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Psoriasis in children: Management of chronic plaque psoriasis

Psoriasis in children: Management of chronic plaque psoriasis
Authors:
Amy S Paller, MD
Emily Broun Lund, MD
Section Editors:
Kristina Callis Duffin, MD
Moise L Levy, MD
Deputy Editor:
Abena O Ofori, MD
Literature review current through: Sep 2022. | This topic last updated: Aug 31, 2022.

INTRODUCTION — Psoriasis is a systemic, immune-mediated disease that can negatively impact the quality of life of affected children and their families (picture 1A-I). In most children, psoriasis can be adequately treated with topical medications. However, children with moderate to severe psoriasis often require phototherapy or systemic therapy.

Although many of the therapies commonly administered for psoriasis in children and adults are similar, high-quality efficacy and safety trials to guide the best approach to psoriasis in children are more limited. As a result, the development of guidelines for the treatment of pediatric psoriasis is challenging. In clinical practice, consideration of patient-specific factors, such as patient age, severity of disease, comorbidities, and tolerance of the risks and side effects of specific medications, guides the approach to treatment (algorithm 1).

The management of chronic plaque psoriasis, the most common clinical variant of psoriasis in children, will be reviewed here. The diagnosis of psoriasis in children and the approach to treatment of other clinical variants of psoriasis and psoriatic arthritis are reviewed separately.

(See "Psoriasis in children: Epidemiology, clinical manifestations, and diagnosis".)

(See "Guttate psoriasis".)

(See "Pustular psoriasis: Management".)

(See "Nail psoriasis".)

(See "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis" and "Psoriatic juvenile idiopathic arthritis: Management and prognosis".)

PATIENT ASSESSMENT — Certain characteristics influence treatment selection. Important aspects of the pretreatment assessment include:

Disease severity – Most children have mild to moderate psoriasis (generally defined as psoriasis involving less than 10 percent of the total body surface area), which can often be adequately treated with topical medications, such as corticosteroids, calcineurin inhibitors, and vitamin D analogs. Approximately 10 to 20 percent of children have moderate to severe psoriasis, defined as psoriasis that involves more than 10 percent of the body surface area or psoriasis that cannot be adequately improved with topical therapy. Moderate to severe psoriasis often requires phototherapy or systemic therapy (algorithm 1). (See 'Mild to moderate plaque psoriasis in children at least four years of age' below and 'Moderate to severe plaque psoriasis in children at least four years of age' below.)

Sites of involvement – The sites of skin involvement influence the approach to topical therapy. In particular, modifications to topical therapy are helpful for patients with facial, intertriginous, or scalp involvement. (See 'Special sites' below.)

Patient age – The availability of efficacy and safety data for specific age groups differs among treatments. Given a paucity of efficacy and safety data for systemic therapy for very young children, a more conservative approach to systemic treatment is often taken for children under the age of four years. (See 'Very young children' below.)

Psoriatic arthritis – The concomitant presence of psoriatic arthritis can justify use of systemic antipsoriatic therapy in children with mild skin involvement and influences the choice of treatment. (See 'Children with psoriatic arthritis' below and "Psoriatic juvenile idiopathic arthritis: Management and prognosis".)

Other comorbidities – Clinician awareness of the multiple other diseases associated with psoriasis facilitates identification of children who may benefit from screening for associated disease [1,2]. (See "Psoriasis in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Comorbidities' and "Psoriasis in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Additional evaluation'.)

MILD TO MODERATE PLAQUE PSORIASIS IN CHILDREN AT LEAST FOUR YEARS OF AGE — Mild to moderate plaque psoriasis is generally defined as psoriasis involving less than 10 percent of the total body surface area. Given the limited amount of skin involvement, topical therapy is usually manageable for patients and their caregivers (algorithm 1).

Treatment selection — Preferred initial therapies for mild to moderate plaque psoriasis in children include topical corticosteroids, topical calcineurin inhibitors, topical vitamin D analogs, and emollients.

Topical corticosteroids are the mainstay for pediatric psoriasis based upon the extensive clinical experience that supports efficacy for this indication and the wide availability and affordability of some of these agents [1]. However, long-term corticosteroid therapy is associated with increased risk for side effects, such as skin atrophy. Thus, topical calcineurin inhibitors and topical vitamin D analogs are often added to (or substituted for) topical corticosteroid therapy to reduce corticosteroid exposure. Emollients can be a useful adjunct to all therapies.

Modifications for treating psoriasis in special sites, including the face, intertriginous skin, and scalp, are reviewed below. (See 'Face and intertriginous skin' below and 'Scalp' below.)

Treatment options

Topical corticosteroids — Various topical corticosteroid therapies can be effective for psoriasis:

Administration:

Regimen – Plaque psoriasis usually responds to topical corticosteroid therapy provided the agent selected has adequate potency. Psoriasis plaques on the trunk and extremities in children can be treated with high-potency to medium-potency (group 2 to 4 (table 1)) topical corticosteroids applied twice daily. Signs of improvement (reduced erythema and plaque thickness) are sometimes evident within the first one to two weeks, with additional improvement occurring with continued use. We continue daily treatment for up to four weeks. Once sufficient improvement occurs, the topical corticosteroid can be discontinued or tapered to intermittent use (two consecutive days per week [eg, weekends]) to maintain the response, if needed. Daily application for up to four weeks is resumed for subsequent flares.

If psoriasis plaques on the trunk or extremities do not respond sufficiently within four weeks of daily treatment with a group 2 to 4 topical corticosteroid, a short course (≤2 weeks) of a super-high potency (group 1 (table 1)) topical corticosteroid may lead to improvement. After two weeks of use, application should be tapered to intermittent use (eg, two consecutive days per week). Alternatively, the patient can be transitioned to a lower-potency corticosteroid.

We often incorporate a vitamin D analog in the treatment regimen when feasible. Patients or caregivers can apply the vitamin D analog simultaneously with the topical corticosteroid during treatment of acute flares. Once the frequency of topical corticosteroid application is reduced to two days per week, application of the topical vitamin D analog may continue on the remaining five days. (See 'Topical vitamin D analogs' below.)

