Continuing Education Activity

Nail psoriasis is a subtype of psoriasis, the common chronic inflammatory skin condition that can also affect the joints. Although cutaneous manifestations of psoriasis are frequently observed, nail involvement significantly impacts patients' social and psychological well-being. This activity comprehensively reviews the clinical presentation, evaluation, and treatment strategies for nail psoriasis, shedding light on the challenges posed by the slow growth pace of nails and the prolonged nature of treatment. The session emphasizes the crucial role of the interprofessional healthcare team in evaluating and treating patients with nail psoriasis, highlighting the need for collaborative approaches to enhance patient outcomes. Learners will gain insights into the diverse clinical manifestations of nail psoriasis, including discoloration, hyperkeratosis, pitting, and onycholysis, equipping them with the knowledge to navigate the complexities of managing this condition. Educating clinicians on setting realistic patient expectations and fostering effective communication within the healthcare team are pivotal aspects addressed in this activity, aiming to improve the quality of care provided to individuals grappling with psoriasis of the nails.

Objectives:

• Determine the etiology, pathophysiology, and exacerbating factors of nail psoriasis.
• Assess history and physical examination findings of nail psoriasis.
• Identify the management options for nail psoriasis according to the severity of the disease.
• Coordinate the interprofessional team to improve outcomes for patients with nail psoriasis.

Introduction

Psoriasis is a common chronic inflammatory skin condition; however, a subtype of psoriasis can include nail involvement, systemic involvement (eg, joints), or both nail and systemic involvement; nail psoriasis can be the first presentation of cutaneous psoriasis, a sequela of cutaneous psoriasis, or a concurrent presentation of psoriasis.[1] Psoriatic involvement of the nail bed or nail matrix is the purported cause of nail psoriasis.[2] Nail involvement is a visible indicator to predict concomitant or future inflammatory joint activity, most prominently in the distal interphalangeal joint, where psoriatic arthritis classically presents.[3]

Nail psoriasis can manifest clinically as a wide variety of nail changes, like nail discoloration (eg, oil drops), subungual hyperkeratosis, pitting (ie, punctate nail depressions), and onycholysis (ie, distal nail plate separation from nail bed), depending on the part of the nail unit affected (see Image. Nail Psoriasis). Patients with nail psoriasis may have impaired quality of life due to the appearance of their nails, and significant morbidity and functional impairments may arise in some cases.[4][5] Nail psoriasis management is challenging since prolonged treatment is required and may not be able to control disease activity entirely. Educating patients on the prognosis and outcomes of treatment is most important to set expectations and prepare for a successful treatment approach.[6]

Etiology

The exact etiology of nail psoriasis is unclear, but multiple factors, including genetic, immunological, and environmental factors, may contribute to nail psoriasis.[1] Ultimately, nail matrix or nail bed inflammation is implicated in nail psoriasis. Dysregulation of innate immunity is putatively the strongest associated factor.[7] However, some genetic factors, like human leukocyte antigens (Cw6, B13, B17), are associated with nail psoriasis, and family history is often significant in individuals with nail psoriasis, suggesting a genetic or inherited basis; however, this is incompletely understood.[8]

Epidemiology

Nail psoriasis affects both children and adults, affecting both males and females equally, with increasing prevalence with increasing age.[9][10] Nail psoriasis mostly develops in association with cutaneous psoriasis and psoriatic arthritis, with studies varying widely on their prevalence; however, a strong association of 80% to 90% between psoriatic arthritis and nail psoriasis is found across multiple studies, likely because psoriatic arthritis classically affects the distal interphalangeal joint, which is the joint closest to the nail.[11] Nail psoriasis may develop as a sole manifestation of psoriasis or concurrently with other symptoms or after the onset of cutaneous symptoms.[6]

Pathophysiology

Nail psoriasis usually results from psoriatic inflammation involving the nail bed or nail matrix.[12] The nail matrix is mainly responsible for nail plate formation and is located beneath the proximal nail fold. The superficial part of the nail plate is formed from the proximal nail matrix, while the deep part is formed from the distal nail matrix. Clinical features related to nail matrix involvement are nail pitting, red spots in the lunula, leukonychia, and crumbling of the complete nail plate.[13] The nail bed lies directly beneath the nail plate and plays a significant role in the adherence of the nail plate to the nail bed.[14] The involvement of the nail bed manifests clinically as onycholysis, splinter hemorrhages, subungual hyperkeratosis, and oil-drop discoloration.[2][15]

Genetic contributions to the formation of nail psoriasis are still uncertain but are likely significant given the high prevalence of psoriasis within a single family.[16] Psoriatic nail disease may, however, align more closely with innate immunity dysregulation. Psoriatic nail disease may correlate with dysregulation of the immune system differently from disease limited to the skin, but this is poorly understood.

