Psoriasis

Pathophysiology references

1. 1. Armstrong AW, Read C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA. 2020;323(19):1945-1960. doi:10.1001/jama.2020.4006

2. 2. 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

3. 3. Grželj J, Sollner Dolenc M. The role of xenobiotics in triggering psoriasis. Arch Toxicol. 2020;94(12):3959-3982. doi:10.1007/s00204-020-02870-8

5. 4. Snast I, Reiter O, Atzmony L, et al. Psychological stress and psoriasis: a systematic review and meta-analysis. Br J Dermatol. 2018;178(5):1044-1055. doi:10.1111/bjd.16116

6. 5. Griffiths CEM, Armstrong AW, Gudjonsson JE, et al. Psoriasis. Lancet. 2021;397(10281):1301-1315. doi:10.1016/S0140-6736(20)32549-6

Choice of therapy

The choice of specific agents and combinations requires close cooperation with the patient, always keeping in mind the adverse effect profile. 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.

Rotational therapy refers to the substitution of one therapy for another after 1 to 2 years to reduce the adverse effects caused by chronic use and to circumvent disease resistance. Sequential therapy refers to initial use of potent agents (eg, cyclosporine) to quickly gain control followed by use of agents with a better safety profile. Immunosuppressants achieve clearance or near clearance of lesions more often than methotrexate or narrowband UVB.Rotational therapy refers to the substitution of one therapy for another after 1 to 2 years to reduce the adverse effects caused by chronic use and to circumvent disease resistance. Sequential therapy refers to initial use of potent agents (eg, cyclosporine) to quickly gain control followed by use of agents with a better safety profile. Immunosuppressants achieve clearance or near clearance of lesions more often than methotrexate or narrowband UVB.

Mild plaque psoriasis can be treated with emollients, keratolytics, tar, topical glucocorticoids, glucocorticoid-sparing topical agents (eg, calcineurin inhibitors, PDE-4 inhibitors, tapinarof), vitamin D3 analogs, or anthralin alone or in combination. Moderate exposure to sunlight is beneficial, but sunburn can induce exacerbations. can be treated with emollients, keratolytics, tar, topical glucocorticoids, glucocorticoid-sparing topical agents (eg, calcineurin inhibitors, PDE-4 inhibitors, tapinarof), vitamin D3 analogs, or anthralin alone or in combination. Moderate exposure to sunlight is beneficial, but sunburn can induce exacerbations.

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 are often difficult to treat because of the physical challenge of applying topical agents and shielding skin from UV light. Scalp disease can be particularly burdensome to patients. Multiple formulations that are more friendly to scalp application include alcohol- or water-based solutions and liquids, foams, shampoos, gels and, in more recalcitrant cases, oils (that are applied overnight and washed off in the morning). A systematic review of randomized trials found that several IL-17 inhibitors, including brodalumab, secukinumab, and ixekizumab (in a subgroup of patients with severe psoriasis), show high efficacy in treating moderate to severe scalp psoriasis, with brodalumab and ixekizumab demonstrating a rapid response (are often difficult to treat because of the physical challenge of applying topical agents and shielding skin from UV light. Scalp disease can be particularly burdensome to patients. Multiple formulations that are more friendly to scalp application include alcohol- or water-based solutions and liquids, foams, shampoos, gels and, in more recalcitrant cases, oils (that are applied overnight and washed off in the morning). A systematic review of randomized trials found that several IL-17 inhibitors, including brodalumab, secukinumab, and ixekizumab (in a subgroup of patients with severe psoriasis), show high efficacy in treating moderate to severe scalp psoriasis, with brodalumab and ixekizumab demonstrating a rapid response (1). Guselkumab (IL-23 inhibitor) is superior to adalimumab (TNF inhibitor), and ixekizumab is superior to etanercept (TNF inhibitor). Apremilast offers long-term efficacy. ). Guselkumab (IL-23 inhibitor) is superior to adalimumab (TNF inhibitor), and ixekizumab is superior to etanercept (TNF inhibitor). Apremilast offers long-term efficacy.