Vehicle selection – Topical corticosteroids are available in a wide variety of vehicles (eg, ointment, cream, lotion, gel, solution, spray, foam). In general, ointments are preferred over other vehicles to enhance penetration of psoriatic scale. However, patient preferences and certain sites (eg, hair-bearing scalp) warrant consideration of other vehicles to maximize the likelihood of adherence to therapy. (See 'Scalp' below.)

Use on hyperkeratotic plaques – Inadequate penetration of topical corticosteroids can lead to poor responses in children with markedly hyperkeratotic plaques. Compounding topical corticosteroids with keratolytics, like 6% salicylic acid, with or without topical tar can facilitate treatment of these plaques.

Efficacy Use of topical corticosteroids for pediatric psoriasis is primarily based upon extensive clinical experience that supports efficacy of these agents and data from randomized trials in adults [3-5]. There is a paucity of randomized trial data in children. In a phase 3, randomized trial that compared clobetasol emulsion formulation foam with vehicle and clobetasol ointment for moderate to severe plaque psoriasis in individuals 12 years and older, among participants ages 12 to 17 years, two of eight children in the clobetasol foam group achieved clearance or near clearance after two weeks compared with zero of one children in the vehicle group [6].

Adverse effects and precautions – Cutaneous atrophy and striae are potential side effects of topical corticosteroid therapy. Risk for these side effects can be reduced by limiting the duration of application, avoiding excessive application (a thin layer is sufficient), and avoiding use of potent corticosteroids on the face and intertriginous areas. (See 'Face and intertriginous skin' below.)

Systemic absorption of topical corticosteroids may also lead to hypothalamic-pituitary axis suppression, particularly in children. To minimize risk of this side effect, avoidance of long-term, daily use of topical corticosteroids on large skin areas is prudent. (See "Topical corticosteroids: Use and adverse effects", section on 'Systemic'.)

Topical calcineurin inhibitors — Topical calcineurin inhibitors are an additional first-line treatment option for psoriasis in children. These agents are primarily used as an alternative to topical corticosteroid therapy for psoriasis in sites with the greatest risk for corticosteroid-induced skin atrophy, including the face and intertriginous areas. (See 'Face and intertriginous skin' below.)

Topical vitamin D analogs — Topical vitamin D analogs utilized for psoriasis include calcipotriene, calcitriol, and tacalcitol. Tacalcitol is not available in the United States:

Administration – The onset of action of topical vitamin D analogs is relatively slow (six to eight weeks). Thus, these agents are generally used in conjunction with or after faster-acting topical corticosteroid therapy. Common regimens include:

As adjunctive treatment – Simultaneous, twice-daily application with a potent corticosteroid. Patients may mix the two agents in their hands prior to application or use a commercially available combination medication (eg, calcipotriene 0.005% and betamethasone dipropionate 0.064%).

As a corticosteroid-sparing agent – Twice-daily application of the topical vitamin D analog five days per week (eg, Monday to Friday) and application of a topical corticosteroid two days per week (eg, weekends).

Efficacy – Topical vitamin D analogs have demonstrated efficacy and safety in randomized trials in adolescents and adults with psoriasis [7,8]. (See "Treatment of psoriasis in adults", section on 'Topical vitamin D analogs'.)

Randomized trial data in children under the age of 12 are limited. In an eight-week, randomized trial in which 77 children with psoriasis (<30 percent body surface area involvement, ages 2 to 14 years) were randomly assigned to apply either calcipotriol ointment or vehicle twice daily, greater reductions in redness and scaliness occurred in the calcipotriol group than in the placebo group, but significant differences in plaque thickness and the Psoriasis Area and Severity Index (PASI) score were not observed between the two groups [9]. Uncontrolled studies also suggest benefit in children with plaque psoriasis [10,11].

Adverse effects and precautions – Topical vitamin D analogs are generally well tolerated. Skin irritation is a potential side effect that can limit use in some children. Daily use of an emollient may help to reduce skin irritation [1]. Reversible hypercalcemia is an additional potential side effect when topical vitamin D analogs are used on large areas of the body.

Emollients — The application of emollients is an important adjunctive measure for psoriasis. Moisturizing the skin can make scale less prominent and reduce pruritus and fissuring. Emollients may also help to minimize the Koebner phenomenon (occurrence of new psoriasis plaques in sites of skin trauma) through reducing the likelihood of skin irritation.

Other therapies — Other topical agents, such as tazarotene, tar, and anthralin, are less frequently used for pediatric psoriasis because of side effects. Skin irritation often limits the use of tazarotene and anthralin in children. Tar is malodorous and can stain skin and clothing:

Tazarotene – Although randomized trial data support the efficacy of once-daily application of tazarotene for plaque psoriasis in adults, such data are lacking in children. A case report describes the successful treatment of nail psoriasis in a child with tazarotene 0.05% [12]. (See "Treatment of psoriasis in adults", section on 'Tazarotene'.)

Topical roflumilastRoflumilast 0.3% cream is a topical phosphodiesterase 4 inhibitor. In 2022, the US Food and Drug Administration (FDA) approved roflumilast 0.3% cream for the treatment of chronic plaque psoriasis, including psoriasis in intertriginous areas, in people 12 years of age and older [13]. The cream is applied to affected areas once daily and is expected to become commercially available in 2022. A phase 2, randomized trial supports efficacy of roflumilast in adults [14]. Roflumilast has also been evaluated in unpublished phase 3 trials [15,16]. (See "Treatment of psoriasis in adults", section on 'Roflumilast'.)

Tar – Tar has anti-inflammatory and antiproliferative effects that can lead to improvement in psoriasis [17]. Tar is commercially available in a variety of products, including coal tar-containing solutions (liquid carbonis detergens [LCD]), crude coal tar, coal tar extract, coal tar distillate, and tar blends [18]. In addition, tar may be compounded with topical corticosteroids and/or salicylic acid. Its objectionable smell, tendency to stain skin and clothing, and associated risk for folliculitis make tar a less appealing treatment option for psoriasis on the face, trunk, or extremities. However, coal tar is commonly used in shampoo formulations for scalp psoriasis. (See 'Scalp' below and "Treatment of psoriasis in adults", section on 'Tar'.)

