Nail psoriasis

INTRODUCTION — Psoriasis is a common, chronic, inflammatory disease that has skin, nail, and systemic manifestations. Nail psoriasis results from psoriatic involvement of the nail bed or nail matrix.

Patients with nail psoriasis can develop a wide variety of nail changes, such as pitting, onycholysis, subungual hyperkeratosis, and nail discoloration (picture 1A-E). Patients may find the appearance of psoriatic nails psychologically distressing, and extensive cases may confer significant morbidity and functional impairments. Therefore, managing nail psoriasis is an integral part of psoriasis therapy.

The clinical manifestations, diagnosis, and management of nail psoriasis will be reviewed here. The diagnosis and treatment of other manifestations of psoriasis and pediatric psoriasis are reviewed separately.

●(See "Psoriasis: Epidemiology, clinical manifestations, and diagnosis".)

●(See "Treatment of psoriasis in adults".)

●(See "Psoriasis in children: Epidemiology, clinical manifestations, and diagnosis".)

●(See "Psoriasis in children: Management of chronic plaque psoriasis".)

●(See "Guttate psoriasis".)

●(See "Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Localized pustular psoriasis'.)

●(See "Pustular psoriasis: Management", section on 'Localized pustular psoriasis'.)

●(See "Clinical manifestations and diagnosis of psoriatic arthritis".)

●(See "Treatment of psoriatic arthritis".)

EPIDEMIOLOGY — Nail psoriasis occurs in both adults and children [1,2]. The prevalence of nail psoriasis among patients with psoriasis is estimated to be 10 to 55 percent [3]. In most patients, nail involvement follows or is concurrent with the onset of cutaneous psoriasis [4]. Occasionally, nail psoriasis is the sole manifestation of psoriasis at the time of clinical presentation [5].

Nail psoriasis is also strongly associated with psoriatic arthritis. It has been estimated that 80 to 90 percent of patients with psoriatic arthritis develop nail involvement [6,7]. This finding may be related to the proximity of the nail to the distal interphalangeal (DIP) joint, a site of predilection of psoriatic arthritis (picture 2A). The enthesis of extensor tendon crossing the DIP joint is linked to the nail root and nail matrix [8]. (See "Clinical manifestations and diagnosis of psoriatic arthritis".)

Some studies suggest that psoriatic arthritis is more tightly associated with psoriatic nail involvement than cutaneous psoriasis alone [6]. However, not all studies have corroborated this finding [9-12].

PATHOGENESIS — Nail psoriasis results from psoriatic inflammation involving the nail matrix or nail bed. The nail matrix is responsible for the formation of the nail plate and is located primarily beneath the proximal nail fold, with the distal one-third visible as the lunula (picture 3 and figure 1). The proximal nail matrix forms the superficial portion of the nail plate. More distal portions of the nail matrix (intermediate and ventral portions) form the deeper portion of the nail plate (figure 2).

The nail bed lies directly beneath the nail plate and extends from the distal end of the lunula to the hyponychium (picture 3 and figure 1). The nail bed contributes epithelial cells to the ventral portion of the nail plate and plays an important role in the adherence of the nail plate to the nail bed [13]. Nail anatomy and physiology is discussed in greater detail separately. (See "Overview of nail disorders", section on 'Anatomy and physiology of the nail unit'.)

The site of psoriasis in the nail apparatus leads to specific effects on nail formation and determines the clinical manifestations. Clinical manifestations related to nail matrix involvement include [13]:

●Pitting – Proximal matrix involvement resulting in clusters of parakeratotic cells in the nail plate. Sloughing of the parakeratotic cells leads to nail plate depressions.

●Leukonychia – Intermediate and ventral nail matrix involvement.

●Red spots in lunula – Intermediate and ventral nail matrix involvement.

●Nail plate crumbling – Severe involvement of the entire nail matrix.

Clinical manifestations related to nail bed involvement include [13]:

●Oil drop discoloration – Nail bed involvement located entirely within the nail bed.

●Onycholysis – Nail bed involvement near the hyponychium.

●Subungual (nail bed) hyperkeratosis – Nail bed involvement resulting in accumulation of cells under the nail plate.

●Splinter hemorrhages – Nail bed involvement resulting in capillary rupture in the dermis beneath the nail plate.

Genetic contributions to the development of nail psoriasis are not well understood. The HLA-Cw6 allele is strongly associated with cutaneous psoriasis [14]. However, psoriatic nail disease may align closer to dysregulation in innate immunity. Therefore, psoriatic nail disease may have a different contribution from innate immunity and adaptive immunity compared with skin-limited disease [15,16].

CLINICAL MANIFESTATIONS — Patients with nail psoriasis may present with involvement of a single nail, multiple nails, both fingernails and toenails, fingernails only, or toenails only [17]. More than one manifestation of nail psoriasis may be present in a single nail or in different nails in an individual patient. The physical changes in nail psoriasis are reviewed below:

●Pitting – Punctate depressions in the nail plate (picture 1A)

●Leukonychia – White discoloration in the nail plate (picture 4)

●Red spots in lunula – Pink to red punctate areas within the lunula

●Nail plate crumbling – Fragility and disintegration of the nail plate (picture 1B)

●Oil drop discoloration – Irregular areas of yellow or pink discoloration, also known as "salmon patches" (picture 1E)

●Onycholysis – Distal separation of the nail plate from the nail bed (picture 1C)

●Subungual hyperkeratosis – Gray-white accumulation of keratinous material overlying the nail bed (picture 1D)

●Splinter hemorrhages – Linear areas of hemorrhage visible through the nail plate (picture 1C)

Other manifestations include onychorrhexis (longitudinal ridges and distal splitting of the nail plate) and Beau lines (transverse grooves) [13]. Patients with nail psoriasis may experience associated pain, psychological distress, and functional impairments resulting in interference with activities of daily living [17].

