Psoriasis in Pediatric Age Group

Abstract

Psoriasis is a common, chronic, immune-mediated, multisystem, inflammatory disorder. It affects all age groups, including infancy. In one-third of the cases, the onset of the disease is in the first and second decades of life. Childhood psoriasis significantly affects the quality of life of the child as well as that of the entire family. Pediatric psoriasis has distinct clinical presentations and evolves with time. Like in adults, chronic plaque psoriasis has been found to be the most common type of childhood psoriasis. Psoriatic plaques in children are less pruritic, smaller and thinner with less prominent scaling. In pigmented skin, the erythema is less prominent and plaques appear violaceous or hyperpigmented. Pediatric psoriasis can be associated with arthritis, metabolic syndrome, depression and anxiety. Hence all children should be screened routinely for associated comorbidities. Management of pediatric psoriasis is challenging owing to the limitation of approved therapies. 'Proactive therapy' is a recent approach in childhood-onset psoriasis that would help to prevent the severity of flare-ups, thus improving the quality of life.

Introduction

Psoriasis is a chronic, inflammatory, immune-mediated papulosquamous disorder affecting all age groups. One-third of the cases are childhood-onset psoriasis.[1] Psoriasis in children significantly affects the quality of life (QoL) of the child and family members. Psoriasis in the pediatric age group differs from the adult onset type with respect to epidemiology, clinical features, treatment options and long-term clinical and psychological outcomes. Due to the lack of guidelines, management of childhood psoriasis remains a challenge for the treating dermatologist. The focus here is on the current aspects of childhood psoriasis.

Epidemiology

Childhood psoriasis is a well-recognized entity, yet its true prevalence is not known. The worldwide prevalence of childhood psoriasis ranges from 0.1% to 1.37%.[2] Das and Adhicari have reported a prevalence of 1.24% in Northeast India.[3] In another study from South India, childhood psoriasis comprised 0.6% of total outpatient cases and 17.8% of total psoriatic patients.[4] Various epidemiological studies of childhood psoriasis in India have shown the prevalence of psoriasis ranging between 0.5% and 2%.[1] Prevalence is much lower in the United States, Asia and Africa ranging from 0.02% to 0.1%. Factors like geographical area, ethnicity and environment may contribute to the worldwide variation in genetically susceptible individuals.[5] The peak age of onset varies in different studies. Indian studies have shown most children developed psoriasis at 6–14 years of age and girls outnumbered the boys.[3,6] Around 30%–48% presented with an affected first-degree relative.[7] Amulticenter, cross-sectional trial from the United States reported a family history of 51.4%, with affected members being first-degree relatives in 59.8%.[5] The risk of psoriasis in children is estimated to be around 25% if one parent is affected and 60%–70% if both parents are affected.[8]

The multifactorial nature of the disease and epidemiological evidence point toward the role of genetic background playing a key role in the pathogenesis. Linkage analysis has shown HLA CW6 identified as the susceptibility allele of PSORS1 and is associated with the early onset of psoriasis.[9] CARD14 mutation is associated with familial form of psoriasis. They present as sporadic, early onset or with severe generalized pustular psoriasis.[10]

Role of precipitating factors

Studies have shown that psoriasis in children can exacerbate during spring and autumn. Trauma and stress are known to precipitate psoriasis.[3] Many environmental triggers are implicated in psoriasis particularly, beta-hemolytic streptococci induced throat infections that can initiate and exacerbate psoriasis. T cells primed by streptococcal antigens in the tonsils may react with homologous antigens in the skin.[11] Few years ago there was no sufficient evidence to demonstrate the efficacy of either antibiotic therapy or tonsillectomy in the treatment of psoriasis, but the recent prospective series have shown that homozygous HLA CW*0602 carriage in plaque psoriasis may predict a favorable outcome after tonsillectomy.[12] A recent randomized controlled trial results suggest that tonsillectomy provides a good clinical response in selected patients with plaque psoriasis, history of sore throat associated exacerbation and HLA CW*0602 genotype.[13]

Peculiarities of childhood psoriasis

The major clinical forms are similar in children and adults. Chronic plaque psoriasis is the most common form of childhood psoriasis. Psoriasis in children more commonly involves the face, scalp, or intertriginous skin than adults. Involvement of the diaper area can be the initial manifestation of psoriasis in infants and young children.[3,6,8] In children with pigmented skin (Fitzpatrick skin type V or VI) the erythema component is less prominent and often plaques appear violaceous or hyperpigmented. The plaques are thinner and smaller with less prominent scaling than adults.[6] Several studies have shown that extremities and scalp are the most common sites of initial presentation.[1,3,4,6] Follicular psoriasis is observed more in children.[14] Widespread psoriasis and palmoplantar psoriasis are difficult scenarios in children as parents are apprehensive about the long-term prognosis.