Anthralin – Similar to tar, anthralin (or dithranol) has antiproliferative and anti-inflammatory effects and can improve psoriasis [19-21]. Anthralin is applied for increasing lengths of time, as tolerated, until effectiveness is achieved. Anthralin can cause skin irritation and may stain skin and clothing, making it a less desirable treatment. The use of anthralin is uncommon in the United States; the drug is more frequently used in Europe. (See "Treatment of psoriasis in adults", section on 'Anthralin'.)

Special sites — Facial, intertriginous, and scalp involvement are common in children with psoriasis (picture 1D-E). Modifying the approach to treatment for these areas is helpful for maximizing results and minimizing side effects.

Face and intertriginous skin — Both topical corticosteroids and topical calcineurin inhibitors are effective for facial and intertriginous psoriasis and are commonly used for these indications (picture 1C-D). Topical calcineurin inhibitors are favored for long-term treatment of these sites given the elevated risk for corticosteroid-induced skin atrophy in these areas. However, topical calcineurin inhibitors are typically more expensive than topical corticosteroids (see "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'):

Administration – When treating facial or intertriginous psoriasis in children, we generally initiate treatment with a topical calcineurin inhibitor (tacrolimus 0.1% ointment or pimecrolimus 1% cream). Tacrolimus is also available as a 0.03% ointment; we typically reserve use of the 0.03% ointment for children who cannot tolerate the 0.1% formulation due to skin irritation. The topical calcineurin inhibitor is applied twice daily until satisfactory improvement. Improvement is expected within the first month of treatment. Once resolution has occurred, treatment can be stopped. Application is resumed upon recurrence of disease.

Alternatively, topical corticosteroids can be used for psoriasis on the face or intertriginous skin. The agent selected should have a low potency (group 6 or 7). The corticosteroid is applied twice daily for up to two weeks. If sufficient improvement is obtained, treatment can be stopped, with the plan to resume treatment during subsequent flares. If the response is insufficient or disease recurs rapidly (eg, within a few weeks), we favor transitioning the patient to topical calcineurin inhibitor therapy.

Efficacy Although randomized trials support the efficacy of topical calcineurin inhibitors for facial and intertriginous psoriasis in adults, there are no randomized trials evaluating these agents for psoriasis in children. A six-month, uncontrolled study that evaluated the efficacy of tacrolimus 0.1% ointment for facial or inverse psoriasis in 11 children (ages 6 to 15 years) supports benefit in children [22]. Among the eight patients who completed the study, all improved, with the most improvement occurring within the first 30 days. By day 30, one patient achieved complete clearance, and the remainder had excellent improvement. Successful treatment of facial or genital psoriasis in children with pimecrolimus cream is documented in case reports [23,24]. (See "Treatment of psoriasis in adults", section on 'Calcineurin inhibitors'.)

Adverse effects and precautions Topical calcineurin inhibitor therapy is generally well tolerated. Transient burning sensations, erythema, and pruritus are the most common side effects. Concerns have been raised regarding the long-term safety of calcineurin inhibitors, particularly in regard to cancer risk. However, a causative relationship between these agents and malignancy has not been established. (See "Treatment of atopic dermatitis (eczema)", section on 'Safety'.)

Scalp — Although scalp psoriasis will typically respond to the same topical medications as plaque psoriasis on the trunk or extremities, the presence of abundant terminal hair demands consideration of the best way to deliver therapy (picture 1E, 1G). Topical corticosteroids, topical vitamin D analogs, tar, and keratolytics are commonly used for therapy.

Often, patients find medications in shampoos, foams, solutions, gels, sprays, or oils preferable for application to the scalp. The vehicle options should be discussed with the child or caregiver to identify the most acceptable regimen. Oils can be particularly helpful for gentle removal of adherent scale.

We find the following initial regimen useful when performed daily for two weeks during flares:

Apply fluocinolone 0.01% in oil to a wet scalp under a shower cap for one to two hours

Wash the hair with one of the following:

Tar shampoo (eg, 0.5 or 1% coal tar)

Keratolytic shampoo (eg, 2, 3, or 6% salicylic acid)

A common alternative approach is treatment with a potent topical corticosteroid alone (eg, clobetasol propionate, fluocinonide, betamethasone dipropionate) or in combination with a topical vitamin D analog. Uncontrolled studies support efficacy of the combination of calcipotriene and betamethasone dipropionate for scalp psoriasis in children [25-27]. As with treatment of the trunk or extremities, daily application of high-potency corticosteroids on the scalp is typically limited to two to four weeks during flares, depending on the potency of the agent selected. (See 'Topical corticosteroids' above.)

MODERATE TO SEVERE PLAQUE PSORIASIS IN CHILDREN AT LEAST FOUR YEARS OF AGE — Topical therapy is often inadequate for children with moderate to severe disease (psoriasis that involves more than 10 percent of the body surface area or psoriasis that cannot be adequately improved with topical therapy). Frequent application of topical medications to large skin areas is difficult for patients and caregivers and may increase risk for side effects of topical therapies.

The major therapeutic options for this population include immunosuppressants (methotrexate, cyclosporine), phototherapy, biologic agents, and oral retinoids. The topical agents used for milder disease are often used in conjunction with phototherapy and systemic therapy to maximize the response to therapy. (See 'Mild to moderate plaque psoriasis in children at least four years of age' above.)

Oral corticosteroid therapy should be avoided due to the potential for precipitating severe psoriasis flares upon withdrawal.

Treatment selection — Guidelines on the therapeutic approach to moderate to severe psoriasis in children are lacking. Selection among the available treatments is dependent upon consideration of patient-specific factors, such as severity of disease, comorbidities, tolerance of risks and side effects, and prior treatment history (algorithm 1). Our general approach to psoriasis in children over the age of four years is outlined here. Other approaches may be reasonable. Special considerations for younger children are reviewed below. (See 'Very young children' below.)

Trial of topical therapy — Although topical therapy is frequently inadequate for children with moderate to severe plaque psoriasis, we typically attempt topical therapy (eg, trial of combination therapy with a potent topical corticosteroid and topical vitamin D analog for two to three months) prior to initiating other interventions (algorithm 1). This allows us to identify those children for whom topical therapy is inadequate. (See 'Treatment options' above.)