HISTOPATHOLOGY — Classic histologic features of nail psoriasis overlap with those of cutaneous psoriasis and include [18]:

●Mild to moderate hyperkeratosis

●Foci of parakeratosis

●Spongiosis

●Psoriasiform epidermal hyperplasia (evident in transverse sections)

●Neutrophilic inflammation

●Dilated, tortuous, inflamed capillaries in the papillary dermis

In addition, there may be a loss of granular layer in the hyponychium and hypergranulosis in the nail matrix and nail bed [18].

DIAGNOSIS — The diagnosis of nail psoriasis is usually established by review of the patient history and performance of a physical examination. Testing for fungal infection is often necessary to rule out onychomycosis as an alternative cause of nail dystrophy. A biopsy of the nail unit is not necessary in most cases.

Patient history — Because most patients with nail psoriasis have concomitant cutaneous psoriasis or psoriatic arthritis, the patient history should include assessment for a personal history of these disorders or signs or symptoms of these disorders. A strong family history of psoriasis may also raise suspicion for nail psoriasis in the occasional patient who presents without other manifestations of psoriasis. (See "Psoriasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Major clinical features'.)

Physical examination — A full skin examination should be performed, including examination of the nails, scalp, and anogenital skin, to assess for nail changes and cutaneous psoriasis. Nail findings that warrant strong consideration of a diagnosis of nail psoriasis include nail pitting, distal onycholysis, oil drop discoloration of the nail plate, and subungual hyperkeratosis. Performance of a nail examination is reviewed in detail separately. (See "Overview of nail disorders", section on 'Nail evaluation'.)

Nail psoriasis is a common finding in patients with psoriatic arthritis and an evaluation for signs of psoriatic arthritis is prudent [5]. Swelling or tenderness of the joints (particularly the DIP joints of the hands or feet) or dactylitis (diffuse swelling of an entire digit) may indicate associated arthritis (picture 2A-B). (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Joint manifestations'.)

Evaluation for fungal infection — Clinical features of nail psoriasis overlap with onychomycosis, and in some cases it can be difficult to distinguish between these disorders clinically. In addition, nails affected by psoriasis may be predisposed to secondary fungal infection. A nail plate clipping for periodic acid-Schiff (PAS) staining, potassium hydroxide (KOH) preparation, or fungal culture is usually performed to assess the possibility of primary or secondary onychomycosis. (See "Onychomycosis: Epidemiology, clinical features, and diagnosis", section on 'Diagnosis'.)

Biopsy — Nail bed and nail matrix biopsies to detect histologic changes consistent with psoriasis are usually not performed because the diagnosis of nail psoriasis can usually be made with relative certainty based upon the patient history and clinical examination. Nail bed and nail matrix biopsies are performed in very select circumstances where the diagnosis is uncertain. (See "Nail biopsy: Indications and techniques".)

DIFFERENTIAL DIAGNOSIS — Other diseases may present with nail changes that resemble nail psoriasis. Onychomycosis is the most common disorder in the differential diagnosis because of shared clinical features with nail psoriasis and the high frequency of this condition. Examples of disorders in the differential diagnosis include:

●Onychomycosis – Nail psoriasis can be difficult to distinguish from onychomycosis, particularly when subungual hyperkeratosis or nail crumbling is present (picture 5A-B). Other manifestations, such as nail pitting, oil drop discoloration, and onycholysis, are more common in nail psoriasis than in onychomycosis. A periodic acid-Schiff (PAS) stain on a nail clipping, fungal culture, or potassium hydroxide (KOH) preparation can identify onychomycosis. Of note, secondary fungal infection can occur in a psoriatic nail. (See "Onychomycosis: Epidemiology, clinical features, and diagnosis".)

●Lichen planus – Nail involvement in lichen planus usually manifests as thin, grooved, or ridged nail plates (picture 6). In some instances, scarring of the cuticle can result in formation of pterygium (picture 7). Lichen planus may also involve the skin or mucosa. The classic cutaneous manifestations of lichen planus are pruritic, violaceous, polygonal papules or plaques. Mucosal lichen planus may present as painful erosions, reticular white plaques, or hyperkeratotic plaques. (See "Lichen planus", section on 'Clinical features' and "Vulvar lichen planus" and "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Clinical manifestations'.)

●Alopecia areata – Nail pitting, trachyonychia (linear ridging), onychorrhexis (longitudinal fissuring), and other nail abnormalities may occur in patients with alopecia areata, a form of hair loss characterized by nonscarring patchy hair loss on the scalp or other areas of the body (picture 8A-B). Severe cases can manifest as loss of all scalp hair (alopecia totalis) or body hair (alopecia universalis). (See "Alopecia areata: Clinical manifestations and diagnosis", section on 'Clinical features'.)

●Pityriasis rubra pilaris – Pityriasis rubra pilaris (PRP) is an uncommon skin disorder that most commonly presents with hyperkeratotic follicular papules, orange-red plaques, and palmoplantar hyperkeratosis. The cutaneous plaques of PRP typically have fine overlying scale rather than the coarse scale characteristically present in psoriasis. The nails in PRP can become thickened and the distal edges sometimes display splinter hemorrhages (picture 9). (See "Pityriasis rubra pilaris: Pathogenesis, clinical manifestations, and diagnosis".)

