physical, and even economic burden. However, the management of nail psoriasis is difficult due to the special anatomical structure and long growth cycle of nails. As there is no standardized therapeutic regimen for nail psoriasis, we searched in PubMed with terms of “nail psoriasis,” “nail,” and“psoriasis” for relevant literature from January 2000 to June 2020. We herein review and summarize the latest developments in nail psoriasis therapy(Fig.1)and propose individualized management strategies in special patient populations (Table 1).

Nail psoriasis

The clinical manifestations of nail psoriasis depend on the affected locations, as the condition can involve the nail matrix and/or nail bed. Nail matrix inflammation is characterized by nail pitting, red spots in the lunula,leukonychia, and crumbling.2Nail pitting is the most common finding in nail psoriasis and reflects the duration of disease,which is positively correlated with the length of a pit.Nail pitting may develop into transverse grooves as an increasing area of the dorsal nail matrix is affected by psoriasis. Compared with the pits that appear in other diseases, such as eczema, alopecia areata, and lichen planus,the pits are usually larger and deeper in people with nail psoriasis. With intermediate and ventral matrix involvement, the nail can present with red spots in the lunula and leukonychia.Long-term severe involvement of the entire nail matrix causes the nail plate to become crumbly.

Figure 1. Overview of the treatment options for nail psoriasis.

Nail bed involvement causes oil drop patches, onycholysis,subungual hyperkeratosis,and splinter hemorrhages.3Focal nail bed parakeratosis leads to the accumulation of serum and cellular debris under the nail bed, which manifests as an oil spot or salmon patch. The extension ofoildroppatchestothehyponychium leadstoonycholysis.The deposition of cells that have not undergone desquamation can cause subungual hyperkeratosis, which is the raising of the nail plate off the nail bed.The detachment of the nail plate from the nail bed offers a moist subungual space and thus contributes to the development of fungal infections.

Nail psoriasis is easily diagnosed in patients with cutaneous manifestations of joint involvement. However,in patients with isolated nail psoriasis,caution is required when differentiating between nail psoriasis and other nail diseases (especially onychomycosis) because the clinical manifestations of nail psoriasis are non-specific. Nail biopsy should be used with great caution due to the risk of scarring and reduction of the nail width. Periodic acid-Schiff staining is recommended for differentiating between nail psoriasis and onychomycosis.3In addition, new diagnostic techniques include dermatoscopy,nail clipping,capillaroscopy,ultrasound(US),optical coherence tomography, and confocal laser scanning microscopy.

There is currently no consensus on the ideal nail psoriasis scoring system.The Nail Psoriasis Severity Index(NAPSI) is an objective tool most frequently used to evaluate the severity of nail psoriasis based on the extent of involvement and location in the nail unit. The nail is divided into four quadrants, and the presence of any manifestations in the nail matrix and nail bed as described above is respectively evaluated; therefore, each nail has a matrix score of 0 to 4 and a nail bed score of 0 to 4,and the maximum score for each nail is 8.4However,as the NAPSI is time-consuming in clinical practice and fails to evaluate the severity of each lesion and the impact on quality of life,many other scoring systems have been created, including the modified NAPSI and the Nail Assessment in Psoriasis and Psoriatic Arthritis. There is a strong consensus that few-nail disease should be defined as nail psoriasis affecting ≤3 nails, and that a NAPSI of <20 indicates mild disease.Furthermore,the nail psoriasis severity scale is used to define nail psoriasis as minimal (<10% of the maximum severity index score), mild (10%–25% of the maximum score), moderate (26%–50% of the maximum score), and severe (>50% of the maximum score).3

Table 1 Treatment strategies for nail psoriasis

Treatment options for nail psoriasis

Patient education

Similar to cutaneous psoriasis, the onset of psoriatic nail changes may be closely associated with Koebner isomorphic response induced by mechanical trauma. Clinicians should recommend the necessary precautions to minimize the Koebner phenomenon.Nails should be kept short and protected from injury by wearing gloves and applying emollient creams on the hands and nails. Habitual biting and tearing of nails should be corrected, especially in children. Patients with nail psoriasis should avoid frequently applying and removing nail cosmetics,excessive manicuring,and wearing poorly fitting shoes.Considering the slow growth of the nail (3–4 mm every month, or 5–7 months from the nail matrix to the distal fingertip),the need for long-term treatment should be emphasized to improve patient compliance.

