|Year : 2018 | Volume
| Issue : 4 | Page : 308-314
Childhood psoriasis: What is new and what is news
Sunil Dogra, Anuradha Bishnoi
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||28-Sep-2018|
Prof. Sunil Dogra
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
Psoriasis is a chronic inflammatory disorder that affects around 2%–4% of the general population, and the prevalence can be higher in selected populations. About one-third of the people affected with psoriasis have the onset of their disease in the first and second decades of life. Of the pediatric population, about 0.5%–2% is affected. Infants are affected rarely. The incidence increases with age and is reported to be ~0.55% in the age group of 0–9 years and 1.37% in the age group of 10–19 years. Flexures, face, periauricular area and medial aspect of the upper eyelid are commonly involved in children. In infants, there is predilection for diaper area. Overall, plaque psoriasis is the most common type, followed by guttate and pustular psoriasis. Lesions are more pruritic, but thinner, less erythematous, and less scaly. Follicular lesions are common. Treating psoriatic erythroderma can pose difficulties, especially in pediatric population. Some cases achieve rapid control of disease activity, while others develop chronic erythroderma with frequent disease flares. The impact of disease on psychosocial parameters is significant in this subgroup of psoriasis and affects patients and parents alike with significantly high rates of absenteeism from school. Pediatric psoriasis therefore needs to be managed effectively. However, effective treatment also poses the risk of producing adverse effects, more so in pediatric age group. A delicate balance therefore should be maintained and overzealous treatment should be avoided.
Keywords: Pediatric psoriasis, childhood psoriasis, biologicals, plaque psoriasis, guttate psoriasis
|How to cite this article:|
Dogra S, Bishnoi A. Childhood psoriasis: What is new and what is news. Indian J Paediatr Dermatol 2018;19:308-14
| Introduction|| |
Psoriasis is a chronic inflammatory disorder that affects around 2%–4% of the general population, and the prevalence can be higher in selected populations. Analogous to vitiligo, in many patients, psoriasis has its onset in childhood. In fact, about one-third of the people affected with psoriasis have onset of their disease in the first and second decades of life. Of the pediatric population, about 0.5%–2% is affected, infants are affected rarely., The prevalence of pediatric psoriasis varies across geographical regions with an overall lesser prevalence in Asian countries than European ones might reflects the effect that ethnicity, genetic makeup, and environmental factors have on disease., In addition, the incidence increases with age and is reported to be ~0.55% in the age group of 0–9 years and 1.37% in the age group of 10–19 years. In an epidemiological study from the USA, it was observed that the incidence of pediatric psoriasis had increased significantly over time from 29.6/100,000 in 1970 to 62.7/100,000 in 1995.
In a study from a tertiary care hospital, North India, 419 children with psoriasis constituted 0.3% of the dermatology outpatients and 12.5% of the total psoriasis patients seen over a period of 13 years. There were 219 (52.2%) boys and 200 (47.7%) girls, with a male-to-female ratio of 1.09:1. The age of onset ranged from 4 days to 14 years. The mean age of onset was 8.1 ± 2.1 years in boys and 9.3 ± 2.3 years in girls. The peak age of onset in boys was in the 6–10-year age group, whereas the majority of girls had onset of psoriasis between the ages of 10 and 14 years. A positive family history was present in only 19 (4.5%) patients. In a French multicenter study comprising 313 children with psoriasis, 27 (8.6%) were infants, 207 (66.1%) were children, and 79 (25.2%) were adolescents.
In a recent epidemiological study carried out in Greece in 842 pediatric patients of psoriasis, the mean age of psoriasis onset was 7.33 years, and the sex distribution was equal between boys and girls. Tollefson et al. from the USA also found no gender predilection. A retrospective review however concluded that pediatric psoriasis was overall more common in girl children and up to 48% of children had an affected first-degree relative.
| Clinical Features in Pediatric Psoriasis|| |
In a study from Greece, limbs and the scalp were the main body areas affected. Similarly, in an Indian study of 419 children having psoriasis, the extensors of the legs were the most common initial site affected (105 [25%] cases), followed by the scalp (87 [20.7%]). In addition, flexures and face are commonly involved in children. Involvement of periauricular area and medial aspect of the upper eyelid is common. In infants, there is predilection for diaper area.