Clinical presentations

Plaque psoriasis

Plaque psoriasis affects 34%–73% of children. The classical plaque is characterized by sharply demarcated, erythematous, hyperpigmented with silvery-white scales. Sites of predilection are similar to adults like extensor surfaces, knees, buttocks, elbow, scalp and trunk. Lesions resolve with hypopigmentation. Facial and anogenital areas may be affected in children.[7]

Guttate psoriasis

There is not much evidence regarding acute onset guttate psoriasis triggered by streptococcal pharyngitis. It is characterized by round to oval erythematous or violaceous papules and plaques varying from 2 mm-3 mm to 1 cm. They are often misdiagnosed as lichen planus. Guttate psoriasis may later evolve into chronic plaque psoriasis. They usually resolve by 3–4 months or can persist for up to a year. Recurrent episodes are common.[1,6] Studies have shown ASO titer positivity in 10.18% and positive throat culture for streptococcal infection in 5.5% of psoriatic children.[4]

Napkin psoriasis

Psoriasis in infancy is not uncommon. Napkin psoriasis presents as well-demarcated, bright-red, glazed plaques on the diaper area including groins and perianal region. Scaling is very minimal in napkin psoriasis due to high moisture content in diaper area.[1] Dissemination can occur and it must be differentiated from candidial diaper dermatitis with psoriasiform ID eruption.

Pustular psoriasis

Pustular psoriasis is very rare in pediatric age group. The prevalence of pustular psoriasis is 0.6%–7% in various studies.[1,15] Generalized pustular psoriasis and annular pustular psoriasis are more commonly seen in children. The Von Zumbusch type is characterized by multiple waves of widespread eruption of sterile pustules on an erythematous base, associated with fever. Juvenile generalized pustular psoriasis can occur at any age, but the onset of the disease is seen as early as 1^st year of life.[15] A mixed clinical pattern is also seen in children. Interleukin 36RN mutation and caspase recruitment domain family member (CARD14) gain of function mutation has been associated as a predisposing factor for generalized pustular psoriasis and palmoplantar psoriasis in children.[16] The deficiency of the IL36 receptor antagonist is characterized by recurrent episodes of generalized pustular psoriasis with systemic inflammation and fever. Deficiency of interleukin-1 receptor antagonist is a rare life-threatening autoinflammatory disease caused by mutations in IL1RN. It is an autosomal recessive disorder that presents clinically with early onset of generalized pustulosis, sterile osteomyelitis, periostitis and elevation of acute phase reactants.[17]

Scalp psoriasis

Scalp psoriasis is also a common form of psoriasis seen in children and is often the first site of presentation documented in a few studies. In early childhood it should be differentiated from atopic dermatitis and seborrheic dermatitis. Severe forms can present as pityriasis amiantacea with thick, fixed, silvery scales.[1]

Less common subtypes of psoriasis

The less common variants of psoriasis include nail psoriasis, palmoplantar psoriasis, psoriatic arthritis and inverse psoriasis. The overall prevalence of nail psoriasis in children ranges from 20% to 40%.[6] Nail involvement was commonly associated with palmoplantar psoriasis, severe disease and psoriatic arthritis. In a recent study of pediatric psoriasis comprising 313 children, nail involvement was seen in 32.3% with girls outnumbering the boys. Pitting of the fingernails was seen in 69.1% followed by onycholysis in 40%.[18] Inverse psoriasis is frequently seen in infants affecting the flexural and intertriginous areas and appears as glazed erythema. Psoriatic arthritis may precede or follow the onset of cutaneous psoriasis. Juvenile psoriatic arthritis is recognized as an inflammatory arthritis in children and affects 0.7%–10% of children with psoriasis and is more commonly seen in the age group of 9–12 years. Younger children present with dactylitis and small joint involvement and older children have enthesitis and axial joint disease.[19]

