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Nail involvement affects 80-90 % of patients with plaque psoriasis, and is even more prevalent in patients with psoriatic arthritis. This review is the result of a systemic approach to the literature and covers topical, intralesional, conventional systemic, and biologic systemic treatments, as well as non-pharmacological treatment options for nail psoriasis. The available evidence suggests that all anti-tumor necrosis factor-α, anti-interleukin (IL)-17, and anti-IL-12/23 antibodies which are available for plaque psoriasis and psoriatic arthritis are highly effective treatments for nail psoriasis. Conventional systemic treatments, including methotrexate, cyclosporine, acitretin, and apremilast, as well as intralesional corticosteroids, can also be effective treatments for nail psoriasis. Topical treatments, including corticosteroids, calcipotriol, tacrolimus, and tazarotene, have also been shown to have a position in the treatment of nail psoriasis, particularly in mild cases. Finally, non-pharmacological treatment options, including phototherapy, photodynamic therapy, laser therapy, and several radiotherapeutic options, are also reviewed but cannot be advised as first-line treatment options. Another conclusion of this review is that the lack of a reliable core set of outcomes measures for trials in nail psoriasis hinders the interpretation of results, and is urgently needed.
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REVIEW ARTICLE
Nail Psoriasis: A Review of Treatment Options
Marcel C. Pasch
1
ÓThe Author(s) 2016. This article is published with open access at Springerlink.com
Abstract Nail involvement affects 80–90 % of patients
with plaque psoriasis, and is even more prevalent in
patients with psoriatic arthritis. This review is the result of
a systemic approach to the literature and covers topical,
intralesional, conventional systemic, and biologic systemic
treatments, as well as non-pharmacological treatment
options for nail psoriasis. The available evidence suggests
that all anti-tumor necrosis factor-a, anti-interleukin (IL)-
17, and anti-IL-12/23 antibodies which are available for
plaque psoriasis and psoriatic arthritis are highly effective
treatments for nail psoriasis. Conventional systemic treat-
ments, including methotrexate, cyclosporine, acitretin, and
apremilast, as well as intralesional corticosteroids, can also
be effective treatments for nail psoriasis. Topical treat-
ments, including corticosteroids, calcipotriol, tacrolimus,
and tazarotene, have also been shown to have a position in
the treatment of nail psoriasis, particularly in mild cases.
Finally, non-pharmacological treatment options, including
phototherapy, photodynamic therapy, laser therapy, and
several radiotherapeutic options, are also reviewed but
cannot be advised as first-line treatment options. Another
conclusion of this review is that the lack of a reliable core
set of outcomes measures for trials in nail psoriasis hinders
the interpretation of results, and is urgently needed.
Key Points
Nail psoriasis can be treated effectively using topical
treatments, intralesional treatments, and systemic
treatments, but an optimal effect may take up to
1 year.
The role of non-pharmacological treatment options,
including phototherapy, photodynamic therapy, and
laser therapy, is limited.
An undesirable heterogeneity of outcome measures
and scoring systems makes it almost impossible to
compare trials.
1 Introduction
Psoriasis is a common inflammatory skin disease that
causes significant stress and morbidity. It most often pre-
sents with well-demarcated, scaling and erythematous
plaques, often at the extensor surfaces of knees and elbows.
The prevalence varies between 0.7 and 2.9 %, with a
preference for the Caucasian population. Plaque psoriasis
(PP, or psoriasis vulgaris) is the most common form of the
disease, affecting 85–90 % of patients, and manifests with
patches on the trunk and extremities. Other common forms
of psoriasis may affect the scalp, joints, creases, or nails,
even in patients without psoriasis of the skin.
Among PP patients, prevalence of nail psoriasis docu-
mented in the literature is over 50 %, with an estimated
lifetime incidence of 80–90 % [1]. A recent survey by
Klaassen et al. found nail involvement in 66.0 % of 1459
&Marcel C. Pasch
marcel.pasch@radboudumc.nl
1
Department of Dermatology, Radboud University Medical
Center, PO Box 9101, 6500 HB Nijmegen (370),
The Netherlands
Drugs
DOI 10.1007/s40265-016-0564-5
psoriasis patients, which indicates that the prevalence of
nail psoriasis might often be underestimated [2]. Among
patients with psoriatic arthritis (PsA), the prevalence of nail
psoriasis may be [80 % [3]. Nail psoriasis in the absence
of cutaneous or joint disease is present in 5–10 % of pso-
riatic patients [4]. Psoriatic nail disease may be considered
an indicator for patients at risk for future psoriatic joint
damage [5,6].
Nail psoriasis may show different clinical presentations
according to the structure that is involved within the nail
apparatus. All signs of nail psoriasis are not specific and
may be found in several other nail conditions. Therefore,
histology of involved tissue is the gold standard for making
the diagnosis of nail psoriasis; however, in most cases, the
diagnosis of nail psoriasis can be made clinically by pattern
recognition. When psoriasis is present in the nail-forming
unit (the nail matrix), it can cause the following manifes-
tations: pitting, leukonychia (white spots within the nail
plate), red spots of the lunula, transverse grooves (Beau’s
lines), and crumbling of the nail plate (Fig. 1). Psoriasis of
the nail bed presents as oil-drop discoloration, splinter
hemorrhages involving the distal third of the nail plate,
subungual hyperkeratosis, and/or detachment of the nail
plate from the nail bed (onycholysis). Psoriasis can also
involve the periungual region, resulting in psoriatic
paronychia. Looking at psoriatic nails, it is important to
evaluate the contribution of nail matrix disease and nail
bed disease separately because some treatment options
have a better effect on matrix disease, while others are
more efficient in treating nail bed disease.
It is known that psoriasis on visible areas of the skin,
such as the face and hands, may have a substantial negative
impact on physical, psychological, and social dimensions
of quality of life (QoL) [711]. In addition, fingernail
psoriasis is highly visible and has a relevant and additional
negative impact on the QoL of psoriasis patients, particu-
larly in patients with both nail matrix and nail bed signs of
the disease [1214]. Patients with only nail bed alterations
scored significant lower QoL scores when compared with
patients with only nail matrix features. The additional
negative consequences of nail involvement in psoriasis on
QoL may be explained by the fact that nail psoriasis is
more than a highly visible variant. Complaints of patients
with nail psoriasis include pain, inability to grasp small
objects, tie shoe laces or button clothes, and cause an
altered sense of fine touch. Pain in nail psoriasis has a high
association with joint pain, therefore the presence of nail
psoriasis may identify patients who are at risk of devel-
oping disabling PsA [13].
The impact of nail psoriasis on individual patients can
be high. A recent survey showed that 47 % of patients with
nail psoriasis would like to receive treatment for their nail
disorder [2]; however, treatment of nail psoriasis is chal-
lenging, and involves topical, intralesional, and systemic
Fig. 1 Nail manifestations seen in nail psoriasis. Nail bed features
aoil-drop discoloration, bonycholysis, csubungual hyperkeratosis,
dsplinter hemorrhages. Nail matrix features epitting of the nail plate,
fcrumbling in proximal quadrants of the nail plate, gleukonychia,
hred spot in the lunula. Courtesy of K. Klaassen
M. C. Pasch
therapies. A recent Cochrane review discussed randomized
controlled trials (RCTs) on nail psoriasis [15]. The prac-
tical use of that review is limited by the fact that most
studies on nail psoriasis are largely anecdotal, case-series,
or derived from open-label, prospective studies. Therefore,
several frequently used, and considered effective, treatment
options are not discussed in that Cochrane review. The aim
of that review was to cover all published data on the
treatment of nail psoriasis, including not only data from
RCTs but also from other studies and case reports.
2 Pathophysiology
Psoriatic lesions highlight the fundamental processes
underlying its pathogenesis, namely inflammation and
epidermal hyperproliferation. Psoriasis appears to be a
multifactorial disease whose exact underlying mechanism
is still unclear, but environmental factors, genetic suscep-
tibility, abnormal function of keratinocytes, and immuno-
logical disturbances of the innate and acquired immune
system are all postulated [16,17].
Environmental factors that have been identified as trig-
gering or exacerbating psoriasis in susceptible persons are
certain infections, drugs, stressful life events, and smoking.
The role of genetic factors has been a matter of research,
particularly in the past decades. Population studies have
shown that the incidence of psoriasis is greater among first-
and second-degree relatives of psoriasis patients than
among the general population [18]. Genome-wide associ-
ation studies have identified nine chromosomal loci
(PSORS1 through PSORS9) that can be linked to psoriasis.
The major genetic determinant seems to be PSORS1,
which probably accounts for 35–50 % of the hereditary
component of psoriasis. Human leukocyte antigen (HLA)-
Cw6, involved in antigen presentation, seems to be the
susceptible allele located on PSORS1. However, patients
with nail psoriasis and/or PsA are more frequently HLA-
Cw6-negative, indicating a separate genotype [19]. In
recent years, several other genome-wide association studies
identified genes related to the skin barrier function and to
both the innate and adaptive immune system [2022].
Over the years, various cells and mediators playing a
role in the immunopathogenesis of psoriasis have been
identified or postulated, including keratinocytes, dendritic
cells, T lymphocytes, complement proteins, and many
cytokines and chemokines. Briefly, in the current concept
an initial trigger (e.g. trauma, infection, and stress) can
induce the production of various cytokines (including
tumor necrosis factor[TNF]-a) by innate immune cells,
resulting in a cascade of events eventually leading to the
activation of dendritic cells [16]. Activated dendritic cells
start to secrete mediators (e.g. interleukin [IL]-12, IL-23)
and present antigens to T cells, leading to the differentia-
tion of type 1 and type 17 helper T cells (Th1, Th17).
These activated T cells subsequently secrete mediators (IL-
17A, IL-17F, and IL-22), which then activate ker-
atinocytes, resulting in keratinocyte hyperproliferation and
the secretion of different chemokines by these ker-
atinocytes. Keratinocyte hyperproliferation is responsible
for the clinical feature of scaling, while the released
chemokines are responsible for attraction of more inflam-
matory cells to the skin. This model of pathogenesis of
psoriasis has resulted in the production of monoclonal
antibodies interfering in several pathogenic steps, the so-
called biologics, which prevent the expression of the full
pathogenic cascade, and thus reducing the clinical features
of psoriasis.
3 Assessment of Nail Psoriasis
The availability of sensitive, responsive, specific, and
validated outcome measures is essential in drug research
and comparison of trials. Unfortunately, these are still
missing in nail psoriasis. Most recent studies on nail pso-
riasis use the Nail Psoriasis Severity Index (NAPSI), target
NAPSI, or one of its many variants as a marker of nail
improvement [23]. To calculate the NAPSI, each nail is
divided into four quadrants, each of which are evaluated
for the presence of any manifestations of psoriasis in the
nail matrix (pitting, leukonychia, red spots in the lunula,
nail plate crumbling) and nail bed (oil-drop discoloration,
onycholysis, hyperkeratosis, splinter hemorrhages). If any
sign is present in all four quadrants, the nail is given a score
of 4, through to a score of 0 if there are no signs in any
quadrant. Each nail is assigned a nail matrix and a nail bed
score of 0–4, which are combined to yield a total score of
0–8 for each nail. All nails may be evaluated, with the total
NAPSI score being the sum of the scores, up to 80 if only
fingers (10 nails) are considered, or up to 160 if toes are
also included (20 nails). In clinical studies, often only the
most seriously involved nail is targeted (target NAPSI) to
assess the effects of drug therapy. Some studies use (target)
NAPSI-50, NAPSI-75, and NAPSI-90 to indicate the per-
centage of patients achieving a (target) NAPSI improve-
ment of at least 50, 75, or 90 %, respectively. Despite its
current popularity in nail psoriasis studies, the NAPSI has
some disadvantages. Its poor validation, the fact that the
important nail psoriasis feature ‘subungual hyperkeratosis’
is not included and, in particular, the lack of correspon-
dence of NAPSI scores with the clinical severity of nail
psoriasis are important disadvantages of this scoring sys-
tem [24]. Most of these limitations are absent in a newly
developed scoring system, the N-NAIL, which has been
partly validated [24]; however, this system has not been
Nail Psoriasis: A Review of Treatment Options
used in any published clinical studies. Older studies have
used many different scoring systems, which, together with
the major differences in study design, inclusion criteria,
and follow-up, make it difficult to compare the results of
individual trials. Furthermore, not only should clinical
severity be part of a core outcome set in nail psoriasis but,
ideally, it should also involve patient-assessed signs, QoL,
patient satisfaction with treatment and outcome, adverse
events, and probably costs. A first attempt at developing a
tool for the assessment of various domains of nail psoriasis
outcomes, known as Nail Assessment in Psoriasis and
Psoriatic Arthritis (NAPPA), has recently been published
[25].
4 Management of Nail Psoriasis
Treating nail psoriasis is often a time-consuming challenge
with an unsecure outcome. Response to treatment may
appear everywhere in the spectrum, from very disap-
pointing to excellent, but relapses are common. Unfortu-
nately, there is a lack of evidence-based treatments and
consequent guidelines [15]. This does not necessarily mean
that available treatments are not efficacious, but that final
statistical evidence is missing. Therapeutic options include
patient education, external topical treatments, intralesional
steroids, systemic treatments, and non-pharmacological
treatment options. Patient education should cover the
avoidance of minor repetitive nail trauma, managing
expectations with regard to the amount of time necessary
for nail clearing, and discussing prevention and treatment
of fungal infections in psoriasis nails [26]. Psoriatic nail
changes can be provoked by minor traumas, such as nail
biting, subungual cleaning, picking, or manicure. Patients
should avoid these habits and keep the nails as short as
possible to prevent trauma or lifting of the poorly attached
nail plate [27]. Before the start of treatment, the clinician
should discuss with the patient that any noticeable nail
improvement will take a long time; many treatments will
show maximal results only after 1 year. The low growth
rate of the nail plate is responsible for a delay of
3–9 months before clinical improvement can be noticed in
cases of effective treatment. Four to 6 months is a rea-
sonable period of treatment before evaluating clinically
relevant results. In the beginning, the improvement may be
so limited that it is advisable to take photographs of the
nails during each visit to convince both the patient and the
physician that the treatment has positive results. Con-
comitant onychomycosis has a high prevalence in psoriatic
nails. A meta-analysis has shown a prevalence of 18.0 % in
psoriasis patients compared with a prevalence of 9.1 % in
control groups [28]. This high prevalence rate should be a
reason for excluding onychomycosis before starting
intensive treatment for nail psoriasis. Obviously, treatment
of concomitant onychomycosis will improve the outcome
of all other treatments.