TREATMENT — The severity of nail involvement plays an important role in determining the approach to treatment (algorithm 1). In clinical practice, consideration of the number of nails involved, associated symptoms, and level of functional impairment is often used to assess severity of disease. (See 'Mild nail psoriasis' below and 'Moderate to severe nail psoriasis' below.)

Although infrequently used in clinical practice, clinical studies evaluating nail psoriasis therapies often use a version of the Nail Psoriasis Severity Index (NAPSI) to assess the severity of nail psoriasis and the response to treatment [19]. To identify the NAPSI score, individual nails are divided into four quadrants and each quadrant is assigned a score of 1 for the presence of signs of nail matrix psoriasis and a score of 1 for the presence of signs of nail bed psoriasis. Therefore, the maximum total NAPSI score per nail is 8, and the maximum total score for all nails is 160. Alternatively, each quadrant of a single target nail can be assessed.

A modified version of the NAPSI has also been validated and used for assessment of a single target nail. The modified NAPSI assigns a severity score of 0 to 3 for each quadrant of the target nail [20].

General measures — Patient education is an important part of therapy. The slow pace of nail growth leads to prolonged treatment courses and a delay in achieving the desired effect. Also, treatment can be challenging and improvement is often incomplete. Clear communication with the patient may foster realistic expectations for treatment results and may promote adherence to therapy.

Gentle hand and foot care may help to minimize symptoms. Recommendations include [5]:

●Avoid trauma to the nails (eg, manicures, nail biting)

●Wear protective gloves during exposure to wet work or harsh chemicals

●Dry nails and periungual skin thoroughly after washing or bathing

●Apply emollients regularly

●Keep nails trimmed

In particular, in patients with onycholysis, trimming the nails reduces risk for additional traumatic separation of the nail plate from the nail bed. Trimming nails also facilitates application of topical treatments to the hyponychium [21].

Clinical photographs are useful for following the response to treatment. Photographs can be taken at baseline and at follow-up visits.

Mild nail psoriasis — Topical therapy is the preferred initial mode of treatment for mild nail psoriasis (nail psoriasis limited to one or two nails and without significant symptoms or functional impairment). Topical treatment achieves a sufficient response for some patients and minimizes risk for serious treatment-related side effects. Although topical therapy is widely used, studies on efficacy are limited.

Systemic therapy is typically reserved for patients with more extensive nail involvement and patients who fail to respond to topical therapy. However, because many systemic treatments used for psoriasis and psoriatic arthritis are also effective for nail psoriasis, patients with mild nail psoriasis who receive systemic treatment for other manifestations may experience improvement in nail disease. (See 'Moderate to severe nail psoriasis' below.)

First-line therapy — First-line therapies for mild nail psoriasis include monotherapy with a topical corticosteroid, monotherapy with a topical vitamin D analog, and combination treatment with a topical corticosteroid and topical vitamin D analog.

Topical corticosteroids and topical vitamin D analogs — High-potency topical corticosteroids, topical vitamin D analogs such as calcipotriol (ie, calcipotriene), and combination treatment with a topical vitamin D analog and a high-potency topical corticosteroid are common initial interventions for mild nail psoriasis [22]. Therapy with these agents takes advantage of the immunomodulatory and antiproliferative effects of vitamin D and the antiinflammatory effects of corticosteroids [5].

When feasible, we prescribe combination therapy with a topical corticosteroid and topical vitamin D analog (eg, calcipotriol) as the initial treatment. In our experience, this approach has seemed most likely to yield some improvement:

●Efficacy – Placebo-controlled randomized trials evaluating the efficacy of topical calcipotriol or topical corticosteroid monotherapy and topical calcipotriol/topical corticosteroid combination therapy are lacking. Examples of studies evaluating these medications include:

•In an investigator-blind trial, 40 adults with fingernail psoriasis were randomly assigned to treatment with calcipotriol 0.005%/betamethasone dipropionate 0.05% ointment once daily or calcipotriol 0.005% ointment twice daily for 12 weeks [23]. Eight patients left the study prior to completion for reasons unrelated to treatment. At the end of the 12-week treatment period, the investigator's global evaluation revealed at least moderate improvement in 8 of 15 patients (53 percent) treated with calcipotriol/betamethasone dipropionate and 9 of 17 patients (53 percent) treated with calcipotriol alone. NAPSI scores were similarly reduced in the two groups.

•A randomized, double-blind trial that compared the efficacy of twice-daily treatment with calcipotriol ointment (50 mcg/g) to twice-daily combination treatment with betamethasone dipropionate and salicylic acid ointment in 58 adults with psoriatic subungual hyperkeratosis (29 with fingernail psoriasis and 44 with toenail psoriasis) found that both regimens reduced subungual hyperkeratosis [24]. Mean reductions in fingernail subungual hyperkeratosis in the calcipotriol and the betamethasone dipropionate/salicylic acid-treated patients were 26 percent and 30 percent, respectively, after three months. Mean reductions in toenail subungual hyperkeratosis were 20 and 23 percent, respectively. The differences were not statistically significant.

In addition to these randomized trials, uncontrolled studies and case series report efficacy of treatment with once-daily calcipotriol/betamethasone dipropionate ointment [25], weekday calcipotriol treatment combined with weekend clobetasol therapy [26], and twice-daily topical calcipotriol monotherapy [27].

