Psoriasis

1. 1. Zhou X, Chen Y, Cui L, et al: Advances in the pathogenesis of psoriasis: From keratinocyte perspective. Cell Death Dis 13(1):81, 2022. doi: 10.1038/s41419-022-04523-3

Corticosteroids are usually used topically but may be injected into small or recalcitrant lesions. (CAUTION: Systemic corticosteroids may precipitate exacerbations or development of pustular psoriasis and should not be used to treat psoriasis.) Topical corticosteroids are used twice daily. Corticosteroids are most effective when used overnight under occlusive polyethylene coverings or incorporated into tape; a corticosteroid cream is applied without occlusion during the day. Corticosteroid potency is selected according to the extent of involvement.

Vitamin D3 analogs

Calcineurin inhibitors

is a topical retinoid. It is less effective than corticosteroids as monotherapy but is a useful adjunct because of its keratolytic effect. It is typically used on thicker psoriasis plaques that may appear on the trunk and extremities but also may be used on the face.

is a topical phosphodiesterase-4 (PDE-4) inhibitor. It is particularly useful as a corticosteroid-sparing treatment for facial and intertriginous areas (eg, buttocks, groin, axillae).

is a topical aryl hydrocarbon receptor (AhR) agonist. It is also useful as a corticosteroid-sparing therapy on facial and intertriginous areas.

• Emollients include emollient creams, ointments, petrolatum, paraffin, and even hydrogenated vegetable (cooking) oils. They reduce scaling and are most effective when applied twice daily and immediately after bathing. Lesions may appear redder as scaling decreases or becomes more transparent. Emollients are safe and should generally be used as an adjunct for mild to moderate plaque psoriasis.

• is a keratolytic that softens scales, facilitates their removal, and increases absorption of other topical agents. It is especially useful as a component of scalp treatments; scalp scale can be quite thick.

• preparations are anti-inflammatory and decrease keratinocyte hyperproliferation via an unknown mechanism. Ointments or solutions are typically applied at night and washed off in the morning. Coal tar products can be used in combination with topical corticosteroids or with exposure to natural or artificial broad-band UVB light (280 to 320 nm) in slowly increasing increments (Goeckerman regimen). Shampoos should be left in for 5 to 10 minutes and then rinsed out.

• is a topical antiproliferative, anti-inflammatory agent. Its mechanism of action is unknown. Effective dose is 0.1% cream or ointment increased to 1% as tolerated. Anthralin may be irritating and should be used with caution in intertriginous areas; it also stains. Irritation and staining can be avoided by washing off the anthralin 20 to 30 minutes after application. Using a liposome-encapsulated preparation may also avoid some disadvantages of anthralin.

UV light therapy is typically used in patients with extensive psoriasis; however, its use is declining because of the availability of various effective systemic therapies. The mechanism of action is unknown, although UVB light reduces DNA synthesis and can induce mild systemic immunosuppression. In psoralen plus ultraviolet A (PUVA), oral methoxypsoralen, a photosensitizer, is followed by exposure to long-wave UVA light (330 to 360 nm). PUVA has an antiproliferative effect and also helps to normalize keratinocyte differentiation. Doses of light are started low and increased as tolerated. Severe burns can result if the dose of medication or UVA is too high.

Although the treatment is less messy than topical treatments and may produce remissions lasting several months, repeated treatments may increase the incidence of UV-induced skin cancer and melanoma. Less UV light is required when used with oral retinoids (the so-called re-PUVA regimen). Narrowband UVB light (311 to 312 nm), which is used without psoralens, is similar in effectiveness to PUVA. Excimer laser therapy is a type of phototherapy using a 308-nm laser directed at focal psoriatic plaques.

taken orally is an effective treatment for severe disabling psoriasis, especially severe psoriatic arthritis or widespread erythrodermic or pustular psoriasis unresponsive to topical agents or UV light therapy (narrowband UVB) or PUVA. Methotrexate seems to interfere with the rapid proliferation of epidermal cells. Hematologic, renal, and hepatic function should be monitored. Dosage regimens vary, so only physicians experienced in its use for psoriasis should undertake methotrexate therapy.

can be used for severe psoriasis. It should be limited to courses of several months (rarely, up to 1 year) and alternated with other therapies. Its effect on the kidneys and potential long-term effects on the immune system preclude more liberal use.

