What is the recommended treatment for mild to moderate psoriasis using calcineurin (CN) inhibitors?

Calcineurin Inhibitors for Mild to Moderate Psoriasis

Topical calcineurin inhibitors (tacrolimus and pimecrolimus) are recommended for mild to moderate psoriasis involving facial and intertriginous areas, where they serve as effective steroid-sparing agents. 1

Specific Recommendations by Location

Facial and Intertriginous Psoriasis

• Tacrolimus 0.1% ointment: Apply twice daily for up to 8 weeks
  • Efficacy: 65% of patients achieve clear or almost clear status vs. 31% with placebo 1
• Pimecrolimus 0.1% cream: Apply twice daily for 4-8 weeks
  • Efficacy: 71% of patients achieve clear or almost clear status vs. 21% with placebo 1

Plaque Psoriasis (Non-facial/intertriginous)

• Standard plaque psoriasis: Calcineurin inhibitors alone are generally not effective 1
• Combination therapy: Tacrolimus with 6% salicylic acid applied for 12 weeks may be used for plaque psoriasis (strength of recommendation: B) 1

Advantages of Calcineurin Inhibitors

• No skin atrophy, telangiectasia, or striae (unlike topical corticosteroids) 2
• Particularly valuable for sensitive areas (face, genitals, skin folds) where corticosteroids may cause adverse effects 1, 2
• Can be used for longer periods (≥4 weeks) as steroid-sparing agents 1
• Mechanism: Block calcineurin phosphorylation, inhibiting T-cell activation and proinflammatory cytokine synthesis 1

Safety Considerations

• Common side effects: Burning and itching, which typically:
  • Improve with continued use
  • Can be mitigated by avoiding application to moist skin 1
• FDA boxed warning: Issued in 2005 regarding theoretical risk of lymphoma with long-term use
  • Important caveat: No clinical evidence shows a causal link between topical use and increased cancer risk 1
• Pregnancy: Category C; not recommended for nursing mothers 1
• Pediatric use: Approved for patients as young as 2 years for atopic dermatitis (off-label for psoriasis) 1

Treatment Algorithm for Mild to Moderate Psoriasis

1. For facial and intertriginous psoriasis:

   • First-line: Tacrolimus 0.1% ointment or pimecrolimus 0.1% cream twice daily
   • Duration: 4-8 weeks initially, with possible long-term maintenance for inverse psoriasis 1

2. For plaque psoriasis on body:

   • First-line: Topical corticosteroids and/or vitamin D analogs
   • For resistant cases: Consider combination of tacrolimus with 6% salicylic acid 1
   • For maintenance: Consider calcineurin inhibitors for long-term control to avoid steroid-related adverse effects 1, 3

Clinical Pearls

• Application of calcineurin inhibitors immediately after bathing may increase burning sensation; wait until skin is dry 1
• Efficacy in facial and intertriginous areas is likely due to reduced induration in these lesions allowing better penetration 2
• The combination of potent corticosteroids with vitamin D analogs is more extensively studied than calcineurin inhibitors for general plaque psoriasis 3
• Topical calcineurin inhibitors have strong evidence for efficacy in facial, genital, and intertriginous psoriasis where they fill an important therapeutic niche 4

Monitoring

• Assess treatment response after 4-8 weeks
• Watch for burning/itching sensations, which typically diminish with continued use
• Consider tapering frequency upon improvement for maintenance therapy 1