Treatment Options for Psoriasis
Disease Severity Classification and Treatment Selection
For mild psoriasis (<5% body surface area and asymptomatic), start with combination topical therapy using calcipotriene/betamethasone dipropionate once daily for 4-8 weeks, which achieves clear or almost clear status in 48-74% of patients. 1
However, patients with symptomatic psoriasis (pain, bleeding, itching) should be considered for systemic or phototherapy regardless of body surface area involvement. 1, 2
Defining Moderate-to-Severe Disease
Patients requiring systemic therapy meet at least one of these criteria: 1
- ≥5% body surface area involvement
- Symptomatic disease (pain, bleeding, itching)
- More than minimal impact on quality of life
- Inadequate response to topical therapy
- Varying degrees of incapacity and disability
First-Line Topical Therapy for Mild Psoriasis
Standard Body/Extremity Treatment
Apply calcipotriene/betamethasone dipropionate combination product once daily for 4-8 weeks as initial therapy. 1, 3
For thick, chronic plaques requiring more aggressive treatment: 1
- Use ultrahigh-potency (class 1) corticosteroids: clobetasol propionate 0.05% or halobetasol propionate 0.05%
- Maximum continuous use: 4 weeks to prevent skin atrophy, striae, telangiectasia, and HPA axis suppression
- Long-term use beyond 12 weeks requires careful physician supervision
Site-Specific Modifications
For facial and intertriginous areas, use low-potency corticosteroids or calcitriol ointment to prevent skin atrophy. 1, 3 The warm, moist environment of flexural areas increases medication penetration but significantly increases risk of atrophy with potent corticosteroids. 1 Tacrolimus is first-line for intertriginous psoriasis due to its efficacy without causing skin atrophy. 1
For scalp psoriasis, use calcipotriene foam or calcipotriene plus betamethasone dipropionate gel for 4-12 weeks. 1, 3
For nail psoriasis, apply calcipotriene combined with betamethasone dipropionate to reduce nail thickness, hyperkeratosis, and onycholysis. 1 Note that topical agents have limited efficacy for severe nail disease due to poor nail matrix penetration. 1
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. 1
Maximum vitamin D analogue use: 100g per week to avoid hypercalcemia. 1, 3
Critical Pitfalls to Avoid
Never combine salicylic acid with calcipotriene simultaneously—the acidic pH inactivates calcipotriene and eliminates its effectiveness. 1, 3
Never use systemic corticosteroids in psoriasis as they cause disease flare during taper. 2, 3
Do not use high-potency corticosteroids on face or flexures—use low-potency agents or tacrolimus instead. 1
Phototherapy for Moderate-to-Severe Psoriasis
UV therapy remains an important therapeutic option for patients with moderate to severe disease, particularly narrowband UVB, which is first-line for pregnant women with moderate to severe psoriasis. 4
Phototherapy is effective in the majority of patients, cost-effective, and lacks the systemic toxicities and immunosuppressive properties of systemic and biologic treatments. 4 However, treatment typically requires two to three times weekly visits, which can lead to work-related difficulties and impact quality of life. 4
Combination Strategies with Phototherapy
Combining methotrexate with BB-UVB, NB-UVB, or PUVA produces a synergistic effect, allowing enhanced efficacy, reduced treatment duration, and lower cumulative UV doses. 4
Acitretin combined with NB-UVB or PUVA increases response rates and decreases total number of treatments, thus reducing cumulative UV exposure. 4 Additionally, oral retinoids suppress the development of cutaneous squamous cell carcinoma in patients treated with PUVA. 4
Apply vitamin D analogues after phototherapy to avoid inactivation. 2
Systemic Non-Biologic Therapies for Moderate-to-Severe Psoriasis
Cyclosporine: Rapid-Onset Option
For patients requiring rapid response, particularly those with erythrodermic psoriasis who are systemically ill, cyclosporine 3-5 mg/kg/day is the logical choice due to rapid and impressive onset of action. 4, 1
Generally only a short 3-4 month "interventional" course of cyclosporine treatment is indicated. 4, 1 With careful monitoring, the majority of patients will tolerate this course well and respond appropriately. 4
Cyclosporine requires monitoring of blood pressure and renal function. 3
Methotrexate
Methotrexate is a competitive inhibitor of dihydrofolate reductase, FDA-approved since 1972 for psoriasis treatment. 1 It may have effects on spermatogenesis, so conception should be avoided in male patients until 3 months after discontinuation. 4
Methotrexate given subcutaneously bypasses the liver and may be reasonable, but the possible need to upwardly titrate the initial dose may limit its usefulness in patients requiring rapid response. 4
Methotrexate requires regular monitoring of complete blood count, liver function tests, and serum creatinine. 3
Acitretin
Acitretin decreases keratinocyte hyperproliferation and restores normal epidermal differentiation. 4, 1 However, it has a slower onset of action and may not be sufficiently predictable to improve disease in a rapid enough time frame in systemically ill patients. 4
Acitretin cannot be used in women of childbearing potential due to teratogenicity. 4, 1
Biologic Therapies for Moderate-to-Severe Psoriasis
Biologics are recommended as an option for first-line treatment of moderate to severe plaque psoriasis because of their efficacy and acceptable safety profiles. 5
TNF-α Inhibitors
TNF inhibitors include etanercept, adalimumab, certolizumab, and infliximab. 4, 5 These are also approved for psoriatic arthritis. 5
Adalimumab (HUMIRA) is FDA-approved for treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. 6
IL-17 Inhibitors
IL-17 inhibitors include secukinumab, ixekizumab, bimekizumab, and brodalumab. 5
IL-12/23 and IL-23 Inhibitors
Ustekinumab inhibits the p40 subunit of IL-12 and IL-23. 4, 5 IL-23 p19 subunit inhibitors include guselkumab, tildrakizumab, risankizumab, and mirikizumab. 5
Biologic Safety Considerations
SERIOUS INFECTIONS: Increased risk of serious infections leading to hospitalization or death, including tuberculosis, bacterial sepsis, invasive fungal infections, and infections due to other opportunistic pathogens. 6
Perform test for latent TB; if positive, start treatment for TB prior to starting adalimumab. Monitor all patients for active TB during treatment, even if initial latent TB test is negative. 6
MALIGNANCY: Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers. 6
Combination Strategies to Enhance Biologic Efficacy
Adding ultrahigh-potency (class 1) topical corticosteroid to standard dose etanercept for 12 weeks enhances efficacy (Level I evidence). 1
Adding calcipotriene/betamethasone to standard dose adalimumab for 16 weeks accelerates clearance of psoriatic plaques. 1
Adding topical calcipotriene to standard dose methotrexate therapy is recommended for moderate to severe psoriasis (Level I evidence). 1
All topical corticosteroids can be used in combination with any biologics. 1
Special Considerations for Erythrodermic Psoriasis
For erythrodermic psoriasis, oral cyclosporine 3-5 mg/kg/day is the logical choice for systemically ill patients due to rapid and impressive onset of action. 1
Initial management for all patients with erythrodermic psoriasis: 4
- Appropriate wet dressings with mid-potency topical steroids
- Attention to fluid balance with control of ankle edema
- Rule out sepsis with blood cultures
Base therapy for erythrodermic psoriasis on short-term efficacy rather than long-term considerations, and transition to maintenance therapy after acute illness improves. 1
Other systemic choices include acitretin, methotrexate, and TNF-α inhibitors, though these may not provide sufficiently rapid response in systemically ill patients. 4