What is the standard stepwise management of psoriasis and the criteria for escalating therapy?

Management of Psoriasis and Criteria for Therapy Escalation

Begin with topical therapy for mild psoriasis (BSA <5-10% or PASI <10), escalate to phototherapy or systemic agents when BSA exceeds 5-10%, PASI exceeds 10, or DLQI exceeds 10, and advance to biologic therapy when methotrexate and ciclosporin have failed, are not tolerated, or are contraindicated. 1, 2

Initial Disease Severity Assessment

Classify psoriasis severity using three objective measures simultaneously to determine the treatment pathway 1, 2:

• Mild disease: BSA ≤10% AND PASI ≤10 AND DLQI ≤10 1, 3
• Moderate-to-severe disease: BSA >10% OR PASI >10 AND DLQI >10 1, 2

Critical exception: Disease at high-impact sites (face, scalp, palms, soles, flexures, genitals, nails) with significant functional impairment or psychological distress qualifies as severe regardless of BSA or PASI scores 1

Step 1: Topical Therapy for Mild Psoriasis

First-line treatment: Calcipotriene/betamethasone dipropionate combination once daily for 4-8 weeks, achieving clear or almost clear status in 48-74% of patients 2

Alternative topical options when first-line fails 1, 4:

• Coal tar: Start with 0.5-1.0% crude coal tar in petroleum jelly, increase every few days to maximum 10% 1, 4
• Dithranol: Begin at 0.1-0.25% concentration, double the concentration as tolerated, using short-contact mode (15-45 minutes every 24 hours) 1, 4
• High-potency corticosteroids: Apply twice daily to thick plaques for maximum 2-4 weeks only 4

Critical monitoring requirement: Limit moderate-potency corticosteroids to maximum 100g per month with no unsupervised repeat prescriptions, and implement periods each year when alternative treatments are employed 1, 4

Step 2: Phototherapy for Moderate-to-Severe Disease

Escalate to phototherapy when: BSA exceeds 5%, inadequate response to optimized topical therapy after 8 weeks, or quality of life remains significantly impaired 2, 4, 5

Narrowband UVB phototherapy is first-line phototherapy, administered 2-3 times weekly 2, 5:

• Start at 70% of minimum phototoxic dose 1, 4
• Increase successive doses by 40% if no erythema, 20% if slight erythema, hold if more than slight erythema 1
• Treatment frequency: no more than every 48 hours 1
• Course duration: typically 8-10 weeks 1

PUVA (psoralen plus UVA) is the least toxic systemic agent and should be considered first-line systemic treatment when phototherapy alone is insufficient 1, 4

Step 3: Conventional Systemic Therapy

Escalate to systemic therapy when: Phototherapy fails, disease is extensive in elderly/infirm patients, or severe psoriatic arthropathy is present 4, 5

Methotrexate

• Dosing: Initial 15 mg weekly, maximum 25-30 mg weekly 5
• Response time: 2-6 weeks 4
• Monitoring: Baseline and regular CBC, liver function tests, serum creatinine 5
• Absolute contraindications: Pregnancy, breastfeeding, wish to father children, significant hepatic damage, anemia, leucopenia, thrombocytopenia 4

Cyclosporine

• Dosing: 2.5-5 mg/kg daily 5
• Response time: Approximately 3 weeks 5
• Monitoring: Baseline and regular serum creatinine and blood pressure 5
• Special indication: For erythrodermic psoriasis, initiate at 4 mg/kg/day immediately for rapid control, with dramatic improvement expected within 2-3 weeks 2

Acitretin

• Dosing: 25-50 mg daily 5
• Response time: As early as 3 weeks 5
• Monitoring: Baseline and regular CBC, lipids, liver function tests 5
• Particularly effective for: Pustular psoriasis 2, 5

Step 4: Biologic Therapy

Offer biologic therapy when: Methotrexate AND ciclosporin have failed, are not tolerated, or are contraindicated, AND DLQI >10 or clinically relevant depressive/anxiety symptoms are present 1