Topical therapies

Topical drugs

In patients with nail psoriasis exclusively, the disease should be managed with topical therapies alone. It is essential to distinguish nail matrix psoriasis from nail bed psoriasis due to the differences in permeability and physical structure between the nail matrix and bed. For psoriasis affecting the nail matrix,topical agents should be applied to the proximal nail fold. For psoriasis affecting the nail matrix only,the recommended first-line treatment is intralesional steroid injections through the proximal nail fold;3the injection of triamcinolone acetonide(maximum of 0.1–0.5 mL every 4–8 weeks)is still the most common method. Considering the severe pain and technical difficulty involved in administering steroid injections into the nail bed,the preferred treatment for patients with nail bed involvement only is the topical application of highpotency corticosteroids alone or in combination with topical vitamin D analogs.2A single-center, intrapatient,the prospective study reported that calcipotriol/betamethasone dipropionate(Cal/BD)is very effective in treating nail psoriasis,especially of the nail bed,with a significant 61% reduction in the mean nail bed score from 3.55 at baseline to 1.4 after treatment.5

Besides steroids and vitamin D analogs, other common topical treatments include tazarotene, topical calcineurin inhibitors, anthralin, 5-fluorouracil, topical cyclosporine,and indigo naturalis extract. A recent, uncontrolled,prospective study of 20 patients with nail psoriasis showed that weekly injections of 2.5mg intramatricial methotrexate (MTX) for 6weeks significantly decreased the NAPSI score from 3.70 to 0.67,with minimal adverse effects and no recurrence in 1year of follow-up.6Therefore, considering the long-term safety, MTX may be a desirable alternative to steroids for intralesional injection. Further study on intralesional MTX injection is warranted.Penetration enhancement strategies for topical therapy

The key to the success of topical therapy is sufficient penetration of drugs into the nail plate. This drug penetration is affected by permeant characteristics (such as molecular size, lipophilicity, and ionic strength),formulation properties (like the nature and pH of the vehicle),nail plate properties(including disease state,nail thickness, hydration, and keratin content), and drug–keratin interactions.7Therefore, topical drugs must be coupled with an appropriate delivery system that can be augmented by mechanical, chemical, and physical methods, especially when treating nail bed psoriasis.

In nail bed psoriasis, the onycholytic part of the nail plate should be clipped off.3Mechanical nail abrasion or surgical removal have been used for many years,but these methods are invasive and potentially painful. Physical methods such as iontophoresis and laser therapies show a high degree of safety and effectiveness in the application of a transungual delivery system. A bilateral, controlled,clinical trial that compared the efficacy of triamcinolone acetonide iontophoresis(TI)versus Cal/BD in 16 patients reported a reduction in the initial NAPSI at the third and fourth follow-up, respectively, in seven (43.75%) and 13(81.25%) patients who received TI, compared with three(18.75%) and 10 (62.5%) patients who received topical Cal/BD;8TI had a more rapid onset of improvement and equal impact on nail bed lesions than topical Cal/BD,without any adverse effects.9In addition, light and laser therapies are applied to improve the penetrability of the nail and increase the vasculature and dermal angiogenesis.A prospective, intrapatient, randomized, placebo-controlled study reported that four sessions of Nd:YAG laser therapy resulted in a significant reduction in the nail matrix, nail bed, and total NAPSI scores in 22 patients.Furthermore,the nail bed showed more improvement than the nail matrix after 4months of therapy and at final follow-up, especially regarding onycholysis, oil drop patches, and subungual hyperkeratosis; this may be due to the increased number of vascular structures in the nail bed than the matrix.10

The formulation selected to deliver antipsoriatic pharmaceuticals is an important part of the transungual delivery system. Compared with lipophilic molecules,hydrophilic molecules better penetrate the nail structure because of the low lipid content in the nail.7Although an aqueous formulation is superior to a lipophilic formulation in enhancing permeation,it has limited use in topical applications because it is easily removed and shows less adherence to the applied surface. Colloidal drug delivery systems (including nail lacquers, adhesive patches, and gels) have attracted attention in recent years due to advantages in the enhancement of nail hydration because of their occlusive properties and long residence time.7A randomized, double-blind, placebo-controlled, parallelgroup trial confirmed the superior effectiveness and tolerability of a hydrosoluble nail lacquer containing hydroxypropyl-chitosan,Equisetum arvense,and methylsulfonylmethane;11the hydroxypropyl-chitosan nail lacquer achieved a significantly better clinical cure rate than placebo in both the intention-to-treat and per-protocol populations.11The use of novel hydrophilic formulations to treat nail psoriasis is promising, but the research work and commercialization in developing a highly effective topical delivery system is still lagging.