The choice of treatments depends on clinical presenta-
tion, as well as patient-related factors. Most patients have
only mild nail psoriasis without signs of PsA or severe PP.
These patients may profit from topical treatment, while
systemic treatment is indicated in patients with severe nail
psoriasis, major impact on QoL, or concomitant moderate
to severe psoriatic skin lesions. Systemic therapy should
also be favored if concomitant PsA is evident. The choice
of treatments further depends on patient factors, including
age, experienced burden of disease, accompanying diseases
and therapies, individual patient preferences, and the risks
of treatment.
This review covers treatment options for nail psoriasis
and is the result of a systemic approach to the literature.
The following databases were searched (to December
2015): the Cochrane Skin Group Specialised Register,
CENTRAL in The Cochrane Library, and Pubmed (from
1948). Essentially, the search strategy included psoria*,
and (nail*, or toenail* or thumbnail*, or ungual, or unguel,
or unguium, or pitting, or punctate, or Beau’s lines, or
subungual hyperkeratosis, or onycholysis) and (trial).
Overall, 120 publications were identified using this search
strategy. The titles and abstracts of each of these publica-
tions were evaluated and a total of 72 studies or case
reports on the treatment of nail psoriasis were selected for
complete reviewing. Publications without original data
were discarded. In addition, the reference lists of all pub-
lications were checked, which resulted in an 69 additional
publications. The number of additional publications
retrieved by checking reference lists was high, and was
mainly caused by the fact that nail psoriasis was often a
secondary endpoint in studies on PP or PsA, and was not
mentioned in the abstract.
5 Topical Treatment Modalities
Penetration of a pharmacological agent into the site of
psoriatic inflammation, the nail bed, or the nail matrix is
essential to achieve therapeutic concentrations. Given the
anatomical structure and physical characteristics of the
nail, it is difficult, or impossible, for antipsoriatic agents to
penetrate through the nail plate to the site of psoriatic
inflammation. To overcome this contrast of desired pene-
tration and an impermeable physical barrier caused by the
nail plate, it is essential to distinguish signs of nail matrix
psoriasis from signs of nail bed psoriasis (Fig. 1). When
signs of nail matrix psoriasis are present, the topical
medication should be applied on the proximal nail fold, i.e.
just above the nail matrix. If signs of nail bed psoriasis are
M. C. Pasch
present, the compound should be able to penetrate to the
psoriatic inflammation of the nail bed. Therefore, the
onycholytic nail should be trimmed as much as possible
before and during treatment to allow the application of the
compound to the nail bed.
5.1 Topical Corticosteroids
Topical corticosteroids have been used for many decades to
suppress psoriatic inflammation in PP. Also in nail psori-
asis, potent and superpotent corticosteroids are used fre-
quently, and appear to be more effective in nail matrix
psoriasis than in nail bed psoriasis. Topical corticosteroids
are available in the form of ointments, creams, lotions,
emulsions, and even nail lacquers, and the frequency of
application frequency is usually once or twice daily. If used
frequently and for a prolonged period, telangiectasia of the
surrounding skin and atrophy of the skin and underlying
phalanx may appear. Others prefer pulse therapy, with
application on four consecutive days each week, in order to
prevent these side effects. Clinical improvement may not
be expected within 4–6 months of treatment, and further
improvement can be seen during the first year.
In spite of the long history of corticosteroids in the
treatment of nail psoriasis, only a few formal trials of their
efficacy have been conducted. Clinical studies on topical
corticosteroid monotherapy are even sparser. RCTs using
betamethasone dipropionate ointment (64 mg/g) twice
daily [29,30] and clobetasol propionate 0.05 % cream
under occlusion once daily [31] identified positive effects
on subungual hyperkeratosis, salmon patches, pitting, and
onycholysis after 12–20 weeks of use. One study compared
betamethasone dipropionate (64 mg/g) and salicylic acid
(0.03 g/g) ointment with calcipotriol ointment (50 lg/g) in
the treatment of nail bed psoriasis with severe subungual
hyperkeratosis [30]. After 3 months of treatment, subun-
gual fingernail and toenail hyperkeratosis was reduced by
20–30 % in both groups (no statistical differences). Rigo-
poulos et al. conducted an RCT comparing tazarotene
0.1 % cream with clobetasol propionate 0.05 % cream
under occlusion once daily for 12 weeks [31]. Patients
showed a significant improvement for pitting, onycholysis,
hyperkeratosis, and salmon patches with both agents,
without significant differences between the two investi-
gated agents. Mild side effects were reported in 18.8 % of
the tazarotene-treated patients, including desquamation and
erythema of the nail-fold skin, periungual irritation,
paronychia, and irritation of the skin of the toe or finger
distanced from the nail area. Formulations with corticos-
teroids in a nail lacquer have been studied more often than
other forms but are not yet commercially available. In
particular, 8 % clobetasol-17-propionate in a nail lacquer
has shown positive results in placebo-controlled, open
studies [3234]. Fifty-two to 90 % of patients showed
improvement after therapy, which was directly related to
the length of treatment. The symptoms that responded best
to therapy were onycholysis and pitting (indicating an
action on the nail matrix); however, improvement of sal-
mon patches and subungual hyperkeratosis has also been
reported, whereas splinter hemorrhages were most persis-
tent. No adverse effects, such as atrophy, hypochromy,
periungual telangiectasia, local pain, and hypersensitivity,
were noted.
5.2 Combination Therapy with Corticosteroids
The assumption that topical corticosteroids in nail psoriasis
are particularly effective in ameliorating nail matrix signs
of this disease has resulted in several studies in which
topical steroids were combined with treatments that are
presumed to be more effective in nail bed signs of nail
psoriasis. In particular, the combination of topical steroids
(clobetasol propionate and betamethasone dipropionate)
with the vitamin D3 analog calcipotriol (50 lg/g) has been
investigated and appears to be effective [3537]. This
combination is currently one of the most widely used
topical treatmentsfor psoriatic nail disease. In one study,
calcipotriol cream was used every night five times per
week, clobetasol propionate cream was used two times per
week for 6 months, and patients were followed-up for a
further 6 months, using only clobetasol propionate cream
two nights per week [35]. After 6 months of treatment, the
mean reduction in hyperkeratosis of the fingernails and
toenails was 72.3 and 69.9 %, respectively, and at
month 12 the decrease was 81.2 and 72.5 %, respectively.
Another study compared once-daily calcipotriol (50 lg/g)
combination therapy with betamethasone dipropionate
(0.05 %) with twice-daily calcipotriol (50 lg/g)
monotherapy in the treatment of nail psoriasis for 12 weeks
[36]. A similar reduction in target NAPSI was noted in both
groups, mainly caused by the improvement of oil-drop
discoloration, because other nail bed and matrix features
failed to improve with either treatment. A third study used
calcipotriol plus betamethasone dipropionate two-
compound ointment once daily [37]. At the end of the
12 weeks of treatment, NAPSI showed a 72 % improve-
ment; however, mean NAPSI at baseline was 5.8, indicat-
ing an extremely mild nail psoriasis at baseline [38].
Adverse events included mild irritation on the fingertips of
two patients, which was self-limited.
Tacalcitol is another chemical vitamin D analog that has
been investigated in a small, open study with both nail bed
and nail matrix psoriasis. Patients were treated with a nail
lacquer containing 8 % clobetasol-17-propionate applied at
bedtime during the weekend, and with tacalcitol 0.1 %
ointment under occlusion on the remaining days, for
Nail Psoriasis: A Review of Treatment Options
6 months [39]. Clinical characteristics of nail bed and nail
matrix psoriasis improved markedly, and target NAPSI had
improved 50 % at 3 months, and 78 % at 6 months.
5.3 Intralesional Corticosteroids
Locally injected steroids have a long history in the treatment
of nail psoriasis [40]. Locally penetrating doses of steroid
into a digit are administered by needle injection or high-
pressure jet from a tool such as the ‘Port-o-jet’, ‘Med-Jet
MBX’, or others. Needle injection is the most common of
these, with the temporary popularity of the Port-o-jet waning
as concern developed over the potential for splash-back of
blood and steroid from the breached epidermis on to the
instrument and practitioner, or the development of epidermal
inclusion cysts. The existing evidence suggests that intrale-
sional injection into the nail bed and matrix are particularly
effective for alleviating lesions caused by psoriasis of the
nail matrix, and also has moderate effects on nail bed signs
(Table 1). Injections in the region of the nail matrix has
almost no effects on nail bed signs of nail psoriasis.
The recommended protocols of treatment differ con-
siderably. Initially, injections of triamcinolone acetonide
(5 mg/ml) were administered monthly for 6 months in the
proximal nail fold, followed by a further four injections
over the next 6 months and then every 2 months for the
final 6- to 12-month period [4043]. More recent publica-
tions prefer a higher concentration of triamcinolone ace-
tonide (10 mg/ml), 0.1 ml administered in each of the four
periungual sites, ensuring symmetrical delivery of the
steroid to the nail matrix and nail bed, and administered
less frequently, such as every 2 months [44,45]. Clinical
results of this modified regimen were investigated in two
studies suggesting improved efficacy on the signs of nail
bed psoriasis (Table 1)[44,45].
Side effects after these procedures are well known:
short-term paresthesia [44,45] and focal pain that may last
for several months [40,45]; hematoma formation is rather
common (up to 20 %) but asymptomatic [45]. Loss of the
nail plate was seen in 9 % of patients in one study [45].
Occasionally, nail-fold atrophy can be encountered, and is
often reversible. Chronic topical therapy can lead to com-
plications of the ‘disappearing digit’ [46] with atrophy of
the underlying phalanx [47]. Rupture of the extensor ten-
don has also been reported after local injection of steroids
[48,49].
5.4 Vitamin D3 Derivates: Calcipotriol, Tacalcitol,
Calcitriol
Vitamin D analogs regulate epidermal cell proliferation
and differentiation, as well as production and release of
proinflammatory cytokines. Topical formulations
containing vitamin D3 (calcitriol) and vitamin D analogs
(calcipotriol, tacalcitol) are effective treatments for PP,
both as monotherapies and in fixed combinations with
corticosteroids. Vitamin D3 derivates appear to be more
effective in treating nail bed signs of psoriasis than in nail
matrix signs. Studies using calcitriol in the treatment of
nail psoriasis are rare. One case was reported whereby the
patient responded well to treatment with calcitriol ointment
[50]; however, it was not completely clear whether this
patient suffered from nail psoriasis. One RCT compared
calcitriol ointment (3 lg/g) twice daily with betamethasone
diproprionate (64 mg/g) on subungual hyperkeratosis [29].
After 20 weeks, nails treated with calcitriol had a 38 %
reduction in thickness compared with a 35 % reduction
seen in nails treated with betamethasone diproprionate (not
significant).
Tacalcitol is a chemical vitamin D analog that has been
investigated as a monotherapy in one open study of 15
patients with both nail bed and nail matrix psoriasis [51].
Patients used the tacalcitol ointment (4 lg/g) every night in
occlusion (with cotton gloves) for 6 months. After
3 months, the NAPSI dropped more than 50 %, and after
6 months of treatment the NAPSI was approximately 75 %
lower than at baseline. Most patients presented with pain at
the beginning of the study, but none reported discomfort
after 6 months. Surprisingly, the greatest improvement was
seen in nail matrix signs of nail psoriasis. Combining
tacalcitol ointment (10 lg/g) with a nail lacquer containing
8 % clobetasol-17-propionate (twice weekly) resulted in
major improvement of both nail bed and nail matrix signs
[39].
Calcipotriol is the vitamin D analog most widely
investigated in nail psoriasis, often in combination with
other treatments but also as monotherapy. One case-series
study evaluated the efficacy of calcipotriol ointment
(50 lg/g) monotherapy twice daily without occlusion in
the treatment of nail psoriasis for 5 months [52]. Cal-
cipotriol was particularly effective in nail bed signs of
subungual hyperkeratosis, onycholysis, and discoloration.
In addition, fingertip tenderness and pain of an involved
distal phalanx were significantly reduced. In a 12-week
study comparing calcipotriol (50 lg/g) monotherapy with
calcipotriol/betamethasone-dipropionate combination ther-
apy, only oil-drop discoloration improved, without differ-
ences between the two groups [36]. The same two
compounds in a single ointment resulted in a 72 % NAPSI
improvement at 12 weeks in patients with extremely mild
nail psoriasis [37]. Other studies of combination therapy of
calcipotriol and corticosteroids are discussed in Sect. 5.2.
