International Journal of Dermatology and Venereology

DOI: 10.1097/JD9.0000000000000187

Nail Psoriasis: Treatment Options and Management Strategies in Special Patient

Populations

Xu-Yue Zhou, Jia-An Zhang and Kun Chen*

Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases
and STIs, Chinese Academy of Medical Science& Peking Union Medical College, Nanjing,
China

The authors declare that there are no conflicts of interest.

*Corresponding author: Kun Chen, PhD

Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin

Diseases and STIs, Chinese Academy of Medical Science & Peking Union Medical
College, Nanjing, Jiangsu 210029, China

E-mail: kunchen181@aliyun.com

ACKNOWLEDGMENT: This study was supported by CAMS Innovation Fund for Medical
Sciences (CIFMS-2017-12M-1-017) and the National Natural Science Foundation of China
（81872545, 81703152）

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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.

1. 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 10–80% and an estimated lifetime incidence of 80–90%, while isolated nail
psoriasis is present in only 5–10% of patients.(1) Furthermore, nail involvement is observed in
about 80% of patients with psoriatic arthritis (PsA), and is considered a predictor of the
development of PsA.(2)

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
literatures from Jan 2000 to Jun 2020. We herein review and summarize the latest
developments in nail psoriasis therapy (Fig 1) and propose individualized management
strategies in special patient populations.

2. 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.(3) Nail
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.(4) 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.

Nail bed involvement causes oil drop patches, onycholysis, subungual hyperkeratosis, and
splinter hemorrhages.(5) Focal 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 of oil drop patches to the hyponychium leads to onycholysis. 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.(4) In addition, local inflammation causes rupture of the delicate capillaries in the
dermis due to splinter hemorrhages, which appear as narrow reddish-dark brown linear
structures that are a few millimeters long.(6) A single-center, cross-sectional, observational
cohort study of 200 patients with psoriasis showed that subungual hyperkeratosis is the only
clinical feature of nail psoriasis correlated with the severity of cutaneous psoriasis.(7)

Nail psoriasis is easily diagnosed in patients with cutaneous manifestations or 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.(5) In addition, new diagnostic techniques include dermatoscopy, nail
clipping, capillaroscopy, ultrasound (US), optical coherence tomography, and confocal laser
scanning microscopy.(6)

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 0–4 and a nail bed score of 0–4, and the maximum score for each nail is 8.(8)
However, 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 ≤ three 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).(5)

3. Treatment options for nail psoriasis

3.1 Patient education

Similar to cutaneous psoriasis, the onset of psoriatic nail changes may be closely
associated with Koebner's isomorphic response induced by mechanical trauma.(7) 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.

3.2 Topical therapies

3.2.1 Topical drugs

In patients with nail psoriasis exclusively and few-nail disease, 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
on 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(5); the 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 high-potency corticosteroids alone or in
combination with topical vitamin D analogues.(3) A single-center, intrapatient, 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.(9)

Besides steroids and vitamin D analogues, other common topical treatments include
tazarotene, topical calcineurin inhibitors, anthralin, 5-fluorouracil, topical cyclosporine, and
indigo naturalis extract.(6) A recent, uncontrolled, prospective study of 20 patients with nail
psoriasis showed that weekly injections of 2.5 mg intramatricial methotrexate (MTX) for 6
weeks significant decreased the NAPSI score from 3.70 to 0.67, with minimal adverse effects
and no recurrence in 1 year of follow-up.(10) Therefore, considering the long-term safety,
MTX may be a desirable alternative to steroids for intralesional injection. Further study on
intralesional MTX injection is warranted.

3.2.2 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.(11) Therefore, 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.(5)
Mechanical 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(12); TI had a more rapid onset of improvement
and equal impact on nail bed lesions than topical Cal/BD, without any adverse effects.(12) In
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.(13)
Furthermore, the nail bed showed more improvement than the nail matrix after 4 months of
therapy and at final follow-up, especially regarding onycholysis, oil drop patches, and
subungual hyperkeratosis(13); this may be due to the increased number of vascular structures
in the nail bed than the matrix.(13)

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 nail.(11) Although 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 the nail hydration because of their occlusive properties and long residence
time.(11) A novel nail lacquer formulation containing dexpanthenol and salicylic acid as a
penetration enhancer significantly improved the penetration of apremilast.(14) A randomized,
double-blind, placebo controlled, parallel-group trial confirmed the superior effectiveness and
tolerability of a hydrosoluble nail lacquer containing hydroxypropyl-chitosan, Equisetum
arvense, and methylsulfonylmethane(15); the hydroxypropyl-chitosan nail lacquer achieved a
significantly better clinical cure rate than placebo in both the intention-to-treat and per-
protocol populations.(15) The 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.

3.3 Systemic therapies

3.3.1 Traditional oral drugs

Systemic treatment is usually advised for patients with > three 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.(5) Acitretin, 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. Six months of 0.2 to 0.3 mg/kg/d acitretin
reportedly leads to a 41% reduction in the NAPSI.(16) 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.(17) A prospective study of
37 patients with nail psoriasis suggested that MTX and cyclosporine had similar moderate
effectiveness after 24 weeks of treatment.(18) Interestingly, 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(18); this is probably due to the stronger effect of
MTX on rapidly dividing cells, and the poor penetration of cyclosporine in the nail matrix.(18)

3.3.2 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 mg or 10 mg tofacitinib twice
daily resulted in significant improvements in nail psoriasis versus placebo from week 16 to
week 52.(19) Apremilast 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.(20)
These 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.

