Psoriasis in Children and Adolescents: Diagnosis, Management and Comorbidities

Psoriasis is a common chronic immune-mediated inflammatory disorder affecting the skin, nails and joints in both children and adults. The skin disorder is estimated to affect 2.0–3.5 % of the global population [1, 2]. A recent publication by Parisi et al. reported even higher percentages, with ranges up to 8.5 % depending on the studied population [3]. Psoriasis begins in childhood in almost one-third of the cases [1, 4, 5], and the published incidence rates in children have more than doubled since 1970 [6]. Psoriatic skin lesions are characterized by well defined erythematous scaly plaques, and tend to have a chronic relapsing and remitting course. Severity ranges from a few scattered plaques to involvement of almost the entire body surface. Psoriasis in children and adolescents can have a significant impact on quality of life by interfering with self-esteem, family and social relationships and school and work [7‐9]. Children suffering from psoriasis also have a higher prevalence of comorbidities, including obesity, diabetes mellitus, hypertension, rheumatoid arthritis, Crohn’s disease and psychiatric disorders, compared with children without psoriasis [1, 10‐12]. Because of the burden of disease and the associated comorbidities, early diagnosis and management in children are essential.

Prevalence rates vary slightly, depending on age, gender, geographical location, definition of prevalence, study design and case definition. Clinical presentation and psoriasis severity may also contribute to variation in prevalence and incidence numbers [3]. Although pediatric psoriasis is not uncommon, limited epidemiology data are available to date. It is estimated that approximately 30–50 % of adults with psoriasis developed psoriasis before 20 years of age [5, 13, 14]. Gelfand et al. found that the prevalence of psoriasis in childhood in the UK was about 0.55 % in children aged 0–9 years and 1.37 % in children aged 10–19 years [4]. This study also demonstrated that the prevalence increased more rapidly in females compared with males younger than 20 years. This finding is probably not due to females paying closer attention to their skin, but suggests an interaction between sex and the development of the psoriasis phenotype in young patients [4]. Comparable prevalence results have been reported within the German (age 0–9, 0.18 %; age 10–19, 0.83 %) [1] and Dutch populations (age 0–10, 0.4 %; age 11–19, 1.0 %) [13]. In contrast to Europe, pediatric psoriasis was almost absent in an epidemiological study on childhood dermatoses performed in Asia [15, 16]. This worldwide geographical variation seems to reflect the fact that psoriasis is a complex disease triggered by environmental factors in genetically susceptible subjects [17].

The incidence of pediatric psoriasis has more than doubled between 1970 and 2000. A study by Tollefson et al. found the overall annual age- and sex-adjusted incidence of psoriasis to be 40.8 [95 % confidence interval (CI) 36.6–45.1] per 100,000. An increase in triggering factors for psoriasis such as psychosocial stress, infections and being obese or overweight could be potential explanations for this development [6]. Other exacerbating factors include trauma or irritation of the skin and the use of certain medications such as lithium, β-adrenergic antagonists and tumor necrosis factor alpha (TNF-α) inhibitors in children with Crohn’s disease or juvenile idiopathic arthritis (JIA) [18‐20]. Most studies report no gender bias in pediatric psoriasis. Tollefson et al. described a female to male gender ratio of 1.10 [6]. These findings were similar to other epidemiological studies from Australia, the USA, India and China [5, 21‐24]. However, a recent multicenter, cross-sectional study performed in 181 children with plaque psoriasis in the USA reported a female to male gender ratio of 1.48 [25]. This female predominance was also demonstrated by others [26, 27]. The mean age of onset varied from 8 to 11 years [6, 28‐30]. Interestingly, Augustin et al. demonstrated an almost linear increase in prevalence rates between 0 and 18 years rather than a “peak of onset” [1].

About 30 % of individuals with psoriasis (children and adults) have an affected first-degree family member [17].

The prevalence of psoriasis patients with an affected family member is observed to be greater in early-onset psoriasis (defined as psoriasis onset before the age of 16) than in adult-onset psoriasis (defined as psoriasis onset after the age of 16) [5, 29, 31, 32]. Chiam et al. compared a Dutch and Singaporean group of children with psoriasis and reported that more Dutch children than Singaporean children had a first- or second-degree family member with psoriasis (73.3 vs. 13.6 %) [26]. In an Australian population, 71 % of children with psoriasis had a first-degree relative with psoriasis. A positive family history of psoriasis was reported in 51.4 % of pediatric psoriasis patients in a multicenter, cross-sectional trial in the USA, with affected members being first-degree relatives in 59.8 % of those cases [25]. These differences point to the role of genetic background within each population of patients with juvenile psoriasis [23, 28].