●Administration – Twice-daily application of topical calcipotriol 0.005% ointment or a high-potency (group 1) topical corticosteroid or, alternatively, once-daily application of a combination ointment containing topical calcipotriol and a high-potency topical corticosteroid (eg, betamethasone dipropionate) are appropriate regimens for nail psoriasis (table 1). An alternative to use of a combination product is once-daily application of topical calcipotriol and a high-potency (group 1 or 2) topical corticosteroid successively on the skin.

Patients should apply a thin layer of the product to the nail plate, hyponychium, and proximal and lateral nail folds. For patients with fingernail psoriasis prescribed once-daily treatment, application before bedtime will allow the medication to remain on the skin. The use of an occlusive dressing at night is encouraged to aid in absorption of the medication.

Our initial course of treatment is typically three months followed by clinical assessment. If no signs of response are evident after three to six months, we proceed with a trial of a second-line therapy. (See 'Second-line therapy' below.)

●Adverse effects – Topical calcipotriol and topical corticosteroid therapy are generally well tolerated. Cutaneous atrophy is a well-known side effect of topical corticosteroids, particularly with occlusion. Systemic adverse effects are unlikely with the limited area of application in the treatment of nail psoriasis. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Second-line therapy — Limited data suggest that topical tacrolimus and topical tazarotene, agents used for the treatment of cutaneous psoriasis, can improve nail psoriasis. For both treatments, signs of improvement are expected within the first three to six months of treatment. (See "Treatment of psoriasis in adults".)

Topical tacrolimus — Tacrolimus is a nonsteroidal topical calcineurin inhibitor that exerts its action by down-regulating antigen-specific T cell activity and proinflammatory cytokine production. Support for the use of topical tacrolimus is derived from a small open-label trial performed in 21 patients with fingernail psoriasis in which one hand was randomly assigned to once-daily application of tacrolimus 0.1% ointment to the nail folds of affected nails and the contralateral hand was given no treatment [28]. After 12 weeks, the reduction in mean single-hand NAPSI scores compared with baseline was greater in the tacrolimus group (reduced from 23 to 10) than in the no-treatment group (reduced from 19 to 16).

Topical tacrolimus 0.1% ointment is applied once daily to the periungual skin (hyponychium, lateral nail folds, and proximal nail folds) and is usually well tolerated. One patient in the open-label trial stopped therapy after nine weeks due to the development of acute paronychia [28].

Topical tazarotene — Tazarotene is a third-generation topical retinoid that can improve nail psoriasis [29-31]. A vehicle-controlled randomized trial that evaluated tazarotene therapy in 31 adults with fingernail psoriasis found a modest but greater reduction in onycholysis, as compared with placebo, with use of tazarotene 0.1% gel nightly for up to 24 weeks with or without occlusion [32]. Tazarotene also reduced nail pitting when used under occlusion.

In addition, a trial that randomly assigned 46 patients to either treatment with tazarotene 0.1% cream applied nightly under occlusion or treatment with clobetasol propionate 0.05% cream applied with the same regimen for 12 weeks found that both treatments were associated with improved NAPSI scores for pitting, onycholysis, hyperkeratosis, and salmon patches [31]. Of note, 14 patients dropped out of the study prior to completion. An urgent need for systemic therapy prompted exiting of the study for 10 of these patients.

Tazarotene 0.1% gel or cream is usually applied once daily to the nail plate and periungual skin. An occlusive dressing is often used. Treatment is generally well tolerated; however, prolonged use under occlusion may be associated with skin redness and irritation. Periungual pyogenic granulomas may be a rare complication [33].

Refractory cases — Patients with mild nail involvement who fail to respond to topical therapy may benefit from interventions used for patients with moderate to severe nail psoriasis. However, the risks and benefits of more aggressive treatment must be considered carefully. (See 'Moderate to severe nail psoriasis' below.)

Moderate to severe nail psoriasis — Moderate to severe nail psoriasis is nail psoriasis associated with marked nail dystrophy involving more than two nails or nail psoriasis associated with significant symptoms or functional impairment.

First-line therapy — Systemic therapy with a biologic agent is the preferred first-line treatment for moderate to severe nail psoriasis. The highest-quality evidence on nail psoriasis treatment resides in trials assessing biologic therapy.

Biologic TNF-alpha inhibitors — Tumor necrosis factor-alpha (TNF-alpha) inhibitors used for the treatment of cutaneous psoriasis and psoriatic arthritis are also effective for nail disease. Adalimumab [34-44], etanercept [39-42,44-46], infliximab [29,39-42,44,47-52], certolizumab pegol [53], and golimumab [54,55] have all demonstrated moderate to high efficacy for psoriatic nail disease:

●Efficacy – Examples of randomized trials that have evaluated the efficacy of biologic TNF-alpha inhibitors are reviewed below:

•Adalimumab – In a 16-week, randomized, placebo-controlled trial (n = 72) that evaluated the efficacy of adalimumab (80 mg loading dose followed by 40 mg every other week during weeks 1 to 15) for moderate to severe chronic plaque psoriasis on the hands or feet, effects on nail psoriasis were evaluated as a secondary endpoint [35]. After 16 weeks, the mean percentage improvement in the NAPSI score in target fingernails was significantly higher among patients treated with adalimumab than among patients in the placebo group (50 versus 8 percent). In another phase 3 randomized trial, 217 patients with moderate to severe plaque psoriasis and moderate to severe fingernail psoriasis were treated with adalimumab (80 mg loading dose followed by 40 mg every other week) or placebo for 26 weeks [56]. The primary endpoint was an improvement of ≥75 percent in the modified NAPSI score compared with baseline. After 26 weeks, more patients in the adalimumab group than those in the placebo group achieved the primary endpoint (47 and 3 percent, respectively).