Rare variants have been reported in children like linear, annular, mucosal, or erythrodermic psoriasis. Tongue involvement is seen in 5%–10% of children. Migratory glossitis also called as geographic tongue is associated with psoriasis in children. Few reports of congenital psoriasis have been described, but the clinical features have not been well characterized. As compared to childhood psoriasis, congenital psoriasis has a lower prevalence of family history and a different anatomical involvement.[20] Although the pathogenesis of psoriasis and atopic dermatitis is different, psoriasis has been found to be associated with atopy and atopic dermatitis. Recent studies have shown concomitant psoriasis and atopic dermatitis presents more frequently in boys and overweight children and had skin lesions equally distributed throughout the body. There were significant differences observed in the concentration of IL-17 between patients with AD and psoriasis and those with only atopic dermatitis or psoriasis.[21]

Comorbidities with pediatric psoriasis

There is well documented adult psoriasis associated with metabolic syndrome. Based on the SORT level C expert recommendation, all pediatric patients having psoriasis should be screened for arthritis, metabolic syndrome, depression and anxiety.[22] A recent systematic review and pooled meta-analysis data have shown that there is a statistically significant association with pediatric psoriasis and overweight/obesity as well as waist: height ratio >0.5 along with metabolic syndrome, diabetes, hyperlipidemia, hypertension, cardiac ischemia and failure.[23] Non-metabolic comorbidities associated with pediatric psoriasis include celiac disease, rheumatoid arthritis, atopic dermatitis, vitiligo, alopecia areata, lichen planus, epilepsy, valvular cardiomyopathy and ischemic heart disease.[24]

The concept of 'psoriatic march' defines the sequence of severe psoriasis causing systemic inflammation, insulin resistance and endothelial dysfunction leading to atherosclerosis, myocardial infarction and cardiovascular comorbidities.[25] In comparison with comorbidities in adult psoriasis, juvenile psoriasis presents with increased prevalence of arterial hypertension, hyperlipidemia, rheumatoid arthritis and Crohn's disease.[26] Recommendation for monitoring comorbidities in pediatric psoriasis is outlined in [Table 1].[23,24] Assessing comorbidities is also important while considering systemic treatment like acitretin and cyclosporine, as they may have an impact on comorbidities.[24]

Table 1.

Monitoring guidelines for comorbidities in pediatric psoriasis

Comorbidity	Guidelines
Obesity	Screen for overweight and obesity using BMI criteria at two years of age
Type 2 diabetes	Screen obese children or overweight using fasting serum glucose with risk factors every three years starting at age ten years or puberty onset
Dyslipidemia	Screen children ages 9-11 years and aged 17-21 years using fasting lipid panel
	Otherwise: screen children with cardiovascular risk factors
Hypertension	Screen yearly starting at age three years (age/sex/height reference charts)
Nonalcoholic fatty liver disease	Screen obese children overweight with risk factors using ALT starting at age 9-11 years, consider repeating in two to three years
Mood changes	Screen yearly for depression and anxiety regardless of age.
	Screen yearly for substance abuse starting at age 11 years.

Challenges in management

Management of pediatric psoriasis is challenging due to limitation of officially approved therapies, paucity of evidence-based data from randomized controlled trials, lack of standardized guidelines and limited long-term safety data about newer therapies. Treatment of pediatric psoriasis is not limited only to the child, as it also affects the QoL of the whole family. The concept of total care should be practiced while managing pediatric psoriasis. Counseling parents about the chronic nature of the disease, systemic associations and available treatment options are necessary. The goal of therapy is to maintain the disease under control rather than obtaining complete clearance of lesions. The various topical and systemic drugs for pediatric psoriasis are outlined in Table 2. The severity of assessment is based on the body surface area and QoL.[27,28]

Table 2.