Overall, plaque psoriasis is the most common type, followed by guttate [Figure 1] and pustular psoriasis. Lesions are more pruritic, but thinner, less erythematous, and less scaly. Follicular lesions are common and a recent study identified follicular lesions only in children affected with psoriasis [Figure 2].
|Figure 1: An adolescent male having small plaque and guttate psoriasis on trunk and significant involvement of hands|
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|Figure 2: A male child with psoriasis having prominent follicular lesions and mild scalp involvement|
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In an Indian study, classical plaque psoriasis was the most frequent clinical presentation (254 [60.6%] patients), followed by plantar psoriasis (54 [12.8%]), an uncommon finding as compared to the world's literature. Koebnerization was observed in 27.9% of patients. Pruritus was the most frequent symptom, reported by 365 (87.1%) children.
In a French multicentric study, plaque psoriasis was the most frequent clinical type of psoriasis seen in children and adolescents (>41%), but it accounted for only 25.9% of psoriasis of infants. Napkin psoriasis (37.0%) and inverse psoriasis (22.2%) were the most common forms of psoriasis seen in infants. Girls presented with scalp psoriasis more frequently (17.7% in girls vs. 8.7% in boys). In a study carried out in Greece, plaque-type psoriasis was the most frequent type (82.1%), followed by perianal, inverse, and guttate types. The affected body surface area (BSA) was more than 10% in only 1.7% of patients, and the overall disease manifestations were considered to be mild.
In another study, it was found that puberty separated childhood psoriasis in two distinct phenotypes. Prepubertal disease onset was associated with significant flexural involvement. Pubertal onset was associated with facial and guttate lesions and HLA-cw06 genotype. Gender did not influence disease onset.
Psoriasis in infants
Psoriasis in infants usually presents with sharply defined, erythematous plaques in diaper area including groins and perianal region. Due to moisture in diaper area, scaling may sometimes be minimal. Perianal lesions likely depict Koebner's response due to repeated minor trauma and maceration typical of this site because of stool and urine exposure. Moreover, perianal streptococcal cellulitis, commonly seen in infancy, can exacerbate psoriasis.
Nail psoriasis in children
Nail findings are similar to adults and can help in making a diagnosis of psoriasis in difficult situations. In a study from Greece, psoriatic nails were detected in 11.8% of patients. In an Indian study, nail involvement was observed in 130 (31%) cases. Pitting was the most common nail change, followed by ridging and discoloration. In a French multicentric study, nail involvement was more common in adolescents (37.2%) and children (32.9%) than in infants (14.8%) and affected boys more than girls (43.6% vs. 22.0%).
In a recent study assessing nail involvement in pediatric psoriasis, of 313 children with psoriasis (mean age 9.1 ± 4.2 years; 149 boys and 164 girls), nails were involved in 32.3% of children. The main clinical features were pitting (69.1%) for fingernails and onycholysis (40.0%) and pachyonychia (27.5%) for toenails. All the fingers were involved at similar frequencies, whereas the big toe was involved twice as commonly. Nail involvement was associated with male sex, palmoplantar psoriasis, severe disease, and psoriatic arthritis.
Psoriatic arthritis in children
In a study from Greece, psoriatic arthritis was found to affect only 6 (0.7%) patients. Five of 419 children (1.1%, three girls and two boys) in an Indian study had psoriatic arthropathy. Overall, the prevalence of psoriatic arthritis in children is around 1%–10% and commonly affects the age group of 9–12 years. Its presence correlates with nail involvement and the skin manifestations of psoriasis often precede the joint involvement.
Severe variants of psoriasis in children
There is lesser preponderance for the development of pustular psoriasis and psoriatic erythroderma in children when compared with adults., Of pustular psoriasis, generalized pustular psoriasis of von Zumbusch and annular pustular psoriasis occur more frequently in children and localized variants occur infrequently. In a systematic review studying 24 pediatric patients with pustular psoriasis, the mean age of onset of pustular psoriasis was 22 months and a biopsy had to be done in 50% of the patients to ascertain the diagnosis. Personal and family history of psoriasis was present in around 70% and 13% of patients, respectively.
Psoriatic erythroderma is defined as erythema and scaling involving >90% of the BSA. Usually, it represents an acute event in response to infections or stress, though some patients also develop chronic psoriatic erythroderma marked by frequent relapses. A study assessing the utility of histopathology in suspected psoriatic erythroderma in nine infants revealed regular acanthosis and dilated papillary capillaries in all biopsies. In a study assessing outcomes in pediatric pustular psoriasis affecting 20 children of age 1.5 months–16 years, with seven patients having a previous history of psoriasis vulgaris, three children entered long-term remission, ten developed psoriasis vulgaris, two were still having pustular psoriasis, and the rest were lost to follow-up.
It was recently seen that the age of onset of psoriasis in childhood does not influence the subsequent course of the disease in adulthood including the disease severity, type of treatments used, or high body mass index.