•Etanercept – A 24-week randomized, open-label, dose-comparison trial (n = 72) that compared the efficacy of etanercept 50 mg twice weekly for 12 weeks, then once weekly for 12 weeks to the efficacy of etanercept 50 mg once weekly for 24 weeks in adults with moderate to severe plaque psoriasis found that both regimens were effective for nail psoriasis that had failed to respond to at least one form of systemic therapy [45]. The mean target nail NAPSI score decreased similarly in the biweekly/once-weekly group and the once-weekly group (-4.3, 95% CI -4.9 to -3.7 and -4.4, 95% CI -5.0 to -3.7, respectively).

•Infliximab – The effect of infliximab therapy on nail psoriasis was evaluated in a 50-week randomized, placebo-controlled, cross-over trial in which patients with moderate to severe plaque psoriasis were randomly assigned to infliximab (5 mg/kg at weeks 0, 2, and 6 followed by every eight weeks) or placebo until week 22, with a placebo crossover to infliximab at week 24. Analysis of the 305 patients with nail psoriasis revealed a 57 percent reduction in the mean NAPSI score at week 24 in the infliximab group versus a 4 percent increase in NAPSI score in the placebo group [51].

•Certolizumab pegol – Benefit of certolizumab pegol for nail psoriasis was demonstrated in a placebo-controlled trial that evaluated the effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis [53]. Patients were randomly assigned to a 400 mg certolizumab pegol loading dose given at weeks 0, 2, and 4 followed by 200 mg given every two weeks, the same loading dose followed by 400 mg given every four weeks, or placebo. The effect on nail psoriasis was evaluated as a secondary endpoint. At week 24, the mean change in the target nail modified NAPSI score was greater in the certolizumab pegol 200 mg and 400 mg groups than in the placebo group (-1.6, -2.0, and -1.1 respectively).

•Golimumab – A trial in which patients with psoriatic arthritis were randomly assigned to every-four-week injections of golimumab 100 mg, golimumab 50 mg, or placebo evaluated the effect on nail psoriasis as a secondary endpoint [54]. At week 24, the median percent improvement in target nail NAPSI score was 54 percent in the 100 mg group, 33 percent in the 50 mg group, and 0 percent in the placebo group.

Studies comparing the efficacy of different TNF-alpha inhibitors for nail psoriasis have yielded mixed results [39-42,44]. Additional study is necessary to confirm the relative efficacy of these therapies:

●Administration – Because the comparative efficacy of different TNF-alpha inhibitors is unclear, selection of a specific TNF-alpha inhibitor is based upon factors such as treatment availability, treatment cost, clinician familiarity with specific agents, patient preferences, and contraindications. The presence of other manifestations of psoriasis also influences treatment selection. Adalimumab, etanercept, and infliximab are indicated for the treatment of both cutaneous psoriasis and psoriatic arthritis, and golimumab and certolizumab pegol are indicated for the treatment of psoriatic arthritis. (See "Treatment of psoriatic arthritis".)

The biologic TNF-alpha inhibitors can be given via subcutaneous injection, with the exception of infliximab, which requires intravenous infusion. Pending additional data to determine optimal dosing for nail psoriasis, the doses used are similar to those used for cutaneous psoriasis or psoriatic arthritis. (See "Treatment of psoriatic arthritis".)

An initial response to TNF-alpha inhibitor therapy is usually evident within the first few months of treatment. Long-term therapy may be necessary to maintain remission of nail disease.

There are insufficient data to determine the best approach to patients who fail to improve. In the event of treatment failure with a particular agent, treatment with an alternative TNF-alpha inhibitor or ustekinumab may be attempted. (See 'Ustekinumab' below.)

●Adverse effects – There are multiple potential adverse effects of TNF-alpha inhibition, including injection site reactions, infusion reactions, neutropenia, infections, demyelinating disease, heart failure, skin disorders, malignancy, and autoimmune disorders. The adverse effects are reviewed in detail separately. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects".)

Ustekinumab — Ustekinumab, an inhibitor of p40 subunit of interleukin (IL) 12/23, is effective for the treatment of cutaneous psoriasis, psoriatic arthritis, and nail psoriasis [57-61] (see "Treatment of peripheral psoriatic arthritis", section on 'Ustekinumab'):

●Efficacy – In a randomized trial that compared the impact of ustekinumab 45 mg, ustekinumab 90 mg, and placebo in 545 patients with nail psoriasis, NAPSI scores were significantly improved by 12 weeks after the start of treatment [58]. The percentage in improvements in NAPSI scores were 26.7 percent (95% CI 18.5-35.0) for ustekinumab 45 mg, 24.9 percent (95% CI 17.8-32.0) for ustekinumab 90 mg, and 11.8 percent (95% CI 4.2-19.3) for placebo. Improvement in nail psoriasis continued to progress among patients who continued ustekinumab treatment beyond 12 weeks, approaching 50 percent reductions in NAPSI by 24 weeks.

●Administration – Ustekinumab is self-administered as a subcutaneous injection. Clinical improvement is usually evident within three months. Our suggested dosing for nail psoriasis in adults is similar to the dosing used for the treatment of psoriasis. Patients weighing less than 100 kg are given 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. Patients weighing more than 100 kg are given 90 mg initially, 4 weeks later, and then every 12 weeks thereafter. As with TNF-alpha inhibitors, continued treatment may be necessary to maintain remission of nail disease.

●Adverse effects – Increased risk for infection is a potential adverse effect of ustekinumab. Side effects of ustekinumab are reviewed in detail separately.