The combination of calcipotriol with oral cyclosporine
was used in a study in which a combination of cyclosporine
and topical calcipotriol cream versus cyclosporine alone
was evaluated [53]. Patients were treated for 3 months with
M. C. Pasch
Table 1 Comparison of trials of steroid injections for nail psoriasis. Adapted with permission from [45]
Study, year Gerstein, 1962 [40] Abell and Samman,
1973 [41]
Bleeker, 1974 [42] Peachey et al., 1976
[43]
de Berker and
Lawrence, 1998 [44]
Saleem and Azim,
2008 [45]
Nantel-Battista et al.,
2014 [165]
No. of patients 4 58 400 28 19 35 17
Dose of
triamcinolone
(mg/ml)
10 5 5 5 10 10 8
Injection site Proximal nail fold Proximal nail fold Proximal nail fold Proximal nail fold Matrix and nailbed Matrix and
nailbed
Proximal nail fold
Regimen 1 90.2 ml
monthly 96 months
1–4 90.1 ml
weekly 93 weeks
0.2–0.3 ml
monthly 96 months
0.1 ml every 4–6 weeks
for 6 months
490.1 ml once 4 90.1 ml once
or twice
490.07 ml every
4 weeks
Follow-up (months) 14 0–24 5–20 1 3–17 2–6 1
Post-therapy improvement (percentage of treated patients)
Matrix signs (%) Combined feature: 35
Pitting 91 68 86 46 71
Ridging 94 58
Thickening 83 18
Nailbed signs (%)
Onycholysis 50 34 19 50 37
Subungual
hyperkeratosis
100 57
Mean target
NAPSI
a
-46 %
Nail matrix target
NAPSI
a
-50 %
Nail bed target
NAPSI
a
-38 %
NAPSI Nail Psoriasis Severity Index
a
Target NAPSI: NAPSI of one target nail [23]. To calculate the target NAPSI, one nail is divided into four quadrants, which are evaluated for the presence of any manifestations of psoriasis in
the nail matrix (pitting, leukonychia, red spots in the lunula, nail-plate crumbling) and nail bed (oil-drop discoloration, onycholysis, hyperkeratosis, splinter hemorrhages). If a sign is present in
all four quadrants, the nail is given a score of 4, through to a score of 0 if there are no signs in any of the quadrants. All eight parameters are evaluated, with the target NAPSI score being the sum
of the scores, giving that one nail a score of 0–32
Nail Psoriasis: A Review of Treatment Options
cyclosporine alone (3–4.5 mg/kg/day) or with cyclosporine
plus topical application of calcipotriol cream twice daily
(with occlusive application at night). Ungual hyperkerato-
sis, onycholysis, and pitting improved in approximately
80 % of patients using cyclosporine plus calcipotriol, and
in approximately 50 % of patients in the cyclosporine-
alone group, emphasizing the positive effect of vitamin D
derivates on nail bed psoriasis.
5.5 Tazarotene
Tazarotene is a member of the acetylenic class of reti-
noids that is selective for band cisotypes of the retinoic
acid receptor. It has been shown to have antiproliferative,
normalizing-of-differentiation, and anti-inflammatory
effects, and is approved for the treatment of psoriasis,
acne, and photodamage. Several studies have been per-
formed to estimate efficacy in nail psoriasis [31,5457].
In these studies, tazarotene 0.1 % gel, ointment, or cream
was used once daily for 12–24 weeks. In one study,
tazarotene was effective for onycholysis and pitting (only
if applied under occlusion) at 24 weeks, but not for
subungual hyperkeratosis, leukonychia, nail plate crum-
bling/loss, or splinter hemorrhages [54]; however, other
studies saw an improvement in hyperkeratosis and oil
spots [55,58]. A better response of nail bed signs than
nail matrix signs was also concluded from another study
[56]. An 88 % improvement in NAPSI at 6 months was
reported from this study, but patients had only mild nail
psoriasis at baseline (median NAPSI 15). Rigopoulos
et al. conducted a randomized, double-blind study com-
paring tazarotene cream with clobetasol propionate
0.05 % cream, both under occlusion [31]. The results of
this study showed a significant time-effect improvement
for pitting, onycholysis, hyperkeratosis, and salmon pat-
ches with both agents, without significant differences
between the two investigated agents. The most recent
study investigating tazarotene in nail psoriasis compared
the efficacy of pulsed dye laser (PDL) plus topical
tazarotene cream versus topical tazarotene alone [57].
After 6 months of tazarotene treatment without occlusion,
no improvement in nail bed or nail matrix psoriasis could
be observed. An explanation for this failure might be the
fact that most patients were also receiving systemic
therapy or using phototherapy. The laser results will be
discussed in Sect. 10.1.
From these studies, tazarotene appears to be effective
for nail bed signs of psoriasis only. Use may be limited by
the preferred use under occlusion and by the relatively
frequently occurring side effects, such as erythema, irrita-
tion, desquamation, and paronychia.
5.6 Topical Calcineurin Inhibitors
Calcineurin is a serine/threonine protein phosphatase that
activates T cells by upregulation of the expression of IL-2.
Increased IL-2 stimulates the growth and differentiation of
T cell responses. Systemic inhibition of calcineurin, par-
ticularly with cyclosporine, has been shown to be an
effective treatment for PP [59]. The use of systemic cal-
cineurin inhibitors in psoriasis is limited by potential sev-
ere side effects; however, topical treatment of nail psoriasis
with calcineurin inhibitors could prevent the majority of
these side effects. Several case reports and studies using
topical cyclosporine and tacrolimus have been published
[6062]. In a prospective, randomized, placebo-controlled
study, nails of eight patients were treated twice daily for
12 weeks with a 70 mg/ml maize-oil-dissolved oral
cyclosporine solution [61]. This study showed excellent
results in the majority of patients; mean improvement was
77 % in the cyclosporine-treated group and 12 % in the
placebo-treated group. Improvement was noted both in nail
matrix signs of nail psoriasis (pitting) and in nail bed signs
(hyperkeratosis, onycholysis, crumbling, and oil-drop dis-
coloration). No local or systemic side effects were detect-
able, but nails may turn yellowish after long-term
application of cyclosporine in maize oil. These positive
results were rather surprising considering the known issue
of difficult penetration of cyclosporine through the skin and
the nail due to its highly lipophilic nature and size of the
molecule [63]. Later, Prins et al. reported pharmaceutical
instability of the used topical cyclosporine emulsion for
nail psoriasis within 4 h after preparation [64]. According
to this study, patients should homogenize the emulsion
before each application in order to prevent treatment fail-
ure. An unpublished study from Rotterdam, The Nether-
lands, sponsored by Novartis (ISRCTN47031769) tried to
confirm the positive results of cyclosporine on nail psori-
asis, but the investigators were unable to find differences
between the cyclosporine-treated nails and the maize-oil-
treated nails (personal communication).
Tacrolimus is a calcineurin inhibitor with much better
skin-penetrating capacities than cyclosporine. In a 12-week
randomized, controlled, open-label study, the efficacy and
safety of topical treatment with tacrolimus 0.1 % ointment
was assessed in 21 patients with nail psoriasis [62].
Application was once daily at bedtime onto the nail folds of
affected nails, without occlusion, and patients were
instructed not to wash their hands until the next morning.
The severity of nail psoriasis improved significantly, as
measured by overall NAPSI (-57 %) and target NAPSI
(-65 %). Tacrolimus ointment proved to be equally
effective on nail bed and nail matrix features. One patient
M. C. Pasch
was withdrawn from tacrolimus application after 9 weeks
because of the appearance of acute paronychia. No other
side effects were recorded in the observation time.These
results suggest that topical tacrolimus is one of the more
effective and tolerable treatments for both nail bed and nail
matrix psoriasis, but these results need confirmation from
additional studies.
5.7 Anthralin
Anthralin (dithranol) was first synthesized as a derivative
of chrysarobin, prepared from the araroba tree in Brazil
over a century ago. It is an effective treatment of skin
lesions in psoriasis by inhibiting keratinocyte hyperpro-
liferation and interfering with several relevant steps of the
immune system [65]. In one uncontrolled study, 20 pso-
riasis patients with nail involvement were treated with
topical anthralin therapy [66]. An ointment of anthralin in
petrolatum was applied to the affected nail bed once daily
and then washed away with water after 30 min. Therapy
was started with 0.4 % anthralin, and in case of lack of
improvement, the concentration was gradually increased
up to 2.0 %. Within 5 months of therapy, approximately
half of the patients showed good improvement of nail bed
signs of onycholysis, hyperkeratosis, and thickening of
the nail. In addition, pitting, a nail matrix sign of nail
psoriasis, had improved, which is surprising since only
the nail bed had been treated. Longitudinal lines or
transverse lines were unresponsive. A disturbing side
effect of anthralin therapy was reversible pigmentation of
the nail plate, in particular accumulating in the pits. This
hyperpigmentation could be reduced, but not abolished,
with 10 % triethanolamine cream applied after washing
away the anthralin cream.
5.8 5-Fluorouracil
5-fluorouracil is a chemotherapeutic agent with antimitotic
and cytotoxic effects that is efficacious for a number of
dermatological disorders, primarily those that result from
keratinocyte hyperproliferation, including superficial basal
cell carcinoma and actinic keratosis. 5-Fluorouracil in
several vehicles has had variable results in the treatment of
nail psoriasis [6769]. Most studies showed no or very
poor response [67,69], but Fritz et al. reported an
improvement of more than 50 % in the clinical signs of nail
psoriasis after treatment with 20 % urea plus 1 % 5-fluo-
rouracil cream over a period of 6 months [68]. Common
treatment-related adverse effects were inflammation,
infection, discoloration, and onycholysis. 5-Fluorouracil is
not used commonly in nail psoriasis because of its frequent
adverse effects and doubtful efficacy.
5.9 Miscellaneous Topical Therapies: Allopurinol,
Intralesional Methotrexate, Colloidal Silicic
Acid, Indigo Naturalis Extract
Allopurinol, intralesional methotrexate, colloidal silicic
acid, and indigo naturalis extract have been investigated in
nail psoriasis but are not routinely used in clinical practice
because of insufficient data, poor study results, or lack of
registration. Allopurinol is a purine analog and an often-
prescribed urate-lowering drug for the management of
gout. It inhibits xanthine oxidase, a key enzyme involved in
the oxidation of hypoxanthine and xanthine, reactions that
ultimately result in the production of uric acid. Case reports
from the early 1970s suggested a positive effect of allop-
urinol on PP. One placebo-controlled study investigated
allopurinol (200 mg three times daily) in PP and nail
psoriasis [70]. Allopurinol was found to be no more
effective than placebo after 8 weeks of treatment.
Methotrexate is a folic acid analog that irreversibly
binds to dehydrofolate reductase and blocks deoxyribonu-
cleic acid synthesis. It is usually taken orally or adminis-
tered by injection (intramuscular, intravenous,
subcutaneous) and has several indications, including pso-
riasis. Intralesional use of methotrexate may limit the dose,
and hence the side effects, but is not a generally accepted
treatment in nail psoriasis. Saricaoglu et al. reported a
26-year-old women who was treated with methotrexate
2.5 mg every week into the proximal nail fold on each side
of the nail [71]. Subungual hyperkeratosis and pitting had
improved after six treatments.
One study has investigated the effect of combined oral
and topical colloidal silicic acid on PP, psoriatic nail dis-
ease, and psoriatic arthropathy [72]. Patients were treated
with oral colloidal silicic acid gel for 90 days, combined
with topical silicic acid gel on psoriatic skin, but not on nail
lesions. Of the 12 evaluable patients in the treated group,
ten had psoriatic nail disease before treatment and five
showed complete cure after treatment. The placebo-treated
patients were not discussed in this publication.
Indigo naturalis, a dark-blue powder extracted from the
leaves of indigo-bearing plants, is known as a dye in the
Western World. In China it has been used orally for the
treatment of many ailments, including psoriasis. In addi-
tion, topical use of indigo naturalis has shown to be
effective in PP [73], but its use in nail psoriasis is limited
by the recalcitrant and intense blue color. A refined for-
mulation of indigo naturalis oil extract has a slight purple–
red color and is much more cosmetically acceptable. This
compound (0.1 and 0.2 mg/ml) is not yet commercially
available but has been investigated in nail psoriasis in three
studies [7375]. In an open-label study, an improvement in
NAPSI of 60 %, and in modified NAPSI of 68 %, was
Nail Psoriasis: A Review of Treatment Options
reported at 24 weeks after application of one drop onto the
lateral nail folds, eponychium, and hyponychium [74].
After these first encouraging results, the same group pub-
lished a randomized, observer-blind, vehicle-controlled,
intrasubject trial that confirmed the previous results: at
12 weeks, the single-hand NAPSI had improved by 50 %,
and the modified target NAPSI had improved by 59 %
[76]. No further improvement was seen between 12 and
24 weeks of treatment. Moreoever, subject global assess-
ment (SGA) and physician global assessment (PGA) were
improved in the indigo naturalis group than in the control
group. In a third report, indigo naturalis extract was com-
pared with topical calcipotriol solution [75]. Indigo natu-
ralis extract showed significantly better results than
calcipotriol for single-hand NAPSI at 24 weeks (-51 vs.
-27 %, respectively; p=0.007). Onycholysis and sub-
ungual hyperkeratosis improved most for both treatments.
Irritation was the most common side effect of indigo nat-
uralis extract; however, if these positive results can be
confirmed by others, it could, in the future, become a
genuine topical treatment option for nail psoriasis.
6 Systemic Treatment Modalities
Topical treatments for nail psoriasis have the obvious
advantage of treating only the nail apparatus without
exposing the rest of the body to the risk of adverse events.
Therefore, topical treatments are generally the treatment of
choice in patients with mild nail disease, unless the severity
of concomitant PP or PsA creates a situation in which
systemic therapy is preferable. Systemic treatments offer a
valuable alternative in patients with severe nail disease
with a major impact on QoL, pain, or on daily life and
profession. Because psoriasis is a chronic disease, treat-
ment must be continued for the long term, and even
indefinitely. For this reason, long-term safety of any
treatment should be considered and discussed in each
patient. The choice for optimal systemic treatment in a
patient does not only depend on the severity of the nail
involvement but also on the presence or absence of psori-
atic joint disease and skin disease, other diseases in the
patient, the patient’s preferences, long-term safety, expe-
rience of the prescriber, side effects, and costs of treatment.
