Psoriasis is a polygenic disorder associated with immunological and environmental factors. Well-known triggers include β-hemolytic Streptococcus infection, abrupt corticosteroid withdrawal, smoking, lithium, antimalarials, β-blockers, and paradoxically TNF inhibitors.1,6

Immunologic process involves innate and adaptive system through activation of T cells, Langerhans cells, and macrophages, dysfunctional keratinocyte differentiation, and impairment of the cutaneous barrier. Autoantigens stimulate dendritic cells within psoriatic plaques to produce Tumor Necrosis Factor-α (TNF-α), Interferon-γ (IFN-γ), Interleukin (IL)-12, and IL-23, thereby directing helper T-lymphocytes (Th) to differentiate into Th1, Th17, and Th22.7,8

T-cells that migrate into psoriatic plaques during the inflammatory phase and acquire the capacity to persist either in the dermis (CD4+CD69+) or in the epidermis (CD8+, CD69+, CD103+) are defined as tissue-resident memory T-cells (TRM). These cells are implicated in lesion reactivation, suggesting that antigen re-exposure, in the presence of TRM and their pro-inflammatory cytokines, are related to disease relapse.9,10 Despite limited data, pediatric lesions show distinct signatures: Kim et al. (2020) reported higher CD8 and TNF-α with lower FoxP3 and IL-17A versus adults.11 Cordoro et al. (2017) found higher IL-22 and lower IL-17 compared with adult lesions and healthy controls.12

Nearly 20% of patients report a family history of psoriasis, about one hundred susceptibility loci have been implicated, and several designated PSORS. HLA-C*06:02 (PSORS1), located within the major histocompatibility complex at 6p21, shows the strongest association with early onset disease and confers up to a fivefold increase in risk.13 It has also been linked to guttate, gestational, and nail psoriasis.14 Genome Wide Association Studies (GWAS) have identified different genes related to psoriasis, such as Th1 (IL12B, TYK2) and Th17 (IL23R, IL17R) signaling pathways, innate immunity (NF-κB, TRAF3IP2), and skin barrier function (DEFB4, LCE3B/C), as shown in Table 1.8 Over the past two decades, advances in the immunobiology and genetics of psoriasis have enabled highly effective targeted therapies against TNF-α, the IL-23/Th17 axis, and JAK signaling.15

Epigenetic mechanisms also contribute to immunopathogenesis by altering gene expression in disease-relevant pathways.9,15

Psoriasis has many different clinical phenotypes, whereas the most frequent is chronic plaque, witch symmetric erythematous scaly plaques on elbows, knees, scalp, and lumbosacral area. Other phenotypes include: inverse (involvement of intertriginous areas), genital, erythrodermic (involving > 75% of body surface area with high risk for hypothermia, electrolyte imbalance and cardiac failure), palmoplantar, nail, guttate, and pustular forms.1,3 Different psoriasis phenotypes commonly coexist. Beyond skin and nail manifestations, psoriasis also encompasses extracutaneous domains such as arthritis, enthesitis, and dactylitis.16

Pediatric psoriasis presents peculiarities compared to adults. Plaque psoriasis is most common form, accounting 41% of pediatric cases. Often with an abrupt onset, plaques are less scaly and may appear hypopigmented or follicular, with predilection for face, periorificial regions, flexures, anogenital areas, scalp implantation, and umbilicus.17 Inverse and diaper psoriasis is the second most common childhood form, followed by guttate, which is characterized by small plaques, often post-infectious.18 Nail involvement occurs in 10%–40%, presenting with pitting, onycholysis, subungual hyperkeratosis, and “oil-drop” discoloration.19 Pustular psoriasis is rare in children and manifests with sterile pustules on an erythematous base and includes generalized (Von Zumbusch), anular, circinate, exanthematous, and localized palmoplantar variants. Generalized Pustular Psoriasis (GPP) is an acute, severe form requiring urgent care and may be triggered by abrupt systemic corticosteroid withdrawal, hypocalcemia, or infection.20Figures 1, 2 and 3 show different clinical presentations of pediatric psoriasis.