Management of Pediatric Psoriasis

Assessment of severity and comorbidities

Topical treatments

Corticosteroids

Calcineurin inhibitors

Vitamin D analogues

Retinoids-tazarotene

Anthralin

Coal tar

Combination therapy

Phototherapy

Narrowband ultraviolet light B

Psoralen and ultraviolet light A

Nonbiologics

Methotrexate

Cyclosporin A

Retinoids

Fumaric acid esters

Biologics

Etanercept

Adalimumab

Ustekinumab

Secukinumab

Apremilast

Topical therapies

Topical medication forms the first line of therapeutic armamentarium for limited extent disease, and also as an adjunct therapy with systemic drugs. Though cost-effective, safe and convenient, non-compliance and self-application to certain body sites may be a liability. Commonly used topical medications include corticosteroids, salicylic acid, vitamin D analogues, calcineurin inhibitors and less used dithranol and coal tar. Topical steroids are the most commonly prescribed medications for pediatric psoriasis alone or in combination with keratolytics. The National Institute for Health and Care Excellence recommends the use of potent topical steroids as the first line of management in pediatric psoriasis.[29] Precaution should be taken while prescribing salicylic acid as even small amounts can lead to salicylism, central nervous system, or renal side effects.

Tacrolimus 0.03% and 0.1% ointment has been used in facial, genital psoriasis and intertriginous areas, although the response rate is around 50% in children.[28] Vitamin D analogs are recommended in children more than two years of age, especially for plaque and scalp psoriasis. Oostveen et al.[29] in their study have shown good efficacy and safety of combination of calcipotriol and betamethasone dipropionate in scalp psoriasis in 73 children aged 4–17 years; however, the available evidence does not show that combination therapy yields significant outcomes in children.[30] Four studies have assessed the efficacy of short-contact dithranol therapy on pediatric plaque psoriasis and have shown a good efficacy of around 69.5%.[30] Anthralin is applied as 0.1% cream daily for 10–30 min and increased every other day up to 3%–4% until mild irritation occurs.[31]

Phototherapy

Phototherapy can also be given to younger children as long they are able to stand in the phototherapy chamber. Narrow band UVB therapy (311–313 nm) is preferred and well tolerated in children with guttate and plaque psoriasis. In children above 12 years of age, psoralens with UVA can be given. Though phototherapy is effective and can be considered the first line of therapy in children with extensive involvement, it has a few drawbacks. Children are not able to adhere to the treatment due to school activities and a prolonged period of therapy. NBUVB is indicated in moderate psoriasis with >15%–20% of body surface area involvement, mild to moderate psoriasis where systemic therapy is contraindicated, focal disabling palmoplantar psoriasis or in children with suboptimal response to topical therapy.[32]

Nonbiologic systemic drugs

Systemic therapy is the treatment of choice in children with generalized involvement in all types of psoriasis and psoriatic arthropathy. To date, there is no consensus regarding the dosing regimen and treatment duration. A few of the systemic drugs in pediatric psoriasis are summarized in Table 3.[28,33] Cautious administration and regular monitoring of infection and immunosuppression along with routine investigations are foremost important to prevent adverse effects of these medications. Though cyclosporine is very effective in extensive psoriasis, relapses are common with the stoppage of the drug. Hence preferably cyclosporine should be used for a few weeks initially in acute stage (crisis management) and gradually replaced by other immunosuppressants. Methotrexate, the least expensive drug, is the first line of treatment for guttate and chronic plaque psoriasis in children. Acitretin is the most commonly used systemic retinoid in children and the first line of management in generalized pustular psoriasis. Acitretin has been used successfully in a four-week-old infant with pustular psoriasis with no side effects.[34] The first author (SD) has vast experience in using these drugs in children with psoriasis. These drugs are quite safe in children if the four checklists are fulfilled: (i) judicious selection of cases; (ii) Given in appropriate dose (not suboptimal dose) and duration in a given patient; (iii) regular monitoring of clinical, hematological and biochemical parameters; (iv) good compliance of the patient/parents.

Table 3.

Nonbiologic systemic drugs in pediatric psoriasis

Drug	Indication	Dosage	Remarks
Methotrexate	Moderate-severe plaque psoriasis Psoriatic arthropathy	Oral/subcutaneous 0.1-0.4 mg/kg/week and up to 1.25-5.0 mg/week Folic acid: 5 mg given daily to minimize size effects, except the day of methotrexate administration	Level of evidence: II-III Grade of recommendation : B
Cyclosporine	Severe unstable psoriasis Generalized pustular psoriasis Erythrodermic psoriasis	2-5 mg/kg/day	Level of evidence: II-III Grade of recommendation : B
Retinoids	Extensive guttate psoriasis Pustular psoriasis Erythrodermic psoriasis	0.3-0.5 mg/Kg/day for first 4 weeks, then increased to 0.5-1.0 mg/kg/day	Level of evidence: II -III Grade of recommendation : B

In a multicenter study including 289 pediatric patients with psoriasis treated with conventional systemic therapy showed 75% reduction in Psoriasis Area and Severity Index Score or a more response rate was obtained in 47.5%, 34.1% and 40% of the children treated with acitretin, methotrexate and cyclosporine, respectively. Treatment was well tolerated without adverse effects in 70.7%, 90.8% and 77.5% of pediatric patients treated with acitretin, methotrexate and cyclosporine.[35] There are not many studies on the efficacy of use of fumaric acid esters in pediatric psoriasis.