Moderate to severe cases of scalp psoriasis may benefit from treatment with systemic immunosuppressants (eg, biologics, small molecules).

Special treatment needs for subtypes of psoriasis are described above.

For psoriatic arthritis, treatment with systemic therapy is important to consider in order to prevent joint destruction, decrease pain, and improve or retain function.

(See also the American Academy of Dermatology Association's Psoriasis Clinical Guideline.)

Topical treatments

Glucocorticoids are usually used topically but can be injected into small or recalcitrant plaques. (CAUTION: Systemic glucocorticoids may precipitate exacerbations or development of pustular psoriasis and should not be used to treat psoriasis.) Topical glucocorticoids are the mainstay for mild to mild-moderate psoriasis, with potency and formulation appropriately tailored to the site and extent of involvement. Topical glucocorticoids are used twice daily. Glucocorticoids are most effective when used overnight under occlusive polyethylene coverings or incorporated into tape; a glucocorticoid cream is applied without occlusion during the day. Glucocorticoid potency is selected according to the extent of involvement. Topical glucocorticoid use may be limited by logistical considerations (eg, cost, inconvenience when treating extensive areas) and potential for adverse effects. Topical glucocorticoids applied for long periods to large areas of the body may also cause systemic effects and paradoxically exacerbate psoriasis.

As lesions abate, the glucocorticoid should be applied less frequently or at a lower potency to minimize local atrophy, striae formation, and telangiectases. Ideally, after approximately 2 to 3 weeks, glucocorticoids should be substituted with a glucocorticoid-sparing agent.

For chronic or maintenance therapy, regimens (eg, twice weekly application) with both topical glucocorticoids, and glucocorticoid-sparing alternatives such as topical tapinarof or roflumilast are recommended to reduce the risk of skin atrophy and maintain remission. Vitamin D analogs are an alternative. Phototherapy and systemic agents should also be considered. If glucocorticoid-sparing options are effective alone, monotherapy may be acceptable, especially for areas more susceptible to glucocorticoid–induced side effects This substitution limits topical glucocorticoid exposure and reduces risk of adverse effects (eg, skin atrophy, telangiectasias, easy bruising, striae). For small, thick, localized, or recalcitrant lesions, high-potency glucocorticoids are used with an occlusive dressing or flurandrenolide tape; these dressings are left on overnight and changed in the morning. Relapses after topical glucocorticoid therapy is stopped often occur faster than with other agents.For chronic or maintenance therapy, regimens (eg, twice weekly application) with both topical glucocorticoids, and glucocorticoid-sparing alternatives such as topical tapinarof or roflumilast are recommended to reduce the risk of skin atrophy and maintain remission. Vitamin D analogs are an alternative. Phototherapy and systemic agents should also be considered. If glucocorticoid-sparing options are effective alone, monotherapy may be acceptable, especially for areas more susceptible to glucocorticoid–induced side effects This substitution limits topical glucocorticoid exposure and reduces risk of adverse effects (eg, skin atrophy, telangiectasias, easy bruising, striae). For small, thick, localized, or recalcitrant lesions, high-potency glucocorticoids are used with an occlusive dressing or flurandrenolide tape; these dressings are left on overnight and changed in the morning. Relapses after topical glucocorticoid therapy is stopped often occur faster than with other agents.

Vitamin D3 analogs (eg, calcipotriol [calcipotriene], calcitriol) are topical medications that induce normal keratinocyte proliferation and differentiation; they can be used alone or in combination with topical glucocorticoids. Some clinicians have patients apply calcipotriol on weekdays and glucocorticoids on weekends.(eg, calcipotriol [calcipotriene], calcitriol) are topical medications that induce normal keratinocyte proliferation and differentiation; they can be used alone or in combination with topical glucocorticoids. Some clinicians have patients apply calcipotriol on weekdays and glucocorticoids on weekends.