First-Line Biologic Selection

Ustekinumab: Offer as first-line biologic agent to adults 1

• Dosing: 45 mg at weeks 0,4, then every 12 weeks (<100 kg); 90 mg at weeks 0,4, then every 12 weeks (>100 kg) 1
• Dose escalation: 90 mg every 12 weeks for <100 kg patients, or 90 mg every 8 weeks for >100 kg patients if inadequate response 1

Adalimumab: Offer as first-line biologic particularly when psoriatic arthropathy is present 1

• Dosing: 80 mg week 0,40 mg week 1, then every other week 1
• Dose escalation: 40 mg weekly if inadequate response 1

Secukinumab: Consider as first-line biologic in adults with or without psoriatic arthritis 1

Etanercept:

• Adults: 25 mg twice weekly (50 mg once weekly up to 24 weeks); or 50 mg twice weekly up to 12 weeks reduced to once weekly thereafter 1
• Children ≥6 years: 0.8 mg/kg up to max 50 mg weekly 1
• Dose escalation: 50 mg twice weekly if inadequate response 1

Infliximab: Reserve for very severe disease (PASI ≥20, DLQI ≥18) or where other available biologic agents have failed or cannot be used 1

• Dosing: 5 mg/kg at weeks 0,2,6, then every 8 weeks 1
• Dose escalation: 5 mg/kg every 6 weeks if inadequate response 1
• Special indication: First-line for generalized pustular psoriasis due to rapid and often complete disease clearance 4

Response Assessment and Treatment Modification

Assess initial response at drug-appropriate time points: 10-14 weeks for etanercept, 14-16 weeks for adalimumab/infliximab, 16-28 weeks for ustekinumab 1

Continue treatment if: PASI reduction ≥75% from baseline 3

Modify treatment if: PASI improvement <50% from baseline 3

**Gray zone (PASI improvement ≥50% but <75%)**: Continue therapy if DLQI ≤5, modify if DLQI >5 3

Switch to alternative biologic when 1:

• Primary failure: Does not achieve minimum response criteria
• Secondary failure: Initially responds but subsequently loses response
• Current biologic cannot be tolerated or becomes contraindicated

When inadequate response to second or subsequent biologic 1:

• Reiterate advice about modifiable factors (obesity, poor adherence)
• Optimize adjunctive therapy (switch from oral to subcutaneous methotrexate)
• Switch to alternative biologic agent
• Consider nonbiologic approaches (inpatient topical therapy, phototherapy, standard systemic therapy)

Special Clinical Scenarios

Psoriatic arthritis: Consider biologic therapy earlier in the treatment pathway (e.g., if methotrexate alone has failed), with TNF inhibitors (infliximab, etanercept, adalimumab) recommended for severe disease 2, 5

Rapidly relapsing disease: Consider biologic therapy earlier if psoriasis relapses rapidly (>50% baseline disease severity within 3 months of completion of treatment that cannot be continued long-term) 1

Guttate psoriasis: UVB phototherapy has the most robust evidence for efficacy 2

Pregnancy: Narrowband UVB phototherapy is the preferred first-line option for moderate-to-severe psoriasis 2

Critical Medications to Avoid

Never prescribe systemic corticosteroids for psoriasis, as they precipitate erythrodermic psoriasis, generalized pustular psoriasis, or very unstable psoriasis when discontinued 1, 4, 5

Other medications that worsen psoriasis: Lithium, chloroquine, mepacrine may cause severe, potentially fatal deterioration 1, 4

Common Pitfalls

Perceived tachyphylaxis to topical corticosteroids is often due to poor patient adherence rather than true receptor down-regulation; address compliance issues before switching therapies 4

Patients who fail one topical agent may respond to another; trial alternative topical agents before escalating to systemic therapy 1

Combination therapy risks: Toxicity from any combination treatment is at least additive; exercise extreme caution and monitor carefully 1, 5