Acrodermatitis enteropathica, candidiasis, deficiency of interleukin (IL)-1/36 receptor antagonist, eczemas, pityriasis rosea, pityriasis rubra pilaris, and guttate lichen planus are important differentials for various morphological patterns of psoriasis.
HLA cw-6 and psoriasis
Psoriasis is a multifactorial disease with a strong genetic background. HLA-Cw6 is one of the most strongly associated psoriasis-susceptibility alleles. The worldwide frequency of the HLA-Cw6 allele varies greatly, and is generally higher in Caucasians than in Asians. HLA cw6 has been earlier found to be associated with a more severe psoriasis having onset at an early age, guttate lesions at onset, and persistent guttate lesions during the course of the disease. Stress, obesity, and streptococcal pharyngitis are commonly observed in HLA-Cw6-positive patients. In addition, patients carrying this allele are more likely to have Koebner's phenomenon.
Patients with psoriatic arthritis and HLA-Cw6 positivity tend to have an early-onset disease and show cutaneous symptoms before musculoskeletal symptoms. HLA-Cw6-positive patients have been shown to be more responsive to methotrexate and ustekinumab. Positivity for HLA-Cw6 seems to be less frequent in patients who fail conventional therapy. Few studies have also associated HLA-Cw6 positivity with photosensitivity and atherosclerosis. In a study evaluating 108 Indian patients with psoriasis and a childhood onset, of the 83 who underwent HLA-Cw6 typing, 46 (55.4%) were positive; the positivity was associated with guttate lesions, scalp involvement, greater BSA involvement, and higher Psoriasis Area and Severity Index (PASI) scores. Another marker, that is Nonsynonymous endoplasmic reticulum aminopeptidase 1 single-nucleotide polymorphism rs26653, has been recently reported in psoriasis and displays a strong association with pediatric disease having onset in 10–20 years of age.
Association with comorbidities
Adult psoriasis has been consistently linked with metabolic syndrome. It has been recently stated in a SORT-C-level expert recommendation that pediatric patients having psoriasis should be screened for the presence of metabolic syndrome, depression, anxiety, and arthritis. A recent cross-sectional study found a significant association of pediatric psoriasis with metabolic (excluding hypertension, diabetes, and overall obesity) and nonmetabolic (atopy, epilepsy, vitiligo, alopecia areata, and celiac disease) comorbidities. Metabolic comorbidities were additionally found to correlate with severe treatment refractory disease, pustulation, erythroderma, face-and-nail involvement, and reduction in quality of life.
The disease in this age group has significant impact on the quality of life of affected children and their parents, and can have profound social ramifications. Therefore, it is essential to treat pediatric psoriasis judiciously. Overzealous treatment should be avoided, but an adequate treatment should be provided timely.
The disease in majority of children is localized and can be managed with topical medications including emollients, keratolytics, humectants, coal tar, dithranol, corticosteroids, Vitamin D analogs, calcineurin inhibitors, and retinoids. Topical corticosteroids have anti-inflammatory and antiproliferative properties, but the disadvantages include development of cutaneous atrophy, depigmentation, striae, steroid-induced rosacea, and hypertrichosis. Therefore, their use should be limited to a lesser duration, after which other agents such as Vitamin D analogs and calcineurin inhibitors can be used. Although they do not produce atrophy, the burning sensation experienced during the initial days of their application can be troublesome for children, but it subsides gradually. Staining and irritation are common with coal tar and dithranol, though newer formulations have better side effect profile.
The National Institute of Health and Care Excellence guidelines for pediatric psoriasis recommend the usage of potent topical steroids for application on scalp, trunk, and limbs in children aged more than 1 year. If the disease does not respond satisfactorily, a different formulation such as shampoo or mousse is advised. Further nonresponse warrants the addition of salicylic acid or Vitamin D analogs. Newer formulations such as foams and steroids under occlusion can be used safely for unresponsive disease on trunk and limbs. The disease on face, flexures, and genitals should be treated with mild-to-moderate potency corticosteroids for a maximum of 2 weeks at a stretch.
Vitamin D analogs are advised to be used in children aged more than 6 years. The risk for hypercalcemia is negligible and should not deter their employment (maximum amount permissible per week is 100 g, for adults and 45 g/m 2/week for children). The efficacy of calcipotriol 50 μg/g as monotherapy was found to be equal to betamethasone valerate 0.1% ointment and greater than short-contact dithranol therapy in adults. Incidentally, the combination of calcipotriol with corticosteroids has not yielded significant outcomes in pediatric disease, though the same combination is significantly effective in adult disease.
