PSORIASIS IN CHILDREN: AN INSIGHT

Abstract

Onset of psoriasis in childhood is quite common. Chronicity, inflammation and hyperproliferation are the cardinal features by which the condition establishes its uniqueness. Clearance of disease may be farfetched in most patients and relapse is frequent. Early recognition and management of psoriasis in children and adolescents is vital in therapy in children.

Introduction

Psoriasis is an inherited papulosquamous disorder with a variable clinical spectrum. As much as 40% of adult patients with psoriasis have reported manifestations of this condition in childhood, with at least one-third of the patients demonstrating features of psoriasis before the age of 16.1 years. The psychosocial impairment, in addition to the physical affliction that can result from psoriasis, is a reminder that early recognition and management of psoriasis in children and adolescents is crucial.[1]

Epidemiology

A definitive paucity of studies exists in the epidemiological backdrop of childhood psoriasis. A study of 419 patients from North India revealed the pattern and prevalence of childhood psoriasis in patients less than 14 years of age. The peak age of onset in boys was in the 6–10-year age group, whereas the majority of girls showed an onset of psoriasis between the ages of 10 and 14 years. A positive family history was present in only 19 (4.5%) patients. These findings differ from those of previous studies in showing a delayed onset, equal sex distribution and a less frequent history of familial occurrence.[2] In a recent study of 137 patients from China, aged between 3 and 14 years, 64 were males (46.7%) and 73 were females (53.3%). Eleven patients (8%) had a family history of psoriasis. Infection was the most common precipitating factor (39, 28.5%). Seasonal influence was found in 57 patients (41.6%). Exacerbations in winter and spring were noted in 29 and 16 patients, respectively.[3]

Multifactorial nature of the disease and epidemiological evidence point to genes playing a key role in the pathogenesis. Two types of psoriasis have been distinguished considering the onset age. Type I (onset 15–40 years) accounts for the majority of cases (>75%) and shows a high degree of familial aggregation and strong association with HLA Cw6. Correspondingly, type II begins after the age of 40 years. Familial prevalence is observed to be greater in childhood psoriasis than in adults, with 37% of adult-onset patients and 49% of pediatric-onset patients having first-degree family members affected with psoriasis. Some studies have reported familial incidence to be as high as 89% in childhood cases of psoriasis.[4,5]

The epidermis of any individual with the psoriatic phenotype has the capacity to express clinical disease. Expression is linked to a complex interaction of cells of the epidermis, cells of the dermis, cells of the immune system, and possibly, other noncellular humoral elements. The keratinocytes of psoriatic patients are unique in that the inherent phenotype has a capacity for hyperproliferation and altered differentiation. Proliferation and differentiation are controlled at the level of the gene. Thus, it is important to consider not only cytokines and growth factors released by the various cell types, but also the role of regulators of transcription, translation, and the modification of the cytokines and growth factors. The large number of alterations of cytokine and growth factor profiles within psoriasis causes us to postulate that the genetic aberration in psoriasis is quite basic, that is, it is proximal to the common element in the cascade of inflammatory events that lead to a lesion of psoriasis. About 20 genetic loci associated with psoriasis have been reported from linkage-based studies; only one of these linkage-based loci, PSORS1, that includes the HLA-C gene on chromosome 6p21, has been universally confirmed and is considered to confer susceptibility to early-onset psoriasis. Accumulating evidence points to triggers like infections (Streptococcus), cold, stress, and drugs (Chloroquine and systemic Corticosteroids) either precipitating or worsening the disease in children.[6,7]

Clinical Features

Pediatric psoriasis consists of three age groups of psoriatic patients like infantile psoriasis, a self-limited disease of infancy, psoriasis with early onset, and pediatric psoriasis with psoriatic arthritis. The varied clinical presentations in childhood include plaque-type, guttate, erythrodermic, napkin, and nail-based disease. Like all forms of auto-immunity, susceptibility is likely genetic, but environmental triggers are required to initiate disease activity.

How Different is the Presentation in Children?

The disease in children is more pruritic, common in girls, and the lesions are relatively thinner, softer, and less scaly. Plaque type is the most common form of disease, but certain clinical variants are rare in children like erythroderma, arthropathy, and localized and generalized pustular psoriasis. Psoriasis in children is more frequently precipitated by infections and manifests as acute guttate psoriasis. However, Indian studies show that children manifest the established plaque type of disease more often, rather than the guttate variety. Facial involvement in children is a frequent observation in majority of the reports, which varies from 18 to 46%, whereas mucosal involvement has been rare in Indian children.[8]

A study from North India reported that extensors of the legs were the most common initial site affected [105 (25%) cases], followed by the scalp [87 (20.7%)]. Classical plaque psoriasis was the most frequent clinical presentation [254 (60.6%) patients], followed by plantar psoriasis [54 (12.8%)]. Nail involvement was observed in 130 (31%) cases. Pitting was the most common nail change, followed by ridging and discoloration. Five children (1.1%) (three girls and two boys) had psoriatic arthropathy. Koebnerization was observed in 27.9% of patients.[9]