Methotrexate and apremilast are oral treatments that are
effective in PP and PsA, while cyclosporine, fumaric acid,
and retinoids are more effective in PP than PsA. The same
consideration must be made in psoriasis patients who are
going to be treated with biologics. While anti-TNFaand
anti-IL-12/23 are effective in PsA, anti-IL-17 appears to be
much more effective in skin involvement of the disease
than in joint involvement.
7 Oral Systemic Treatments
7.1 Methotrexate
As an orally or subcutaneously administered systemic
compound, methotrexate is one of the most used systemic
treatments in PP, PsA, and nail psoriasis. It is cost effective
and its efficacy in PP and PsA has been known for many
years [59]. A wide range of potential side effects limit its
use, including hepatotoxicity, ulcerative stomatitis, lym-
phopenia, nausea, low white blood cell count, and nausea.
Studies focussing on methotrexate in nail psoriasis show
efficacy, but significantly less than most biologics
(Table 2)[7780]. One RCT comparing methotrexate and
cyclosporine in nail psoriasis showed a mean NAPSI
improvement of 43 % in methotrexate-treated patients and
37 % in cyclosporine-treated patients at 24 weeks (not
significant) [77]. The methotrexate group showed a sig-
nificant improvement in nail matrix scores only, while the
cyclosporine group showed significant improvement in nail
bed scores only [77]. Methotrexate efficacy to treat nail
psoriasis has also been compared with briakinumab in an
RCT [78]. Target NAPSI improved 38 % in methotrexate-
treated patients and 56 % in briakinumab-treated patients.
Patients were treated with an extremely slowly increasing
dose of methotrexate for 24 weeks, which might have had a
negative impact on outcome. Smaller, non-controlled
studies showed NAPSI improvements in the same range
[79,80].
7.2 Cyclosporine
The calcineurin inhibitor cyclosporine is a powerful
immunosuppressive drug that, in dermatology, has a posi-
tion in the treatment of several disorders, such as severe
eczema, PP, and alopecia areata. Topical use of cyclos-
porine in nail psoriasis has been discussed in Sect. 5.6,but
systemic use has also been the topic of several reports that,
despite the lack of efficacy in PsA, show reasonable efficacy
in the treatment of both nail bed and nail matrix signs of
psoriasis [53,79,8184]. One study indicated more efficacy
of cyclosporine in nail bed psoriasis than in nail matrix
psoriasis [77]. The efficacy of cyclosporine in comparison
with other drugs has been reported in several studies. While
Gumusel et al., who used the NAPSI as a scoring system,
were unable to see significant differences between cyclos-
porine and methotrexate, most other studies used uncom-
mon endpoints [77]. Mahrle et al. reported on a study of
cyclosporine versus an obsolete retinoid—etretinate—using
an unspecified 4-point scale [82]. Nail involvement had
decreased by 46 and 34 % compared with baseline after
22 weeks of treatment with cyclosporine and etretinate,
M. C. Pasch
Table 2 Literature data on efficacy of conventional systemic therapies on nail psoriasis
Study, year Dose Study
design
Inclusion Outcome
measure
Observations
(weeks)
Baseline 10–20 weeks 21–30 weeks [30 weeks No. of
patients
Acitretin (A)/etretinate (E)
Demirsoy et al.,
2013 [80]
A: unknown PCS PP NAPSI 16 23.8 -25 % 25
Mahrle et al.,
1995 [82]
E: 0.5–0.75 mg/kg/day RCT PP Not specified 10 -9% 47
Sanchez-
Regana et al.,
2011 [79]
A: 25 mg/day, [6–12 weeks:
2–49/week
RCS PP NAPSI 12, 24, 48 12.7 -19 % -41 % -52 % 7
Tosti et al.,
2009 [87]
A: 0.2–0.3 mg/kg/day PCS Nails
only
NAPSI, target
NAPSI
26 NAPSI: 31.5,
target NAPSI:
7.6
NAPSI: -41 %,
target NAPSI:
-50 %
36
Apremilast
Papp et al.,
2015 [89]
30 mg bid RCT PP Target NAPSI,
NAPSI-50
d
16, 32 -23 % -44 % 558
Rich et al.,
2016 [91]
30 mg bid RCT PP Target NAPSI,
NAPSI-50
e
16, 32 -29 % -60 % 266
Cyclosporine
Feliciani et al.,
2004 [53]
3–4.5 mg/kg/day PCS PP Involved area
(\10/10–50/
[50 %)
14 -48 % 21
Feliciani et al.,
2004 [53]
3–4.5 mg/kg/day,
calcipotriol cream bid
PCS PP Involved area
(\10/10–50/
[50 %)
14 -79 % 33
Gumusel et al.,
2011 [77]
5 mg/kg/day PCS PP NAPSI 24 16.3 -37 % (NS)
c
17
Karanikolas
et al., 2011 [84]
2.5–3.75 mg/kg/day PCS PsA NAPSI-50 52
f
18
Karanikolas
et al., 2011 [84]
2.5–3.75 mg/kg/day, 40 mg
adalimumab EOW
PCS PsA NAPSI-50 52
g
21
Mahrle et al.,
1995 [82]
2.5–5 mg/kg/day RCT PP Not specified 10, 22 -18 % -46 % 90
Sanchez-
Regana et al.,
2011 [79]
3 mg/kg/day RCS PP NAPSI 12, 24, 48 12.7 -38 % -72 % -89 % 9
Syuto et al.,
2007 [83]
3 mg/kg/day, in case of
improvement 1.5 mg
PCS PP Not specified 16–65
a
16
Nail Psoriasis: A Review of Treatment Options
Table 2 continued
Study, year Dose Study
design
Inclusion Outcome
measure
Observations
(weeks)
Baseline 10–20 weeks 21–30 weeks [30 weeks No. of
patients
Leflunomide
Behrens et al.,
2013 [94]
According to daily clinical practice PCS PsA 5-point scale 24 32 % of treated patients showed improvement at 24 weeks 466
Methotrexate
Demirsoy et al.,
2013 [80]
Unknown PCS PP NAPSI 16 25.1 -18 % 20
Gumusel et al.,
2011 [77]
Initial dose 15 mg qw PCS PP NAPSI 24 16.3 -43 % (NS)
b
17
Reich et al.,
2011 [78]
5–15 mg qw (weeks 0–9), 20 mg qw
(weeks 10–15), 25 mg qw
([week 16)
RCT PP Target NAPSI 24 4.8 -30 % 108
Sanchez-
Regana et al.,
2011 [79]
7.5–25 mg qw RCS PP NAPSI 12, 24, 48 12.7 -7% -31 % -35 % 9
bid twice daily, EOW every other week, NAPSI Nail Psoriasis Severity Index, NAPSI-50 percentage of patients achieving a (target) NAPSI improvement of at least 50 %, NS not significant, PCS
prospective cohort study, PP plaque psoriasis, PsA psoriatic arthritis, qw once weekly, RCS retrospective cohort study, RCT randomized controlled trial, target NAPSI Nail Psoriasis Severity
Index of one target nail
a
15/16 improved: 2 complete resolution, 109significant improvement, 39slight improvement
b
Significant improvement in nail matrix, no significant improvement in nail bed
c
No significant improvement in nail matrix, significant improvement in nail bed
d
33.3 % (16 weeks), 45.2 % (32 weeks)
e
NAPSI-50: 44.6 % (16 weeks), 55.4 % (32 weeks)
f
NAPSI-50: 44 % (52 weeks)
g
NAPSI-50: 100 % (52 weeks)
M. C. Pasch
respectively. A 12-month comparison of cyclosporine with
an anti-TNFabiologic—adalimumab—in PsA patients also
suffering from nail psoriasis showed a NAPSI-50 in 44 %
of patients receiving cyclosporine, 56 % of patients
receiving adalimumab, and 100 % of patients receiving a
combination of the two drugs [84]. The finding that
cyclosporine was comparable to biologics in treating nail
psoriasis was also confirmed in a retrospective database
study: cyclosporine was the most effective classical sys-
temic treatment; NAPSI improved 89 % at 48 weeks of
treatment [79]. Concomitant use of cyclosporine and topical
calcipotriol cream three times daily may further improve
treatment results [53]. While most studies use doses
between 3 and 5 mg/day, one study from Japan investigated
a lower dose of cyclosporine per day; the initial dose of
3 mg/kg/day was successfully reduced to 1.5 mg/kg/day in
responders [83]. Cyclosporine use may be limited by the
relatively high rates of side effects; the most serious adverse
reactions are mostly reversible renal dysfunction and
hypertension. Other side effects include fatigue, headache,
paresthesia, hypertrichosis, gingival hyperplasia, and gas-
trointestinal disorders. After prolonged use, cyclosporine
may play a role in the development of renal failure and
several malignancies. For this reason, it is often considered
as an effective treatment for severe cases of (nail) psoriasis,
but only for a period of 6–12 months.
7.3 Retinoids
Acitretin is a non-immunosuppressing antipsoriatic drug
that can be used for years in patients who can tolerate its
side effects, such as cheilitis, dry mouth, and skin exfoli-
ation [85]. Acitretin normalizes cellular differentiation and
controls inflammation. The position of acitretin in the
treatment of nail psoriasis is that of a rather slow-acting
compound with moderate efficacy and action, particularly
on nail bed signs of psoriasis (Table 2)[79,80,82,86,87].
Two open studies and one retrospective analysis indicated
that a NAPSI improvement of 40–50 % at 6–12 months
may be expected [79,87]. At earlier time points, acitretin is
considerably less effective [79,80]. Acitretin can also be
used as an adjuvant therapy to psoralen plus ultraviolet A
(PUVA) and ultraviolet B (UVB), as discussed in
Sect. 10.3.
7.4 Apremilast
Apremilast is an oral, small-molecule inhibitor of phos-
phodiesterase 4 that alters the expression of a variety of
immune mediators [88]. It is USA FDA- and European
Medicines Agency (EMA)-approved for the treatment of
adults with psoriasis and PsA. Two RCTs (ESTEEM 1 and
2) in which nail psoriasis was a secondary endpoint
investigated its efficacy in nail psoriasis (Table 2)[8991].
At 16 weeks, target NAPSI improvement was limited, but
after 32 weeks of apremilast, NAPSI had improved 43.6
and 60.0 % in ESTEEM 1 and ESTEEM 2, respectively.
Both nail matrix and nail bed psoriasis improved signifi-
cantly. The percentage of patients achieving NAPSI-50 at
32 weeks in ESTEEM 1 and ESTEEM 2 was 45.2 and
55.4 %, respectively. The very liberal definition of nail
psoriasis in these studies (NAPSI C1) makes it hard to
draw conclusions about efficacy in clinically relevant nail
psoriasis. Because apremilast is generally well tolerated
and has no need for biochemical follow-up it may be an
attractive choice for patients in who systemic treatments
are indicated. The very high costs of treatment may limit its
use in many patients.
7.5 Miscellaneous Systemic Therapies: Fumaric
Acid Esters, Sulfasalazine, and Leflunomide
Fumaric acid esters (FAEs), sulfasalazine, and leflunomide
have also been reported to be effective in nail psoriasis;
however, based on the current knowledge, they cannot be
advised for this indication. FAEs have been used for the
treatment of chronic PP since 1959. The commercially
available form, containing mainly dimethylfumarate, is
currently a first-line systemic therapy for severe chronic PP
in several European countries; it is not effective in PsA.
The general opinion is that it has little efficacy in nail
psoriasis, but one case has been reported in which it was
effective both on nail bed and nail matrix psoriasis [92].
Side effects are frequent in patients using FAEs, such as
episodes of flushing, abdominal pain, and a decrease in
lymphocyte count.
Sulfasalazine is an aminosalicylate used as a traditional
disease-modifying antirheumatic drug (DMARD) for the
treatment of peripheral involvement in PsA. Sulfasalazine
is metabolized by gut flora into sulfapyridine and
5-aminosalicylic acid, which act as anti-inflammatory
agents. The role of sulfasalazine in cutaneous psoriatic
lesions and nail psoriasis is not generally accepted. One
case has been reported on the use of sulfasalazine in the
treatment of psoriatic nail lesions [93]. After 3 months, nail
lesions started to recede and disappeared progressively. No
other cases have been reported in literature.
Leflunomide is another DMARD used to treat PsA. It is
a de novo pyrimidine biosynthesis inhibitor with
immunomodulatory properties. One prospective study
assessed the clinical effectiveness and safety of lefluno-
mide in patients with PsA, and also in psoriatic nail disease
[94]. Unlike most studies on PP, patients in this study also
received concomitant antiinflammatory/antirheumatic
drugs, systemic corticosteroids, and other DMARDs, pre-
dominately methotrexate. Significant improvements were
Nail Psoriasis: A Review of Treatment Options
experienced in 32 % of patients with nail lesions. The most
frequent adverse events were diarrhea, alopecia, hyper-
tension, and pruritus.
8 Biologics
The introduction of biologics has led to a major step for-
ward in the treatment of severe PP and PsA, and may have
the potential to revolutionize the management of patients
with disabling psoriatic nail disease. Anti-TNFatreatments
were the first, very effective biologics that became avail-
able to psoriasis patients. More recently, other mechanisms
of the psoriatic inflammatory reaction can be suppressed
with anti-IL-17, and anti-IL-12/23 monoclonal antibodies.
Consequently, the therapeutic armamentarium is expanding
for patients with moderate to severe PP or PsA who are
unresponsive to conventional systemic therapies or have
contraindications for these therapies. Infliximab, etaner-
cept, and adalimumab are anti-TNFatreatments available
both for PP and PsA patients, while golimumab and cer-
tolizumab pegol only have registration for PsA. The bio-
logic ustekinumab, which targets IL-12/23, and the anti-IL-
17 antibody secukinumab are also available for both PP
and PsA. All these biologics appear to have a positive
effect on nail psoriasis, without major differences in effi-
cacy between the populations they are investigated in, i.e.