Although children present with the same clinical subtypes of psoriasis seen in adults, lesions may differ in distribution and morphology, and their clinical symptoms at presentation may vary from those reported by adults. In childhood, typical erythematous plaques with overlying white scale are often thinner and smaller and psoriasis lesions tend to develop more often on the face and flexural areas. These lesions are characterized by maceration and less prominent scale [22, 28]. Despite these predilection sites, psoriasis papules and plaques can develop on any skin area and are usually symmetrically distributed [33]. Young children usually present with a diaper rash that is unresponsive to irritant diaper dermatitis treatment. Psoriatic diaper rash is seen in young infants and is characterized by sharply demarcated, minimally elevated erythematous plaques in the diaper area, involving the inguinal folds. The lesions are often macerated, and can develop into a widespread eruption within 1–2 weeks [32]. Morris et al. reported that 26 % of patients had a history of psoriasis diaper rash, but the diagnosis of true psoriasis in these infants remains controversial. Diaper psoriasis can be particularly difficult to treat [23]. In older children, up to 75 % manifests with chronic plaque psoriasis [26, 34]. This is the most common type of psoriasis in children and adults and is characterized by well defined erythematosquamous papules or plaques with overlying silvery-white scale. The lesions vary in size and develop primarily on the scalp, face and extensor surfaces of the elbow and knee. The scalp is the most frequently involved area and often the first site of presentation in children [29, 35].

Guttate psoriasis is the second most common type of psoriasis in children [21, 29]. Griffiths and Barker defined guttate psoriasis as an acute form of psoriasis in which papules erupt on the trunk approximately 2 weeks after a β-hemolytic streptococcal or viral infection [17]. According to this definition, guttate psoriasis is self-limiting, resolving within 3–4 months of onset [17]. It has been reported that a proportion of individuals with guttate psoriasis eventually develop plaque psoriasis [22, 24, 25, 36, 37]. Mercy et al. suggested that the risk of severe disease is higher if psoriasis started as guttate psoriasis which persisted [25]. Prospective cohort studies are needed to further determine features and percentages of children with guttate psoriasis who develop plaque psoriasis.

Pustular psoriasis is seen in only 1.0–5.4 % of children with psoriasis. In a minority of these patients, mutations of the interleukin-36 (IL-36) receptor antagonist (IL36RN) gene and subsequent upregulation of IL-1 production have been identified [38]. Pustular psoriasis is characterized by localized or generalized superficial sterile pustules and can be accompanied by fever, malaise and arthralgias in the case of classical von Zumbusch type. Although pustular psoriasis is more common in adults, von Zumbusch pustular psoriasis and pustular psoriasis with an annular configuration occur more frequently in childhood [31, 39].

Other less common subtypes of psoriasis are inverse psoriasis, palmoplantar psoriasis, isolated facial psoriasis, linear psoriasis and erythrodermic psoriasis [17]. Erythrodermic psoriasis is characterized by erythema and scaling on more than 90 % of the body surface area. The condition is extremely rare in children and can be life-threatening because of severe hypothermia, hypoalbuminemia and cardiac failure [17, 32].

Psoriasis of the skin can be accompanied by changes of the nail plate and nail bed. Nail changes have been reported in up to 40 % of children with psoriasis and more often in boys than in girls [25, 26, 33]. Nail changes can precede, coincide with, or develop after skin psoriasis. Whether these changes relate to patient age or disease severity vary among studies [25, 40]. The most common presentation is pitting of the nail plate. Other characteristics include oil spots, onycholysis (distal separation of the nail plate from the nail bed), subungual hyperkeratosis, onychodystrophy and splinter hemorrhages [41]. Juvenile psoriatic arthritis (JPsA) is another manifestation of psoriasis in children. Because of difficulties in diagnosis and classification of psoriatic arthritis in children, prevalence data range from 1 to 10 % of children with psoriasis [22, 25]. Approximately 7 % (range 0–11 %) of all patients with JIA appear to have JPsA [42‐46]. JPsA is included under the term JIA. Following the introduction of the International League of Associations for Rheumatology (ILAR) criteria for JIA, JPsA has become a better recognized inflammatory arthritis in children. According to these criteria, JPsA can be diagnosed in the presence of skin psoriasis, or in the absence of a rash, if there are nail changes and/or a first-degree relative with psoriasis [47]. Psoriatic arthritis is more common in adults, with prevalence data up to 30 % [34, 48, 49]. The peak of onset in childhood is between ages 9 and 12, and the skin psoriasis often precedes psoriatic arthritis. Although a relationship between nail involvement and psoriatic arthritis in adults has been suggested, recent studies in both children and adults do not support this correlation [25, 32, 50].