Another study showed that plaque psoriasis was the most common type (52.6%), followed by guttate psoriasis (25.5%), psoriasis pustulosa (10.9%), and psoriasis erythroderma (5.1%). Scalp was the most common initial site affected (50.3%), nail changes were found in 25.5%, but no mucosal involvement was observed.[3]

Associated Skin Conditions

The co-morbidities of childhood psoriasis include allergic contact dermatitis, eczema, vitiligo and alopecia areata. Psoriasis is sometimes misdiagnosed as dermatitis seborrheica, neurodermatitis and balanitis.

Natural History of the Disease and Triggers

The goal of control versus cure is a more practical outcome of treatment. Many randomized controlled clinical trials involving children under the age of 12 years have reported on two topical treatments: calcipotriol and corticosteroids. Avoidance of triggers like trauma (Koebner phenomenon), including physical, surgical, or inflammatory trauma, should be borne in mind in this age group. A strong association between pharyngitis by group A beta-hemolytic streptococci and the clinical activity of psoriasis (guttate psoriasis) is now well established and should be properly investigated where relevant.[4,10]

Management Strategies

Many studies have investigated the use of standard psoriasis therapies in children with psoriasis, including topical treatments, phototherapy, and systemic therapies. Inflammatory nature of psoriasis has initiated study of the use of biologic agents in children, where targeted treatments have a better safety profile.

Topical Therapy

Moisturizers have a role in normalizing hyperproliferation, and they exert anti-inflammatory effects by way of the physiologic lipids. An improved barrier function and hydration makes the epidermis less vulnerable to external trauma, thereby reducing the induction of Koebnerization. Pretreatment with emollients like mineral oil or vaseline augments the therapeutic efficacy of narrow-band ultraviolet-B therapy, possibly because it penetrates the intercellular space, producing an optical matching effect which enhances the UV transmission.[11]

Salicylic acid (6% ointment and 3% shampoo) is a keratolytic agent that can be used for small plaques on the scalp, palms, and soles in children older than 6 years.[12]

Coal tar is antiproliferative and can be used as ointment, cream or solution in concentrations from 0.5 to 20%. Tar is safe and effective for childhood psoriasis, mainly for plaque type lesions. It can be used in combination with other medications like topical corticosteroids, salicylic acid and with UV irradiation. It is irritating on the face and flexures in children. Anthralin (dithranol) is a potent anti-inflammatory and antiproliferative agent used as “short-contact” or “minute” therapy, to reduce side effects like irritation and temporary perilesional staining of the skin. In an open study of 58 children aged 5–10 years treated with dithranol at concentrations up to 1%, remission was achieved in 47 (81%) patients.[13]

Goeckerman therapy for psoriasis was first described at the Mayo Clinic in 1925, and in a study undertaken, the responses were excellent (62% of patients had 90% clearance or greater, 23% had 80–89% clearance of lesions), hence proving it as an option for children with moderate to severe psoriasis.[14]

Corticosteroids still remain the mainstay topical treatment of psoriasis, as they have anti-inflammatory and antiproliferative properties and reduce erythema, scaling, and pruritus. Topical corticosteroids are used in chronic plaque type psoriasis as monotherapy or in combination with topical treatments like calcipotriol and tazarotene. Lower potency preparations are indicated for facial, genital and intertriginous skin areas, whereas thick hyperkeratotic areas, such as the palms and soles, require high potency agents. Halobetasol cream 0.05% and clobetasol propionate emulsion 0.05% seem to be efficacious treatments in childhood plaque psoriasis. Reported side effects were relatively mild in the treatment period of 2 weeks. A case report described the use of hydrocortisone 1% ointment in a 2-year-old child with pustular psoriasis.[15,16]

Calcipotriene (calcipotriol) is a nonsteroidal alternative in the treatment of mild to moderate plaque type psoriasis and has utility as monotherapy, as well as in combinations with topical steroids. Oranje performed a randomized double-blind study in 77 juvenile patients with twice daily applications for 8 weeks. The investigators reported a decrease in psoriasis area-and-severity index (PASI) score of 52% in the vitamin D group. The amount for use in children is a maximum dose of 75 g/week for children aged over 12 years and 50 g/week for those aged 6–12 years.[17]

Topical tacrolimus (0.03%, 0.1%) ointment and pimecrolimus (1%) cream are nonsteroidal immunomodulating macrolactams which block the enzyme calcineurin, thereby inhibiting the production of IL-2 and subsequent T-cell activation and proliferation. In two nonrandomized clinical trials, treatment of facial and flexural psoriasis with tacrolimus 0.1% was evaluated in which all patients showed clearance after a treatment period varying from 2 to 30 days. Tacrolimus 0.1% was also used in one case report in which facial psoriasis cleared totally.[18]