Selection of systemic therapy — Our most frequent initial therapies for pediatric plaque psoriasis that cannot be managed with topical therapy are methotrexate, narrowband ultraviolet B (NBUVB) phototherapy, and antipsoriatic biologic therapies:

Methotrexate – Globally, methotrexate is the most common systemic medication used for psoriasis in children. Advantages of methotrexate include a long history of use for pediatric psoriasis, availability of an oral formulation, and low cost compared with other psoriasis therapies. Disadvantages of methotrexate include a relatively slow onset of action, the need for laboratory monitoring during treatment, and the potentially serious side effect of hepatotoxicity. In addition, methotrexate may be less effective than some biologic agents. A randomized trial found methotrexate inferior to adalimumab for severe, chronic plaque psoriasis in children [28]. Of note, the average methotrexate dose given in the trial was relatively low. (See 'Methotrexate' below and 'Biologic agents' below and "Treatment of psoriasis in adults", section on 'Systemic therapies'.)

Ideal candidates for methotrexate therapy are children with relatively stable psoriasis who can tolerate a delayed onset of action, can tolerate laboratory monitoring, and lack risk factors for methotrexate-induced hepatotoxicity. Methotrexate should be used with caution in patients of childbearing potential due to risk for teratogenicity. (See "Treatment of psoriasis in adults", section on 'Methotrexate'.)

Phototherapy – Our use of phototherapy for moderate to severe plaque psoriasis is based upon the absence of risk for the serious, systemic side effects that may occur with systemic therapies. However, phototherapy requires frequent office visits (unless home phototherapy is implemented), which is difficult for some families, and phototherapy is not recommended for very young children. In addition, there is some uncertainty regarding the long-term risk for skin cancer in children treated with NBUVB phototherapy. (See "UVB therapy (broadband and narrowband)", section on 'Short- and long-term adverse effects'.)

Ideal candidates for NBUVB phototherapy are children who can come for frequent visits and who are old enough to follow instructions and safely remain in a light booth alone. We typically consider phototherapy in children over the age of six years (most commonly, preadolescents and adolescents), although even young children can be treated when a parent or caregiver accompanies the child in the booth and can provide entertainment. Phototherapy is also a useful option for children and families who desire to avoid systemic therapy. (See 'Phototherapy' below.)

Biologic therapies – Emerging data suggest that biologic agents are safer and more effective than nonspecific immunosuppressants (eg, methotrexate, cyclosporine) for pediatric psoriasis [29,30]. Data from randomized trials support efficacy of ustekinumab, etanercept, adalimumab, ixekizumab, and secukinumab for plaque psoriasis in children. (See 'Biologic agents' below and "Treatment of psoriasis in adults", section on 'Biologic agents'.)

There is no single biologic therapy that is preferred for the initial treatment of all patients. Shared decision making with the patient and/or caregiver(s) plays an important role and involves discussion of factors such as drug efficacy and safety, patient comorbidities, dosing frequency, and drug availability:

Relative efficacy – Data from studies in adults or children demonstrate lesser efficacy of etanercept compared with other biologic therapies. Ustekinumab was more effective for plaque psoriasis than etanercept in a randomized trial in adults [31]. Other randomized trials have found greater efficacy of secukinumab compared with etanercept in children and adults, ixekizumab compared with etanercept in adults, and secukinumab and ixekizumab compared with ustekinumab in adults [32-36]. In addition, a network meta-analysis of randomized trials in adults supports greater efficacy of ixekizumab and secukinumab when compared with ustekinumab, adalimumab, and etanercept, as well as greater efficacy of ustekinumab and adalimumab when compared with etanercept [37].

Although etanercept appears less effective than other antipsoriatic biologic agents, it has the longest history of use for children with psoriasis. The extent of experience with etanercept in children is reassuring for some patients and caregivers and may contribute to the preferred use of etanercept in some patients.

Frequency of dosing – Given that biologic therapies are administered via injection, less frequent dosing is helpful for some children and their families. Agents with less frequent dosing include ustekinumab (every three months), ixekizumab (every four weeks), and secukinumab (every four weeks, with the exception of weekly dosing during the first month of treatment). In contrast, etanercept is administered once weekly, and adalimumab is administered every other week.

ComorbiditiesSecukinumab and ixekizumab may be associated with increased risk for exacerbations of inflammatory bowel disease (IBD). Therefore, these therapies should be used with caution in children with a personal history of IBD [38]. (See "Treatment of psoriasis in adults", section on 'Inhibitors of the IL-17 pathway'.)

Children with moderate to severe plaque psoriasis and psoriatic arthritis can benefit from therapies that simultaneously treat skin and joint disease. All of the biologic agents used in children with psoriasis have efficacy for psoriatic arthritis. (See 'Children with psoriatic arthritis' below and "Psoriatic juvenile idiopathic arthritis: Management and prognosis".)

Drug availability – In the United States, health insurance requirements related to drug cost or US Food and Drug Administration (FDA) approval often determine the availability of therapy. Ustekinumab, ixekizumab, and secukinumab are FDA approved for the treatment of moderate to severe plaque psoriasis in children at least six years of age. Etanercept is the only biologic agent FDA approved for moderate to severe plaque psoriasis in children as young as four years of age. Adalimumab is not FDA approved for the treatment of psoriasis in children. In contrast, the European Medicines Association (EMA) has approved adalimumab for the treatment of severe plaque psoriasis in children at least four years of age.

Other therapiesCyclosporine can be rapidly effective for psoriasis. However, the drug has the potential for serious adverse effects and is generally reserved for children with acute, severe flares of disease that require immediate relief and severe psoriasis types, such as acute generalized pustular psoriasis and erythrodermic psoriasis. The side effects of cyclosporine limit the recommended duration of therapy to less than one year. The low cost of cyclosporine compared with biologic therapy is an advantage of this therapy. (See 'Cyclosporine' below.)

Oral retinoids can be effective for psoriasis but are less favored for chronic plaque psoriasis based upon lower efficacy as monotherapy compared with other agents. Advantages of oral retinoids include oral administration and lack of immunosuppression. Teratogenicity of oral retinoids is a concern for female adolescent patients, particularly for treatment with acitretin. Pregnancy should be avoided for three years after acitretin treatment. (See 'Acitretin' below.)

Fumaric acid esters and apremilast are additional systemic therapies that may be of benefit. (See 'Other' below.)