PP or PsA (Table 3). In general, nail responses are slow but
continue to improve, lagging behind cutaneous responses
over time. While the onset of response in nail psoriasis is
mostly noticeable after approximately 12 weeks, further
improvement or even complete clearance can be seen
through to 1 year of treatment. Nonetheless, nail, skin, and
joint manifestations of psoriasis generally improved in
parallel based on correlation between NAPSI, Psoriasis
Area Severity Index (PASI), and American College of
Rheumatology (ACR) responses over time. Overall,
patients with greater skin or joint responses also demon-
strated better nail responses. On the other hand, the pres-
ence of nail disease was not shown to predict good
response of the arthritis [95], and improvement of nail
psoriasis by a biologic did not depend on the presence or
absence of PsA [96].
8.1 Inhibition of Tumor Necrosis Factor-a
TNFais a proinflammatory cytokine that plays a major role
in psoriasis by promoting an inflammatory infiltrate into
the skin and inducing keratinocyte proliferation and pre-
venting keratinocyte apoptosis, which directly contributes
to the characteristic skin and nail lesions. Anti-TNFahas
shown to be a relatively safe and very effective treatment
for PP, PsA, and nail psoriasis (Table 3). The originally
high cost of these treatments has limited their use in nail
psoriasis, but since lower-cost biosimilars for infliximab
and etanercept have been approved in the US and/or the EU
they may become available to more patients with nail
psoriasis. Infliximab, etanercept, adalimumab, golimumab,
and certolizumab pegol all appear to be effective treat-
ments for nail psoriasis and will be discussed individually
in the following sections. The most often reported adverse
effects related to the use of TNFaantagonists are activation
of opportune infections, including mycobacterium tuber-
culosis (TB), demyelinating diseases, congestive heart
failure, induction of the formation of autologous antibod-
ies, and antibodies neutralizing anti-TNFadrugs [97]. The
development of anti-TNFa-induced lupus or classical drug-
induced lupus is more rarely reported. Contraindications
for the use of anti-TNFamedications are related to the
adverse events, i.e. chronic infection, such as active TB or
other severe infections, moderate to severe heart failure, as
well as pregnancy and nursing. TB should be ruled out
before starting therapy. Patients with hematological chan-
ges, demyelination processes, and recent neoplasms should
not be treated, or should be treated only in close collabo-
ration with other relevant specialists.
8.1.1 Infliximab
Infliximab was approved in the US in 1998 for the treat-
ment of Crohn’s disease. Thereafter, infliximab has had its
indication expanded, and in 2005/2006 became available
for the treatment of PsA and PP. It is a chimeric anti-TNFa
immunoglobulin (Ig) G1 monoclonal antibody that is
comprised of human antibody constant regions and murine
variable regions. Infliximab binds both soluble and mem-
brane-bound TNFa, preventing it from binding its receptor,
resulting in a decrease in epidermal T-cell infiltration. The
chimeric character of infliximab may result in a higher
formation of neutralizing antibodies than occurs with fully
human(-ized) antibodies. A concern related to the forma-
tion of these antibodies is the decreased efficacy of
infliximab over time, which may require increased infusion
frequencies, higher doses to maintain a clinical response
and disease control, and infusion reactions, occurring in
16 % of infliximab-treated patients [98]. These reactions
can involve chills, fever, headache, flushing and urticaria,
myalgia and arthralgia, nausea, dyspnoea, and hypotension
[99101]. Most infusion-related reactions are mild and can
usually be ameliorated by reducing the rate of infusion
rather than discontinuing therapy. However, anaphylactic
reactions are also possible, requiring surveillance during
and for 1 h after infusion. A type IV delayed hypersensi-
tivity reaction may also present 3–12 days after infusion
and produce a serum sickness-like reaction [102]. A study
comparing the incidence of onychomycosis inpatients
M. C. Pasch
Table 3 Literature data on efficacy of biologics on nail psoriasis
Study, year Dose Study
design
Inclusion Outcome
measure
Observation
(weeks)
Outcomes (as defined in ‘Outcome measure’) No. of
patients
Baseline
(target)
NAPSI
11–20 weeks 21–30 weeks [30 weeks NAPSI-50 NAPSI-75 NAPSI-90 Complete
clearance
Adalimumab
Al-Mutairi
et al., 2013
[103]
80 mg at
baseline,
40 mg q2w
ROL PP NAPSI 24 32.9 -71 % 105
Bardazzi et al.,
2013 [123]
Unknown RCS PP NAPSI, NAPSI-
75
12, 24, 36 32.0 -66 % -89 % -94 % 89 %
(36 weeks)
16
Van den Bosch
et al., 2010
[95]
40 mg q2w PCS PsA NAPSI, NAPSI-
50
12 14 -57 % 54 % 259
Karanikolas
et al., 2011
[84]
40 mg q2w PCS PsA NAPSI-50 52 56 % 16
Karanikolas
et al., 2011
[84]
40 mg q2w,
CsA
2.5–3.75 mg/
kg/day
PCS PsA NAPSI-50 52 100 % 21
Kyriakou
et al., 2013
[124]
80 mg at
baseline,
40 mg q2w
RCS PP NAPSI 12, 24, 48 25.8 -36 % -71 % -87 % 14
Leonardi et al.,
2011 [119]
80 mg at
baseline,
40 mg q2w
RCT PP Target NAPSI 16, 28 3.9 -50 % -54 % 28
Ozmen et al.,
2013 [125]
80 mg at
baseline,
40 mg q2w
PCS PP NAPSI,
modified
NAPSI,
NAPSI-50,
NAPSI-75,
NAPSI-90
48 NAPSI:
72.0,
modified
NAPSI:
71.8
NAPSI:
-54 %,
modified
NAPSI:
-49 %
75% 13% 0% 0%
(48 weeks)
8
Rigopoulos
et al., 2010
[96]
80 mg at
baseline,
40 mg q2w
PCS PP,
PsA-
NAPSI 12, 24 10.6 -47 % -85 % 7
Rigopoulos
et al., 2010
[96]
80 mg at
baseline,
40 mg q2w
PCS PP,
PsA?
NAPSI 12, 24 24.9 -46 % -86 % 14
Rudwaleit
et al., 2010
[116]
40 mg q2w PCS PsA
e
NAPSI 12 18 -42 % 36
Rudwaleit
et al., 2010
[116]
40 mg q2w PCS PsA
f
NAPSI 12 14 -33 % 223
Saraceno et al.,
2013 [126]
80 mg at
baseline,
40 mg q2w
PCS PP NAPSI, NAPSI-
75
12, 24 33.1 -37 % -66 % 50 % 20
Sanchez-
Regana et al.,
2011 [79]
80 mg at
baseline,
40 mg q2w
RCS PP NAPSI 12, 24, 48 17.5 -37 % -73 % -84 % 8
Nail Psoriasis: A Review of Treatment Options
Table 3 continued
Study, year Dose Study
design
Inclusion Outcome
measure
Observation
(weeks)
Outcomes (as defined in ‘Outcome measure’) No. of
patients
Baseline
(target)
NAPSI
11–20 weeks 21–30 weeks [30 weeks NAPSI-50 NAPSI-75 NAPSI-90 Complete
clearance
Sola-Ortigosa
et al., 2012
[122]
80 mg at
baseline,
40 mg q2w
RCS PP NAPSI 24 18,9 -57 % 15
Thaci et al.,
2015 [117]
80 mg at
baseline,
40 mg q2w
RCT PP NAPSI, matrix
NAPSI, bed
NAPSI
8, 16 25.4 -40 % 457
Briakinumab
Reich et al.,
2011 [78]
200 mg weeks
0, 4,
?100 mg
q4w
RCT PP Target NAPSI 24 4.8 -56 % 115
Certoluzimab Pegol
Mease et al.,
2014 [135]
200 mg q2w RCT PsA Modified target
NAPSI
24 3.1 -52 % 92
Mease et al.,
2014 [135]
400 mg q4w RCT PsA Modified target
NAPSI
24 3.4 -59 % 105
Etanercept
Al-Mutairi
et al., 2013
[103]
50 mg biw,
[12 weeks:
25 mg biw
ROL PP NAPSI 24 33.8 -68 % 110
Bardazzi et al.,
2013 [123]
Unknown RCS PP NAPSI, NAPSI-
75
12, 24, 36 32.0 -62 % -85 % -90 % 89 %
(36 weeks)
18
Barrera et al.,
2008 [131]
25 mg biw RCS PP Descriptive 24 Significant improvement \12 weeks 39
Barrera et al.,
2008 [131]
50 mg biw,
[12 weeks:
25 mg biw
RCS PP Descriptive 24 Significant improvement \12 weeks 27
Kyriakou
et al., 2013
[124]
50 mg biw,
[12 weeks:
25 mg biw
RCS PP NAPSI 12, 24, 48 23.4 -42 % -76 % -92 % 13
Luger et al.,
2009 [13]
50 mg biw,
[12 weeks:
25 mg biw
PCS PP Target NAPSI 12, 54 4.6 -29 % -51 % 30 %
(54 weeks)
562
Ortonne et al.,
2013 [132]
50 mg biw,
[12 weeks:
50 mg qw
ROL PP NAPSI, target
NAPSI,
NAPSI-50,
NAPSI-75,
CC
24 NAPSI:
34.8,
target
NAPSI:
6.0
NAPSI:
-65 %,
target
NAPSI:
-72 %
58 %
(12 weeks),
82 %
(24 weeks)
57 %
(24 weeks)
14 %
(24 weeks)
38
Ortonne et al.,
2013 [132]
50 mg qw ROL PP NAPSI, target
NAPSI,
NAPSI-50,
NAPSI-75,
CC
24 NAPSI:
31.4,
target
NAPSI:
5.8
NAPSI:
-72 %,
target
NAPSI:
-76 %
51 %
(12 weeks),
81 %
(24 weeks)
69 %
(24 weeks)
31 %
(24 weeks)
34
M. C. Pasch
Table 3 continued
Study, year Dose Study
design
Inclusion Outcome
measure
Observation
(weeks)
Outcomes (as defined in ‘Outcome measure’) No. of
patients
Baseline
(target)
NAPSI
11–20 weeks 21–30 weeks [30 weeks NAPSI-50 NAPSI-75 NAPSI-90 Complete
clearance
Ozmen et al.,
2013 [125]
50 mg biw,
[12 weeks:
25 mg biw
PCS PP NAPSI,
modified
NAPSI,
NAPSI-50,
NAPSI-75,
NAPSI-90
48 NAPSI:
86.7,
modified
NAPSI:
81.2
NAPSI:
-58 %,
modified
NAPSI:
-60 %
78%0%0%0%
(48 weeks)
9
Saraceno et al.,
2013 [126]
50 mg biw,
[12 weeks:
25 mg biw
PCS PP NAPSI, NAPSI-
75
12, 24 34.8 -32 % -70 % 45 % 20
Sanchez-
Regana et al.,
2011 [79]
50 mg biw,
[12 weeks:
50 mg qw
RCS PP NAPSI 12, 24, 48 17.5 -24 % -68 % -87 % 9
Golimumab
Kavanaugh
et al., 2009
[133],
Kavanaugh
et al., 2012
[134]
50 mg/4 weeks RCT PsA Target NAPSI,
PGA
a
14, 24, 52 4.7 -25 % -43 % -52 % 95
Kavanaugh
et al., 2009
[133],
Kavanaugh
et al., 2012
[134]
100 mg/
4 weeks
RCT PsA Target NAPSI,
PGA
b
14, 24, 52 4.6 -33 % -54 % -66 % 109
Infliximab
Al-Mutairi
et al., 2013
[103]
5 mg/kg weeks
0, 2, 6, ?8w
ROL PP NAPSI 24 34.1 -86 % 100
Bardazzi et al.,
2013 [123]
Unknown RCS PP NAPSI, NAPSI-
75
12, 24, 36 32.0 -64 % -86 % -91 % 89 %
(36 weeks)
14
Bianchi et al.,
2005 [114]
5 mg/kg weeks
0, 2, 6, ?8w
PCS PP NAPSI 16, 22 28.3 -65 % -100 % 100 %
(22 weeks)
9
Bianchi et al.,
2005 [114]
5 mg/kg weeks
0, 2, 6, ?8w
PCS PsA NAPSI 16, 22 33.3 -61 % -100 % 100 %
(22 weeks)
16
Fabroni et al.,
2011 [113]
5 mg/kg weeks
0, 2, 6, ?8w
RCS PP NAPSI, NAPSI-
50, NAPSI-
75, NAPSI-90
14, 22, 38 49.7 -63 % -81 % -86 % 98 %
(38 weeks)
81 %
(38 weeks)
29 %
(38 weeks)
10 %
(38 weeks)
48
Kyriakou
et al., 2013
[124]
5 mg/kg weeks
0, 2, 6, ?8w
RCS PP NAPSI 12, 24, 48 25.2 -49 % -80 % -95 % 80 %
(48 weeks)
12
Nail Psoriasis: A Review of Treatment Options
Table 3 continued
Study, year Dose Study
design
Inclusion Outcome
measure
Observation
(weeks)
Outcomes (as defined in ‘Outcome measure’) No. of
patients
Baseline
(target)
NAPSI
11–20 weeks 21–30 weeks [30 weeks NAPSI-50 NAPSI-75 NAPSI-90 Complete
clearance
Ozmen et al.,
2013 [125]
5 mg/kg weeks
0, 2, 6, ?8w
PCS PP NAPSI,
modified
NAPSI,
NAPSI-50,
NAPSI-75,
NAPSI-90
48 NAPSI:
69.6,
modified
NAPSI:
72.7
NAPSI:
-40 %,
modified
NAPSI:
-40 %
55%0%0%0%
(48 weeks)
11
Reich et al.,
2005 [100]
5 mg/kg weeks
0, 2, 6, ?8w
RCT PP Target NAPSI,
CC target
finger
c
10, 24 4.6 -56 % 26 %
(24 weeks)
235
Rich et al.,
2008 [106]
5 mg/kg weeks
0, 2, 6, ?8w
RCT PP Target NAPSI,
CC target
finger
50 4.6 -56 % 45 %
(50 weeks)
235
Rigopoulos
et al., 2008
[105]
5 mg/kg weeks
0, 2, 6, ?8w
PCS PP NAPSI 14, 22, 38 55.8 -47 % -61 % -94 % 61 %
(38 weeks)
18
Saraceno et al.,
2013 [126]
5 mg/kg weeks
0, 2, 6, ?8w
PCS PP NAPSI, NAPSI-
75
12, 24 33.3 -55 % -91 % 65 % 20
Sanchez-
Regana et al.,
2011 [79]
5 mg/kg weeks
0, 2, 6, ?8w
RCS PP NAPSI 12, 24, 48 17.5 -50 % -81 % -92 % 81 %
(48 weeks)
8
Torii et al.,
2010 [108]
5 mg/kg weeks
0, 2, 6, ?8w
RCT PP Target NAPSI,
involved
number of
nails
10, 14, 26,
42, 62
Target
NAPSI:
3.7,
involved
nails: 7.3
-28 % Target
NAPSI:
-46 %,
involved
nails: 3.0
Target
