What are the treatment options for a patient with chronic plaque psoriasis?

Management of Chronic Plaque Psoriasis

Initial Treatment for Mild Disease (≤5% Body Surface Area)

Start with a fixed-combination product containing calcipotriene (vitamin D analogue) and betamethasone dipropionate 0.05% applied once daily for 4 weeks, which achieves superior efficacy compared to either agent alone. 1, 2, 3

Topical Corticosteroid Selection by Body Site

• Body plaques: Apply clobetasol propionate 0.05% or betamethasone dipropionate 0.05% (potent to very potent corticosteroids) twice daily for maximum 2-4 weeks 2, 4, 3
• Scalp: Use clobetasol propionate 0.05% shampoo twice weekly or calcipotriene/betamethasone foam for 4-12 weeks 1, 2, 3
• Face, genitals, intertriginous areas: Apply low-potency corticosteroids (hydrocortisone) or tacrolimus 0.1% to avoid skin atrophy 1, 4, 3
• Nails: Use calcipotriene combined with betamethasone dipropionate to reduce thickness, hyperkeratosis, and onycholysis 1

Alternative Combination Regimens

If fixed-combination products are unavailable, use separate products with these evidence-based schedules:

• Morning-evening split: Apply potent corticosteroid in morning and calcipotriene in evening 1, 4
• Weekday-weekend rotation: Apply calcipotriene twice daily on weekdays and high-potency corticosteroid twice daily on weekends for maintenance 1, 4
• Tazarotene combination: Add tazarotene 0.1% gel or cream once daily at night with moderate-to-high potency corticosteroid in morning to enhance efficacy (treatment success defined as 50-74% improvement after 12 weeks) 1, 4

Critical Safety Protocols for Topical Corticosteroids

• Mandatory clinical review every 4 weeks during active treatment with no unsupervised repeat prescriptions 1, 4, 3
• Limit moderate-potency corticosteroids to maximum 100g per month 1, 4, 3
• Require dermatological supervision for very potent (class 1-2) preparations 1, 4, 3
• Plan annual treatment-free periods or switch to alternative agents to minimize long-term adverse effects 1, 4

Agents to Avoid in Combination

• Never combine salicylic acid with calcipotriene as the acidic pH inactivates calcipotriene and reduces effectiveness 1, 4, 3

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Escalation to Phototherapy for Moderate Disease (5-10% Body Surface Area)

When topical therapy fails after 8 weeks of optimized treatment, initiate narrowband UVB phototherapy or PUVA (photochemotherapy) as first-line systemic intervention. 2, 3

Phototherapy Protocols

• PUVA: Start at 70% of minimum phototoxic dose; this is the least toxic systemic agent for moderate-to-severe psoriasis 2, 3
• Narrowband UVB: First-line option alongside PUVA for moderate-to-severe disease 2
• 308-nm excimer laser: Use for selective targeting of localized resistant areas (scalp, skin folds) 2

Phototherapy Combination Strategies

• Apply vitamin D analogues after phototherapy treatment to avoid inactivation by UVA and blocking of UVB radiation 1

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Systemic Non-Biologic Therapy for Moderate-to-Severe Disease (>10% Body Surface Area)

For patients requiring rapid disease control, initiate cyclosporine 3-5 mg/kg/day in two divided doses, which provides the most rapid onset of action (3 weeks) among systemic agents. 1, 2, 3

Cyclosporine Protocol

• Dosing: 2.5-5.0 mg/kg/day in two divided doses 1, 2
• Response time: 3 weeks 1, 2
• Duration: Use as short-term "interventional therapy" for 3-4 months, then discontinue or switch to maintenance therapy 1, 2
• Dose adjustments: Reduce by 0.5-1.0 mg/kg when clearance achieved or if hypertension/decreased renal function develops 1
• Monitoring: Check blood pressure, BUN, and creatinine every 2 weeks for first 3 months, then monthly 1

Cyclosporine Contraindications

• Abnormal renal function, uncontrolled hypertension, malignancy, concomitant PUVA/UVB/methotrexate, history of ≥200 PUVA treatments 1, 3

Alternative Systemic Agents

Methotrexate (FDA approved since 1972):

• Response time: 2 weeks 2
• Mechanism: Competitive inhibitor of dihydrofolate reductase 2
• Absolute contraindications: Pregnancy, breastfeeding, wish to father children, significant hepatic damage, anemia, leukopenia, thrombocytopenia 3

Acitretin:

• Response time: 6 weeks 3
• Efficacy: 23% achieve PASI 75 at 50 mg/day over 8 weeks; 41% achieve clearance or marked improvement at doses up to 70 mg/day 1
• Maintenance: 75% and 88% reach PASI 50 at 6 and 12 months, respectively 1
• Absolute contraindication: Pregnancy or wish to conceive within 2 years of stopping treatment 3
• Special indication: Rapid and impressive responses in pustular psoriasis 1