Fig. 1.

Clinical presentations of psoriasis – (A) disseminated, (B) Genital.

Fig. 2.

Clinical presentations of psoriasis – (A) Erythrodermic with scalp involvement, (B) Pustular.

Fig. 3.

Clinical presentations of psoriasis – (A) Plantar, (B) Nail and palmar.

Burden-Teh et al. (2022) proposed seven diagnostic criteria for pediatric psoriasis (Fig. 4). The presence of two or more positive criteria has 78% of sensitivity.21

Fig. 4.

Diagnostic criteria for pediatric psoriasis. Adopted by Burden-Teh et al. 2022.21

Differential diagnosis in children include: (i) Inflammatory dermatoses, such as atopic, contact or seborreic dermatites, pityriasis rosea, (ii); Infections, such as impetigo, dermatophytosis, candidiasis;6 and (iii) Lymphoproliferative disorder, mycosis fungoides and histiocytosis; and (iv) Genodermatoses with erythema and scales ichthyoses and erythrokeratodermia (Fig. 5).

Fig. 5.

Differential diagnoses for psoriasis – (A) Eritroqueratodermia variabilis, (B) Atopic Dermatitis.

Reports of Psoriasis (PSO) and Atopic Dermatitis (AD) overlap have increased with the advent of biologics, particularly in children and in Asian populations, where clinical, genetic, immunologic, and histopathologic features of both diseases may converge. Asian type AD often shows Th17/Th22 pathway predominance, resembling the erythrodermic forms of PSO or AD. A recent pragmatic classification includes: (i) PSO with AD-like features; (ii) AD with PSO-like features (Asian type AD); (iii) Coexistence “psoriasis dermatitis”; (iv) AD emerging during biologic therapy for PSO; and (v) PSO emerging during biologic therapy for AD.22

Autoinflammatory Keratinization Diseases (AIKDs) expand the pediatric psoriasis differential. They are monogenic disorders with innate immune activation, diseases with mixed pathomechanisms of autoinflammation and autoimmunity, superficial dermal and epidermal inflammation, and disordered keratinization. Examples include type V pityriasis rubra pilaris (CARD14), acrodermatitis continua of Hallopeau (AP1S3), and CARD14-associated papulosquamous eruption. Suspect AIKD with early onset, familial clustering, systemic inflammation, or poor response to conventional therapy like methotrexate or acitretin.23

In common syndromic pustular conditions should also be considered, including SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis): Fig. 6, DIRA (deficiency of the IL-1 receptor antagonist)8,24 and DITRA (deficiency of the IL-36 receptor antagonist). These entities typically present with very early onset, associated with osteomyelitis, sterile arthritis, and severe systemic inflammation.8,25

Fig. 6.

Palmoplantar pustulosis in SAPHO Syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis).

The diagnosis of psoriasis is primarily clinical, based on recognition of elementary lesions such as erythematous-scaly macules or papules, pustules, palmoplantar hyperkeratosis, and nail dystrophy. In children, attention to typical sites of involvement is essential. Brocq’s methodical curettage supports the diagnosis by demonstrating the candle-grease sign (lamellar scaling) and the Auspitz sign (pinpoint bleeding after scale removal).6 When required, histopathological examination reveals parakeratosis, hyperkeratosis, acanthosis, absence or thinning of the granular layer, elongation of the rete ridges, papillary dermal edema, dilated capillaries, and a perivascular inflammatory infiltrate composed mainly of T-lymphocytes. Aggregates of neutrophils infiltrating the epidermis and dermis may also be observed, forming Munro’s microabscesses or Kogoj’s pustules.1

Laboratory and imaging tests are not mandatory for diagnosis but may assist clinical evaluation in the presence of systemic symptoms such as fever, recurrent infections, pain, diarrhea, or in extensive or pustular forms. These include erythrocyte sedimentation rate, C-reactive protein, complete blood count, hepatic and renal function tests, chest X-Ray, or ultrasonography in cases with arthralgia or arthritis, primarily to exclude differential diagnoses or identify associated comorbidities. When genodermatoses or autoinflammatory diseases are suspected, a genetic panel or whole-exome sequencing may be indicated.