NAPSI:
-46 %,
involved
nails: 1.6
29
Torii et al.,
2011 [109]
5 mg/kg weeks
0, 2, 6, ?8w
PCS PP Target NAPSI 10, 25, 50 4.4 -59 % -57 % 59 %
(50 weeks)
56
Ixekizumab
Langley et al.,
2015 [143]
RCT PP NAPSI 24, 48 36.4 -78 % -79 % 51 %
(48 weeks)
50
Leonardi et al.,
2012 [142]
10 mg, weeks
0–2–4–8–12
RCT PP NAPSI 20 41.9 14 % 13
Leonardi et al.,
2012 [142]
25 mg, weeks
0–2–4–8–12
RCT PP NAPSI 20 34.9 -24 % 10
Leonardi et al.,
2012 [142]
75 mg, weeks
0–2–4–8–12
RCT PP NAPSI 20 45.0 -57 % 10
Leonardi et al.,
2012 [142]
150 mg, weeks
0–2–4–8–12
RCT PP NAPSI 20 26.5 -49 % 10
Secukinumab
Paul et al.,
2014 [139]
150 mg week
0
RCT PP Composite
fingernail
score
(affected
area)
12 8.9 -4% 51
M. C. Pasch
Table 3 continued
Study, year Dose Study
design
Inclusion Outcome
measure
Observation
(weeks)
Outcomes (as defined in ‘Outcome measure’) No. of
patients
Baseline
(target)
NAPSI
11–20 weeks 21–30 weeks [30 weeks NAPSI-50 NAPSI-75 NAPSI-90 Complete
clearance
Paul et al.,
2014 [139]
150 mg weeks
0, 4, and 8
RCT PP Composite
fingernail
score
(affected
area)
12 8.9 -11 % 110
Paul et al.,
2014 [139]
150 mg weeks
0, 1, 2, and 4
RCT PP Composite
fingernail
score
(affected
area)
12 8.9 -19 % 101
Ustekinumab
Bardazzi et al.,
2013 [123]
Unknown RCS PP NAPSI, NAPSI-
75
12, 24, 36 32.0 -51 % -82 % -88 % 89 %
(36 weeks)
6
Igarashi, 2012
[149]
45 mg (weeks
0–4–16–28)
RCT PP Target NAPSI 12
g
3.7 NS -57 % 44
Igarashi et al.,
2012 [149]
90 mg (weeks
0–4–16–28)
RCT PP Target NAPSI 12
g
4.1 NS -64 % 40
Patsatsi et al.,
2013 [148]
45 mg (weeks
0–4–16–28)
PCS PP NAPSI 12, 28, 40 76.7 -44 % -87 % -97 % 27
Rich et al.,
2014 [150]
45 mg (weeks
0–4–16–28)
RCT PP Target NAPSI,
number of
nails involved
12, 24 Target
NAPSI:
4.4,
involved
nails: 6.6
Target
NAPSI: -
27 %,
involved
nails: 6.1
Target
NAPSI:
-47 %,
involved
nails: 5.1
182
Rich et al.,
2014 [150]
90 mg (weeks
0–4–16–28)
RCT PP target NAPSI,
number nails
involved
12, 24 Target
NAPSI:
4.4,
involved
nails: 6.7
Target
NAPSI: -
25 %,
involved
nails: 6.0
Target
NAPSI:
-49 %,
involved
nails: 5.3
187
Rigopoulos
et al., 2011
[147]
\100 kg:
45 mg
(weeks 0–4–
16–28);
[100 kg:
90 mg
PCS PP NAPSI, QoL 4, 16, 28, 40 19.6 -50 % -80 % -90 % 27
Nail Psoriasis: A Review of Treatment Options
Table 3 continued
Study, year Dose Study
design
Inclusion Outcome
measure
Observation
(weeks)
Outcomes (as defined in ‘Outcome measure’) No. of
patients
Baseline
(target)
NAPSI
11–20 weeks 21–30 weeks [30 weeks NAPSI-50 NAPSI-75 NAPSI-90 Complete
clearance
Vitiello et al.,
2013 [146]
\100 kg:
45 mg
(weeks 0–4);
[100 kg:
90 mg
h
RCS PP NAPSI,
modified
target NAPSI
12 NAPSI:
22.3,
modified
target
NAPSI:
6.3
NAPSI:
-34 %,
modified
target
NAPSI:
-17 %
13
biw twice weekly, CC complete clearance,CsA cyclosporine, NAPSI Nail Psoriasis Severity Index, NAPSI-50 percentage of patients achieving a (target) NAPSI improvement of at least 50 %, NAPSI-75 percentage of patients achieving
a (target) NAPSI improvement of at least 75 %, NAPSI-90 percentage of patients achieving a (target) NAPSI improvement of at least 90 %, NS not significant, PASI-50 50 % reduction in the Psoriasis Area Severity Index, PCS
prospective cohort study, PGA Physician Global Assessment, PP plaque psoriasis, PsA psoriatic arthritis, QoL quality of life, qw once weekly, q2w every 2 weeks, q4w every 4 weeks, RCS retrospective cohort study, RCT randomized
controlled trial, ROL randomized, open-label study, target NAPSI Nail Psoriasis Severity Index of one target nail, TNF tumor necrosis factor,
a
PGA improvement 24 weeks: 48 %
b
PGA improvement 24 weeks: 63 %
c
Week 24: matrix NAPSI -53 %, bed NAPSI -69 %
d
Week 16: matrix NAPSI -39 %, bed NAPSI -60 %
e
PsA, history of anti-TNFa
f
PsA, no history of anti-TNFa
g
64 weeks if PASI-50 at week 28
h
69also methotrexate, 29also cyclosporine
M. C. Pasch
treated with infliximab, etanercept, and adalimumab has
shown a statistical positive association between fungal
infections of the nail in psoriasis patients and the use of
infliximab [103]. Thirty-three percent of patients receiving
infliximab had a positive fungal culture, while in patients
receiving etanercept and adalimumab, as well as controls,
this percentage was 15.5, 13.3, and 13.9 %, respectively.
Several studies have proven the beneficial effect of
infliximab on nail psoriasis, both in PsA and PP patients,
and also in patients with severe nail psoriasis at baseline
(Table 3). No differences between efficacy in nail bed and
nail matrix psoriasis have been reported. Patients with a
high PASI response have a more rapid and profound nail
response than patients with a poorer PASI response [104].
In addition, QoL improves during infliximab treatment in
nail psoriasis [105].
The first report on infliximab in nail psoriasis came from
the EXPRESS study. Reich et al. reported on 235 psoriatic
patients who also had nail involvement [100] and who were
further analyzed by Rich et al. [106]. Patients were treated
with infliximab or placebo up to week 46. Complete
clearance of a target finger was seen in 26 and 45 % of
patients at week 24 and week 50, respectively, while at
both time points the mean improvement in target NAPSI
was 56 %. At week 24, the mean percentage improvements
in nail matrix and nail bed features were 52.9 and 69.2 %,
respectively. Improvement of both nail bed and nail matrix
psoriasis was also reported from Japan [107]. These
authors also reported a randomized, double-blind, placebo-
controlled multicenter trial [108]. Improvements in target
NAPSI at weeks 26–66 was 46 %, and the number of
affected nails had decreased by 78 % at week 66. An open-
label, uncontrolled study resulted in a target NAPSI
improvement of 59 % at week 26, and 57 % improvement
at week 50 [109]. Other case reports and open-label studies
reported even more improvement in severity of nail pso-
riasis [105,110112]. A retrospective study of 48 patients
in a group of patients with severe nail psoriasis (NAPSI at
baseline, 49.7) also showed excellent real-life results [113].
At 22 weeks, NAPSI had improved to 80.8 %, and at
38 weeks had improved to 85.9 %. Almost all patients
achieved NAPSI-50, 81 % achieved NAPSI-75, and 29 %
achieved NAPSI-90. Complete clearance was seen in 10 %
of patients.
Infliximab appears to be equally effective for the treat-
ment of nail psoriasis in patients with PsA and PP. Bianchi
et al. reported on nine patients with PP and 16 patients with
arthropathic psoriasis who were treated for 16 weeks in an
open-label, non-controlled, prospective study [114]. At
week 16, NAPSI improvement in PP patients was 64.7 %,
and 60.7 % in PsA patients.
Prospective and retrospective studies comparing several
systemic and biologic therapies have been conducted and
will be discussed in Sect. 9. The efficacy of infliximab in
these trials is in the same range as in the above-mentioned
studies.
Considering the results of these studies, one can con-
clude that while nail response generally lags behind cuta-
neous response in these patients, similar excellent degrees
of response can be attained following 6–12 months of
infliximab treatment. Comparing data from trials on all
discussed biologics, infliximab might be the fastest-acting
treatment for nail psoriasis.
8.1.2 Adalimumab
PP and PsA are both indications for adalimumab, a fully
human anti-TNFaIgG1 monoclonal antibody. On binding
TNFa, adalimumab neutralizes the biological activities of
this cytokine by blocking its interaction with the p55 and
p75 cell surface TNF receptors, and modulating biological
responses that are induced or regulated by TNFa. Initially,
its efficacy in nail psoriasis was claimed in a case report
[115] but clinical studies have followed (Table 3). The first
study was an open-label study in patients with mild to
moderate nail psoriasis [96]. After 24 weeks of treatment,
the fingernail NAPSI had improved 85 %. No differences
in efficacy were seen between patients with PP only and
patients with both PP and PsA. Another open-label study
investigated the efficacy of adalimumab in 259 PsA
patients only [116]. At week 12, NAPSI improvement in
patients naive for anti-TNFa(-33 %) was not significantly
different from patients with prior treatment with infliximab
and/or etanercept (-42 %). In the STEREO study, another
prospective, open-label, uncontrolled study that evaluated
the effectiveness of adalimumab in patients with active
PsA, the median reduction in NAPSI score was 57 % in
259 patients with both active arthritis and nail psoriasis at
12 weeks [95]. NAPSI-50 was recorded in 54 % of patients
with a baseline NAPSI score of at least 10. This study also
searched for predictors of good clinical responses for
arthritis, skin, and nail lesions. Nail disease turned out to be
unable to predict good response of the arthritis.
The BELIEVE study and the REACH study are two
randomized, double-blind, controlled studies in PP patients
reporting on the efficacy of adalimumab in nail psoriasis
[117121]. A subgroup analysis of the BELIEVE study of
457 patients also with nail psoriasis claimed a reduction in
the NAPSI nail matrix component of 39 % and NAPSI nail
bed component of 60 % at week 16 [117]. These results
appear to contradict the overall NAPSI reduction of 40 %
at week 16 because both the matrix and bed signs are
equally important in the calculation of the overall NAPSI.
Another subgroup analysis of the BELIEVE study focussed
on the influence of PsA on the efficacy of adalimumab
[120]. Numerically larger decreases in mean NAPSI scores
Nail Psoriasis: A Review of Treatment Options
were observed over time for patients without a history of
PsA compared with patients with a history of PsA; how-
ever, the differences between groups were not statistically
significant. Efficacy on nail psoriasis has been a secondary
endpoint in the REACH study investigating adalimumab
for the treatment of moderate to severe chronic PP of the
hands and feet [119]. Target NAPSI in 28 patients with nail
psoriasis had improved 50 and 54 % at weeks 16 and 28,
respectively. In a post hoc analysis of the REACH study
among 31 patients with nail psoriasis, a greater percentage
of adalimumab-treated patients achieved NAPSI-50
(56.5 %) versus placebo (12.5 %) at week 16 [121]. A
remarkable finding in this study was that NAPSI-50
responders experienced a greater mean reduction in pain
visual analog scale (VAS) score (86.1 %) than NAPSI-50
non-nesponders (1.4 %) among patients treated with
adalimumab.
Daily practice studies were published by Sola-Ortigosa
et al. [122], Bardazzi et al. [123], and Kyriakou et al. [124].
Sola-Ortigosa measured NAPSI improvement of 57 % in
15 patients after 24 weeks of adalimumab treatment, while
a better NAPSI improvement (89 %) at this time point was
shown by Bardazzi et al. in 16 patients receiving adali-
mumab, increasing to 94 % at 36 weeks of follow-up. In
the study by Kyriakou et al., the 14 patients receiving
adalimumab had a NAPSI improvement of 71 % at week
24 and 87 % at week 48.