Systemic retinoidsisotretinoinisotretinoin, but the agent is not retained in the body beyond 1 month. Long-term treatment may cause diffuse idiopathic skeletal hyperostosis (DISH).

Several classes of biologics (therapeutic monoclonal antibodies) have shown efficacy for the treatment of moderate to severe plaque psoriasis (1, 2):

• TNF inhibitors:

• Interleukin (IL)-23 inhibitors:

• IL-17 inhibitors:

a PDE-4 inhibitor, is an oral small-molecule medication for plaque psoriasis; however, postmarketing data suggest it is less effective than biologics (3).

is an oral small-molecule agent that inhibits tyrosine kinase 2 (part of the Janus kinase family) and has shown efficacy for treatment of psoriasis (4, 56); however, more studies are needed before it is routinely used for this indication.

is an IL-36 inhibitor that may be used to treat generalized pustular psoriasis.

Biosimilar medications are being developed and used for various therapeutic monoclonal antibodies as their patents expire (7). These medications have very similar efficacies and toxicities to reference products; slight differences in components are not clinically meaningful.

Other immunosuppressantsprogressive multifocal leukoencephalopathy.

Choice of specific agents and combinations requires close cooperation with the patient, always keeping in mind the untoward effects of the treatments. There is no single ideal combination or sequence of agents, but treatment should be kept as simple as possible. Monotherapy is preferred, but combination therapy is the norm. First-line treatment for psoriasis includes topical corticosteroids and topical vitamin D3 analogs (either as monotherapy or in combination).

Mild plaque psoriasis

Moderate to severe plaque psoriasis should be treated with topical agents and either phototherapy or systemic agents. Immunosuppressants are used for moderate to severe disease unresponsive to other agents.

Scalp plaques

Severe cases of scalp psoriasis may need to be treated with systemic immunosuppressants (eg, biologics, small molecules).

Special treatment needs for subtypes of psoriasis are described above.

For psoriatic arthritis

(See also the American Academy of Dermatology's clinical guideline for psoriasis.)

1. 1. Sbidian E, Chaimani A, Garcia-Doval I, et al: Systemic pharmacological treatments for chronic plaque psoriasis: A network meta-analysis. Cochrane Database Syst Rev 12(12):CD011535, 2017. doi: 10.1002/14651858.CD011535.pub2

2. 2. Armstrong AW, Read C: Pathophysiology, clinical presentation, and treatment of psoriasis: A review. JAMA 323(19):1945–1960, 2020. doi: 10.1001/jama.2020.4006

3. 3. Armstrong AW, Puig L, Joshi A, et al: Comparison of Biologics and Oral Treatments for Plaque Psoriasis: A Meta-analysis. JAMA Dermatol 156(3):258–269, 2020. doi: 10.1001/jamadermatol.2019.4029

4. 4. Armstrong AW, Gooderham M, Warren RB, et al: Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol 88(1):29–39, 2023. doi: 10.1016/j.jaad.2022.07.002

5. 5. Strober B, Thaçi D, Sofen H, et al: Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol 88(1):40–51, 2023. doi: 10.1016/j.jaad.2022.08.061

6. 6. Bachelez H, van de Kerkhof PC, Strohal R, et al: Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: A phase 3 randomised non-inferiority trial. Lancet 386(9993):552-561, 2015. doi: 10.1016/S0140-6736(14)62113-9

7. 7. Ruda RC, Kelly KA, Feldman SR: Real-world outcomes following switching from anti-TNF reference products to biosimilars for the treatment of psoriasis. J Dermatolog Treat 34(1):2140569, 2023. doi: 10.1080/09546634.2022.2140569