Calcineurin inhibitors (eg, tacrolimus, pimecrolimus) are available in topical form and are generally well-tolerated. They are not as effective as glucocorticoids but may avoid the complications of glucocorticoids when treating facial and intertriginous psoriasis. Data from large cohort studies and meta-analyses evaluating the risk of lymphoma associated with topical calcineurin inhibitor use are mixed. Some studies have reported a small but statistically significant increase in lymphoma risk ((eg, tacrolimus, pimecrolimus) are available in topical form and are generally well-tolerated. They are not as effective as glucocorticoids but may avoid the complications of glucocorticoids when treating facial and intertriginous psoriasis. Data from large cohort studies and meta-analyses evaluating the risk of lymphoma associated with topical calcineurin inhibitor use are mixed. Some studies have reported a small but statistically significant increase in lymphoma risk (2), while others have found no increased risk (3). In addition, the overall evidence does not support an increase in skin cancer risk.

TazaroteneTazarotene is a topical retinoid. It is less effective than glucocorticoids 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.

RoflumilastRoflumilast is a topical phosphodiesterase-4 (PDE-4) inhibitor. It exerts anti-inflammatory and antipruritic effects by downregulating proinflammatory cytokines and normalizing keratinocyte function. It is available in cream and foam formulations. Roflumilast cream is particularly useful as a glucocorticoid-sparing treatment for delicate facial and intertriginous areas (eg, buttocks, groin, axillae). The foam formulation is useful in penetrating lesions in the scalp and/or other hirsute (hair-covered) areas. The most common side effect of topical roflumilast use is headache.is a topical phosphodiesterase-4 (PDE-4) inhibitor. It exerts anti-inflammatory and antipruritic effects by downregulating proinflammatory cytokines and normalizing keratinocyte function. It is available in cream and foam formulations. Roflumilast cream is particularly useful as a glucocorticoid-sparing treatment for delicate facial and intertriginous areas (eg, buttocks, groin, axillae). The foam formulation is useful in penetrating lesions in the scalp and/or other hirsute (hair-covered) areas. The most common side effect of topical roflumilast use is headache.

TapinarofTapinarof is a topical aryl hydrocarbon receptor (AhR) agonist used as monotherapy or in combination with topical glucocorticoids or phototherapy for the treatment of mild to moderate psoriasis. It is also useful as a glucocorticoid-sparing therapy on facial and intertriginous areas. Common adverse effects include irritant erythema, burning, and pruritus at the site of application, especially when used in intertriginous areas; acne and folliculitis have also been described.

Other adjunctive topical treatments include emollients, salicylic acid, coal tar, and anthralin:Other adjunctive topical treatments include emollients, salicylic acid, coal tar, and anthralin:

• Emollients include emollient creams, ointments, petrolatum, paraffin, and even hydrogenated vegetable (eg, coconut) 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. While emollient creams and ointments do not provide disease-modification, they enhance skin barrier repair and reduce scaling and/or dryness, which can improve appearance and comfort. Thicker emollients (like petrolatum) can enhance the penetration of topical active agents, and mineral oil can enhance UV penetration if coadministered with phototherapy.include emollient creams, ointments, petrolatum, paraffin, and even hydrogenated vegetable (eg, coconut) 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. While emollient creams and ointments do not provide disease-modification, they enhance skin barrier repair and reduce scaling and/or dryness, which can improve appearance and comfort. Thicker emollients (like petrolatum) can enhance the penetration of topical active agents, and mineral oil can enhance UV penetration if coadministered with phototherapy.

• Salicylic acidSalicylic acid 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.

• Coal tarCoal tar 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 glucocorticoids 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.

• AnthralinAnthralin (dithranol) is a topical antiproliferative, anti-inflammatory agent that is not a preferred treatment in geographical regions where other agents are available. 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.

Given the availability and convenience of other agents, coal tar and anthralin are being used less frequently in resource-rich settings where alternative therapies are available.Given the availability and convenience of other agents, coal tar and anthralin are being used less frequently in resource-rich settings where alternative therapies are available.