Systemic therapies

Traditional oral drugs

Systemic treatment is usually advised for patients with>3 nails involved,those resistant to topical therapy, or those for whom the disease has significantly decreased their quality of life, especially those with concomitant skin manifestations and arthritic symptoms.3Acitretin, MTX,and cyclosporine are the systemic agents that have been most extensively explored in the treatment of nail psoriasis. Low-dose systemic acitretin should be used in the initial treatment of nail psoriasis until at least a moderate improvement is documented;patients should be monitored for adverse effects of acitretin, such as intense brittleness, onycholysis, and pyogenic granulomas. A retrospective study of 84 patients reported that the percentage change in the NAPSI was significantly higher in patients treated with cyclosporin than in patients treated with acitretin and MTX.12A prospective study of 37 patients with nail psoriasis suggested that MTX and cyclosporine had similar moderate effectiveness after 24 weeks of treatment.8Interestingly, the MTX group showed a significant improvement in the nail matrix score while the cyclosporine group showed a significant improvement in the nail bed score;8this is probably due to the stronger effect of MTX on rapidly dividing cells,and the poor penetration of cyclosporine in the nail matrix.8

Novel oral drugs

The limitations of traditional oral systemic treatments include unsatisfactory and slow-onset efficacy, toxicity,and teratogenicity.However,emerging oral drugs such as Janus-associated kinase(JAK)inhibitors,phosphodiesterase 4 inhibitors, and other anti-inflammatory compounds may offer more treatment options for nail psoriasis.Tofacitinib is a small-molecule JAK inhibitor that selectively inhibits JAK1 and JAK3. A post hoc analysis of two 52-week, randomized, multisite, phase 3 studies including 1,196 patients with moderate-to-severe plaque psoriasis showed that treatment with either 5 or 10mg tofacitinib twice daily resulted in significant improvements in nail psoriasis versus placebo from week 16 to week 52.13Apremilast elevates the level of intracellular cyclic adenosine monophosphate and downregulates the expression of pro-inflammatory cytokines. Two-phase 3, randomized, controlled trials showed that apremilast significantly reduced the severity of nail psoriasis, with a significantly greater NAPSI50 response versus placebo from week 16 to week 52.14These novel oral therapeutic options for moderate-to-severe plaque psoriasis with nail involvement are promising, but require further clinical studies and long-term prospective cohort studies to confirm the long-term safety and efficacy.

Biologic agents

Targeted biological therapy is a new trend in the treatment of nail psoriasis in patients with concomitant severe skin and arthritic manifestations or in patients for whom other basic topical and systemic anti-psoriatic methods are not sufficiently effective.

The first biological agents developed for the treatment of psoriasis were tumor necrosis factor-α(TNF-α)inhibitors,including infliximab, etanercept, adalimumab, golimumab, and certolizumab. One study showed that all anti-TNF agents (including infliximab, etanercept, and adalimumab) resulted in a significant improvement in the NAPSI;11in particular,infliximab had the greatest efficacy followed by adalimumab at weeks 12 and 24, but the differences between agents disappeared at week 48.11A retrospective study suggested that adalimumab, infliximab, etanercept, and ustekinumab have equal effectiveness in reducing the NAPSI,but require a longer treatment period to achieve a satisfactory outcome for patients with nail psoriasis compared with those with psoriasis without nail involvement.15Certolizumab pegol is a humanized mouse monoclonal antibody against TNF-α modified by PEGylation. One retrospective study of 56 patients with psoriasis arthritis (PsA) and nail involvement reported a significant decrease in the mean modified NAPSI from 14.64 at baseline to-12.92 at week 52.16Golimumab is a human monoclonal anti-TNFα antibody that has been approved for use in treating PsA.Golimumab also seems to be beneficial for psoriatic nails in patients with PsA,resulting in a significantly greater improvement in the median target lesion score from baseline to weeks 14 and 24 versus placebo.17

Although the pathogenesis of psoriasis is complex and not fully elucidated,it is thought to mainly involve IL-23-mediated regulation of the Th17 pathway.Ustekinumab is an IgG1κ monoclonal antibody that specifically inhibits the p40 subunit of IL-12/23.In the PHOENIX 1 study (a prospective, randomized, controlled trial designed to evaluate nail psoriasis),ustekinumab effectively improved nail manifestations in 545 patients for up to 1 year,regardless of the presence or absence of PsA.18Furthermore, another prospective study of 13 patients with nail involvement showed that ustekinumab achieved significant improvement in splinter hemorrhages, but no improvement in subungual hyperkeratosis and red spots in the lunula after 52 weeks of treatment;19this suggests that treatment effects on the nail bed appear earlier than those on the nail matrix, and relatively long treatment may be required for nail matrix disease.