There are several tools for severity assessment, including the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), Physician’s Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI).26 For children aged 4- to 16-years, the Children’s Dermatology Life Quality Index (CDLQI) is employed.27 Severe psoriasis is defined as PASI > 10, BSA > 10, DLQI > 10,28 or pustular psoriasis flare.14 In pediatric cases, BSA and CDLQI are more commonly applied.19

The most common comorbidity associated with pediatric psoriasis is Psoriatic Arthritis (PSA), affecting approximately 0.7% of children, with peaks of incidence between 2–3 years and 10–12 years of age. Children with psoriasis also exhibit a two- to four-fold increased prevalence of Crohn’s disease and rheumatoid arthritis compared with those without psoriasis.18,29 In adults, the association of psoriasis with metabolic syndrome, cardiovascular disease, and mood disorders is well established, particularly in severe cases.1,14 In children, however, the evidence remains conflicting. A meta-analysis including over 40.000 pediatric psoriasis cases demonstrated an association between severe psoriasis and overweight/obesity, as well as an increased risk of metabolic syndrome, diabetes mellitus, hypertension, and ischemic cardiovascular disease, thereby justifying screening in this population.30 Other authors argue that in the absence of obesity, cardiovascular risk assessment should follow the pediatric society recommendations according to age group, clinical signs, and symptoms.29 Evidence to support systematic screening for non-cardiometabolic comorbidities in children with psoriasis is limited; therefore depending on clinical assessment.19

Psoriasis has extensive evidence of quality-of-life impairment, with physical symptoms as itch, skin pain and higher risks of anxiety and depression. Social burden as bullying and stigma, consistently harms their development and is greatest with large body surface area or special site involvement like face, scalp, palms/soles and genital.31,32 In Brazilian cohorts, the highest CDLQI means occur in atopic dermatitis and psoriasis.27 Early onset, greater severity, and comorbidities contribute to Cumulative Life Course Impairment (CLCI), affecting school and professional performance, relationships and family planning.32 Caregivers' impact is measurable by the Family Dermatology Life Quality Index (FDLQI), reflecting the impact of added tasks and costs with appointments and medication management.18

Patients with psoriasis should be classified as candidates for topical or systemic therapy, according to disease severity metrics, comorbidities, psoriatic arthritis, patient and family preferences.33 General measures include regular emollient use and cardiometabolic risk reduction with physical activity and weight control.

The use of emollients and keratolytic agents plays an important role in the management of pediatric dermatoses. Moisturizers and keratolytic agents, such as urea (2%–10%) and salicylic acid (3%–6%), may be incorporated into therapeutic regimens. Urea improves skin barrier function and reduces pruritus, scaling, and hyperkeratosis in patients with psoriasis,34 however, evidence regarding the use of urea in children is limited.

Salicylic acid is commonly used as a keratolytic agent, often in combination with topical corticosteroids such as betamethasone dipropionate or mometasone, preferably in children aged ≥12-years. Its application over large body surface areas or at higher concentrations should be avoided due to the risk of salicylism.14

Topical corticosteroids are the first-line treatment for pediatric psoriasis. Employed as monotherapy or in combination with vitamin-D analogues. Their use should be avoided on the face, genital and intertriginous areas. Prolonged or extensive use can lead to stretch marks and skin atrophy, in addition to systemic complications, including iatrogenic Cushing's syndrome, growth retardation, diabetes mellitus and high blood pressure.19

Topical calcineurin inhibitors, such as tacrolimus and pimecrolimus, are considered safe alternatives for special sites.35 Tacrolimus 0.03% is approved for children older than 2-years, and 0.1% for those above 16-years, whereas pimecrolimus 1% is indicated from three months of age.14 Vitamin-D analogues are recomended in children more than two years of age, and their combination with topical corticosteroids is considered safe.6 See Table 214,19,36 for topical treatment.