Histopathology

Histopathological findings of nail psoriasis are similar to cutaneous psoriasis, including mild-to-moderate hyperkeratosis, focal parakeratosis (which is responsible for nail pitting), and spongiosis.[17] Other prominent features are a neutrophilic inflammatory infiltrate, hypergranulosis, and psoriasiform epidermal hyperplasia.[18] The papillary dermis in affected skin contains dilated, tortuous capillaries, while the hyponychium shows the loss of the granular layer with hypergranulosis in the nail bed and nail matrix.[14]

History and Physical

Because nail psoriasis can be associated with cutaneous and systemic findings (eg, psoriatic arthritis), a thorough history and physical should be performed in patients with nail psoriasis. 

History

A thorough history of the nail findings consistent with psoriasis should be explored, including:

• Onset
• Location (eg, number of nails involved or quadrants of nails involved)
• Duration
• Other patterns
• Joint symptoms (eg, swelling, pain, timing, onset, duration)
• Social history (eg, smoking)
• Medical history (eg, heart disease, metabolic disease, psoriasis)
• Family history (eg, history of psoriasis)
• Recent infections [19]

Physical Examination

Physical examination should focus on identifying the characteristic findings of nail psoriasis (see Image. Nail Pitting). Nail pitting is commonly seen in patients with psoriasis. The disease may affect 1 or more nails of the hands or feet, and this number should be noted as it is relevant for treatment. There may be 1 or more findings, which can include:[20][21]

• Pitting: Studded depressions in the nail plate
• Subungual hyperkeratosis: White keratin debris overlying the nail bed
• Onycholysis: Distal separation of the nail plate from the underlying nail bed)
• Oil-drop discoloration: Pink macule or patch (usually appearing on the proximal nail) or red, discolored spots on the lunula
• Nail crumbling: Disintegration of the distal nail
• Leukonychia: White lines on the nail plate
• Splinter hemorrhages: Red, linear streaks on the nail

Patients can also have other manifestations of nail psoriasis, such as onychorrhexis, trachyonychia, or Beau lines, but these are less characteristic and may indicate many other inflammatory or infectious findings.[22] Other than the nails, a thorough full-body skin examination should be performed to evaluate the coexistence of cutaneous psoriasis. Common areas affected classically in psoriasis include the extensor surfaces, anogenital area, and scalp.[23][14] 

Other physical examination maneuvers should include inspection and palpation of any affected joints, such as the distal interphalangeal joints; in some cases, bedside ultrasound can be used to better characterize the joint and nail disease.[24] In combination, the presence of one or more nails with characteristic findings, possible skin involvement, and possible systemic symptoms can be collectively used to evaluate the extent of the disease. 

Evaluation

Nail psoriasis can be diagnosed based on a thorough history and physical examination. The exclusion of fungal nail disease is important as onychomycosis can appear clinically indistinct from nail psoriasis.[9] A periodic acid-Schiff stain of a nail clipping, potassium hydroxide (KOH) stain of nail clippings, or a fungal culture can be used to rule out onychomycosis. However, the presence of onychomycosis should not immediately rule out the possibility of coexisting nail psoriasis; instead, after treatment of onychomycosis, the patient should be evaluated for resolution of the fungal nail disease and should later be examined for any nail, skin, or systemic findings suspicious for nail psoriasis.[25] Ultrasound may be used as an adjunctive evaluation method in some patients, but this is not required and is under study as a tool for psoriatic arthritis.[26] A nail biopsy is generally unnecessary, but in cases with significant diagnostic uncertainty, a biopsy of the nail matrix or nail bed may be used in histopathologic examination to identify the characteristic findings of psoriasis.[27]

Treatment / Management

The treatment of nail psoriasis can include topical or systemic therapy, which is based on the severity or extent of disease; mild disease (ie, disease limited to 1 or 2 nails with no functional impairment or systemic involvement) can usually be treated with topical therapy, whereas moderate-to-severe disease (ie, disease beyond 2 nails or disease with functional impairment or systemic involvement) may require initiating systemic therapy.[10] There are myriad options for systemic treatment, including biologic agents, phototherapy, intense pulsed light, lasers, and photodynamic therapy. The factors that need to be considered for treatment options are the age of the patient, comorbidities, relative or absolute contraindications to therapy, concomitant skin and joint involvement, impact on quality of life, patient preference, and cost of treatment.[28]

