Treatment Options for Psoriasis

Disease Severity Classification

Treatment selection for psoriasis depends primarily on disease severity, with mild disease (<5% body surface area and asymptomatic) treated with topical therapy alone, while moderate-to-severe disease (≥5% BSA) or any symptomatic psoriasis (pain, bleeding, itching) requires systemic therapy or phototherapy regardless of body surface area involvement. 1, 2

Mild Psoriasis: Topical Therapy

First-Line Topical Treatment

Start with calcipotriene/betamethasone dipropionate combination product applied once daily for 4-8 weeks, which achieves clear or almost clear status in 48-74% of patients. 1, 2

This combination represents the most effective topical approach based on current evidence 1
For trunk and extremities, use high-potency corticosteroids such as clobetasol propionate 0.05% or halobetasol propionate 0.05% 1
Maximum vitamin D analogue use is 100g per week to avoid hypercalcemia 1, 2

Site-Specific Modifications

For facial/intertriginous areas: Use low-potency corticosteroids or calcitriol ointment to avoid skin atrophy 2
For scalp psoriasis: Apply calcipotriene foam or calcipotriene plus betamethasone dipropionate gel for 4-12 weeks 2
For nail psoriasis: Use calcipotriene combined with betamethasone dipropionate, though efficacy is limited due to poor nail matrix penetration 2

Maintenance Strategy After Initial Control

Transition to weekend-only high-potency corticosteroid application (twice daily on weekends) with weekday vitamin D analogue therapy (twice daily on weekdays) to minimize corticosteroid exposure while maintaining efficacy. 2

Limit continuous high-potency corticosteroid use to maximum 4 weeks to prevent skin atrophy, striae, telangiectasia, and HPA axis suppression 2
Never use high-potency corticosteroids on face or flexures—use low-potency agents instead 2

Combination Strategies to Enhance Efficacy

Tazarotene plus medium/high-potency corticosteroid: Combine tazarotene 0.1% gel once daily with medium- or high-potency corticosteroid for 8-16 weeks to increase efficacy while reducing local adverse events and prolonging remission 1, 2
Apply tazarotene sparingly to lesions only, avoiding perilesional skin 2

Critical Pitfall to Avoid

Never combine salicylic acid with calcipotriene simultaneously—the acidic pH inactivates calcipotriene and eliminates its effectiveness. 2

Moderate-to-Severe Psoriasis: Phototherapy

First-Line Phototherapy

Narrowband UVB phototherapy is recommended as first-line systemic treatment for patients with ≥5% BSA or inadequate response to topicals. 1

UV therapy is effective in the majority of patients, is cost-effective, and lacks the systemic toxicities and immunosuppressive properties of systemic and biologic treatments 3
Narrowband UVB is particularly useful for treatment of psoriasis in pregnancy and should be considered first-line for pregnant women with moderate to severe disease 3
Phototherapy options include narrowband UVB, oral PUVA, and bath PUVA with or without acitretin 1

Phototherapy Combinations

Methotrexate with phototherapy: Combining MTX with BB-UVB, NB-UVB, or PUVA produces a synergistic effect, allowing enhanced efficacy, reduced treatment duration, and lower cumulative UV doses 3
Acitretin with phototherapy: Acitretin is effective in combination with NB-UVB or PUVA, increasing response rates and decreasing total number of treatments 3
Oral retinoids suppress the development of cutaneous SCC in patients treated with PUVA, making this an attractive combination therapy 3

Important Consideration

Treatment requires two to three times weekly visits, which can lead to work-related difficulties and impinge on quality of life 3
Apply vitamin D analogues after phototherapy to avoid inactivation 2

Moderate-to-Severe Psoriasis: Traditional Systemic Agents

Methotrexate

Methotrexate inhibits dihydrofolate reductase and increases endogenous adenosine with anti-inflammatory effects 1
Requires regular monitoring of complete blood count, liver function tests, and serum creatinine 1
MTX given subcutaneously bypasses the liver and may be reasonable, though possible need to upwardly titrate the initial dose may limit usefulness in patients requiring rapid response 3
Conception should be avoided in male patients until 3 months after discontinuation of MTX due to effects on spermatogenesis 3

Cyclosporine

For patients requiring rapid disease control, particularly erythrodermic psoriasis, use cyclosporine 3-5 mg/kg/day in short 3-4 month "interventional" courses. 1, 2