IL-17 inhibitors are a class of biologics including secukinumab, ixekizumab, and brodalumab that target either the IL-17 ligand or its receptor. In the TRANSFIGURE study, a randomized, placebo-controlled, parallelgroup, multicenter, phase 3b trial including 198 patients with moderate-to-severe nail psoriasis,different dosages of secukinumab were compared with placebo to evaluate the long-term efficacy and safety.20It is the first study to demonstrate that secukinumab therapy provides a strong,clinically meaningful, and durable response for up to 2.5 years;300mg and 150mg doses of secukinumab achieved mean NAPSI improvements of -73.3% and -63.6%,respectively.20Ixekizumab is a humanized monoclonal antibody against IL-17A.The IXORA-S study(a multicenter,randomized,head-to-head trial comparing ixekizumab and ustekinumab), demonstrated that ixekizumab had a greater ability to clear nail psoriasis than ustekinumab at 1 year oftreatment.More patients achieveda NAPSI of0 with ixekizumab(61.9%)versus ustekinumab(28.6%)during a 52-week period.21Brodalumab is a fully human monoclonal antibody that inhibits IL-17 receptor α. In phase 3,randomized,placebo-controlled studies(AMAGINE-1,-2,and-3),more patients who received brodalumab achieved a NAPSI of 0 at week 52(63.8%)compared with those who received ustekinumab (39.1%).22Both ixekizumab and brodalumab are reportedly superior to ustekinumab in the treatment of psoriatic nail changes,and further research is warranted to determine whether IL-17 is more important than other ILs in the pathogenesis of nail psoriasis.

Nail psoriasis in special populations

Pediatric patients

Early intervention is advocated, as nail involvement is considered a potential predictor of a more severe disease course and higher morbidity of palmoplantar psoriasis and PsA.The most common clinical feature of nail psoriasis in children is nail pitting, which is more frequent on fingernails rather than toenails; the second is onycholysis associated with subungual hyperkeratosis, which is more evident in toenails than fingernails. The combination of calcipotriol and betamethasone dipropionate is safe and effective in treating pediatric nail psoriasis.23Intralesional steroid injections may be hard to execute due to the sharp pain and poor compliance. One case report showed the therapeutic value of 0.05%tazarotene gel in a 6-year-old girl with nail psoriasis,24while another reported that indigo naturalis oil extract drops successfully treated psoriatic nails with a periodic pustular eruption in a 13-year-old girl.25None of the traditional oral agents are approved by the USA Food and Drug Administration for the treatment of pediatric psoriasis; however, they are considered safe for intermittent and short-term use in the pediatric population. Oral drugs approved for use in children by the Food and Drug Administration or the European Medicines Agency include etanercept (for patients ≥4years), ustekinumab (for patients ≥12years),and adalimumab(for patients ≥4 years).In one report,an 8-year-old girl with nail psoriasis resistant to multiple therapies was successfully treated after 3months of secukinumab (150 mg monthly).26However, no study has evaluated the efficacy and safety of treatments for nail psoriasis in children. In addition, pediatric patients with nail involvement have a high risk of metabolic comorbidities. Therefore, it is important for children with nail psoriasis to undergo regular weight monitoring, follow a healthy lifestyle, and manage stress.

Geriatric patients

Nail plates grow at a slower rate and have a smaller negative impact on patient quality of life with age. In contrast to the toenails, which thicken with age, the fingernails become thinner with age.The treatment of nail psoriasis in older adults follows the therapeutic regimen of adults in clinical practice. However, some characteristics of the geriatric population should be considered when proposing a therapeutic protocol. It may be difficult for older adults with poor flexibility, dexterity, and vision to apply medicine frequently,and so it is important to select topical agents with long-lasting formulations. The frequency of application should be adjusted in accordance with the difference in the thickness of the fingernails versus the toenails. MTX and cyclosporine should be used with great caution and at lower doses in older adults due to the higher incidence of adverse effects such as renal impairment, hepatotoxicity, or hypertension. The incidence of adverse events is significantly higher in older adults treated with cyclosporine versus MTX.27In comparison, acitretin may be more acceptable, as the resulting xeroderma and hyperlipemia can generally be well controlled and are rarely life-threatening. Clinicians should be aware of the risk of possible drug interactions,particularly in geriatric patients who are more likely to have concomitant diseases and need to take multiple drugs.In addition, the incidence and type of adverse events in elderly patients treated with apremilast and biologic agents(including infliximab, etanercept, adalimumab, or certolizumab)do not significantly differ from those in younger patients.28Apremilast and biologic agents are expected to be safe and effective options after rigorous screening and monitoring of elderly patients,although further long-term clinical studies are warranted.