Mild Disease

For mild disease, high-potency topical corticosteroids and topical vitamin D analogs (eg, calcipotriol) are recommended twice daily on the affected nails, alone or together. However, some studies have shown improved use by patients with a combined topical betamethasone diproprionate and calcipotriol therapy; these have been used as a topical therapy with success as a combined or separate solution or foam, and the combined foam was used in 1 study following ablative fractionated laser as a pretreatment with successful results.[5][29] 

When topical therapy is unsuccessful with topical corticosteroids and topical vitamin D analogs, other therapies to consider may include topical tacrolimus and topical tazarotene.[30] Fractionated CO₂ laser has been used with tazarotene for nail psoriasis with success in at least 1 study.[31] Topical tofacitinib, a modulator of the janus kinase family, has shown some promise as a 2% solution for recalcitrant nail psoriasis.[32] When these therapies are unsuccessful or are otherwise contraindicated, intralesional corticosteroids may be considered, or systemic therapy, as used for moderate-to-severe disease, may need to be considered.[33]

Moderate-to-Severe Disease

For moderate-to-severe nail psoriasis, with significant disease severity or extent, first-line therapy should include a biologic agent where feasible and not contraindicated.[34][35] Biologic agents have significantly improved nail psoriasis across multiple studies.[36] A network meta-analysis of multiple biologic agents has shown that at 24 to 28 weeks, ixekizumab, followed by brodalumab and bimekizumab, was most efficacious for complete resolution of nail psoriasis, whereas at weeks 48 to 52, ixekizumab, followed by adalimumab and brodalumab, had the highest absolute probability to achieve complete resolution of nail psoriasis.[37]

• Tumor necrosis factor-α inhibitors (eg, adalimumab, infliximab, etanercept, certolizumab, golimumab): Adalimumab was shown to be efficacious in multiple studies for nail psoriasis, though it has been outperformed in other studies by guselkumab and ixekizumab.[36][38] Similar data have been observed for the class of medications being successful for the treatment of nail psoriasis across other studies.[36][39][40][41][42][43]
• Interleukin-17 inhibitors (eg, secukinumab, ixekizumab, brodalumab): Secukinumab has been shown to provide sustained treatment for patients with nail psoriasis.[44] Brodalumab has been shown to be efficacious in an open-label study.[45] Meanwhile, ixekizumab, which is dosed every 4 weeks, has been shown to be the most efficacious treatment when compared across multiple biologic agents.[37][46][47] The interleukin-17 inhibitors should be avoided in patients with active hepatitis infection and active inflammatory bowel disease, while brodalumab should be avoided in patients with recent suicidality.[48]
• Interleukin-23 inhibitors (eg, guselkumab, risankizumab, tildrakizumab): In a subset of patients with psoriatic arthritis, nail psoriasis severity indices improved significantly with guselkumab versus placebo at week 16 and at week 24.[49] Risankizumab, which is dosed every 12 weeks, has also been shown to be efficacious for nail psoriasis endpoints in a randomized controlled trial, whereas tildrakizumab has been supported through individual cases and in other forms of psoriasis.[50][51]
• Interleukin-12 and interleukin-23 inhibitors (eg, ustekinumab): Ustekinumab was shown to improve nail psoriasis in patients with moderate-to-severe psoriasis in one study, and it has been used for psoriasis across populations.[52][53]

If moderate-to-severe nail psoriasis does not improve after biologic agent use, even after switching between classes, or if biologic agent use is not feasible or contraindicated, second-line treatment can include methotrexate (oral or intralesional), apremilast, intralesional corticosteroids, topical therapies used in mild disease, or pulsed dye laser.[54][55][56][57] Although these therapies have been shown to be efficacious, additional therapies for consideration include tofacitinib (oral or topical), acitretin, cyclosporine, fractional CO₂ laser, excimer laser, and narrowband ultraviolet B phototherapy.[32][58][59][60]

Differential Diagnosis

Many conditions need to be distinguished from nail psoriasis. Because nail dystrophy and other characteristic findings in nail psoriasis can be found in other disease states, distinguishing these can be challenging. For instance, age-related changes from trauma, vascular lower extremity diseases (eg, peripheral artery disease, chronic venous stasis, trauma), and peripheral neuropathy can cause nail changes that may be confused for nail psoriasis; however, these findings will be unlikely to show other findings of psoriasis if they are the cause of nail changes.[13] Many medications can also cause nail changes, so ruling out medication changes is essential.[13] Some other pertinent differential diagnoses with nail changes most similar to nail psoriasis are listed below.