Secukinumab — Secukinumab is a monoclonal antibody that inhibits the IL-17A ligand. It is effective for the treatment of psoriasis, psoriatic arthritis, and nail psoriasis [62-64]:

●Efficacy – The TRANSFIGURE trial, in which 198 patients with moderate to severe plaque psoriasis and moderate to severe nail psoriasis were randomly assigned to secukinumab 300 mg, secukinumab 150 mg, and placebo groups (each given once weekly at week 0, 1, 2, 3, and 4, and then every four weeks thereafter), found both secukinumab dose regimens superior to placebo for improving nail psoriasis [64]. The mean percentage reductions in NAPSI at week 16 for secukinumab 300 mg, secukinumab 150 mg, and placebo were 45, 38, and 11 percent, respectively. Moreover, nail improvement continued beyond 16 weeks when all patients received open-label secukinumab; at week 32, the mean reduction in NAPSI for patients receiving secukinumab 300 mg and secukinumab 150 mg were 63 and 53 percent, respectively.

●Administration – Secukinumab is self-administered as a subcutaneous injection. The suggested dosing for nail psoriasis is the same as that for plaque psoriasis: 300 mg at weeks 0, 1, 2, 3, and 4, and then every four weeks thereafter.

●Adverse effects – Secukinumab may increase risk for superficial fungal infections. A possible association between secukinumab and increased risk for development of inflammatory bowel disease (IBD) has been reported [65]; however, a pooled safety analysis of over 7000 patients treated for psoriasis, psoriatic arthritis, or ankylosing spondylitis in 21 clinical trials found the occurrence of IBD uncommon and did not detect increases in exposure-adjusted incidence rates over time [64]. Additional study is necessary to confirm whether secukinumab increases risk for IBD.

Ixekizumab — Ixekizumab is a monoclonal antibody that targets the IL-17A ligand. In addition to nail psoriasis, ixekizumab has demonstrated efficacy for psoriasis and psoriatic arthritis:

●Efficacy – Efficacy of ixekizumab for nail psoriasis was evaluated in a subgroup analysis in UNCOVER-3, a trial in which patients with moderate to severe psoriasis were randomly assigned to ixekizumab (80 mg every four weeks after an initial 160 mg dose), ixekizumab (80 mg every two weeks after an initial 160 mg dose), etanercept (50 mg twice weekly), or placebo [66]. At the end of the 12-week randomized phase, greater improvement in the mean percent NAPSI occurred in patients with nail psoriasis in the ixekizumab every four weeks and ixekizumab every two weeks groups (37 and 35 percent improvement, respectively) compared with patients with nail psoriasis in the etanercept and placebo groups (20 percent improvement and 34 percent worsening, respectively). After week 12, patients were continued on or transitioned to open-label ixekizumab given every four weeks. By week 60, the mean percent improvement in NAPSI was greater than 80 percent, and more than 50 percent of patients had complete resolution of nail psoriasis.

●Administration – Ixekizumab is given through subcutaneous injection. The initial dose is 160 mg, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12. Subsequently, ixekizumab is given every four weeks.

●Adverse effects – Ixekizumab may increase risk for superficial fungal infections. A small number of patients on ixekizumab experienced exacerbation of IBD, although this appears to be uncommon [65,67]. Additional study is necessary to determine whether ixekizumab therapy promotes IBD.

Brodalumab — Brodalumab is a monoclonal antibody that inhibits the IL-17 receptor alpha. In addition to nail psoriasis, brodalumab has demonstrated efficacy for psoriasis and psoriatic arthritis:

●Efficacy – In an analysis of data from three phase 3, randomized trials, patients receiving brodalumab had a greater likelihood of complete clearance of nail psoriasis (NAPSI-0), a lower mean NAPSI, and higher mean percent improvement rates from baseline NAPSI than patients receiving ustekinumab [68]. Specifically, at week 52, 64 percent of patients on brodalumab achieved NAPSI-0 compared with 39 percent of patients on ustekinumab.

●Administration – Brodalumab is given 210 mg subcutaneously at weeks 0, 1, and 2 and then every two weeks thereafter.

●Adverse effects – Brodalumab may increase risk for superficial fungal infections. Exacerbation of IBD has been reported, although this appears to be uncommon in patients treated for psoriasis [69,70].

IL-23 inhibitors

●Efficacy – IL-23 inhibitors used to treat plaque psoriasis can also be effective for nail psoriasis. Guselkumab and risankizumab have demonstrated efficacy for psoriatic nail disease [71-73]. Case report data for tildrakizumab suggest potential efficacy [74]. Examples of randomized trials that have evaluated the efficacy of IL-23 inhibitors include:

•Guselkumab – In an analysis of two phase 3, randomized trials that compared guselkumab, adalimumab, and placebo in patients with moderate to severe plaque psoriasis, the proportion of patients with mild or worse nail psoriasis (n = 928) who achieved the target NAPSI-0 (100 percent improvement) at week 16 was higher for the guselkumab group than for the placebo group (16 versus 5 percent) [71]. The proportion of patients who achieved NAPSI-0 was comparable between the guselkumab and adalimumab groups at week 24 (31 versus 33 percent). An analysis of nail response in one of the trials found that patients treated with guselkumab were more likely to achieve clear or minimal nail psoriasis on the fingernail Physician Global Assessment (PGA-F) after 48 weeks than patients treated with adalimumab [72].

