dermatologic disorders
Psoriasis
Treatment of Psoriasis
Topical treatments Ultraviolet (UV) light therapy Systemic therapies Treatment options are extensive and range from topical treatments (eg, corticosteroids, vitamin D3 analogs, calcineurin inhibitors,tazarotene,roflumilast,tapinarof, emollients,salicylic acid,coal tar,anthralin) to UV light therapy to systemic treatments (eg,methotrexate, oral retinoids,cyclosporine, biologics, small molecules). .) 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. Anti-inflammatory agents is selected according to the extent of involvement. As lesions abate, the corticosteroid should be applied less frequently or at a lower potency to minimize local atrophy, striae formation, and telangiectases. Ideally, after about 2 to 3 weeks, an emollient, vitamin D3 analog, or calcineurin inhibitor should be substituted for the corticosteroid for 1 to 2 weeks (as a rest period); this substitution limits corticosteroid dosage, reduces risk of topical corticosteroid adverse effects (eg, skin atrophy, telangiectasias, easy bruising, striae), and prevents tachyphylaxis (diminishing response to an agent after successive dosing). Topical corticosteroid use can be expensive because large quantities (about 1 oz or 30 g) are needed for each application when a large body surface area is affected. Topical corticosteroids applied for long duration to large areas of the body may cause systemic effects and exacerbate psoriasis. For small, thick, localized, or recalcitrant lesions, high-potency corticosteroids are used with an occlusive dressing orflurandrenolidetape; these dressings are left on overnight and changed in the morning. Relapse after topical corticosteroid therapy is stopped is often 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 corticosteroids. Some clinicians have patients apply calcipotriol on weekdays and corticosteroids on weekends. Calcineurin inhibitors(eg,tacrolimus,pimecrolimus) are available in topical form and are generally well-tolerated. They are not as effective as corticosteroids but may avoid the complications of corticosteroids when treating facial and intertriginous psoriasis. It is not clear whether they increase the risk of lymphoma and skin cancer. Tazaroteneis 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. Roflumilastis 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). Tapinarofis a topical aryl hydrocarbon receptor (AhR) agonist. It is also useful as a corticosteroid-sparing therapy on facial and intertriginous areas. Other adjunctive topical treatments include emollients,salicylic acid,coal tar, andanthralin: Emollientsinclude 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. Salicylic acidis 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 tarpreparations 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 tarproducts 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. Anthralinis 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.Anthralinmay be irritating and should be used with caution in intertriginous areas; it also stains. Irritation and staining can be avoided by washing off theanthralin20 to 30 minutes after application. Using a liposome-encapsulated preparation may also avoid some disadvantages ofanthralin. Given the availability and convenience of other agents,coal tarandanthralinare being used less frequently. UV light therapyis 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. Methotrexatetaken 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.Methotrexateseems 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 undertakemethotrexatetherapy. Cyclosporinecan 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. Mycophenolatemofetilcan be an alternative option for patients who do not respond tomethotrexateorcyclosporineor those who develop toxicity from the above medications. , but the agent is not retained in the body beyond 1 month. Long-term treatment may cause Diagnosis (DISH). (therapeutic monoclonal antibodies) have shown efficacy for the treatment of moderate to severe plaque psoriasis ( Treatment references , TNF inhibitors:Etanercept,adalimumab,infliximab, andcertolizumab pegol(does not cross the placenta) Interleukin (IL)-23 inhibitors:Tildrakizumab,risankizumab,guselkumab, andustekinumab(targets both IL-12 and IL-23) IL-17 inhibitors:Secukinumab,ixekizumab, andbrodalumab a PDE-4 inhibitor, is an oral small-molecule medication for plaque psoriasis; however, postmarketing data suggest it is less effective than biologics ( Treatment references ). 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 ( Treatment references , Spesolimabis 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 ( Treatment references ). These medications have very similar efficacies and toxicities to reference products; slight differences in components are not clinically meaningful. ) have narrow safety margins and are reserved for severe, recalcitrant psoriasis. Efalizumab is no longer available in the United States or Canada because of increased risk of Progressive Multifocal Leukoencephalopathy (PML) . 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). 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 thanmethotrexateor narrowband UVB. Mild plaque psoriasiscan be treated with emollients, keratolytics, tar, topical corticosteroids, corticosteroid-sparing topical agents (eg, calcineurin inhibitors, PDE-4 inhibitors,tapinarof), vitamin D3 analogs, oranthralinalone or in combination. Moderate exposure to sunlight is beneficial, but sunburn can induce exacerbations. Moderate to severe plaque psoriasisshould be treated with topical agents and either phototherapy or systemic agents. Immunosuppressants are used for moderate to severe disease unresponsive to other agents. Scalp plaquesare notoriously difficult to treat because they resist systemic therapy, and because hair blocks application of topical agents and scale removal and shields skin from UV light. A suspension of 10%salicylic acidinmineral oilmay be rubbed into the scalp at bedtime manually or with a toothbrush, covered with a shower cap (to enhance penetration and avoid messiness), and washed out the next morning with a tar (or other) shampoo. More cosmetically acceptable corticosteroid solutions can be applied to the scalp during the day. These treatments are continued until the desired clinical response is achieved. Resistant skin or scalp patches may respond to local superficial intralesional injection oftriamcinoloneacetonide suspension diluted with saline to 2.5 or 5 mg/mL, depending on the size and severity of the lesion. Injections may cause local skin atrophy, which is usually reversible. 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 , treatment with systemic therapy is important to prevent joint destruction; (See also the American Academy of Dermatology'sclinical guideline for psoriasis.) 1.Sbidian E, Chaimani A, Garcia-Doval I, et al: Systemic pharmacological treatments for chronic plaque psoriasis: A network meta-analysis.Cochrane Database Syst Rev12(12):CD011535, 2017. doi: 10.1002/14651858.CD011535.pub2 2.Armstrong AW, Read C: Pathophysiology, clinical presentation, and treatment of psoriasis: A review.JAMA323(19):1945–1960, 2020. doi: 10.1001/jama.2020.4006 3.Armstrong AW, Puig L, Joshi A, et al: Comparison of Biologics and Oral Treatments for Plaque Psoriasis: A Meta-analysis.JAMA Dermatol156(3):258–269, 2020. doi: 10.1001/jamadermatol.2019.4029 4.Armstrong AW, Gooderham M, Warren RB, et al:Deucravacitinibversus placebo andapremilastin 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 Dermatol88(1):29–39, 2023. doi: 10.1016/j.jaad.2022.07.002 5.Strober B, Thaçi D, Sofen H, et al:Deucravacitinibversus placebo andapremilastin 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 Dermatol88(1):40–51, 2023. doi: 10.1016/j.jaad.2022.08.061 6.Bachelez H, van de Kerkhof PC, Strohal R, et al:Tofacitinibversusetanerceptor placebo in moderate-to-severe chronic plaque psoriasis: A phase 3 randomised non-inferiority trial.Lancet386(9993):552-561, 2015. doi: 10.1016/S0140-6736(14)62113-9 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 Treat34(1):2140569, 2023. doi: 10.1080/09546634.2022.2140569 