• Onychomycosis: The changes of onychomycosis resemble nail psoriasis; sometimes, it is difficult to distinguish between the two. Nail pitting, onycholysis, and the oil drop sign (ie, discoloration of the nail) are the main features of nail psoriasis and are less likely to be found in onychomycosis. Onychomycosis can be diagnosed by fungal culture or nail clipping analysis with periodic acid-Schiff (PAS) or potassium hydroxide (KOH) preparations.[2]
• Alopecia areata: The nail changes of alopecia areata can vary and include trachyonychia, linear ridging, nail pitting, nail fissuring, or other nail abnormalities with nonscarring patchy alopecia, typically on the scalp.[61][62]
• Lichen planus: Nail involvement presents as thinning of the nails with ridges and grooves of the nail plate, which can scar the cuticle and lead to pterygium formation. Lichen planus also often involves the mucosa or skin with characteristic pruritic, purple, and polygonal papules or plaques.[63]
• Pityriasis rubra pilaris: Though nail changes in pityriasis rubra pilaris can include thickened nails with splinter hemorrhages, which are less common findings in nail psoriasis, the cutaneous findings of this disease can be similar to those in psoriasis. Skin findings in pityriasis rubra pilaris, though, will usually include hyperkeratotic follicular papules, orange-red plaques with fine scales, and hyperkeratosis of the palms and soles.[9][64]

Many other dermatologic conditions may also present with nail findings that can overlap with nail psoriasis, including atopic dermatitis, Darier disease, and Hailey-Hailey disease. These conditions should also be considered when evaluating a patient with nail changes.[13]

Prognosis

Patients with nail psoriasis have a chronic and protracted course with periods of improvement and worsening, which can impact quality of life. Patients with nail psoriasis may have more difficulty with treatment and thus poorer disease control, since there are limited data on treatments compared with cutaneous psoriasis.[65] Worsening of nail disease may occur due to nail trauma, which is often unavoidable, due to koebnerization. However, treatment with topical or systemic agents for mild and moderate-to-severe disease, respectively, may alter the disease process, though with some concern for adverse effects.[66]

Complications

The patient with nail psoriasis may develop complications due to the disease process or medications used for treatment. The major complications can be grouped into functional disability, psychological distress, and infections, including bacterial (eg, paronychia) and fungal infections (eg, onychomycosis).

Deterrence and Patient Education

Nail psoriasis is a chronic disease process; treatment may be prolonged, so patient education to set expectations is essential.[67] Patients should be educated that toenails take approximately 12 months to grow fully, whereas fingernails take almost 6 months, so changes to nails before and after treatment will occur slowly. Therefore, photographs of the patient's nails should be taken and stored to monitor changes. Patients should avoid trauma to their nails, since koebnerization may worsen the disease. Patients may need to consider wearing gloves when handling chemicals or moisture, and their hands should be kept dry, other than emollient use. Nails should be kept neat, trimmed, and clean, particularly when onycholysis is present, as this can introduce microorganisms that lead to infection. Although psoriasis is usually associated with decreased infection, patients should be aware of the risk of infection, especially onychomycosis.

Enhancing Healthcare Team Outcomes

Nail psoriasis is a difficult condition to manage, and its management is best done by an interprofessional team.[2] Nail psoriasis can be disfiguring and lead to distress or anxiety, particularly for patients who may need to display their nails for their personal or professional lives (eg, hand model). The healthcare team can aid in recognizing anxiety or psychiatric issues and initiating appropriate referrals in this case. Pharmacists should be involved in educating patients on the appropriate use of topical and systemic medications since topical medications will need to be applied in a particular fashion to ensure the medication reaches the hyponychium, whereas systemic agents may require self-injection. Since nail psoriasis is strongly linked to psoriatic arthritis, a team-based approach with other specialists may be needed. Although nail psoriasis can be managed by a primary care provider, a referral to a dermatology specialist is most prudent to provide appropriate counseling, education, diagnosis, treatment, and monitoring. Close communication between interprofessional team members is vital to achieving desired outcomes in nail psoriasis.[14]

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Disclosure: Hira Muneer declares no relevant financial relationships with ineligible companies.

Disclosure: Nishad Sathe declares no relevant financial relationships with ineligible companies.

Disclosure: Sadia Masood declares no relevant financial relationships with ineligible companies.