Candidates for systemic therapy include patients meeting at least one of the following criteria: 1) BSA or PASI or DLQI > 10%; 2) Involvement of special sites including face, palms and soles, genital area, scalp or nail; 3) Failure of topical therapy; 4) Occurrence of pustular psoriasis flares,14 and 5) Comorbidities such as psoriatic arthritis, uveitis, or inflammatory bowel disease.33

The therapeutic goal is the achievement of PASI 75, whereas treatment failure is defined as not reaching PASI 50. Patients achieving PASI 50–75 with a DLQI ≤ 5 are considered treatment success.14,19 For biologic therapies, the target outcome is PASI 90 or an absolute PASI < 3.14

For children with moderate to severe psoriasis, phototherapy is an effective therapeutic option. Narrowband UVB (311–313 nm) is considered safe and is particularly indicated for plaque and guttate psoriasis.19

Acitretin is an oral, non-immunosuppressive retinoid that can be used from six weeks of age, at a dose of 0.1–1 mg/kg/day,35 and in young children, capsules may be opened and mixed with milk due to its lipophilicity. Clinical response is generally seen within two months, although pustular psoriasis may improve within 72 -hs. Adverse effects include mucocutaneous xerosis, hyperlipidemia, especially hypertriglyceridemia, and hepatic transaminases elevation. Skeletal abnormality has not been demonstrated at doses up to 1 mg/kg/day, and routine bone imaging is not required unless there are symptoms such as bone pain or impaired mobility. Because acitretin is teratogenic for up to three years after cessation, it is contraindicated in females of childbearing potential. Baseline and periodic monitoring of liver enzymes, lipid profile, and complete blood count is recommended.19

Methotrexate is an immunosuppressive agent that targets Th1 and Th17 pathways. The recommended dose is 0.2–0.7 mg/kg/week, given orally or subcutaneously. Tablets may be crushed and diluted for easier administration in children. Folic acid supplementation: 1 mg daily except on the methotrexate day, or 5 mg once weekly 24 hours after the dose is recommended to reduce adverse effects such as mucositis, nausea, vomiting, and bone marrow suppression. Less common in children, the adverse effects include pancytopenia, hepatotoxicity, pulmonary toxicity and renal insufficiency. Females of childbearing potential should use contraception and undergo pregnancy testing.26 Monitoring includes complete blood count, liver enzymes, and creatinine before and during treatment, as well as serologies for hepatitis B/C and HIV, and chest radiography at baseline. Due to its low cost, effectiveness, and safety profile, methotrexate remains widely used in dermatology.36

Cyclosporine inhibits T-lymphocyte activation and suppresses IL-2 and interferon-γ production, thereby blocking inflammatory pathways in psoriasis. It is generally well tolerated and is considered an excellent option for rapid control of severe or pustular pediatric psoriasis.19

Available as an oral solution (100 mg/mL), the recommended dose is 2–5 mg/kg/day, divided into two doses, starting at the higher dose and tapering after disease control. Clinical response is often observed within two weeks. Major adverse events include arterial hypertension, nephrotoxicity, hepatotoxicity, and oncogenic potential. Others include hypertrichosis, gingival hyperplasia, hyperlipidemia, hyperuricemia, and hypomagnesemia. Baseline evaluation should include blood pressure, urea, creatinine, electrolytes, complete blood count, lipid profile, liver enzymes, viral serologies, chest radiograph, and pregnancy testing. Blood pressure, complete blood count, lipid profile, and electrolytes should be monitored every two weeks during the first month and monthly thereafter.26

Targeted therapies for psoriasis include biologic agents and small-molecule inhibitors. The first approved class was TNF-α inhibitors (etanercept, infliximab, adalimumab, certolizumab). Subsequent biologics were developed against specific interleukin pathways: IL-12/23 (ustekinumab), IL-17 (ixekizumab, secukinumab, brodalumab, bimekizumab), and IL-23 (risankizumab, tildrakizumab, guselkumab). More recently, the oral TYK2/JAK-pathway inhibitor deucravacitinib was introduced.37,38

