What is the recommended treatment approach for an otherwise healthy adult with extensive generalized plaque psoriasis and no contraindications such as severe liver disease, uncontrolled hypertension, active infection, or pregnancy?

Treatment of Generalized Plaque Psoriasis

For an otherwise healthy adult with extensive generalized plaque psoriasis and no contraindications, initiate treatment with PUVA photochemotherapy as first-line systemic therapy, starting at 70% of the minimum phototoxic dose (read at 72 hours) with successive doses increased by 40% if no erythema develops, as it is the least toxic systemic agent with expected response within four weeks. 1, 2

First-Line Treatment Approach

Photochemotherapy (PUVA)

• PUVA is the systemic treatment of first choice for extensive chronic plaque psoriasis, considered the least toxic of all systemic agents 1, 2
• Start with 70% of minimum phototoxic dose (determined at 72 hours), increasing successive doses by 40% of the preceding dose if no erythema present 1, 2
• Expected response time is four weeks 1
• Requires pretreatment liver function tests and eye examination 1
• Mandatory precautions include contraception, ultraviolet A eye protection, and shielding of genitalia unless specifically treating those areas 1

Alternative: Narrowband UVB

• Narrowband UVB is a primary option for moderate-to-severe psoriasis and may be preferred if PUVA contraindications exist 2, 3
• This is the most commonly prescribed light therapy for plaque psoriasis 3

Second-Line Systemic Options

If phototherapy fails or is contraindicated, proceed with traditional systemic agents:

Methotrexate

• Especially useful for extensive chronic plaque psoriasis in elderly or infirm patients 1, 2
• Fastest response time of systemic agents: two weeks 1
• Initial dose should not exceed 0.2 mg/kg body weight, with gradual increases if laboratory results remain normal 1
• Requires pretreatment full blood count, liver function tests, and serum creatinine 1
• Mandatory contraception for both men and women; avoid in those wishing to father children 1

Cyclosporine

• Provides most rapid onset of action at 3-5 mg/kg/day for moderate-to-severe psoriasis requiring rapid response 2
• Expected response time: three weeks 1
• Absolutely contraindicated with abnormal renal function or uncontrolled hypertension 1
• Requires blood pressure and serum creatinine monitoring 1

Oral Retinoids (Acitretin)

• Very effective in acral or generalized pustular forms 1, 2
• Slowest response time: six weeks 1
• Absolutely contraindicated in women of childbearing potential due to 3-year post-dosing pregnancy moratorium 1
• Causes dose-dependent elevations in liver enzymes (up to 16%) and triglycerides (25-50%) 1

Third-Line: Biologic Therapy

TNF-α Inhibitors

• Biologics are recommended as an option for first-line treatment of moderate to severe plaque psoriasis due to efficacy and acceptable safety profiles 3
• Adalimumab is FDA-approved for moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy when other systemic therapies are medically less appropriate 4
• Infliximab demonstrates rapid and often complete disease clearance 2
• Etanercept, adalimumab, certolizumab, and infliximab are all highly effective options 3, 5

IL-12/23 and IL-17 Inhibitors

• Ustekinumab (p40 subunit of IL-12/IL-23) offers similar efficacy and safety to anti-TNF agents 3, 5
• IL-17 inhibitors (secukinumab, ixekizumab, brodalumab) and IL-23 inhibitors (guselkumab, risankizumab) are additional options 3

Adjunctive Topical Therapy

Regardless of systemic treatment choice, add topical therapy for focal resistant lesions:

• Fixed-combination calcipotriene 0.005% and betamethasone dipropionate 0.064% has demonstrated efficacy even in severe psoriasis 6
• High-potency topical corticosteroids (clobetasol propionate 0.05% or betamethasone dipropionate 0.05%) twice daily for maximum 2-4 weeks to thick plaques 2
• Combination products simplify regimens and improve compliance 2, 6

Critical Pitfalls to Avoid

• Never use systemic corticosteroids as they can cause severe, potentially fatal deterioration upon discontinuation and may trigger erythrodermic or generalized pustular psoriasis 2, 7, 8
• Avoid lithium, chloroquine, and mepacrine as they are associated with severe, potentially fatal psoriasis deterioration 2, 7
• All systemic agents are absolutely contraindicated in pregnancy and require strict contraception counseling before initiation 1, 7

Monitoring Requirements

• PUVA: Contraception, UV-A eye protection, genital shielding 1
• Methotrexate: Full blood count, liver function tests; avoid interacting drugs 1
• Cyclosporine: Blood pressure, serum creatinine 1
• Retinoids: Liver function tests, fasting serum lipids 1
• Biologics: Screen for tuberculosis, hepatitis B, fungal infections before initiation 8