Treatment options

Methotrexate — Methotrexate, the most common therapy used for pediatric psoriasis, is a low-cost therapy that is typically given orally or subcutaneously once per week:

Administration – The starting dose is typically 0.3 mg/kg given once weekly and can subsequently be increased up to 0.7 mg/kg once weekly to a maximum of 25 mg per week. Improvement can occur within the first month, but more often, the onset of action takes at least 10 weeks. We generally assess the response every three months and increase the weekly dose by 0.1 to 0.2 mg/kg (up to the maximum total dose of 0.7 mg/kg per week) if the child is tolerating the methotrexate but has an inadequate response.

Folic acid supplementation (1 mg taken six or seven days per week) is indicated during methotrexate therapy [39]. Folic acid reduces risk for some adverse effects of methotrexate therapy [1,39].

Once excellent improvement has been achieved, weaning from methotrexate can be attempted to achieve the lowest effective dose for maintenance of the response. If disease control is maintained at a stable dose for six months, we typically begin to taper the weekly dose by 0.1 mg/kg each month as tolerated. Most children require continued treatment to maintain improvement. If flares occur during tapering, increasing the maintenance dose by 0.1 mg/kg above the dose at which the flare occurred often regains control of disease.

Efficacy – Uncontrolled studies support benefit of methotrexate for pediatric psoriasis [40-42]. In a series of 25 children treated with methotrexate (maximum dose ranging from 0.14 to 0.63 mg/kg per week) for moderate to severe plaque psoriasis, 4 percent achieved at least 75 percent improvement in the Psoriasis Area and Severity Index (PASI 75) score 12 weeks after the start of treatment [40]. After 24 weeks, approximately one-third of children achieved this outcome. Benefit of methotrexate is also documented in a retrospective study in which 24 children with psoriasis (including 17 with plaque psoriasis) received methotrexate (0.2 to 0.4 mg/kg per week). All but two children achieved at least a PASI 75 score during treatment (mean duration of use 4.97 months, range 2 to 16 months) [41].

Adverse effects and precautions – The most common side effects are gastrointestinal upset, upper respiratory infections, fatigue, and headaches. Bone marrow suppression and transaminase abnormalities may also occur. Administration of folic acid and subcutaneous, rather than oral, administration of methotrexate may help to diminish the gastrointestinal side effects [43]. Concomitant sulfa drugs should be avoided.

Baseline and subsequent laboratory monitoring to assess for hematologic and hepatic adverse effects is necessary for methotrexate therapy, generally monthly for the first three months and then every three to six months [1]. Tuberculosis screening should be performed prior to therapy. Female adolescent patients should be counseled about the drug's teratogenicity, and all children should avoid live vaccines while on methotrexate. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Precautions and prevention of adverse effects'.)

Phototherapy — Controlled administration of artificial ultraviolet light, specifically NBUVB, can be an appropriate therapy for some children. Phototherapy options include NBUVB and targeted phototherapy with the excimer laser. Of these, NBUVB is more commonly used for the treatment of children. The excimer laser provides the advantage of minimizing exposure of unaffected skin to ultraviolet B (UVB), but data on the efficacy and safety of the excimer laser in children are limited. Psoralen plus ultraviolet A (PUVA) phototherapy is rarely used in children due to concern for greater risk for side effects compared with NBUVB (see "UVB therapy (broadband and narrowband)" and "Targeted phototherapy" and "Psoralen plus ultraviolet A (PUVA) photochemotherapy"):

Administration – Phototherapy is usually administered in the outpatient setting two to three times per week. Once satisfactory improvement is achieved, the frequency of treatments is tapered as tolerated. The child must be able to follow instructions and should be comfortable with standing still in an enclosed space alone. School-age children are typically able to manage phototherapy; some younger children are reasonable candidates as well [44]. The multiple office visits can be time consuming and logistically challenging for some families.

Home phototherapy is a convenient alternative for children who have had phototherapy safely and effectively initiated in an outpatient setting. Patients and caregivers should be given clear instructions for the advancement of ultraviolet light exposure, and intermittent clinical follow-up is necessary. (See "Treatment of psoriasis in adults", section on 'Home phototherapy'.)

Efficacy – Uncontrolled studies support the efficacy of NBUVB phototherapy for psoriasis in children [45-47]. One of the largest studies is a retrospective study that included 88 children treated with NBUVB for psoriasis [45]. Of the 79 children available for final analysis, 73 (92 percent) achieved at least 75 percent clinical improvement, including 40 children (51 percent) who achieved complete clearance of skin lesions. The mean duration of treatment was approximately three months, and the median duration of remission was approximately 20 months.

Adverse effects and precautions – Potential side effects of NBUVB phototherapy include cutaneous erythema, dryness, pruritus, and blistering. Available data suggest that NBUVB does not increase the long-term risk for skin cancer; however, additional studies are necessary to confirm this, particularly in children. Topical vitamin D analogs should be applied after (not before) phototherapy sessions.

There are conflicting data on the impact of UVB phototherapy on serum folate levels [48]. Some authors have suggested supplementation with folic acid (0.8 mg per day) for all patients of childbearing potential who are receiving UVB phototherapy based upon studies that suggest UVB phototherapy may photodegrade folate and decrease folate levels [48]. (See "Folic acid supplementation in pregnancy".)

Xeroderma pigmentosum and lupus erythematosus are absolute contraindications to phototherapy. (See "UVB therapy (broadband and narrowband)", section on 'Short- and long-term adverse effects' and "UVB therapy (broadband and narrowband)", section on 'Contraindications'.)

Biologic agents — Efficacy of the tumor necrosis factor (TNF)-alpha inhibitors etanercept and adalimumab, the interleukin (IL) 12 and IL-23 inhibitor ustekinumab, and the IL-17A inhibitors ixekizumab and secukinumab for pediatric psoriasis has been demonstrated in randomized trials [32,49-52]. Unlike adalimumab, etanercept, ustekinumab, ixekizumab, and secukinumab are approved by the FDA for the treatment of psoriasis in children. FDA approval for these drugs is limited to children at least four years old for etanercept and at least six years old for ustekinumab, ixekizumab, and secukinumab (see "Treatment of psoriasis in adults", section on 'Biologic agents'):

Administration – Typical pediatric dose regimens for biologic agents are:

Etanercept – 0.8 mg/kg given once weekly up to a maximum dose of 50 mg.