Phototherapy

UV light therapy is typically used in patients with extensive psoriasis; however, its use is declining because of the availability of effective alternative systemic therapies. The mechanism of action is poorly characterized; however, UVB light is known to reduce DNA synthesis and can induce mild systemic immunosuppression. Narrowband UVB light (311 to 312 nm), which is used without psoralens, is similar in effectiveness to psoralen plus ultraviolet A (PUVA). However, in settings where narrow-band UVB is available, that is clinically preferred to PUVA. One study has demonstrated that home-based narrow-band UVB phototherapy for plaque or guttate psoriasis is as effective as and less burdensome than office-based therapy (4).

In 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. However, adverse effects limit its use. 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). Excimer laser therapy is a type of phototherapy using a 308-nm laser directed at focal psoriatic plaques

Systemic therapies

MethotrexateMethotrexate taken orally is a modestly effective treatment for moderate to severe psoriasis with mixed efficacy data for psoriatic arthritis. Methotrexate may also be used in some cases of pustular psoriasis and palmoplantar disease unresponsive to topical agents or UV light therapy (narrowband UVB). Hematologic, renal, and hepatic function should be monitored. Dosage regimens vary, so only clinicians experienced in its use for psoriasis should undertake taken orally is a modestly effective treatment for moderate to severe psoriasis with mixed efficacy data for psoriatic arthritis. Methotrexate may also be used in some cases of pustular psoriasis and palmoplantar disease unresponsive to topical agents or UV light therapy (narrowband UVB). Hematologic, renal, and hepatic function should be monitored. Dosage regimens vary, so only clinicians experienced in its use for psoriasis should undertakemethotrexate therapy.

CyclosporineCyclosporine 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 retinoids (eg, acitretin, isotretinoin) may be effective for severe and recalcitrant cases of psoriasis vulgaris, pustular psoriasis (in which (eg, acitretin, isotretinoin) may be effective for severe and recalcitrant cases of psoriasis vulgaris, pustular psoriasis (in whichisotretinoin may or may not be preferred), and hyperkeratotic palmoplantar psoriasis. Because of the teratogenic potential and long-term retention of acitretin in the body, it should not be used in pregnant patients or those with child bearing potential; such patients should also be warned against becoming pregnant for at least 3 years after treatment ends. Pregnancy restrictions also apply to may or may not be preferred), and hyperkeratotic palmoplantar psoriasis. Because of the teratogenic potential and long-term retention of acitretin in the body, it should not be used in pregnant patients or those with child bearing potential; such patients should also be warned against becoming pregnant for at least 3 years after treatment ends. Pregnancy restrictions also apply toisotretinoin, but the agent is not retained in the body beyond 1 month. Long-term treatment may be associated with diffuse idiopathic skeletal hyperostosis (DISH).

Several classes of biologics (therapeutic monoclonal antibodies) have shown efficacy for the treatment of moderate to severe plaque psoriasis (5, 6):

• Tumor necrosis factor (TNF) inhibitors: Etanercept, adalimumab, infliximab, golimumab (only for psoriatic arthritis) and certolizumab pegol (does not cross the placenta)Etanercept, adalimumab, infliximab, golimumab (only for psoriatic arthritis) and certolizumab pegol (does not cross the placenta)

• Interleukin (IL)-23 inhibitors: Tildrakizumab, risankizumab, guselkumab, and ustekinumab (targets both IL-12 and IL-23)Tildrakizumab, risankizumab, guselkumab, and ustekinumab (targets both IL-12 and IL-23)

• IL-17 inhibitors: Secukinumab, ixekizumab, bimekizumab, and brodalumabSecukinumab, ixekizumab, bimekizumab, and brodalumab

Apremilast,Apremilast, a PDE-4 inhibitor, is an oral small-molecule medication for plaque psoriasis; however, data suggest it is less effective than biologics (7).

DeucravacitinibDeucravacitinib is an oral small-molecule agent that inhibits tyrosine kinase 2 and has shown efficacy for treatment of psoriasis (8, 9).

Janus kinase inhibitors (eg, tofacitinib, upadacitinib) are used to treat psoriatic arthritis, and also appear to be effective for psoriasis ((eg, tofacitinib, upadacitinib) are used to treat psoriatic arthritis, and also appear to be effective for psoriasis (10); however, more studies are needed before they are routinely used for this indication.