Phototherapy is preferred in older children and adolescents with moderate to severe disease in which topical treatments have failed. Guttate and thin plaque type lesions respond best to phototherapy. NB-UVB shows good results in the treatment of plaque and guttate psoriasis in childhood and has comparatively milder side effects for the treatment duration studied. Two open-label studies were performed. Jain et al. examined NB-UVB treatment for 12 weeks. PASI 90 was achieved in 60% of patients. It needs to be mentioned that all the patients had skin type IV.[19] Tay et al. also studied NB-UVB treatment, where after a mean treatment of 11.9 weeks, clearance was reached in all the patients.[20]

Systemic Agents

Role of oral antibiotics remains controversial. In one study, thiamphenicol was used and there was less than 50% clearance of lesions. Four patients in a case series were treated with erythromycin (50 mg/kg/d) for 2 weeks; in all the patients, the psoriasis lesions disappeared completely. A patient with guttate psoriasis was treated with amoxicillin/clavulanic acid (50 mg/kg/d), which cleared all lesions after 20 days.[21,22]

Methotrexate (MTX) is an antimetabolite agent with immunomodulatory and anti-inflammatory properties, and has advantages of efficacy, affordability and convenient weekly oral dose. In children, 0.2–0.4 mg/kg/wk orally is recommended. A review of 10 cases of childhood psoriasis treated with MTX showed a complete clearance in 20% cases, almost complete clearance in 60% cases, and no response in 10% of cases. MTX was given at an initial dose of 0.03–0.24 mg/kg/wk and was increased according to the patient's response to 0.10–0.41 mg/kg/wk; duration of treatment was from 6 to 178 weeks. A study revealed the treatment results in childhood psoriasis with MTX in seven children (four boys, three girls) over 7.5 years. Their ages and duration of disease varied from 3.5 to 16 years (mean 12.14 years) and from 4.8 months to 5 years (mean 2.2 years), respectively. Psoriatic erythroderma was seen in three patients, generalized pustular psoriasis in two, and recalcitrant psoriasis and psoriatic arthropathy in one each. Pre-MTX liver biopsy performed in four children showed grade I changes. MTX was given in a single weekly oral dose of 3.75-25 mg (mean 16.6 mg). The duration of treatment necessary to control the disease varied from 6 to 10 weeks (mean 7.9 weeks). Total duration of MTX therapy was from 31.2 to 46.4 weeks (mean 38.8 weeks). Post-therapy disease-free interval ranged between 14.4 and 16.8 weeks (mean 15.5 weeks). Follow-up after withdrawal of MTX was from 16 to 28 weeks (mean 22.3 weeks). Total cumulative MTX dose ranged from 390 to 960 mg (mean 683.6 mg). Side effects were nausea and vomiting reported in three patients.[23,24]

Acitretin is an aromatic retinoid that acts in psoriasis by its anti-inflammatory activity. Treatment should be initiated and maintained at dosages at or below 0.5–1 mg/kg/d to limit short- and long-term toxicities and therapy should be continued for about 2 months after clinical remission. Major limitation of oral retinoids (acitretin) in children is the risk of growth retardation due to premature closure of epiphyses on long-term use. In the open-label study, three patients with psoriasis erythroderma were treated with etretinate in a dosage ranging from 0.5 to 0.9 mg/kg/d. After 4–5 months of treatment, they all had complete clearance of erythema and scaling.[25] Etretinate was used as a treatment for plaque psoriasis in two children where both the patients had an excellent response.[26]

Cyclosporine primarily acts by inhibiting T-cell function and interleukin (IL)-2 and is effective in severe forms of psoriasis such as pustular or erythrodermic psoriasis or when other therapies are ineffective. Three patients with pustular psoriasis have been described in whom the administered dose was from 1 to 2 mg/kg/d. Complete disappearance of lesions was seen in two patients who were treated for 12 and 6 months, and the third patient showed a significant improvement after 5 months of treatment.[27]

The inflammatory nature of psoriasis has also prompted further study of the use of biologic therapeutics in children, where targeted treatments may offer a safer option. Biologics are drugs including antibodies and fusion proteins targeting cytokines like tumor necrosis factor that plays an important role in psoriasis.[28] Etanercept has been found to be overall effective and well tolerated in children and adolescents with moderate-to-severe plaque psoriasis. In a 48-week study, 211 patients with psoriasis (4–17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram of body weight (to a maximum of 50 mg), followed by 24 weeks of once-weekly open-label etanercept. At week 36, 138 patients underwent a second randomization to placebo or etanercept to investigate the effects of withdrawal and retreatment. The primary end point was 75% or greater improvement from baseline in the PASI 75 at week 12.[29]

Counseling

This chronic disease, punctuated by remissions and exacerbations, has a profound impact on the quality of life of the child. The family must learn to deal with the illness, considering the psychological burden on the child.