In addition to the clinical features described above, children often present with a thinner surface scale compared with adults. When scraping off scales, punctuate bleeding spots occur, a phenomenon known as the Auspitz sign. The occurrence of lesions in areas of trauma, also called isomorphic response or Koebner phenomenon, and residual pigmentation following healing of lesions are other typical diagnostic features of psoriasis [34].

Although the diagnosis of psoriasis is primarily based on clinical features, biopsy can help to confirm the diagnosis in children with atypical presentations. Histological features of psoriasis include parakeratosis, loss of the granular cell layer, elongation of the rete ridges, neutrophilic aggregates within the epidermis (microabscesses of Munro), dilated blood vessels in the dermis, and perivascular lymphocytic infiltrates [17, 51, 52]. These characteristics may vary depending on site of biopsy, psoriasis subtype, and whether children have been treated with topical and/or systemic treatments. Given that the diagnosis is usually made on the basis of morphology and distribution, a biopsy is virtually never performed, especially not in children. In atypical cases in which a diagnosis is required, topical therapy should ideally be discontinued prior to biopsy to avoid alteration of histological features [53].

Dermoscopy has become a standard diagnostic tool in dermatology. Although this technique permits visualization of morphological structures invisible to the naked eye, it is not commonly used in the diagnosis of psoriasis. Lallas et al., however, suggested that dermoscopy could distinguish psoriasis from other common skin diseases such as dermatitis [55]. Dotted vessels regularly distributed over a light red background and diffuse superficial white scales are typical dermatoscopic characteristics of a psoriasis plaque [54, 55]. Further research is warranted to determine the added value of dermoscopy in diagnosis and predicting response to treatment.

Treating pediatric psoriasis can be challenging and requires careful compliance to a specific treatment regimen. Poor treatment adherence is rampant in psoriasis, in particular to topical agents [56, 57]. Educating the patient and family on the chronicity of psoriasis, triggering factors, and treatment modalities is important, in addition to prescribing treatment. Timing of the first return visit may be a practical tool to enhance patient adherence [29]. Return visits can induce “white coat compliance” in which the expectation of frequent monitoring can enhance patients’ use of medication [58]. Psychosocial support is another important component of therapy for children with psoriasis [7].

There are currently no international standardized guidelines for medical treatment of pediatric psoriasis. To date, treatment is primarily based on published case reports, guidelines for adult psoriasis, expert opinions and experience with these drugs in other pediatric disorders. The range of psoriasis treatments has been expanded during the past several years, and multiple topical agents, phototherapy and systemic and biological agents are available to date [53]. Several factors need to be taken into account when selecting a specific treatment, e.g., age, quality of life, severity of psoriasis, location of psoriasis, type of psoriasis, tolerability, safety and patient preferences [59‐61].

The majority of children with psoriasis can be managed with topical treatment, which is considered first-line therapy in psoriasis. However, most are not approved for pediatric use, requiring off-label prescribing [61]. The most commonly used topical agents will be reviewed below. The vehicle for treatment is important and depends on the location of psoriasis, lesional characteristics, and patient preference [62]. Available vehicles include creams, ointments, foams, gels and lotions.

In children with moderate to severe psoriasis recalcitrant to topical treatment, systemic treatments are indicated [63]. However, the choice of agent remains a challenge because of the limited number of clinical trials and lack of guidelines in this age group [84]. Most of the systemic treatments are not approved to use in children and are used off-label. Therefore, daily practice clinical decision making can be complicated and challenging. A systematic review on the efficacy and safety of all systemic treatments in pediatric psoriasis by van Geel et al. provided evidence-based recommendations for the use of these agents in the pediatric psoriasis population [85].

As in adult psoriasis, recent studies suggest the association of pediatric psoriasis with certain comorbidities. In an analysis of German health insurance data, a twofold increased risk of hyperlipidemia, obesity, hypertension, diabetes mellitus and rheumatoid arthritis was found in psoriasis patients under 18 years of age, as compared with healthy controls. Crohn’s disease is noted four times more often as compared with unaffected controls [1]. Similar results have been found in a smaller insurance company database [119].

