What is the recommended treatment approach for chronic plaque psoriasis based on disease severity?

Treatment Approach for Chronic Plaque Psoriasis Based on Disease Severity

Treatment for chronic plaque psoriasis should be stratified by disease severity: mild disease (BSA ≤10%, PASI ≤10, DLQI ≤10) is managed with topical corticosteroids combined with vitamin D analogues, while moderate-to-severe disease (BSA >10% or PASI >10 and DLQI >10) requires escalation to phototherapy or systemic agents, with biologic therapy reserved for patients who have failed, cannot tolerate, or have contraindications to both methotrexate and cyclosporine. 1

Severity Classification and Assessment

Mild disease is defined as all three criteria met: BSA ≤10% AND PASI ≤10 AND DLQI ≤10. 1

Moderate-to-severe disease requires BSA >10% OR PASI >10 AND DLQI >10. 1

High-impact sites (face, scalp, palms, soles, flexures, genitals, nails) with functional or psychological impairment are classified as severe regardless of BSA or PASI scores. 1

The assessment must include both objective disease extent (PASI score or BSA) and quality of life impact (DLQI). 2 A PASI score ≥10 correlates with indicators of severe disease such as need for hospital admission or systemic therapy. 2

Treatment Algorithm for Mild Chronic Plaque Psoriasis

First-Line Topical Therapy

High-potency corticosteroids combined with calcipotriol achieve 58-92% clearance rates and should be initiated as first-line therapy. 3

For body plaques:

• Apply clobetasol propionate 0.05% or betamethasone dipropionate 0.05% twice daily for maximum 2-4 weeks. 3
• Combine with calcipotriol (vitamin D analogue) for synergistic effect superior to either agent alone. 3
• Fixed-combination calcipotriene/betamethasone dipropionate gel or foam provides convenient once-daily application for 4-12 weeks. 3

For sensitive areas (face, genitals, intertriginous regions):

• Use low-potency corticosteroids or topical calcineurin inhibitors to minimize atrophy risk. 3

For scalp involvement:

• Apply clobetasol propionate 0.05% shampoo twice weekly, providing rapid symptom relief within 3-4 weeks. 3

Alternative Topical Agents

If first-line therapy fails, trial alternative topical agents before escalating to systemic therapy, as patients who fail one topical agent may respond to another. 2, 4

Coal tar:

• Start with 0.5-1.0% crude coal tar in petroleum jelly and increase concentration every few days to maximum 10%. 2, 1
• Cruder tar extracts are messier but more effective than refined products. 2

Dithranol (anthralin):

• Start at 0.1-0.25% concentration and increase in doubling concentrations as tolerated. 2, 1
• Use short contact mode (15-45 minutes every 24 hours) to minimize irritation and staining. 1
• Exercise great care on sensitive sites (face, flexures, genitalia). 2

Critical Safety Monitoring for Topical Corticosteroids

• Implement mandatory clinical review every 4 weeks with no unsupervised repeat prescriptions. 2, 3
• Limit moderate-potency corticosteroid use to maximum 100g per month. 2, 1
• Require dermatological supervision for very potent (grade I) or potent (grade II) preparations. 2
• Implement periods each year when alternative treatments are employed to prevent tachyphylaxis. 1

Common pitfall: Perceived "tachyphylaxis" to topical corticosteroids is usually due to poor patient adherence rather than true receptor down-regulation; address compliance issues before switching therapies. 1, 4

Treatment Algorithm for Moderate-to-Severe Chronic Plaque Psoriasis

Indications for Escalation to Systemic Therapy

Escalate when:

• BSA involvement exceeds 5% with inadequate response to optimized topical therapy after 8 weeks. 3
• Disease has been severe (PASI ≥10 or BSA ≥10% and DLQI >10) for 6 months and is resistant to topical treatment. 2
• Signs of erythrodermic or pustular psoriasis develop. 3

First-Line Systemic Therapy: Phototherapy

Narrowband UVB:

• Initiate at approximately 70% of the patient's minimum phototoxic dose. 1
• Increase subsequent doses by 40% if no erythema occurs, by 20% if only slight erythema appears, and hold if erythema exceeds slight. 1
• Administer 2-3 times per week, never more frequently than every 48 hours, for a typical course of 8-10 weeks. 1

PUVA (psoralen + UVA):

• Recommended as first-line systemic option when phototherapy alone is insufficient, given its relatively low toxicity among systemic agents. 1, 4
• Start at 70% of minimum phototoxic dose. 1
• Increase successive doses by 40% of preceding dose if no erythema develops. 1
• Expect response within 4 weeks. 4

Conventional Systemic Agents

Consider when phototherapy is insufficient or impractical:

Methotrexate:

• Response time: 2 weeks. 1
• Absolute contraindications: pregnancy, breastfeeding, wish to father children, significant hepatic damage, anemia, leucopenia, thrombocytopenia. 1, 3

Cyclosporine:

• Response time: 3 weeks. 1
• Contraindicated with abnormal renal function, uncontrolled hypertension, or malignancy. 3

Acitretin:

• Response time: 6 weeks. 1
• Requires contraception with absolute contraindication for pregnancy or wish to conceive within 2 years of stopping treatment. 3

Eligibility Criteria for Biologic Therapy

Biologic therapy should be initiated when:

• Severe disease is present (PASI ≥10 or BSA ≥10% and DLQI >10) for 6 months. 2
• AND the patient fulfills at least one of the following: 2
  • Developed or at higher than average risk of developing clinically important drug-related toxicity from standard therapy
  • Intolerant to or cannot receive standard systemic therapy (methotrexate, cyclosporine, PUVA)
  • Unresponsive to standard therapy
  • Disease controlled only by repeated inpatient management
  • Significant coexistent unrelated comorbidity