Women of childbearing age

For ethical reasons, it is not practical to conduct prospective, randomized, controlled trials of women who are pregnant, lactating, or planning to become pregnant. In this population, emollient creams are preferred as they rarely cause adverse reactions.As highly potent topical corticosteroids may be associated with fetal growth restriction, intralesional steroid injections should be used with caution. MTX and acitretin are contraindicated in reproductive-aged women due to a high risk of teratogenesis.Current studies have shown that cyclosporine is not teratogenic, and its application at the lowest dosage for the shortest time may be relatively safe. As certolizumab has minimal transplacental transfer, it may be relatively safe to use during pregnancy in severe cases.Nail psoriasis is mostly a chronic and rarely lifethreatening condition; therefore, a risk-benefit analysis of treatment options should be carefully considered for women who are pregnant, lactating, or planning to become pregnant.

Patients with concomitant onychomycosis

It is difficult to differentiate between nail psoriasis and onychomycosis, as these conditions share many similar clinical features and may coexist. Furthermore, the association between onychomycosis and nail psoriasis remains unclarified and is sometimes contradictory. A systematic review of 10 studies showed that the prevalence of onychomycosis in psoriatic patients ranges widely from 4.6% to 63.1%.29The prevalence of onychomycosis is 18% in psoriatic patients and 9.1% in the normal population.29Although seven studies reported no significant differences between the prevalence of onychomycosis in psoriatic patients versus controls, almost all 10 studies reported a higher prevalence in psoriatic patients.29One hypothesis is that the nail plate abnormalities cause a loss of protection due to the damaged physical barrier,and the detachment of the nail plate from the nail bed provides a moist subungual space that predisposes to invasion by microorganisms. Psoriasis treatments such as immunosuppressive drugs (including MTX, cyclosporine, and biologic agents) are positively associated with nail infections. The prevalence of onychomycosis in patients with nail psoriasis using MTX alone is reportedly 92.8%(13/14; P<0.05).30Among patients treated with TNF-α inhibitors, the positive fungal scraping results were obtained for 33% (33/100) of patients on infliximab,15.45% (17/110) of patients on etanercept, 13.33% (14/105)of patients on adalimumab,and 13.89%(25/180)of controls.31However, the rapid growth of psoriatic nails may protect against fungal invasion. In addition, the presence of antimicrobial peptides like psoriasis in the skin and nail units and the increased expression of IL-17A may strengthen the immune defense against pathogens.Mycological examination should be considered in patients with nail psoriasis that is resistant to treatment or in those with clinical signs of onychomycosis. For patients with both psoriasis and onychomycosis,systemic antifungal therapy should be selected in accordance with the causative fungus and should be administered for at least 3months until the mycotic infection clears. Topical steroids should be avoided during antifungal treatment, as steroids may impair the effectiveness of antifungal therapy. Regular testing for mycological infection is required to monitor for possible relapses of onychomycosis.