3.3.3 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 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(17); in particular, infliximab had the greatest
efficacy followed by adalimumab at weeks 12 and 24, but the differences between agents
disappeared at week 48.(17) A 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.(21) Certolizumab pegol is a
humanized mouse monoclonal antibody against TNF-α modified by PEGylation. One
retrospective study of 56 patients with PsA and nail involvement reported a significant
decrease in the mean modified NAPSI from 14.64 at baseline to -12.92 at week 52.(22)
Golimumab 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.(23)

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.(24) Furthermore, 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(25); this suggests that treatment effects on the nail bed
appear earlier than those on the nail matrix, and a relatively longer 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, parallel-group, 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.(26) It is the first study to
demonstrate that secukinumab therapy provides a strong, clinically meaningful, and durable
response for up to 2.5 years; 300 mg and 150 mg doses of secukinumab achieved mean
NAPSI improvements of -73.3% and -63.6%, respectively.(26) Ixekizumab 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 of treatment. More patients
achieved a NAPSI of 0 with ixekizumab (61.9%) versus ustekinumab (28.6%) during a 52-
week period.(27) Brodalumab 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%).(28) Both 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.

4. Nail Psoriasis in Special Patient Populations

4.1 Nail psoriasis in pediatric patients

Nail psoriasis is rare in children, affecting only 0.11% of the total pediatric population and
18.2% of children with psoriasis.(29) 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.(29, 30) The combination of calcipotriol and betamethasone dipropionate is safe
and effective in treating pediatric nail psoriasis.(31) Intralesional steroid injections may be
hard to execute due to the sharp pain and poor compliance. One case report showed the
therapeutic value of tazarotene 0.05% gel in a 6-year-old girl with nail psoriasis,(32) while
another reported that indigo naturalis oil extract drops successfully treated psoriatic nails with
periodic pustular eruption in a 13-year-old girl.(33) None of the traditional oral agents are
approved by the 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 ≥ 4 years), ustekinumab (for
patients ≥ 12 years), and adalimumab (for patients ≥ 4 years).(34) In one report, an 8-year-old
girl with nail psoriasis resistant to multiple therapies was successfully treated after 3 months
of secukinumab (150 mg monthly).(35) However, 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.(36)

4.2 Nail psoriasis in 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.(37) 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. MTX is the only traditional systemic drug that
has been evaluated in clinical trials in the older population.(38) The incidence of adverse
events is significantly higher in older adults treated with cyclosporine versus MTX.(39) In
comparison, acitretin may be more acceptable, as the resulting xeroderma and hyperlipemia
can generally be well controlled and are rarely life-threatening.(40) 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.(40, 41) Apremilast 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.

4.3 Nail psoriasis in 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.(42) 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.(43) As certolizumab has minimal transplacental transfer, it may be relatively safe to use
during pregnancy in severe cases.(34) Nail psoriasis is mostly a chronic and rarely life-
threatening condition; therefore, a risk-benefit analysis of treatment options should be
carefully considered for women who are pregnant, lactating, or planning to become pregnant.

4.4 Nail psoriasis 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%.(44) The prevalence of onychomycosis is 18% in
psoriatic patients and 9.1% in the normal population.(44) Although 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.(44) One
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.(45) Furthermore, a
multicenter study showed that the factors associated with increased risk of onychomycosis in
nail psoriasis are a high NAPSI, obesity, elevated diastolic blood pressure, long duration of
disease (> 10 years), and current smoking status.(46) 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).(47) Among 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.(48) However, the rapid growth of
psoriatic nails may protect against fungal invasion. In addition, the presence of antimicrobial
peptides like psoriasins in the skin and nail units and the increased expression of IL-17A may
strengthen the immune defense against pathogens.(45) 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 3 months 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.(45)

4.5 Psoriatic arthritis with nail involvement

PsA is a chronic, heterogeneous, inflammatory, 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%.(49)
Furthermore, 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%.(49) Patients
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.(50) 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 encloses 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.(51, 52) Enthesitis is associated with the pathogenesis of PsA with DIP joint
involvement and may be asymptomatic, particularly in the early stages of PsA. 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.(51) Patients 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.(52) As the early diagnosis of PsA and
enthesopathies has a strong influence on the prognosis, more attention should be paid to nail
changes. 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.(5) The
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 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.(53) Two patients with PsA who received ixekizumab and
secukinumab treatment, respectively, reportedly showed complete improvement of skin
lesions but poor improvement in nail damage; after switching to adalimumab, both of their
nail conditions improved.(54, 55) Considering 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, severity of nail changes, presence of complications, and patients’ preferences.
Patient education is fundamental for patient compliance and successful treatment. For
patients with isolated nail psoriasis affecting ≤ three nails, topical treatment alone is
recommended in accordance with the affected portion of the nail. For moderate-to-severe 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. 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 novel small molecule oral drugs, have
included nail 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 for Medical Sciences (no. CIFMS-
2017-12M-1-017) and the National Natural Science Foundation of China (no. 81872545, no.
81703152）
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Fig 1 Overview of the treatment options for nail psoriasis

Table 1 Treatment strategies for nail psoriasis

Disease Conditions Recommended options Alternative options
isolated nail psoriasis sole topical therapies tazarotene, topical
affecting ≤ 3 nails calcineurin inhibitors,
nail matrix involvement: anthralin, 5- fluorouracil,
topical cyclosporine,
intralesional steroid injections indigo naturalis extract
and et al
nail bed involvement:

high-potency topical
corticosteroids alone or in
combination with topical vitamin
D analogues
> 3 nails involved or Topical therapy combined with acitretin, methotrexate,
resistant to topical therapy systemic treatment according to cyclosporine, tofacitinib,
or with severe skin and patient’s condition apremilast, biologic agents
arthritic manifestations