For infliximab specifically: Very severe disease (PASI ≥20, DLQI ≥18) where cyclosporine, methotrexate, or PUVA has failed or cannot be used. 2

First-Line Biologic Selection and Dosing

Ustekinumab (Preferred First-Line)

Dosing:

• Patients <100 kg: 45 mg at weeks 0 and 4, then every 12 weeks. 1
• Patients ≥100 kg: 90 mg at weeks 0 and 4, then every 12 weeks. 1

Dose escalation if inadequate response:

• <100 kg patients: increase to 90 mg every 12 weeks. 1
• ≥100 kg patients: increase to 90 mg every 8 weeks. 1

Response assessment: 16-28 weeks after initiation. 1

Efficacy: 67-72% of patients achieve PASI 75 by week 12, with maximal efficacy between weeks 20-24. 2

Adalimumab (Especially with Psoriatic Arthritis)

Dosing:

• 80 mg at week 0,40 mg at week 1, then 40 mg every other week. 2, 1

Dose escalation if inadequate response:

• Increase to 40 mg weekly (unlicensed). 2, 1

Response assessment: 14-16 weeks after initiation. 1

Efficacy: 80% of patients achieve PASI 75 by week 16. 2

Combination therapy: May be combined with methotrexate to reduce immunogenicity and increase effectiveness, particularly for psoriatic arthritis. 2

Etanercept

Dosing for adults:

• 25 mg twice weekly (or 50 mg once weekly) for up to 24 weeks. 2, 1
• May intensify to 50 mg twice weekly for ≤12 weeks, then reduce to once weekly. 1

Dosing for children ≥6 years:

• 0.8 mg/kg (maximum 50 mg) weekly. 2, 1

Response assessment: 10-14 weeks after initiation. 1

Dose equivalence: 25 mg twice weekly is equivalent to 50 mg once weekly in terms of efficacy. 2

Infliximab (Reserved for Very Severe Disease)

Indication: Very severe plaque psoriasis (PASI ≥20, DLQI ≥18) or when other biologics have failed or are unsuitable. 2, 1

Dosing:

• 5 mg/kg at weeks 0,2,6, then every 8 weeks. 2, 1

Dose escalation if inadequate response:

• Increase to 5 mg/kg every 6 weeks. 1

Response assessment: 14 weeks after initiation (10 weeks per NICE criteria). 2

Efficacy: 79% achieve PASI 75 by week 10, with rapid onset evident within 2 weeks. 2 Response maintained with 74% and 53% achieving PASI 75 at 6 and 12 months, respectively. 2

Special indication: First-line biologic for generalized pustular psoriasis due to rapid and often complete disease clearance. 3

Response Assessment and Treatment Modification

Continuation Criteria

Maintain therapy when:

• PASI reduction ≥75% from baseline. 1

Modification Criteria

Switch or adjust therapy if:

• PASI improvement <50% from baseline. 1

In the "gray zone" (PASI ≥50% but <75%):

• Continue if DLQI ≤5. 1
• Modify if DLQI >5. 1

Switching Biologics

Indications for switching:

• Primary failure (no minimum response). 1
• Secondary failure (initial response lost). 1
• Intolerance or emerging contraindication. 1

If inadequate response to second or later biologic:

• Re-address modifiable factors (obesity, adherence). 1
• Optimize adjunctive therapy (switch oral methotrexate to subcutaneous). 1
• Switch to alternative biologic. 1
• Consider non-biologic options (inpatient topical therapy, phototherapy, conventional systemic agents). 1

Rapidly Relapsing Disease

When disease relapses to >50% of baseline severity within 3 months after a treatment course that cannot be continued long-term, earlier initiation of biologic therapy is advised. 1

Critical Medications to Absolutely Avoid

Systemic corticosteroids are absolutely contraindicated because abrupt withdrawal can precipitate erythrodermic, generalized pustular, or highly unstable psoriasis. 2, 1, 3

Lithium, chloroquine, and mepacrine may cause severe, potentially fatal exacerbations of psoriasis and should be avoided. 2, 1, 3

Other medications that may worsen psoriasis:

• Alcohol. 2, 3
• Beta-blockers (in some patients). 2, 3
• Non-steroidal anti-inflammatory agents (in some patients). 2, 3

Salicylic acid with calcipotriene: Acidic pH inactivates calcipotriene and reduces effectiveness. 3

Common Pitfalls and Practical Considerations

Topical therapy failure: Failure of one topical agent does not predict failure of another; trial alternative topicals before escalating to systemic therapy. 2, 1, 4

Corticosteroid "tachyphylaxis": Usually represents poor adherence rather than true receptor down-regulation; address compliance before switching. 1, 4

Dermal atrophy monitoring: Only 25 trials have assessed clinical cutaneous dermal atrophy; clinical measurements are insensitive and detect only the most severe cases. 5 Long-term safety data remain inadequate. 5, 6

PASI limitations: PASI is less precise when regional area of involvement is <10% of BSA for a specific anatomical region, as the area score defaults to '1' for 0-10% involvement. 7 For localized disease involving high-impact sites (genitalia, hands, feet, head and neck), highly significant functional and/or psychosocial morbidity may exist with PASI <10. 2

Supervision requirements: Most patients with stable chronic plaque psoriasis should be cared for by general practitioners, but patients with severe psoriasis requiring systemic agents should be under continuing supervision of a consultant dermatologist due to potential toxicity. 2