Prospective and retrospective studies comparing several
systemic and biologic therapies have been conducted and
will be discussed in Sect. 9. The efficacy of adalimumab in
these trials is in the same range as in the above-mentioned
studies [79,84,125,126]. Briefly, Ozmen et al. [125]
reported a reduction in NAPSI of 54 % in eight patients
receiving adalimumab at 48 weeks, Saraceno et al. [126]
reported a NAPSI reduction of 66 % in 20 adalimumab-
treated patients, and in the eight patients reported by
Sanchez-Regana et al. [79], the percentage of reduction in
the NAPSI score was 37, 73, and 84 % at 12, 24, and 48
weeks, respectively. Finally, after 12 months of treatment,
Karanikolas et al. [84] reported NAPSI-50 in 56 % of
patients receiving adalimumab, 44 % of patients receiving
cyclosporine, and 100 % of patients receiving a combina-
tion of the two drugs. Summarizing these results, it is clear
that adalimumab is an effective treatment for psoriasis of
the nail bed and the nail plate, both in PP patients and in
PsA patients. The most commonly reported side effects of
adalimumab are comparable with those of other biologics.
A prospective study was unable to see an increased inci-
dence of onychomycosis in psoriasis patients treated with
adalimumab for 24 weeks [103].
8.1.3 Etanercept
Etanercept is a fusion protein of the TNF receptor and Fc
end of the IgG1 antibody, which binds with and antago-
nizes the action of TNFa. It is approved for the treatment
of rheumatoid arthritis, juvenile rheumatoid arthritis,
ankylosing spondylitis, PsA, and PP. Its efficacy in PP has
been shown in many clinical trials since 2003 [127] but its
usefulness in nail psoriasis started to be reported several
years later in case reports [128130]. Another publication
claiming the clinical efficacy of etanercept in nail psoriasis
was published in 2008, and reports from a retrospective and
observational study in PP patients [131]. No data on nail
psoriasis were given, but a significant improvement of nail
involvement was noticed within 12 weeks. In 2009, a post
hoc analyses of the CRYSTEL study was published [13].
At 12 weeks of etanercept treatment, target NAPSI had
improved 29 %. At 54 weeks, at end of follow-up, target
NAPSI improvement had increased to 51 %. Patients with
nail psoriasis also showed significant and clinically
meaningful improvement with etanercept therapy in the
Dermatology Quality of Life Index (DLQI) and EQ-5D
VAS, QoL measures for which they had worse scores than
psoriasis patients without nail involvement at baseline
(p\0.001). A clinically meaningful improvement in QoL
was also shown in the NAIL study, a 24-week randomized
clinical trial investigating the efficacy and safety of two
doses of etanercept in which improvement of nail psoriasis
was the primary endpoint [132]. This study was unable to
show statistical differences between etanercept 50 mg
twice weekly for 12 weeks followed by 50 mg once
weekly for another 12 weeks (Group A), and etanercept
50 mg once weekly for 24 weeks (Group B). Target
NAPSI in Group A had improved 72 % and target NAPSI
had improved 76 % in Group B. In addition, overall NAPSI
showed an important improvement (see Table 3). Daily
practice studies were published by several other authors
[122124]. Bardazzi et al. studied 18 patients receiving
etanercept, and showed a NAPSI response of 85 % at
24 weeks of treatment, and 94 % NAPSI improvement at
36 weeks of follow-up. The 13 patients receiving etaner-
cept in the study by Kyriakou et al. had a NAPSI
improvement of 76 % at week 24, and 92 % at week 48.
Other studies of etanercept in nail psoriasis are com-
parative studies that will be discussed in Sect. 9. These
studies report improvement of nail psoriasis in the same
range as the above-mentioned studies. Briefly, Sanchez-
Regana et al. treated nine patients with etanercept [79], and
reduction in the NAPSI score was 24 % at week 12,
increasing to 87 % at 48 weeks. Ozmen et al. reported a
M. C. Pasch
57 % NAPSI in nine patients after 48 weeks of etanercept
treatment reduction [125], and Saraceno et al. measured
NAPSI improvement of 70 % in etanercept-treated patients
[126]. The most commonly reported side effects of adali-
mumab are comparable with those of other biologics, but
antibody formation and its consequences are claimed to
occur less frequently. A prospective study was unable to
see an increased incidence of onychomycosis in psoriasis
patients treated with etanercept for 24 weeks [103].
8.1.4 Golimumab
Golimumab is a human monoclonal anti-TNFaantibody
that has a registration for the treatment of PsA but not for
PP. In an RCT in PsA patients—the GO-REVEAL study—
nail involvement was a secondary endpoint (Table 3)
[133]. Approximately half of the patients were also taking
methotrexate. In patients treated with the common dose of
golimumab 50 mg every 4 weeks, improvement was
reported both in target NAPSI (-43 %), and PGA (-48 %)
at 24 weeks. Target NAPSI improvement was even slightly
higher (-52 %) at 52 weeks [134].
8.1.5 Certolizumab Pegol
Certolizumab pegol is a humanized mouse monoclonal
antibody to TNFathat is chemically modified by PEGy-
lation, resulting in a final product that has a prolonged half-
life in patients. In the maintenance phase of treatment,
patients receive one dose every 2–4 weeks, which is
slightly less frequent than with other anti-TNFaantibodies.
It is registered for PsA patients but several trials in PP
patients are ongoing. The RAPID-PsA study was an RCT
investigating certolizumab pegol in PsA patients in which
psoriatic nail involvement was a secondary endpoint [135].
As in many studies primarily focussing on PsA, concomi-
tant use of methotrexate, sulfasalazine, leflunomide, or oral
corticosteroids was permitted. Mean target NAPSI change
from baseline at week 24 was -52 % with certolizumab
pegol 200 mg every 2 weeks and -59 % with cer-
tolizumab pegol 400 mg every 4 weeks versus -32 % with
placebo (p=0.003 and p\0.001, respectively) [Table 3].
Common side effects are nasopharyngitis, upper respira-
tory tract infection, headache, and pruritus.
8.2 Anti-Interleukin (IL)-17 Treatments
Fundamental immunological research pointed to a central
pathogenic pathway in which IL-17A is the most critical
T-cell-derived cytokine in altering skin function, while, in
turn, IL-17-producing T cells (T17 cells) are regulated by
IL-23. There is thus an intimate link between dissection of
pathogenic pathways for psoriasis and new emerging
therapies for this disease [136]. Several clinical trials in PP
have suggested this concept being correct (Table 3)[137
139], but others have criticized some of these trials [140,
141]. Two IL-17 neutralizing agents (i.e. secukinumab and
ixekizumab) have been investigated in nail psoriasis.
Common adverse effects of anti-IL-17 treatments are
nasopharyngitis, upper respiratory tract infection, and
headache. Secukinumab may exacerbate Crohn’s disease,
and anaphylaxis and cases of urticaria are reported. These
drugs should be used with caution in patients with chronic
infection or a history of recurrent infection, and all patients
should be evaluated for TB before initiating.
8.2.1 Secukinumab
Secukinumab is a human monoclonal IgG1 k antibody that
targets IL-17A and has been approved for the treatment of
PP and PsA. Little is known about the efficacy of secuk-
inumab in nail psoriasis. One subanalysis of a dose-finding
RCT reported secukinumab improvement of nail lesions in
moderate to severe PP [139]. Unfortunately, the NAPSI
scale was not used but rather a never before described
composite score (range 0–20) was used, and no patients
were treated using the eventually approved dose for PP.
From this study, no conclusions on efficacy in nail psoriasis
can be drawn; patients treated with secukinumab 150 mg at
baseline and weeks 1, 2, and 4 had an improvement of
19 % in the composite fingernail score. In patients treated
with 150 mg at baseline and weeks 4 and 8, this
improvement was 11 % (Table 3). A multicenter RCT
investigating the efficacy of subcutaneous secukinumab
150 and 300 mg at 16 weeks in subjects with moderate to
severe nail psoriasis has recently been conducted but the
results have not yet been published in a peer-reviewed
journal. This TRANSFIGURE study also assesses safety,
tolerability and long-term efficacy up to 132 weeks.
8.2.2 Ixekizumab
Ixekizumab is a humanized IgG4 monoclonal antibody
neutralizing IL-17A intended to treat PP. Although this
drug does not yet have a registration, some data are
available suggesting efficacy in nail psoriasis (Table 3)
[142]. Significant reductions in NAPSI scores were
observed as early as 2 weeks, and these effects were sus-
tained through 20 weeks. At 12 weeks, NAPSI had
decreased significantly (-57 %) in patients treated with
ixekizumab 75 mg at weeks 0, 2, 4, 8, and 12. The same
patients have also been reported in an open-label extension
receiving 120 mg of ixekizumab subcutaneously every
4 weeks from week 20, however only in patients not
achieving a PASI 75 [143]. In these patients, mean NAPSI
had improved 78 % at week 24 of the extension (week 44
Nail Psoriasis: A Review of Treatment Options
of the trial), and 79 % at week 48 of the extension
(week 68 of the trial). Complete clearance of the nails was
achieved in a high proportions of patients: 43 % at
week 44, and 51 % at week 68. Common side effects are
nasopharyngitis, upper respiratory tract infection, head-
ache, and injection site erythema.
8.3 Anti-IL-12/23 Treatments
Ustekinumab is the only anti-IL-12/23 treatment currently
available for the treatment of PP and PsA. This antibody
binds with high specificity and affinity to the shared p40
protein subunit of cytokines IL-12 and IL-23, blocking the
differentiation and expansion of Th1 and Th17 populations.
Briakinumab is another human monoclonal antibody tar-
geting IL-12/23 being developed for the treatment of
rheumatoid arthritis, inflammatory bowel disease, and
multiple sclerosis. Further development for psoriasis has
been discontinued, possibly because of cardiovascular
adverse events [144]. Clinical efficacy of briakimumab in
nail psoriasis has been shown in an RCT in which it was
compared with methotrexate (Table 3)[78]. At 24 weeks,
target NAPSI improved 56 % in briakinumab-treated
patients, and 38 % in methotrexate-treated patients.
8.3.1 Ustekinumab
Ustekinumab is a human anti-IL-12/23 IgG1 monoclonal
antibody that is indicated for the treatment of moderate to
severe PP and for PsA, while early case reports also sug-
gested good efficacy on nail involvement in psoriasis [145].
In a series of 13 cases, a reduction in overall NAPSI of
34 % and modified target NAPSI of 17 % was reported as
early as week 12 (Table 3)[146]. The first prospective
study focussing on nail improvement by ustekinumab was
an open, unblinded study in a population treated with
ustekinumab for cutaneous psoriasis [147]. Statistically
significant improvement was present from week 4 (NAPSI
-13 %) and was relevant at weeks 16 (-50 %), 38
(-80 %), and 40 (-90 %). Similarly, QoL scores signifi-
cantly improved at all time points. Another open-label,
uncontrolled study of ustekinumab in nail psoriasis con-
firmed these excellent results [148]. Patients were treated
for 40 weeks, resulting in a reduction in mean NAPSI of 87
and 97 % at weeks 28 and 40, respectively. Two ran-
domized, placebo-controlled trials were also able to report
efficacy of ustekinumab in nail psoriasis but at a slightly
lower range [149,150]. The PHOENIX-1 study was a
randomized, placebo-controlled, crossover study in 766
psoriasis patients who were treated with ustekinumab
45 mg (or 90 mg if [100 kg) in a normal regimen [150].
Over 70 % of patients had nail psoriasis. An interesting but
not surprising finding was that nail improvements were
higher in patients with a good PASI response; improvement
in NAPSI ranged from 30 % (PASI \50) to 57 %
(PASI C90) at 24 weeks. Compared with baseline, the
proportion of ustekinumab-treated patients with pitting
decreased by approximately 20 %, and the proportion with
onycholysis decreased by over 30 % in both groups, indi-
cating positive effects of ustekinumab, both on nail bed and
nail matrix psoriasis. Substantial improvements in nail
PGA scores were also observed, with the majority of
patients with a baseline nail PGA score of C3 (moderate)
achieving improvement by at least 1 point. Igarashi et al.
investigated the safety and efficacy of normal- and high-
dose ustekinumab in 102 Japanese patients with moderate-
to-severe plaque-type psoriasis [149]. At week 12, no
significant NAPSI improvement compared with placebo
was measured. At week 64, these investigators reported a
mean improvement in target NAPSI scores of 57 and 68 %
for the ustekinumab 45 and 90 mg groups, respectively.
Only patients with at least a PASI-50 improvement were
treated longer than 28 weeks. Because improvement of
NAPSI often follows improvement in PASI, as has been
shown in the PHOENIX-1 study, the reported percentages
of nail improvement at 64 weeks may be an
overestimation.
Ustekinumab studies show nail responses similar to the
responses with other biologics. Comparative studies are
discussed in Sect. 9, but a small retrospective study was
unable to show differences between clinical efficacy on
nail psoriasis of ustekinumab compared with several anti-
TNFatreatments [123]. Contraindications and adverse
events of ustekinumab are comparable with anti-TNFa
treatments. Patients should be evaluated for TB infection
prior to administration, and any active serious infection
should be treated before starting therapy. Ustekinumab
may increase the risk of infections and reactivation of
latent infections; serious bacterial, fungal, and viral infec-
tions. It may also increase the risk of malignancy, and all
patients need to be monitored for non-melanoma skin
cancer.