In a trial comparing ixekizumab with guselkumab for moderate to severe plaque psoriasis, patients on ixekizumab were more likely to achieve clear nails or minimal nail psoriasis (PGA-F score of 0 or 1 with ≥2 point improvement) at week 24 than patients on guselkumab (75 versus 54 percent). Complete clearance of nail psoriasis (PGA-F score of 0) at week 24 occurred in 52 versus 31 percent, respectively [75].

•Risankizumab – In a randomized, controlled trial comparing risankizumab and ustekinumab for moderate to severe plaque psoriasis, the mean reduction in the NAPSI score at week 12 was approximately 40 percent in the 90 and 180 mg risankizumab groups and increased to 61 and 73 percent, respectively, at week 48 [73]. In comparison, those in the ustekinumab group had a mean 20 percent increase in the NAPSI score at week 12 and an 18 percent decrease by week 48.

●Administration – Like most biologics used to treat plaque psoriasis, IL-23 inhibitor biologics can be given via subcutaneous injection. The dose frequency is less for IL-23 inhibitors compared with IL-17 inhibitors or TNF-alpha inhibitors. For example, for maintenance, guselkumab is dosed once every eight weeks, whereas tildrakizumab and risankizumab are dosed once every 12 weeks.

●Adverse effects – As a class, IL-23 inhibitors have a good safety and tolerability profile. Rates of malignancy, serious infections, or development of IBDs do not appear to be increased in patients with psoriasis treated with IL-23 inhibitors. Common adverse events associated with IL-23 inhibitors include nasopharyngitis, headache, and injection site reactions. (See "Guselkumab: Drug information" and "Risankizumab: Drug information".)

Second-line therapy — Biologic therapy is considered the most effective therapy for moderate to severe nail psoriasis. However, various factors (eg, cost, patient preference, contraindications) may contribute to the need to use alternative therapies. Alternative therapies for patients who will not receive biologic agents include methotrexate, apremilast, and local interventions such as topical medications, intralesional corticosteroids, and pulsed dye laser therapy. However, our experience suggests that local interventions may be most useful as adjuncts to systemic biologic therapy. (See 'First-line therapy' above.)

Methotrexate — Methotrexate is one of the oral treatment options for patients who are unable to receive biologic therapy due to cost, lack of availability, or other factors. Moderate improvement in nail psoriasis after methotrexate therapy has been demonstrated in randomized trials [76,77].

Methotrexate is usually administered as an oral or intramuscular injection. Typical doses for adults range from 7.5 mg to 25 mg given once weekly.

Potential side effects of methotrexate include gastrointestinal distress, hepatotoxicity, hematologic toxicity, and pulmonary toxicity. Monitoring for hematologic and liver abnormalities is necessary during treatment. Methotrexate is teratogenic and should not be taken during pregnancy. (See "Major side effects of low-dose methotrexate" and "Treatment of psoriasis in adults".)

Data on the use of intramatrical or intralesional injection of methotrexate are limited. (See 'Additional therapies' below.)

Apremilast — Apremilast is an oral phosphodiesterase 4 inhibitor used in the treatment of plaque psoriasis. Data from two similar phase 3, randomized, placebo-controlled studies evaluating the efficacy of apremilast for moderate to severe plaque psoriasis (ESTEEM 1 and ESTEEM 2) indicate that apremilast also improves nail psoriasis [78]. In the trials, a total of 1255 patients with moderate to severe plaque psoriasis were randomly assigned to either apremilast (30 mg twice daily) or placebo in a 2:1 ratio. Approximately two-thirds of the trial patients had associated nail psoriasis. At week 16, a 23 percent reduction in the mean target nail NAPSI score was detected in the apremilast group in ESTEEM 1 compared with a 7 percent increase in the placebo group. In ESTEEM 2, there were 29 and 7 percent mean reductions in target nail NAPSI scores in the apremilast and placebo groups at 16 weeks, respectively. A limitation of the trials is that baseline randomization was not stratified for nail psoriasis.

Apremilast is administered in a dose titration schedule to minimize risk for drug-induced diarrhea. Examples of other side effects include nausea, upper respiratory infection, headache, and weight loss. There is a possible slight increase in risk for depression.

Topical therapy — Topical therapies used for mild nail disease, such as topical tazarotene, topical calcipotriol, high-potency topical corticosteroids, and topical tacrolimus have limited efficacy for moderate to severe nail disease. Clinical experience suggests that these agents may be most helpful as adjuncts to systemic therapy. Treatment regimens are similar to the regimens used for mild nail disease. (See 'Mild nail psoriasis' above.)

Intralesional corticosteroids — Open-label studies suggest that intralesional corticosteroid therapy is moderately effective in treating specific psoriatic nail dystrophies, particularly abnormalities of the nail matrix [29]. Although there is a long history of use of intralesional corticosteroids for this indication, efficacy data are limited. No randomized trials have been performed.

The efficacy of intralesional corticosteroid injections can vary depending on dosing amount and frequency [29]. Typically, 0.05 to 0.3 mL of triamcinolone acetonide (2.5 to 10 mg/mL) is injected with a 30-gauge needle at multiple sites in the proximal nail fold at monthly intervals for up to five months [29]. Initial signs of improvement are usually evident within the first three months. (See "Intralesional corticosteroid injection".)

The main drawback of intralesional corticosteroid injection is that it can be very painful, and the procedure is generally not very well tolerated. Use of a needleless injector may reduce the pain associated with intralesional injection. Improvement in nail psoriasis has been reported in open studies evaluating corticosteroid delivery with needleless injectors [29,79].