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Biologic Therapy for Severe or Refractory Disease

For generalized pustular psoriasis or erythrodermic psoriasis requiring immediate control, initiate infliximab 5 mg/kg infused at weeks 0,2, and 6, then every 8 weeks, which demonstrates rapid and often complete disease clearance. 1, 2, 3

Infliximab Protocol

• Standard dosing: 5 mg/kg at weeks 0,2,6, then every 8 weeks 1, 2
• Dose escalation: May increase frequency to every 4 weeks or dose up to 10 mg/kg for better disease control 1
• Indications: Moderate-to-severe plaque psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis 1, 3

Alternative Biologics

Adalimumab (FDA approved 2002):

• Dosing: 80 mg initial dose, then 40 mg every other week starting one week after initial dose 5
• Indication: Moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy 5
• Special consideration: Effective for both skin and joint symptoms in psoriatic arthritis 2

Etanercept:

• Dosing: 50 mg subcutaneously twice weekly for first 12 weeks, then 50 mg once weekly 1
• Efficacy: 48% achieve PASI 75 at 12 weeks 1

Biologic Safety Monitoring

• Screen for latent tuberculosis before initiating therapy; if positive, start TB treatment prior to biologic 5
• Monitor for serious infections during treatment; discontinue if serious infection or sepsis develops 5
• Malignancy risk: Lymphoma and other malignancies reported, including hepatosplenic T-cell lymphoma in adolescents and young adults with inflammatory bowel disease 5

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Combination Strategies to Enhance Systemic/Biologic Efficacy

Add ultrahigh-potency topical corticosteroid or calcipotriene/betamethasone to standard-dose biologics or systemic agents to accelerate clearance and improve outcomes. 2

Evidence-Based Combinations

• Etanercept + ultrahigh-potency topical corticosteroid for 12 weeks accelerates clearance 2
• Adalimumab + calcipotriene/betamethasone for 16 weeks accelerates plaque clearance 2
• Methotrexate + topical calcipotriene improves outcomes 2
• Infliximab + topical corticosteroids with or without vitamin D analogue augments efficacy 1

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Critical Medications That Worsen Psoriasis (Absolute Avoidance)

Never prescribe systemic corticosteroids for psoriasis, as abrupt discontinuation can precipitate life-threatening erythrodermic or generalized pustular psoriasis. 1, 2, 4, 3

Other Medications to Avoid or Use Cautiously

• Lithium, chloroquine, mepacrine: Associated with severe, potentially fatal psoriasis deterioration 1, 4, 3
• Beta-blockers and NSAIDs: May precipitate or worsen psoriasis in some patients 1, 4, 3
• Alcohol: Can precipitate or worsen psoriasis 1, 4, 3

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Special Psoriasis Subtypes

Pustular Psoriasis

• First-line: Infliximab for rapid and complete clearance 2, 3
• Alternative: Acitretin shows rapid and impressive responses 1, 3

Erythrodermic Psoriasis

• First-line: Cyclosporine 3-5 mg/kg/day for rapid onset of action 2, 3
• Supportive care: Mid-potency topical corticosteroids and emollients under occlusion to restore barrier function, though systemic treatment is inevitably necessary 2

Palmoplantar Psoriasis

• Topical: Maxacalcitol ointment (not available in US) as initial treatment 1
• Systemic: Infliximab can be used for plaque-type palmoplantar psoriasis 1

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Adjunctive Therapies

Evidence-Based Supplements

• Fish oil/omega-3 fatty acids: May augment effects of topical, systemic, and phototherapy; select mercury-free, dioxin-free, and polychlorinated biphenyl-free supplements 1
• Oral curcumin: May benefit patients as adjunctive therapy 1, 2

Topical Alternatives with Limited Evidence

• Aloe vera: 83.3% cure rate (complete clearance) with thrice-daily application for 4 weeks in one RCT, but another RCT showed no difference from placebo; risk of contact dermatitis 1
• Topical indigo naturalis: Must be carefully formulated; some herbal remedies contain undisclosed corticosteroids 1

Therapies NOT Recommended

• Oral vitamin D supplementation: Does not directly improve disease activity at safe dosages 1
• Oral zinc: Associated with headaches, nausea, vomiting, and in high doses with severe adverse effects 1

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Referral Criteria

Refer to dermatology when:

• Body surface area >5% despite 8 weeks of optimized topical therapy 2, 3
• Systemic agents required (due to potential toxicity) 1, 4
• Pustular, erythrodermic, or unstable psoriasis develops 1, 3
• Significant psoriatic arthritis present 1

Most patients with stable chronic plaque psoriasis and guttate psoriasis can be managed in primary care with topical agents. 1, 4