9 Comparative Studies with Systemic Therapies
As discussed above, biologics and conventional systemic
treatments have been shown, in numerous studies, to be
potent suppressors of psoriatic nail disease. The degree of
improvement of clinical signs attributed to individual
treatments is very different, even between different studies
of the same drug. This makes it virtually impossible to
compare results of distinct studies with different drugs. The
explanations for these differences are manifold. The
‘NAPSI’ scoring systems used are extremely heteroge-
neous, the primary inclusion criterion for a study can be
M. C. Pasch
PP, PsA, or nail psoriasis, the quality of the studies differs,
and some studies use very liberal criteria to define nail
psoriasis, while others included only patients with severe
psoriasis. Finally, the period of follow-up is of the utmost
importance in the judgment of the results because further
improvement may occur up to 1 year. These reasons
underline the need for studies in which several treatments
are compared, without other factors interfering with the
outcome. It is desirable to have comparative double-
blinded RCTs but hitherto all comparative studies are ret-
rospective studies or open, prospective studies. Neverthe-
less, these studies have supplied us with relevant
information about efficacy and speed of conventional sys-
temic therapy versus biologics, and about efficacy of
conventional and anti-TNFatherapy compared with other
drugs in the same group. Secukinumab and ustekinumab
were not included in any of these studies; therefore, the
relative effectiveness of these anti-IL-17 and anti-IL-12/23
biologics remain to be seen.
The results of a prospective study comparing anti-TNF
biologics with acitretin, methotrexate, and narrowband
(NB)-UVB phototherapy draws attention to the importance
of adequate follow-up [80]. The short follow-up of only
16 weeks resulted in no significant change in NAPSI for any
of the conventional therapies, contrary to the six patients
receiving anti-TNFa. On the other hand, this study also
showed that patience is more important when using con-
ventional therapies than using biologics. These differences
in speed between biologics and conventional treatments
(with the exception of cyclosporine) were also noted by
Sanchez-Regana et al. [79], whose retrospective study
compared phototherapy and several systemic and biologic
therapies: acitretin, methotrexate, cyclosporine, PUVA, NB-
UVB, retinoid (RE)-PUVA, RE-NB-UVB, infliximab,
efalizumab, etanercept, or adalimumab [79]. Significant
reductions were identified in the mean NAPSI scores at 12,
24, and 48 weeks for all antipsoriatic agents, with the
exception of NB-UVB. In the group treated with conven-
tional systemic drugs, nail psoriasis improvement was sig-
nificantly higher in patients treated with cyclosporine
(p\0.01) than in those treated with acitretin, methotrexate,
PUVA, and RE-NUVB at 12 and 24 weeks. In the biological
treatment group, differences between distinct biological
treatments had disappeared at 48 weeks, although the per-
centage of reduction in the NAPSI score was significantly
greater with infliximab and adalimumab at 12 and 24 weeks.
Cyclosporine was as effective as infliximab and adali-
mumab. Similar efficacy of cyclosporine and adalimumab
was also concluded from a prospective comparison of adal-
imumab with cyclosporine in PsA patients also suffering
from nail psoriasis [84]. Patients were treated with cyclos-
porine, adalimumab (40 mg every other week), or a combi-
nation of cyclosporine and adalimumab. After 12 months of
treatment, NAPSI-50 was achieved in 44 % of patients
receiving cyclosporine, 56 % of patients receiving adali-
mumab, and 100 % of patients receiving a combination of
the two drugs.
Other comparative studies included only biologics. Two
open, randomized, prospective studies investigated inflix-
imab, etanercept, and adalimumab in a limited number of
patients [125,126]. After 48 weeks of treatment, Ozmen
et al. reported a reduction in NAPSI of 40, 57, and 54 % in
patients receiving infliximab, etanercept, and adalimumab,
respectively (not significant) [125]. Saraceno et al. studied
the efficacy and differences in efficacy of the same three
anti-TNFatreatments in 60 patients with moderate nail
psoriasis [126]. At 24 weeks (the end of follow-up in this
study), no significant differences between the three bio-
logics could be measured, but mean NAPSI had reduced to
91 % in infliximab-treated patients, 70 % in etanercept-
treated patients, and 66 % in adalimumab-treated patients.
However, at week 14, efficacy was higher in the infliximab
group compared with the adalimumab and etanercept
groups. NAPSI-75 could be achieved in 65, 45, and 50 %
of patients treated for 24 weeks with infliximab, etaner-
cept, and adalimumab, respectively. The lack of major
differences in efficacy on nail psoriasis can also be con-
cluded from several daily practice and retrospective studies
[122124]. Sola-Ortigosa et al. measured a NAPSI
improvement of 57 % in 15 patients after 24 weeks of
adalimumab treatment [122], while the study of Bardazzi
et al. in 16 patients receiving adalimumab showed a better
NAPSI response at this time point (-89 %), and 94 %
NAPSI improvement at 36 weeks follow-up [123]. The
third retrospective study comparing the efficacy of anti-
TNFabiologics on nail psoriasis also failed to show dif-
ferences between infliximab, etanercept, and adalimumab
in 39 patients [124]. After 48 weeks of treatment, a
reduction in NAPSI of 95, 92, and 87 %, respectively, was
observed. One retrospective study focusing on determining
which biologic is the most effective in the treatment of nail
psoriasis also included ustekinumab [123]. At 36 weeks, no
significant differences were seen in the reduction of
NAPSI, and the percentage of patients achieving NAPSI-
75 (89 %) was also similar in all groups.
The efficacy of biologics has not only been a matter of
research but differences in the occurrence of adverse events
have also been investigated. A prospective, randomized,
open-label study compared the incidence of onychomyco-
sis in 315 patients with nail psoriasis treated with inflix-
imab, etanercept, and adalimumab, and a statistically
positive association between fungal infections and the use
of infliximab was shown [103]. At the end of week 24,
33 % of patients receiving infliximab had a positive fungal
culture. In patients receiving etanercept and adalimumab,
and controls, this percentage was 15.5, 13.3, and 13.9 %,
Nail Psoriasis: A Review of Treatment Options
respectively. On the other hand, NAPSI improved more
(86 %) in infliximab-treated patients than in patients
receiving etanercept (68 %) and adalimumab (71 %).
The preliminary conclusions that can be drawn from
these studies are that conventional therapies are less pow-
erful and are slower-acting treatments for nail psoriasis
than biologics, possibly with the exception of cyclosporine.
No single biologic appears to be superior above another
biologic. Evidence suggests that infliximab may act faster,
but after 1 year of treatment these potential differences
have vanished. On the other hand, the use of infliximab
may result in higher percentages of onychomycosis.
10 Non-Pharmacological Treatment Options
10.1 Laser Therapy
Laser treatment is an emerging physical therapy option
claiming an indication in increasing numbers of skin and
nail disorders. In nail psoriasis, PDL (595 nm) treatments
are also offered. A positive clinical effect of the laser is
supposed to be caused by its effect on angiogenesis and
vascularity within the psoriatic nail unit. Several case
reports and clinical studies have been reported [57,151
155], and the results of these reports are rather contradic-
tory. While some authors claim effects mainly on nail bed
psoriasis [155], others see more positive results on nail
matrix psoriasis [57,152154], or even negative effects on
nail bed psoriasis [57]. The reported NAPSI improvement
by laser therapy ranges from a disappointing 2 % at
6 months [57] to a sensational 86 % at 1 month [155]. In
addition, a rapid decrease in NAPSI, followed by a sig-
nificant increase after the third month of treatment despite
ongoing treatment, has been reported [154]. Several pro-
tocols to treat nail psoriasis with PDL have been advocated
but comparisons did not show significant differences
between 6-ms pulse duration, 9 J/cm
2
, 7 mm spot size, and
0.45-ms, 6 J/cm
2
, 7 mm spot size [152,154]. Combining
PDL with photodynamic therapy [153] or tazarotene [57]
has been studied. Additional photodynamic therapy with
methylaminolevulinic acid or tazarotene did not signifi-
cantly change the NAPSI results; however, a significantly
higher percentage of patients had improvement in PGA and
SGA scores after 6 months of treatment with topical
tazarotene plus PDL than after tazarotene treatment alone.
The major side effect of PDL treatment is pain, which
may last for 24 h. Other adverse events are petechiae and
hyperpigmentation in 30 % of the nail folds, i.e. in virtu-
ally all patients. Pain, but also petechiae, is worse if a
longer pulse duration is chosen. Summarizing these often
conflicting results with PDL, one must conclude that a
randomized study comparing PDL treatment with sham
laser treatment is urgently needed to justify this painful
treatment in patients with nail psoriasis.
10.2 Phototherapy: Topical Phototherapy, Systemic
Phototherapy, Photodynamic Therapy
Phototherapy refers to a therapeutic technique based on the
beneficial effect of light waves on several pathological
conditions. In dermatology, the light of several wave-
lengths are used (UVA, UVB, visible light), sometimes in
combination with oral or topical photosensitizers (pso-
ralens in PUVA, or aminolevulinic acid in photodynamic
therapy). All these phototherapeutic options have been
investigated in nail psoriasis. Photodynamic therapy has
been shown to be ineffective in nail psoriasis, both as
monotherapy and as a pretreatment in PDL [153]. PUVA
phototherapy with either oral or topical psoralens appears
to be effective and beneficial in both nail bed and nail
matrix disease [79,156,157]. In a small, retrospective
study, adding an oral retinoid to PUVA has been shown to
increase NAPSI improvement from 69 to 85 % [79]. NB-
UVB therapy, as well as with the Excimer laser, appears to
be much less effective, or not effective at all, in treating
nail psoriasis [79,80,158]. The positive results of UVA
and NB-UVB are surprising considering that the mean
penetration of UVA light through the fingernails is only
1.65 %, and UVB is completely blocked [159]. A major
problem with PUVA is the risk of development of non-
melanoma skin cancer after prolonged treatment.
10.3 Radiotherapy
Radiotherapy is rarely used in the daily clinical care of
patients with nail psoriasis. Nevertheless, cases and clinical
trials with several radiotherapeutical modalities have been
reported [160164], resulting in the inclusion of these
treatments in the conclusions of the Cochrane review on
the treatment of nail psoriasis [15]. Efficacy of superficial
radiotherapy [160,162,164], Grenz ray therapy [161], and
electron beam therapy [163] was confirmed in case reports
and RCTs. Improvement of nail psoriasis was generally
limited and only temporary, and local hyperpigmentation
can be seen with most of these treatments. Safety concerns
are another reason why radiotherapy cannot be recom-
mended as a first-choice therapy for the long-term treat-
ment of nail psoriasis.
11 Conclusions
Growing attention for the impaired QoL and high associ-
ation with potential joint-damaging PsA has resulted in
increased attention for nail psoriasis. Almost all recent
M. C. Pasch
clinical trials on biologics have included nail psoriasis as a
secondary endpoint, and all anti-TNFa, anti-IL-17, and
anti-IL-12/23 antibodies studied have shown slow but
excellent response for psoriatic nail disease; however,
topical, intralesional, and conventional systemic treatments
have also proven their value for patients with nail psoriasis.
The important heterogeneity in design, outcome measure,
baseline disease, and follow-up make it virtually impossi-
ble to conduct a meta-analysis, or to even compare the
results of the studies.
The optimal treatment for a patient depends on many
individual factors, including the impact on QoL, disease
severity, nail bed or nail matrix disease, number of
involved nails, patience and motivation, concomitant
arthritis, and other comorbidities. The hierarchy of treat-
ments comprises topical, intralesional, and systemic treat-
ments. Topical treatments are often slowly acting but
helpful in mild to moderate cases in patients who can
adhere to the treatment for a long period. Corticosteroids
may be more effective in nail matrix psoriasis than in nail
bed psoriasis, while calcipotriol shows an inverse profile.
Intralesional steroids may be the second step and, consid-
ering the painful procedure, are mainly indicated in
patients with only a few involved fingernails. Conventional
systemic therapy, including newer small molecules, are
indicated in therapy-resistant nail psoriasis, with or without
PP and PsA. Its efficacy on nail psoriasis appears to be less
than, and slower than, that of biologics, but cyclosporine
may be a more powerful and faster treatment option than
the other conventional systemic therapies. Biologics may
be on the highest step of the hierarchical ladder. All bio-
logics available for PP or PsA appear to have excellent
results on the nail, apparently without major differences
between individual biologics or the epitope they target. In
addition, non-pharmacological treatment options of radio-
therapy, PUVA, and RE-PUVA have proven their value,
but the disadvantage of these treatment options is the risk
of adverse events, making long-term treatment unattrac-
tive. Better studies are needed to justify the use of laser
treatment.
A major wish for the future is the development and
implementation of a reliable core set of outcome measures
for future trials in nail psoriasis in order to obtain data that
will make it possible to compare data.
Compliance with Ethical Standards
Marcel C. Pasch has received research support from Pfizer (support
paid to institution) and has sat on advisory boards for Amgen and
Celgene (honorarium paid to institution). No funding or assistance
was received for the preparation of this manuscript.
Open Access This article is distributed under the terms of the
Creative Commons Attribution-NonCommercial 4.0 International
License (http://creativecommons.org/licenses/by-nc/4.0/), which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided you give appropriate credit to the original
author(s) and the source, provide a link to the Creative Commons
license, and indicate if changes were made.
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Nail Psoriasis: A Review of Treatment Options
... Difficult penetration of the drug into the nail unit is the main treatment obstacle. Moreover, it can take up to one year to observe an evident response with a successful treatment owing to the slow growth rate of the nails [18]. ...
... Those patients may profit from topical treatment, while systemic treatment is preferred in patients with severe nail psoriasis, or concomitant psoriatic skin lesions [22]. Meanwhile, topical treatment is limited by poor penetration and the patient needs to apply daily treatment under occlusion for up to 6 months [18]. Intralesional injection of corticosteroids is now considered the modality of choice in nail psoriasis. ...
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Hintergrund und ziele: Die Behandlung der Nagelpsoriasis ist wegen mangelnder Penetration topischer Therapeutika durch die Nagelplatte häufig unbefriedigend. Daher sind innovative Methoden zur adäquaten Verabreichung des Arzneimittels in den Nagel erforderlich. In dieser Studie vergleichen wir die Wirksamkeit der intraläsionalen Corticosteroid-Injektion mit topischer Applikation nach fraktionierter CO2 -Laser-Behandlung bei Fingernagelpsoriasis. Patienten und methoden: In der Studie wurden 36 Patienten mit Fingernagelpsoriasis in zwei Gr