Adalimumab – 0.8 mg/kg given at weeks 0 and 1 and then every other week to a maximum dose of 40 mg.

Ustekinumab – Weight-based dosing; for children ≤60 kg, 0.75 mg/kg; for children >60 kg to ≤100 kg, 45 mg; for children >100 kg, 90 mg; ustekinumab is given at weeks 0 and 4 and then every 12 weeks.

Ixekizumab – Weight-based dosing; for children <25 kg, 40 mg at week 0 and then 20 mg every four weeks; for children 25 to 50 kg, 80 mg at week 0 and then 40 mg every four weeks; for children >50 kg, 160 mg at week 0 and then 80 mg every four weeks.

Secukinumab – Weight-based dosing; for children <50 kg, 75 mg; for children ≥50 kg, 150 mg; secukinumab is given at weeks 0, 1, 2, 3, and 4 and then every four weeks.

Efficacy – Published randomized trials have demonstrated the efficacy and safety of etanercept, adalimumab, ustekinumab, ixekizumab, and secukinumab. Brief summaries of these trials are provided below:

Etanercept – In a 48-week trial in which 211 children with moderate to severe plaque psoriasis (ages 4 to 17 years) were randomly assigned to receive either etanercept (0.8 mg/kg [maximum dose 50 mg]) or placebo once weekly for 12 weeks, more children treated with etanercept achieved at least a PASI 75 score than children in the placebo group (57 versus 11 percent) at 12 weeks [50]. In addition, sustained efficacy of etanercept for pediatric psoriasis has been demonstrated through 96 weeks [53].

Adalimumab – In a trial in which 114 children (ages 4 to 17 years) with severe plaque psoriasis were randomly assigned to methotrexate (0.1 to 0.4 mg/kg per week) or one of two dose regimens of adalimumab (0.4 or 0.8 mg/kg every other week), more patients in the adalimumab 0.8 mg/kg dose group achieved a PASI 75 score than patients in the methotrexate group (58 versus 32 percent) after 16 weeks [28]. Sustained efficacy of adalimumab over 52 weeks in children aged 4 to 18 years has also been reported [54].

Ustekinumab – In a trial in which 110 adolescents with moderate to severe plaque psoriasis (ages 12 to 17 years) were randomly assigned to one of two regimens of ustekinumab (standard dosing or half-standard dosing), adolescents who received standard or half-standard dosing were more likely to achieve at least a PASI 75 score than children treated with placebo (81, 78, and 11 percent, respectively) [49].

Use of ustekinumab for children aged 6 to 11 years was evaluated in an open-label, single-arm study (CADMUS Jr study) of 44 children (≥6 to <12 years of age) with moderate to severe plaque psoriasis [55]. Patients received weight-based dosing of ustekinumab (<60 kg: 0.75 mg/kg; ≥60 to <100 kg: 45 mg; >100 kg: 90 mg) at weeks 0 and 4 and then every 12 weeks through week 40. At week 12, 34 patients (77 percent) achieved the primary endpoint of a score of 0 or 1 (clear or almost clear) on the 5-point Physician's Global Assessment scale. In addition, 37 patients (84 percent) achieved a PASI 75 score. The most common adverse events were nasopharyngitis, pharyngitis, and upper respiratory tract infections. Three patients experienced serious adverse events (infectious mononucleosis, eyelid injury, and attention deficit hyperactivity disorder), none of which were considered by the investigators to be related to treatment.

Ixekizumab – In a trial in which 171 pediatric patients (ages 6 to <18 years of age) with moderate to severe plaque psoriasis were randomly assigned to weight-based dosing of ixekizumab or placebo, 102 of 115 patients (89 percent) in the ixekizumab group achieved PASI 75 at week 12 compared with 14 of 56 patients (25 percent) in the placebo group [52].

Secukinumab – A trial in which 162 pediatric patients (ages 6 to 18 years) with severe chronic plaque psoriasis were randomly assigned to weight-based low-dose secukinumab, weight-based high-dose secukinumab, etanercept, or placebo found both dose regimens for secukinumab more effective than placebo [32]. At week 12, 80, 78, 63, and 15 percent of patients in the low-dose secukinumab, high-dose secukinumab, etanercept, and placebo groups, respectively, achieved PASI 75, with a statistically significant difference between each secukinumab group and the placebo group.

Low-dose secukinumab was 150 mg for patients ≥50 kg and 75 mg for patients 25 to <50 kg; high-dose secukinumab was 300 mg for patients ≥50 kg and 150 mg for patients 25 to <50 kg. All patients <25 kg received 75 mg doses. The most common adverse events in the secukinumab group were nasopharyngitis, headache, pharyngitis, and rhinitis. Serious adverse events were infrequent and occurred at a similar frequency across study groups.

The efficacy and safety of other antipsoriatic biologic agents, including brodalumab, certolizumab pegol, guselkumab, tildrakizumab, and risankizumab, for pediatric psoriasis remains to be determined.

Adverse effects and precautions – The most common side effects of biologic agents are injection site reactions and upper respiratory tract infections. Although there is concern for increased risk of opportunistic infections and malignancies, serious adverse events are rare in children. In the randomized trial that compared adalimumab with methotrexate, rates of infection were similar among the treatment groups [28]. Patients treated with IL-17 inhibitors, such as ixekizumab and secukinumab, may have an increased risk for IBD [56,57]. Increased risk of malignancy has not been documented in children treated with biologic agents for psoriasis. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects".)

Pretreatment screening for tuberculosis is indicted for children who will receive biologic therapy, and continued annual screening during therapy is indicated for children receiving TNF-alpha inhibitors [1]. The value of annual screening is uncertain for children receiving other biologic drugs. For these patients, the decision to screen may be based upon risk factors for tuberculosis infection (see "Latent tuberculosis infection in children", section on 'Whom to test'). Until evidence of safety is available, live vaccines should be avoided during therapy.

Other therapies — Less commonly used therapies include cyclosporine, acitretin, fumaric acid esters, and apremilast.