SpesolimabSpesolimab is an IL-36 inhibitor that is used for the treatment of generalized pustular psoriasis.

Biosimilar medications for many of the biologic classes above are available or under development (11). These medications have very similar efficacies and side effect profiles to reference products; slight differences in components do not appear to be clinically meaningful.

Other immunosuppressants (eg, hydroxyurea, 6-thioguanine) have narrow safety margins and are reserved for severe, recalcitrant psoriasis. Efalizumab is not available in the United States or Canada because of increased risk of (eg, hydroxyurea, 6-thioguanine) have narrow safety margins and are reserved for severe, recalcitrant psoriasis. Efalizumab is not available in the United States or Canada because of increased risk ofprogressive multifocal leukoencephalopathy.

Emerging therapeutics for psoriasis include targeted oral peptides. Icotrokinra, which is an IL-23 inhibitor, has shown efficacy and a tolerable safety profile in randomized trials of adults with moderate-to-severe psoriasis (12, 13).

Fumaric acid esters (eg, dimethyl fumarate, monoethyl fumarate) are compounds with immunomodulatory properties sometimes used for the treatment of moderate to severe plaque psoriasis, particularly in Europe, where they are a common first-line systemic therapy ((eg, dimethyl fumarate, monoethyl fumarate) are compounds with immunomodulatory properties sometimes used for the treatment of moderate to severe plaque psoriasis, particularly in Europe, where they are a common first-line systemic therapy (14).

Treatment references

1. 1. Alsenaid A, Ezmerli M, Srour J, et al. Biologics and small molecules in patients with scalp psoriasis: a systematic review. J Dermatolog Treat. 2022;33(1):473-482. doi:10.1080/09546634.2020.1770167

2. 2. Lam M, Zhu JW, Tadrous M, Drucker AM. Association Between Topical Calcineurin Inhibitor Use and Risk of Cancer, Including Lymphoma, Keratinocyte Carcinoma, and Melanoma: A Systematic Review and Meta-analysis. JAMA Dermatol. 2021;157(5):549-558. doi:10.1001/jamadermatol.2021.0345

3. 3. Arana A, Pottegård A, Kuiper JG, et al. Long-Term Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus and Pimecrolimus: Final Results from the Extension of the Cohort Study Protopic Joint European Longitudinal Lymphoma and Skin Cancer Evaluation (JOELLE). . Long-Term Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus and Pimecrolimus: Final Results from the Extension of the Cohort Study Protopic Joint European Longitudinal Lymphoma and Skin Cancer Evaluation (JOELLE).Clin Epidemiol. 2021;13:1141-1153. Published 2021 Dec 29. doi:10.2147/CLEP.S331287

4. 4. Gelfand JM, Armstrong AW, Lim HW, et al. Home- vs Office-Based Narrowband UV-B Phototherapy for Patients With Psoriasis: The LITE Randomized Clinical Trial. JAMA Dermatol. 2024;160(12):1320-1328. doi:10.1001/jamadermatol.2024.3897

5. 5. 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

6. 6. 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

7. 7. 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

8. 8. 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

9. 9. 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

10. 10. 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

11. 11. 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

12. 12. Bissonnette R, Pinter A, Ferris LK, et al. An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis. N Engl J Med. 2024;390(6):510-521. doi:10.1056/NEJMoa2308713

13. 13. Ferris LK, Bagel J, Huang YH, et al. FRONTIER-2: A phase 2b, long-term extension, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2025;92(3):495-502. doi:10.1016/j.jaad.2024.10.076

14. 14. Landeck L, Asadullah K, Amasuno A, et al. Dimethyl fumarate (DMF) vs. monoethyl fumarate (MEF) salts for the treatment of plaque psoriasis: a review of clinical data. . Dimethyl fumarate (DMF) vs. monoethyl fumarate (MEF) salts for the treatment of plaque psoriasis: a review of clinical data.Arch Dermatol Res. 2018;310(6):475-483. doi:10.1007/s00403-018-1825-9