What is the recommended management of nail psoriasis, including topical, intralesional, systemic, and biologic therapies?

Management of Nail Psoriasis

For nail psoriasis affecting ≤3 nails with matrix involvement, intralesional triamcinolone acetonide 5-10 mg/cc is the treatment of choice; for >3 nails or significant functional impairment, biologic DMARDs (particularly IL-17 inhibitors, TNF inhibitors, or IL-12/23 inhibitors) should be initiated as first-line systemic therapy. 1, 2

Disease Severity Classification and Treatment Thresholds

Nail psoriasis severity determines the treatment approach:

• Mild disease (≤3 nails affected): Topical or intralesional therapy is appropriate 1, 3
• Moderate-to-severe disease (>3 nails, functional impairment, or concurrent psoriatic arthritis): Systemic therapy is warranted 1, 2
• Critical consideration: Hands and nails are designated "vulnerable areas" that mandate systemic therapy regardless of body surface area involvement, reflecting their disproportionate impact on quality of life and function 1

Topical Therapy for Mild Disease

First-Line Topical Regimen

• Apply high-potency topical corticosteroid (clobetasol 0.05% cream) under occlusion to the affected nail unit 1, 2
• Add calcipotriene (vitamin D analogue) to improve nail thickness, hyperkeratosis, and onycholysis 1, 2
• Tazarotene 0.1% cream can be used as an alternative retinoid option, particularly effective under occlusion 2

Critical Topical Therapy Pitfalls

• Never combine calcipotriene with salicylic acid: The acidic pH inactivates calcipotriene and eliminates its effectiveness 1, 2
• Tazarotene is teratogenic: Contraindicated in pregnancy; women of reproductive potential must use effective contraception 1, 2
• Topical agents have limited efficacy for severe nail disease due to poor nail-plate penetration 1, 2

When to Escalate from Topical Therapy

If no improvement occurs after 4 weeks of topical therapy, proceed to intralesional injections or systemic therapy 1

Intralesional Therapy

For ≤3 nails with matrix involvement, inject triamcinolone acetonide 5-10 mg/cc into the nail matrix 1, 2, 3

• This approach is highly effective for nail matrix disease specifically 1, 2
• Matrix involvement responds better to intralesional steroids, while nail bed involvement responds better to topical treatments 2
• This option is impractical when >3 nails are affected 1, 3

Systemic Therapy for Moderate-to-Severe Disease

Biologic DMARDs: First-Line Systemic Therapy

Biologic DMARDs are the most effective treatment option and should be initiated as first-line therapy for moderate-to-severe nail psoriasis 1, 2

IL-17 Inhibitors (Secukinumab, Ixekizumab)

• May provide superior short-term nail-psoriasis clearance compared to other biologic classes 1, 2
• Long-term efficacy is similar to TNF inhibitors 2

TNF Inhibitors

Adalimumab:

• Achieves 47% mNAPSI 75 response at 26 weeks 1, 2
• 49% of patients reach clear or minimal disease with ≥2-grade improvement 1, 2
• Grade A recommendation from AAD-NPF guidelines 1

Etanercept:

• Dosing: 50 mg twice weekly for 12 weeks, then 50 mg weekly maintenance 4, 1
• Level II-III evidence for nail psoriasis 4
• Caution: May be less effective in patients with high body-mass index 1, 2
• Grade A recommendation for psoriasis with psoriatic arthritis 4

Infliximab:

• Recommended as monotherapy for moderate-to-severe plaque-type palmoplantar and nail psoriasis 4
• Standard dosing: 5 mg/kg at weeks 0,2,6, then every 8 weeks 4
• Grade B recommendation specifically for nail psoriasis 4

IL-12/23 Inhibitor (Ustekinumab)

• Median NAPSI improvement: 42.5% at week 16,86.3% at week 28,100% at week 40 1
• Dosing: 45 mg (<100 kg) or 90 mg (≥100 kg) at weeks 0,4, then every 12 weeks 1
• Can be intensified to 90 mg for all patients or every 8 weeks for inadequate response 1
• Grade A recommendation from AAD-NPF guidelines 1

Combination Biologic + Topical Therapy

Adding topical corticosteroids to biologics enhances efficacy:

• Etanercept + high-potency (class 1) topical corticosteroid: Grade A recommendation 4
• Adalimumab + calcipotriene/betamethasone: Grade B recommendation to accelerate plaque clearance 4
• Ustekinumab + topical corticosteroids (with or without vitamin D analogue) enhances outcomes 1

Conventional Systemic Agents: Second-Line Options

When biologics are unsuitable or unavailable:

Acitretin:

• Dosing: 0.2-0.4 mg/kg/day 1, 2, 3
• Particularly effective for pustular variants 1
• Mandatory 3-year contraception requirement after stopping for women of childbearing potential due to teratogenicity 1

Methotrexate:

• Dosing: 15 mg/week 1, 2
• Especially useful when extensive skin disease co-exists 1, 2
• Grade A recommendation when combined with topical calcipotriene 4
• Regular monitoring for hepatotoxicity and bone-marrow suppression required 1

Cyclosporine:

• Effective but limited to ≤12 consecutive months due to cumulative nephrotoxicity 1, 2, 3
• Grade B recommendation when combined with calcipotriene/betamethasone dipropionate ointment at low dose (2 mg/kg/day) 4

Apremilast:

• Oral second-line agent 1, 2
• Grade B recommendation when combined with etanercept 4

Special Considerations for Psoriatic Arthritis

• When psoriatic arthritis co-exists, biologic DMARDs are strongly recommended as first-line therapy 1, 2
• Nail involvement heightens the risk of progressive psoriatic arthritis, supporting earlier initiation of systemic therapy 1, 2
• Etanercept receives Grade A endorsement for any severity psoriasis with psoriatic arthritis 4, 1
• Ustekinumab receives Grade A endorsement for any severity psoriasis with psoriatic arthritis 1

Critical Clinical Pitfalls to Avoid

• Never use systemic corticosteroid monotherapy for psoriasis: It can precipitate pustular or erythrodermic flares during tapering 1, 2
• Do not rely solely on topical therapy for severe nail disease: Poor nail-plate penetration renders topicals ineffective 1, 2
• Never mix calcipotriene with salicylic acid: The acidic environment inactivates the vitamin D analogue 1, 2
• Recognize teratogenic agents: Both tazarotene and acitretin require effective contraception in women of reproductive potential 1, 2

Treatment Algorithm Summary

1. ≤3 nails affected, matrix involvement: Intralesional triamcinolone acetonide 5-10 mg/cc 1, 2, 3
2. ≤3 nails affected, nail bed involvement: High-potency topical corticosteroid + calcipotriene under occlusion 1, 2
3. >3 nails affected OR functional impairment OR concurrent psoriatic arthritis: Initiate biologic DMARD (IL-17 inhibitor, TNF inhibitor, or IL-12/23 inhibitor) 1, 2
4. Biologics unsuitable: Consider acitretin, methotrexate, cyclosporine, or apremilast 1, 2, 3
5. Enhance biologic efficacy: Add high-potency topical corticosteroid ± vitamin D analogue 4, 1