Psoriatic arthritis with nail involvement

PsA is a chronic, heterogeneous, inflammatory, and musculoskeletal disease. The early diagnosis of PsA is important to improve quality of life and prevent permanent joint damage. A prospective, single-center trial including 90 patients with psoriasis reported that a target NAPSI of ≥4 can be used to predict the presence of entheseal abnormalities in distal interphalangeal (DIP)joints, with a sensitivity of 60.9% and a specificity of 71.6%.32Furthermore,the involvement of more than five nails was also predictive of the presence of entheseal abnormalities,with a sensitivity of 69.6%and a specificity of 59.7%.32Patients with PsA demonstrate more frequent onycholysis, transverse grooves, crumbling, and splinter hemorrhages than those with psoriasis without arthritis,but the incidence of pitting does not significantly differ between these two groups.These specific clinical psoriatic nail features may be useful in the early diagnosis of arthritis.The DIP joint is intimately linked with the dorsal,volar,and lateral aspects of the nail bed by fibers,and the tendon attachments of the digital extensor crossing the DIP joint enclose the nail root and its associated matrix.Because of these special anatomical features,inflammation associated with nail psoriasis spreads to adjacent structures and progresses proximally to affect DIP joints and digital extensor tendons.33-34Enthesitis is associated with the pathogenesis of PsA with DIP joint involvement and may be asymptomatic, particularly in the early stages of PsA. The US can be used to identify the early changes(thickened nail bed and blurry outline of the ventral plate)and late events (thickened ventral and dorsal plates) in psoriatic nails and is considered a sensitive and noninvasive imaging method for the evaluation of enthesitis.33Patients with onycholysis and/or hyperkeratosis reportedly have greater thickening of the tendon than those with pitting-type changes, and the thickness of the nail bed is correlated with the thickness of the digital extensor tendon.In addition,Power Doppler can be used to assess inflammation-associated vascularization in the area of the extensor digitorum tendon in DIP joints,which is increased in patients with nail involvement.34As the early diagnosis of PsA and enthesopathies has a strong influence on the prognosis, more attention should be paid to nail changes.The US may be a promising risk-prediction tool for PsA at the entheseal level in patients with nail changes, but this needs further investigation.Early US screening and regular monitoring during follow-up of patients with specific psoriatic nail characteristics relevant to PsA may aid in the early diagnosis of PsA.For patients with nail psoriasis and concomitant PsA,systemic treatment is recommended regardless of the severity of nail psoriasis.3The European League Against Rheumatism recommends treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including MTX, sulfasalazine, or leflunomide for patients with monoarthritis or oligoarthritis and concomitant nail involvement. For patients with peripheral arthritis who respond insufficiently to at least one csDMARD,biological agents should be included in the therapeutic regimen. TNF-α inhibitors are often the preferred choices,and IL-12/23 inhibitors or IL-17 inhibitors are recommended when there is skin involvement.35Considering that nail involvement in patients with PsA is usually closely associated with enthesitis and potential inflammation in the DIP joints, TNF-α inhibitors are likely to play an important role in the recovery of nail lesions.

Conclusion

Nail psoriasis is an often overlooked but important aspect of psoriasis management,and the evidence and guidelines for treating nail disease are still inadequate.The management strategies should be individualized and consider various factors including clinical presentation,the severity of nail changes, the presence of complications, and patient’s preferences. Patient education is fundamental for patient compliance and successful treatment. For patients with isolated nail psoriasis affecting ≤3 nails,topical treatment alone is recommended in accordance with the affected portion of the nail. For moderate-tosevere nail psoriasis that is often combined with skin and arthritic symptoms, both topical and systemic therapies are recommended. The developments of biologic agents and novel oral drugs such as JAK or phosphodiesterase 4 inhibitors have broadened the treatment options for nail psoriasis, but further study is needed to investigate the long-term safety and efficacy (Table 1). In pediatric and geriatric populations, the safety of the treatment, patient compliance,and differences in nail growth rate are major limiting factors for the establishment of treatment protocols.For women of childbearing age,the risks versus benefits of treatment should be carefully considered.Patients with concomitant onychomycosis should be administered systemic antifungal therapy for at least 3 months prior to the treatment of nail psoriasis and should undergo regular mycological examination. Although the specificity and sensitivity need further investigation,some psoriatic nail features and US abnormalities at the nail and entheseal levels may be associated with the occurrence of PsA,suggesting that regular US monitoring may enable the early diagnosis of PsA to prevent a functionally limited outcome. When patients with monoarthritis or oligoarthritis have nail involvement, csDMARDs are recommended.If patients respond poorly to csDMARDs,TNF-α inhibitors may be effective and should be considered in patients with PsA and nail involvement.

This review provides a summary of the current treatments for nail psoriasis and their scope of application in different populations. However, the following limitations remain:Firstly, there is a lack of relevant expert consensus or guidelines for the treatment of nail psoriasis in special populations, mostly referring to the guidelines for the treatment of psoriasis vulgaris.However,as nail has special anatomical structure and drug absorption and penetration characteristics,more careful assessments of the effectiveness and safety of relevant therapies in special populations are requiring. Furthermore, only a few studies about new advances in psoriasis treatment,such as biologic agents and novelsmallmolecule oral drugs,have includednail psoriasis as one of the observation indicators.And there is a lack of large, randomized controlled studies in nail psoriasis,especially on the efficacy of different biologic agents on different types and severity of nail damage.

Source of funding

This study was supported by CAMS Innovation Fund forMedical Sciences (No. CIFMS-2017-12M-1-017) and the National Natural Science Foundation of China(Nos.81872545 and 81703152).