In a systematic review of therapies for adult plaque psoriasis, Sbidian et al. (2021) reported that IL-17, IL-12/23, IL-23, and TNF-α inhibitors were significantly more effective in achieving PASI 90 compared with conventional therapies and JAK inhibitors, with better results to IL-23 inhibitor.38 Sun et al. (2022), using the same study design in pediatric psoriasis, confirmed the efficacy and safety of TNF-α, IL-17, and IL-12/23 inhibitors, although they highlighted limitations due to heterogeneity in study designs.39

Biologic agents: adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab, were approved for pediatric psoriasis according to the U.S. Food and Drug Administration (FDA) and European Medicines Association (EMA).40 Guselkumab, a IL-23 inhibitor, represents a recent therapeutic advances in pediatric psoriasis, approved by FDA for children aged ≥ 6-years and ≥ 40 kg, with moderate-to-severe psoriasis and psoriatic arthritis.41 In Brazil, therapeutic options for pediatric psoriasis expanded since the approval of TNF-α, IL-12/23, and IL-17 inhibitors for ≥ 6-years,14 and most recently guselcumabe for ≥ 12-year-old.42 The safety profile of biologics in pediatric patients is comparable to that observed in adults, with mostly mild adverse events such as injection site erythema, upper respiratory tract infections, headache, and náusea.40

Etanercept, a TNF-α inhibitor, is the only biologic available in the Brazilian public health system for children ≥6-years with moderate-to-severe psoriasis. It is indicated as second-line therapy when there is inadequate response or contraindication to conventional systemic agents such as methotrexate, cyclosporine, or acitretin.43 It is a recombinant fusion protein that blocks TNF-α receptors; its short half-life (2–5 days) and the receptor binding mechanism confer rapid onset and low antigenicity, supporting a favorable safety profile,44 although its efficacy is lower than IL inhibitors.45

Ixekizumab and secukinumab are anti–IL-17A monoclonal antibodies approved for use in children ≥6-years of age. Both demonstrate high efficacy and safety; however, patients should be monitored for Candida infections and for signs of inflammatory bowel disease.46

Ustekinumab is a fully human monoclonal antibody that binds with high affinity and specificity to the p40 subunit shared by IL-12 and IL-23. It is approved for the treatment of psoriasis and psoriatic arthritis in patients ≥6-years of age.

With IL-17 inhibitors, approximately 80%–90% of pediatric patients achieve PASI 75, and more than 70% achieve PASI 90 by week-12. With IL-12/23 inhibition, about 80% achieve PASI 75 and 54% achieve PASI 90 by week-12. By contrast, etanercept shows lower skin clearance rates, with PASI 75 in 56% and PASI 50 in 86% of patients at week-12.45

Guselkumab is a selective IL-23 inhibitor that targets the p19 subunit. A recent phase III randomized placebo-controlled study (PROTOSTAR) enrolled patients aged ≥ 6 to < 18 years with moderate-to-severe plaque psoriasis. Approximately 66% of patients receiving guselcumab achieved PASI 90 compared to 16% of patients receiving placebo at week-16.41 Dosing is based on body weight: 1.3 mg/kg (maximum 90 mg) for patients < 70 kg and 100 mg for those ≥ 70 kg, administered subcutaneously at weeks-0 and-4, then every 8-weeks.41,42

Before initiating biologic therapy, baseline assessment includes liver enzymes, creatinine, complete blood count, tuberculosis screening, hepatitis B and C serologies, HIV testing, and additional tests guided by clinical history. Vaccination status should be updated prior to initiation of immunosuppressive therapy.44 Non-live vaccines may be administered during treatment. Live or attenuated vaccines (BCG, rotavirus, oral polio, yellow fever, MMR, varicella, dengue) should generally be administered 2–4 weeks prior to starting immunosuppressive therapy. If discontinuation of immunosuppressants is required, a period of 4–5 half-lives should be observed before vaccination, and the biologic may be reintroduced 2–4 weeks thereafter.14

Table 3 summarizes the recommendations for systemic therapy from medical societies,14,19,36,47 and Table 4 presents a guideline for biological therapy regarding pediatric psoriasis.14