Cyclosporine — Cyclosporine is generally reserved for severe and refractory psoriasis, such as erythrodermic psoriasis:

AdministrationCyclosporine is typically given orally at a dose of 4 to 5 mg/kg per day in two divided doses. Improvement can be rapid, with marked improvement often occurring within the first month of treatment. Once the disease is controlled, the dose can be tapered as tolerated. The duration of treatment should be limited to less than one year because of toxicities, particularly hypertension, renal and hepatic injury, and future malignancies.

Efficacy – Although cyclosporine has a long history of use for adult psoriasis, data on use for pediatric plaque psoriasis are limited [58]. In a retrospective study of 38 children and adolescents given cyclosporine for plaque psoriasis (median daily dose 3.2 mg/kg, range 2 to 5 mg/kg), 15 (39 percent) achieved at least a PASI 75 score after 16 weeks [59]. Eight patients had to discontinue treatment due to side effects. (See "Treatment of psoriasis in adults", section on 'Cyclosporine'.)

Adverse effects and precautions – Serious side effects of cyclosporine include nephrotoxicity, hypertension, hepatotoxicity, hyperlipidemia, metabolic abnormalities, and increased risk for infections and malignancy. Laboratory monitoring to detect side effects and blood pressure checks are required during treatment. Live vaccines and macrolide antibiotics, which increase cyclosporine levels, should be avoided during treatment.

Acitretin — Oral retinoids are accepted, effective treatments for pustular, palmoplantar, and erythrodermic psoriasis but are generally considered less effective for plaque psoriasis than other systemic therapies [60,61]. Acitretin is the oral retinoid of choice for psoriasis. In our practice, we most often use acitretin for pustular psoriasis:

AdministrationAcitretin is typically given at a dose of 0.5 to 1 mg/kg per day for plaque psoriasis and typically takes two to three months for efficacy [1]. Upon achievement of a satisfactory response, dosing can be tapered to the lowest dose necessary to maintain improvement.

Efficacy – Efficacy data for pediatric plaque psoriasis are limited [58,62,63]. In a retrospective study of 154 children treated with systemic therapy for moderate to severe psoriasis, of the 78 children treated with acitretin for plaque psoriasis, 27 (35 percent) achieved at least 75 percent clearance of skin disease [63].

Adverse effects and precautions – The most common side effects are skin and mucosal membrane dryness and elevation of serum triglyceride levels. Laboratory monitoring for hematologic abnormalities, hepatotoxicity, and hyperlipidemia is necessary during treatment. Oral retinoids are teratogenic, and pregnancy must be avoided for three years after cessation of acitretin.

Other — Fumaric acid esters are an additional type of treatment that is not available in the United States. Limited data suggest benefit of apremilast in pediatric psoriasis:

Fumaric acid esters – Fumaric acid esters are used for the treatment of psoriasis in Europe. A trial in which 135 children (ages 10 to 17 years) with moderate to severe plaque psoriasis were randomly assigned in a 2:1 ratio to fumaric acid esters tablets or placebo supports efficacy of fumaric acid esters [64]. At week 20, 55 percent of patients in the fumaric acid esters group achieved PASI 75 compared with only 19 percent in the placebo group. Gastrointestinal disorders were the most common adverse events.

Retrospective studies, case series, and case reports also support efficacy in children [58]. One of the largest studies, a retrospective study of 127 children (ages 6 to 17 years) treated with fumaric acid esters for psoriasis (including 96 children with plaque psoriasis), found that disease severity improved during treatment [65]. An approximately 50 percent improvement in the mean PASI score occurred within the first three months of treatment. Gastrointestinal disorders and flushing were the most common side effects.

In a separate case series of 14 children with recalcitrant plaque psoriasis, treatment with fumaric acid esters (maximum daily dose 180 to 1200 mg per day and mean treatment duration of 48.6 weeks, range 12 to 124 weeks) was associated with improvement in the PASI score in nine children (64 percent) [66].

Lymphopenia is a potential side effect of fumaric acid esters. Progressive multifocal leukoencephalopathy has been reported in lymphopenic patients who continued fumaric acid esters therapy [67-69].

Apremilast – Limited data suggest that apremilast, an oral phosphodiesterase 4 inhibitor, may be an option for chronic plaque psoriasis in children. A phase 2, open-label study in which 42 pediatric patients aged 6 to 17 years with moderate to severe plaque psoriasis received apremilast (20 or 30 mg given twice daily based upon weight and age) for two weeks, followed by a 48-week extension phase in which treatment was continued, found a mean improvement in the week 12 PASI score of 68 percent among adolescents (age 12 to 17 years) and 79 percent among children (age 6 to 11 years) [70]. The most common adverse events were nausea, headache, abdominal pain, nasopharyngitis, diarrhea, and vomiting.

Of the 42 patients, 31 completed the treatment extension phase. Five patients had adverse events that led to temporary drug interruption, and two patients had adverse events that led to drug withdrawal. Other reasons for treatment cessation included study withdrawal by the patient (six patients), loss to follow-up (one patient), dissatisfaction with response to treatment (one patient), and patient-reported suicidal ideation (one patient). Of note, dose titration at the start of therapy, which is often utilized to reduce adverse events from apremilast in adults, was not performed.

Additional study is necessary to confirm efficacy and safety of apremilast for plaque psoriasis in children. (See "Treatment of psoriasis in adults", section on 'Apremilast'.)

SPECIAL POPULATIONS — Modifications to the therapeutic approach are warranted in children with concomitant psoriatic arthritis and very young children.

Children with psoriatic arthritis — Appropriate management of psoriatic arthritis is important to minimize risk for poor outcomes and disability. Often, joint disease warrants systemic therapy that improves concomitant skin disease. Methotrexate and all of the biologic therapies typically used for psoriasis in children (etanercept, adalimumab, ustekinumab, ixekizumab, and secukinumab) can be effective for psoriatic arthritis. (See "Psoriatic juvenile idiopathic arthritis: Management and prognosis".)

Very young children — Although mild to moderate plaque psoriasis in children under the age of four years is likely to respond to the general approach described above, modifications are appropriate for this population. In general, less potent topical corticosteroids (groups 4 to 7 (table 1)) are preferred over higher-potency agents. For children in diapers, treatment of this area with topical corticosteroids should be monitored closely, since the occlusive effect of the diaper may increase risk for cutaneous side effects (picture 1I). (See 'Face and intertriginous skin' above.)