Biologic therapies

Recent uses of targeted therapies have altered the outlook on management of psoriasis. Biologics are immunomodulators that regulate inflammation by specifically targeted pathways involving cell signaling, immune cell development, recruitment and apoptosis. Some of the approved biologics in pediatric psoriasis are summarized in Table 4.[27,28,31] Etanercept, adalimumab and ustekinumab are approved therapies for pediatric psoriasis. Little is published about the use of IL-17A antagonist in children, although there are anecdotal case reports of secukinumab's use in adolescents for treatment of deficiency of IL36 receptor antagonist. Secukinumab has shown good efficacy and safety profile for treating pediatric patients less than one year of age.[36] There is a lack of data for the use of infliximab in children. Apremilast, a PDE-4 inhibitor, has shown to be useful in moderate to severe plaque psoriasis in a few case series, but larger studies are required to establish its efficacy and safety profile in children. Injection site reactions, infusion reactions, hypersensitivity and angioedema are a few of the side effects encountered during administration of biologic agents. Live vaccines can be administered based on risk-benefit issues.

Table 4.

Approved biologics in pediatric psoriasis

Biologic drug	Approved age	Molecular basis	Dosage	Schedule
Etanercept	>4 years	Soluble fusion protein of TNF-alpha receptor and Fc portion of human IgG	Subcutaneous injection of 0.8 mg/kg or 0.4 mg/kg	Weekly
Ustekinumab	>12 years	Humanized monoclonal antibody against p40 subunit of IL-12 and IL-23	0.75 mg/kg	Week 0,4 followed by every 12 weeks
Adalimumab	>12 years	Humanized monoclonal IgG antibody targeting TNF-alpha	24 mg/m2 or 0.8 mg/kg, maximum of 40 mg	Weekly for first two weeks then every two weeks

Newer trials with JAK-STAT inhibitors like tofacitinib, baricitinib, abrocitinib have been tried in children with good efficacy. Long-term studies are required for its safety profile. Topical tofacitinib is still under trial in pediatric psoriasis.[37] Precision medicine approach is on the new horizon for the management of psoriasis.

Proactive therapy

The concept of proactive therapy mainly used in 'atopic atopic dermatitis is also described in childhood psoriasis. Proactive approach decreases the episodes of flares, frequency of relapses, treatment related toxicity and also improves the QoL and avoids poor performances in school. The stages of proactive therapy include initial treatment with systemic/topical medications till complete clearance of psoriatic lesions, education of patients/parents/caregivers regarding course of disease and appropriate plan of management and prevention of triggers like infections, trauma, stress and medications.[38] Lifestyle modifications are required especially when associated with obesity.

Proactive topical therapy

It is useful in mild types of psoriasis where plaques recur at the same sites. Emollients and topical medications are prescribed based on the site of occurrence of lesions. Various approaches include:

• Gradual withdrawal over several months to prevent frequent relapses (topical corticosteroids).

• Weekend therapy (topical corticosteroids and calcipotriol).

• On-demand therapy – early treatment of first symptom of flare effectively prevents further episodes (topical corticosteroids and calcipotriol).

Proactive systemic therapy

• Maintenance of remission with minimum effective dose: After initial phase of active treatment, systemic drug is either tapered to lowest maintenance dose (nonbiologics) or interval of intake is spaced (biologics).

• Weekend therapy: The minimal effective dose is given on weekends (cyclosporine).

• Intermittent therapy: It is the reintroduction of drug during initial stages of relapse (cyclosporine/etanercept).

Conclusions

Childhood psoriasis is an immune mediated inflammatory disease with a strong genetic predisposition. The natural history and course are unpredictable. All children with psoriasis should be screened for comorbidities. Management of childhood psoriasis requires multidisciplinary approach along with appropriate proactive therapy for long-term remissions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.