Pulsed dye laser — The 595 nm pulsed dye laser is occasionally used to treat psoriatic nails [80,81]. A randomized left-right trial that compared the efficacy of two different pulsed dye laser settings (6 versus 0.45 ms pulse duration) in 20 patients with bilateral fingernail psoriasis found similar and statistically significant reductions in NAPSI scores with both regimens [81]. Patients were given six treatments at one-month intervals.

Pulsed dye laser treatments are typically given once monthly for six months. Signs of improvement are expected within the first few treatments [81].

Side effects of pulsed dye laser therapy include petechiae, transient hyperpigmentation, moderate to severe pain and burning sensations. Longer pulse durations do not appear to result in greater efficacy and may cause greater side effects [80,81]. Patients may relapse or experience remissions of 15 months or longer after the completion of treatment [81].

Additional therapies — A variety of other interventions may improve nail psoriasis. However, additional data are necessary prior to a recommendation for the use of these agents as first- or second-line therapies:

●Oral tofacitinib – Tofacitinib, an oral Janus kinase inhibitor, appears effective for nail psoriasis. In two identical phase 3 trials, patients with moderate to severe plaque psoriasis were randomly assigned in a 2:2:1 ratio to tofacitinib 5 mg, tofacitinib 10 mg, or placebo given twice daily [82]. In a post-hoc analysis of the 1196 patients with nail involvement, more patients in the tofacitinib 5 mg and 10 mg groups achieved at least a 50 percent improvement in NAPSI score than patients in the placebo group (34, 44, and 12 percent, respectively). Complete clearance (100 percent improvement in NAPSI score) occurred in 10, 18, and 5 percent of patients, respectively.

●Topical cyclosporine – Topical cyclosporine may be effective. A trial in which 16 adults were randomly assigned to treatment with cyclosporine in 70% maize oil solution or maize oil alone found a higher rate of improvement in patients given topical cyclosporine [83].

●Topical indigo naturalis – Indigo naturalis, a Chinese herb, may be a promising treatment for nail psoriasis [84,85]. A 24-week, split-body randomized trial that compared twice-daily application of indigo naturalis extract in oil to twice-daily topical calcipotriol solution (50 mcg/mL) in 33 patients with bilateral fingernail psoriasis found greater improvement in disease severity scores on nails treated with indigo naturalis than in nails treated with calcipotriol [85]. The greatest improvement occurred in onycholysis and subungual hyperkeratosis.

●Oral acitretin and cyclosporine – Limited data suggest that acitretin and cyclosporine, therapies with a long history of use in the treatment of psoriasis, have some efficacy for nail disease [76,86]. However, efficacy of acitretin in nail psoriasis is modest, at best. Cyclosporine is not appropriate for long-term use in nail psoriasis due to its associated nephrotoxicity.

●Phototherapy – Phototherapy is typically not recommended as first- or second-line treatment due to limited evidence for its efficacy in nail psoriasis [87,88].

●Intramatrical or intralesional injection of methotrexate – Data from a small, uncontrolled study and an open-label, comparative study suggest intramatrical injections of methotrexate may improve nail psoriasis [89,90]. Intralesional injection of methotrexate into the nail bed was also associated with clinical improvement in a series of four patients [91].

Treatment of children — Nail disease can occur in both children and adults. In children, the treatment of nail disease is typically limited to topical treatment options, such as topical corticosteroids, vitamin D analogs, calcineurin inhibitors, and tazarotene because of safety concerns. Oral medications are typically not recommended to treat nail psoriasis in children. For severe nail disease, etanercept may be used in the pediatric population.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Psoriasis".)

SUMMARY AND RECOMMENDATIONS

●Overview – Nail psoriasis is characterized by nail deformities that result from psoriatic involvement of the nail matrix or the nail bed. Nail psoriasis is common in patients with psoriatic arthritis or cutaneous psoriasis. Proximity to the distal interphalangeal joint may contribute to the relationship between nail psoriasis and psoriatic arthritis. (See 'Epidemiology' above and 'Pathogenesis' above.)

●Clinical manifestations – The location of psoriasis in the nail apparatus influences the clinical presentation. Psoriasis involving the nail matrix results in pitting, leukonychia, red spots in the lunula, or nail plate crumbling. Nail bed involvement results in oil drop discoloration, onycholysis, subungual hyperkeratosis, or splinter hemorrhages (picture 1A-E). (See 'Clinical manifestations' above.)

●Diagnosis – The diagnosis of nail psoriasis can usually be made based upon recognition of the characteristic clinical features, particularly if concomitant psoriasis or psoriatic arthritis is present. Onychomycosis can closely resemble nail psoriasis and an evaluation for fungal infection is often necessary. Of note, psoriatic nails may develop concomitant fungal infection. (See 'Differential diagnosis' above.)

●Treatment – The severity of nail psoriasis influences the approach to treatment (algorithm 1):

•Mild disease – For patients with mild nail psoriasis (psoriasis limited to two or fewer nails without significant symptoms or functional impairment) we recommend topical therapy, rather than systemic therapy, as initial treatment (Grade 1B). We typically prescribe combination therapy with a high-potency topical corticosteroid and topical vitamin D analog (eg, calcipotriol). Monotherapy with a high-potency topical corticosteroid and monotherapy with a topical vitamin D analog are alternative first-line treatments. (See 'Mild nail psoriasis' above.)

•Moderate to severe disease – Patients with moderate to severe psoriasis (nail psoriasis associated with marked nail dystrophy involving more than two nails, significant symptoms, or functional impairment) often require systemic therapy to achieve satisfactory improvement. (See 'Moderate to severe nail psoriasis' above.)