As with older children, the primary treatments for facial and intertriginous psoriasis are topical calcineurin inhibitors and low-potency topical corticosteroids. We prefer to use topical calcineurin inhibitors (tacrolimus 0.03% or pimecrolimus 1%) for facial and intertriginous psoriasis, particularly when continuous corticosteroid therapy is required for disease control or side effects from topical corticosteroid therapy have occurred. Safety concerns regarding the use of topical calcineurin inhibitors are reviewed separately. (See "Treatment of atopic dermatitis (eczema)", section on 'Safety' and "Treatment of atopic dermatitis (eczema)", section on 'Off-label use in infants'.)

Topical vitamin D analogs and topical retinoids are rarely used in the treatment of infants because of the common side effect of skin irritation.

Our approach to moderate to severe psoriasis in children under the age of four primarily consists of optimization of topical therapy. We typically avoid phototherapy and systemic therapies in this age group because of safety concerns with use in this population. However, use of these interventions is necessary in rare, refractory cases.

PROGNOSIS — Psoriasis in children is typically chronic, but its course is unpredictable. Spontaneous remissions and exacerbations are common. Occasionally, alleviating conditions, such as sun exposure during the summer months, or triggers, including infections and trauma, can be identified. The available therapies provide satisfactory disease control for the majority of pediatric patients.

PATIENT AND FAMILY SUPPORT — The National Psoriasis Foundation is a useful informational and support resource for patients and their families.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Psoriasis" and "Society guideline links: COVID-19 – Index of guideline topics".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Psoriasis (The Basics)" and "Patient education: Psoriatic arthritis in children (The Basics)")

Beyond the Basics topics (see "Patient education: Psoriasis (Beyond the Basics)" and "Patient education: Psoriatic arthritis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Overview – Psoriasis is an immune-mediated disease that occurs in children and adults. Chronic plaque psoriasis is the most common type of psoriasis in children (picture 1A-I). (See "Psoriasis in children: Epidemiology, clinical manifestations, and diagnosis".)

Many of the treatments used for plaque psoriasis in children and adults are similar; however, efficacy and safety data in children are more limited. Major treatment options include topical therapies (corticosteroids, calcineurin inhibitors, and vitamin D analogs), narrowband ultraviolet B (NBUVB) phototherapy, and systemic therapies. Options for systemic therapy include methotrexate, various biologic agents, cyclosporine, acitretin, and apremilast. Fumaric acid esters are additional treatment options that are not available in the United States. (See 'Introduction' above.)

Treatment selection – Patient-specific factors, such as severity of disease (mild to moderate versus moderate to severe plaque psoriasis), patient age, comorbidities, and tolerance of the risks and side effects of specific medications, guide the approach to treatment (algorithm 1). Mild to moderate psoriasis can often be treated with topical therapies; moderate to severe psoriasis often requires phototherapy or systemic therapy. (See 'Patient assessment' above.)

Mild to moderate plaque psoriasis – For children with mild to moderate plaque psoriasis (psoriasis involving less than 10 percent of the body surface area), we recommend topical agents as initial therapy rather than systemic therapy or phototherapy (Grade 1B). Topical corticosteroids are the mainstays of treatment. Topical calcineurin inhibitors and topical vitamin D analogs are additional, common, corticosteroid-sparing treatments. Tazarotene, tar, and anthralin are less frequently used topical treatments. (See 'Mild to moderate plaque psoriasis in children at least four years of age' above.)

Modification of the approach to topical treatment is helpful for children under the age four years and children with psoriasis on the face, intertriginous skin, and scalp (picture 1D-E). (See 'Special sites' above and 'Very young children' above.)

Moderate to severe plaque psoriasis – Our typical treatments for children with moderate to severe plaque psoriasis (psoriasis involving more than 10 percent of the body surface area or that cannot be successfully treated with topical therapy) who are at least four years of age include methotrexate, NBUVB phototherapy, and antipsoriatic biologic agents. We typically attempt a trial of topical therapy prior to proceeding to phototherapy and systemic therapy. (See 'Trial of topical therapy' above.)

The choice among methotrexate, phototherapy, and biologic therapy is based upon consideration of factors such as severity of disease, comorbidities, tolerance of risks and side effects, treatment availability, and prior treatment history. Methotrexate can be administered orally and has a long history of use for pediatric psoriasis but requires laboratory monitoring. Phototherapy is favored when there is a desire to avoid systemic therapy but requires frequent clinic visits. Biologic agents can be highly effective but are administered via injection, which can be challenging for some children (see 'Selection of systemic therapy' above):

Selection of biologic therapy – Biologic therapies typically used for chronic plaque psoriasis in children include ustekinumab, ixekizumab, secukinumab, etanercept, and adalimumab. Data on the relative efficacy of individual biologic agents for pediatric psoriasis are limited. There is no single biologic therapy that is preferred for the initial treatment of all patients. Shared decision making with the patient and/or caregiver(s) plays an important role in treatment selection (see 'Selection of systemic therapy' above):

-Children ≥4 years old – For children who are proceeding with biologic therapy, we suggest ustekinumab over other biologic drugs given the lower burden of treatment associated with less frequent dosing (Grade 2C). Ixekizumab, secukinumab, and adalimumab are reasonable alternatives. Although studies in adults indicate that secukinumab and ixekizumab are more effective than ustekinumab, there is lower-quality evidence to support superiority in children. (See 'Biologic agents' above.)

Access to specific treatments may influence the selection of biologic therapy. In the United States, the status of etanercept as the only US Food and Drug Administration (FDA) approved biologic therapy for psoriasis in children four and five years of age often necessitates use of etanercept for initial therapy in this population. However, etanercept may be less effective than other biologic therapies and requires weekly injection. (See 'Biologic agents' above.)

-Children <4 years old – Optimization of topical therapy is preferred for children under four years of age because of safety concerns with use in this population. However, use of phototherapy or systemic therapy is necessary in rare, refractory cases. (See 'Very young children' above.)

Prognosis – Psoriasis in children tends to be chronic but has an unpredictable course. Spontaneous remissions and exacerbations are common. (See 'Prognosis' above.)

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Topic 112983 Version 14.0

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