Obesity as a comorbidity of psoriasis has been the focus of much investigation. Koebnick et al. demonstrated that children who were overweight, moderately obese and extremely obese had 1.31-, 1.39- and 1.78-fold greater odds, respectively, of having psoriasis than children with normal weight [120]. Further, Paller et al. demonstrated the increased risk of being overweight or obese in pediatric psoriasis in a large international cross-sectional study in 5- to 17-year-old children with psoriasis [10]. The odds ratios (ORs) for obesity [body mass index (BMI) percentile ≥95th] and excess adiposity (BMI percentile >85th) in psoriatic children were 4.29 and 2.65, respectively. More children with severe psoriasis [OR 4.92 (95 % CI 2.20–10.99)] than with moderate psoriasis [OR 3.60 (95 % CI 1.56–8.30)] were obese compared with control subjects. Waist circumference and waist-to-height ratio, surrogates for central adiposity and sensitive indicators of metabolic risk, were also seen more frequently increased in psoriatic children [10].

The relationship between obesity and pediatric psoriasis deserves further investigation. Pediatric psoriasis has been associated with decreased quality of life as well as decreased tendency to participate in physical activities because of increased pruritus with sweating and increased visibility of the psoriatic lesions to peers [7, 9, 12, 121]. These factors theoretically could contribute to pediatric obesity, but only after the occurrence of psoriasis. On the other hand, psoriasis could instead be a complication of obesity, with systemic inflammation associated with obesity predisposing to the occurrence of psoriasis [10, 122]. Becker et al. demonstrated in a pilot study that being overweight or obese preceded psoriasis by at least 2 years in 93 % of children with psoriasis [11]. In these children, percentages of immediate family members with obesity and psoriasis were 48 and 41 %, respectively. Although it is unclear whether weight loss reduces psoriasis severity in children, just as it remains controversial in adults, lifestyle education and weight-loss programs in these families should be recommended [11, 123].

In addition to obesity, the presence of the metabolic syndrome is an issue in pediatric psoriasis patients. The metabolic syndrome in children is defined as having at least three of the following: (1) fasting triglycerides ≥1.1 mmol/L; (2) high-density lipoprotein <1.3 mmol/L, except in boys aged 15–19 years, in whom the cut-off point is <1.2 mmol/L; (3) fasting glucose ≥6.1 mmol/L; (4) waist circumference >75th percentile for age and gender; and (5) systolic blood pressure >90th percentile for gender, age and height (Fig. 1) [124]. In a small study in 20 children, the prevalence of metabolic syndrome was significantly higher in pediatric psoriasis patients (30 %) compared with the age- and gender-matched control subjects (7.4 %). No differences in BMI or individual components of metabolic syndrome were found [125]. Childhood onset of psoriasis does not seem to be an additional risk factor for the higher prevalence of metabolic comorbidities and cardiovascular disease in adulthood [126].

Pediatric psoriasis could have detrimental effects on quality of life. Because of substantial developmental changes in early life, children are a vulnerable group. Psoriasis can disrupt their social relationships and interfere with school and sport [7]. The Children Dermatology Life Quality Index (CDLQI) was developed to allow quality-of-life assessment in children with psoriasis and other skin disorders [127]. Oostveen et al. conducted a prospective observational study of children with psoriasis from a registry containing daily clinical practice data [9]. They assessed the CDLQI in a cohort of 125 patients, finding that psoriasis has a negative impact on quality of life. The questions related to itching and their treatment regimens seemed to have the highest impact on the quality of life of these children. Effective interventions had a positive effect on quality of life, primarily through improving complaints of itch and sleep disturbance [9, 128].

Previous research in adult populations reported psychiatric symptoms and diagnoses, such as depression and anxiety, in up to 60 % of psoriasis patients. Although studies regarding psychiatric symptoms in pediatric psoriasis are limited, it is known that pain, itching and the visible psoriasis lesions can result in embarrassment, social discomfort and anxiety in pediatric psoriasis patients [129, 130]. In line with these findings, Kimball et al. demonstrated an increased risk of developing depression, anxiety and bipolar disorder in psoriatic children compared with control subjects [12]. In addition, children suffering from psoriasis had a 47 % greater risk of taking psychotropic medications. Since the rate of antidepressant and anxiolytic medication use is higher than the incidences of depression and anxiety disorder in this study, and psychotropic medications are more likely to be used for more severe cases, the true incidence of psychiatric diagnoses may be even higher [12]. The relationship between psoriasis and depression and impaired quality of life in children has also been reported by other research groups [8, 131].

Psoriasis begins in childhood in almost one-third of the cases and is increasing in prevalence and incidence. However, the evidence on treatment efficacy and safety is still limited, and long-term data in pediatric patients are lacking. A prospective, multicenter, international registry is needed to evaluate these treatments in a standardized manner and ultimately to develop international guidelines on pediatric psoriasis.