Cyclosporine provides rapid and impressive onset of action for systemically ill patients 3, 2
With careful monitoring, the majority of patients will tolerate this course well and respond appropriately 3
After acute illness improves, transition to maintenance therapy 2

Acitretin

Acitretin decreases keratinocyte hyperproliferation and restores normal epidermal differentiation 2
Cannot be used in women of childbearing potential due to teratogenicity 3, 2
Has slower onset of action compared to cyclosporine, which may not be sufficiently rapid for patients with erythrodermic psoriasis who are systemically ill 3

Moderate-to-Severe Psoriasis: Biologic Therapies

Biologics are recommended as an option for first-line treatment of moderate to severe plaque psoriasis due to their efficacy and acceptable safety profiles. 1, 4

TNF-α Inhibitors

Include etanercept, adalimumab, certolizumab, and infliximab 4
Adalimumab dosing for plaque psoriasis: 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose 5
Also approved for treatment of psoriatic arthritis 4

IL-17 Inhibitors

Include secukinumab, ixekizumab, bimekizumab, and brodalumab 4
Also approved for treatment of psoriatic arthritis 4

IL-23 Inhibitors (Newer Generation)

IL-23 inhibitors (guselkumab, tildrakizumab, risankizumab, and mirikizumab) represent newer generation biologics with favorable efficacy profiles 1
Target the p19 subunit of IL-23 4

IL-12/23 Inhibitor

Ustekinumab inhibits the p40 subunit of IL-12 and IL-23 4

Critical Safety Warnings for Biologics

Increased risk of serious infections leading to hospitalization or death, including tuberculosis, bacterial sepsis, invasive fungal infections, and infections due to opportunistic pathogens. 5

Perform test for latent TB; if positive, start treatment for TB prior to starting biologic therapy 5
Monitor all patients for active TB during treatment, even if initial latent TB test is negative 5
Discontinue biologic if patient develops serious infection or sepsis 5
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers 5

Combination Strategies with Biologics

Adding ultrahigh-potency topical corticosteroid to biologic therapy for 12 weeks accelerates clearance and improves outcomes. 1, 2

Adding ultrahigh-potency (class 1) topical corticosteroid to standard dose etanercept for 12 weeks is recommended with Level I evidence 2
Adding calcipotriene/betamethasone to standard dose adalimumab for 16 weeks accelerates clearance of psoriatic plaques 2
Adding topical calcipotriene to standard dose methotrexate therapy is recommended with Level I evidence 2
All topical corticosteroids can be used in combination with any biologics 2

Special Considerations: Erythrodermic Psoriasis

Initial Management for All Patients

Apply appropriate wet dressings with mid-potency topical steroids 3
Attention to fluid balance with control of ankle edema 3
Rule out sepsis with blood cultures 3

Treatment Algorithm for Erythrodermic Psoriasis

First-line options (in alphabetical order): 3

Acitretin
Biologic agents (Infliximab, Adalimumab, Ustekinumab)
Cyclosporine 3-5 mg/kg/day for approximately 3-4 month course (preferred for rapid response)
Methotrexate

Second-line options (in alphabetical order): 3

Acitretin and cyclosporine
Acitretin and TNF blocker
Cyclosporine and methotrexate
Etanercept
Methotrexate and TNF blocker
Base therapy on short-term efficacy rather than long-term considerations, then transition to maintenance therapy after acute illness improves 2

Psoriatic Arthritis Treatment

Mild Peripheral Arthritis

NSAIDs for control of joint symptoms 1
Intra-articular glucocorticoid injections may be given judiciously, avoiding injection through psoriatic plaques 1

Moderate or Severe Disease

DMARDs such as sulfasalazine, leflunomide, methotrexate, or cyclosporine are recommended 1
TNF inhibitors are considered for failure of at least one DMARD 1
TNF inhibitors like adalimumab are effective for both skin and joint symptoms 6

Drugs That Worsen Psoriasis

Avoid or use with extreme caution: 1

Lithium, chloroquine, and mepacrine: May cause severe deterioration
Beta-blockers, NSAIDs, and alcohol: May precipitate or worsen psoriasis in some patients
Systemic corticosteroids: Should generally be avoided in psoriasis as they can cause disease flare during taper 2

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