Topical calcineurin inhibitors (tacrolimus) have largely proved unsuccessful in the treatment of plaque psoriasis because of their larger molecular size and reduced penetrance through the thickened skin. However, their use in facial, flexural, and genital psoriasis has proved beneficial, although the response rate was around 50%, which is significantly lesser than that achieved with topical steroids.
Treating psoriatic erythroderma can pose difficulties, especially in pediatric population. Some cases achieve rapid control of disease activity, while others develop chronic erythroderma with frequent disease flares. The impact of disease on psychosocial parameters is significant in this subgroup of psoriasis and affects patients and parents alike with significantly high rates of absenteeism from school. Pediatric psoriasis therefore needs to be managed effectively. However, effective treatment also poses the risk of producing adverse effects, more so in pediatric age group. A delicate balance therefore should be maintained and overzealous treatment should be avoided.
The subset of children having severe, rapidly evolving, and relapsing disease needs systemic medications such as methotrexate, cyclosporine, acitretin, phototherapy, and biologics. In a retrospective study assessing the role of narrowband-ultraviolet B (NB-UVB) phototherapy in 12 patients followed up for an year, the highest doses administered ranged from 380 to 2333 mJ/cm.2 The number of treatments ranged from 9 to 136 (mean 57.3). The duration of phototherapy ranged from 1 to 30 months (mean 11 months). Response to NB-UVB was excellent (>90% reduction in BSA) in five patients and good (70%–90% reduction in BSA) in four patients. Four patients experienced worsening of their psoriasis after 6 months–5 years (mean 28.5 months) of stopping NB-UVB, but had good response after recommencement of phototherapy. None of the patients required systemic therapy during or after treatment with NB-UVB.
A recent retrospective chart review assessed the efficacy of cyclosporine in pediatric patients having extensive plaque-type, erythrodermic, and pustular psoriasis. Excellent efficacy (>75% reduction in PASI) was observed in all but three patients. Time taken to disease control (50% reduction in PASI) was 4.2 weeks. One child had pain abdomen and other had rise in serum creatinine. The authors concluded that under supervision, cyclosporine has significant beneficial role as a crisis management drug in severe pediatric psoriasis.
In a retrospective multicentric French study assessing the systemic treatments administered for severe childhood psoriasis, it was found that, in total, 261 treatments were used among the 154 children. The mean age of onset of systemic treatment was 10.3 years, with a mean duration of treatment of 11.7 years. The mean delay between the onset of psoriasis and treatment was 2.6 years. Acitretin was the most frequently used treatment (54.4%) and was used mainly as a first-line treatment (76.6%). Topical treatments were co-administered with systemic treatments in 73.9% of the cases. The best efficacy was for phototherapy plus acitretin (80%). Overall, the efficacy tended to be similar across all systemic treatments and was classified as good or partial (>75% and 50%–75% clearance). Absence of response was seen in approximately 10% of cases. The main reasons for stopping the treatment were clearance of disease (26.1% of cases) and inefficacy (26.8%). The efficacy rate was best for acitretin in plaque and pustular psoriasis; for methotrexate in plaque and guttate psoriasis; for cyclosporine in guttate psoriasis; and for biological therapy in the palmoplantar and erythrodermic forms. Side effects were noticed in 88 treatments (33.7%) among 55 children. Most were benign and had no influence on the duration of treatment. Only 15 side effects induced stopping of the treatment. Cyclosporine was associated with the highest rate of severe side effects requiring discontinuation of treatment (20%). The authors concluded that acitretin and methotrexate should be considered the first-line therapy and though, cyclosporine could be used as the first-line therapy, the side effects are more frequent.
Methotrexate is a cost-effective and reasonably safe drug to be used in severe childhood psoriasis under supervision. adequate laboratory monitoring should be carried out twice weekly initially and monthly after a month of initiating methotrexate. We have experienced the use of methotrexate in severe plaque-type, generalized pustular, and erythrodermic psoriasis in 24 children. The mean time to achieve 50% reduction in PASI was 5.1 weeks. Mean total cumulative dose of methotrexate administered in the first episode was 215 mg. The duration of remission varied from 1.5 months to 3 years. Side effects were mild and were observed in 9 children, which included nausea, vomiting, and loss of appetite.,,
There is a lack of randomized clinical trials assessing the treatment outcomes for pustular psoriasis in pediatric patients. Recommended initial treatments include acitretin (0.5–1 mg/kg/day), cyclosporine (4–5 mg/kg/day), and methotrexate (0.3–0.4 mg/kg/week). Phototherapy, biologics, and combination of two or more treatments are also employed frequently to control severe disease in childhood. Various case reports have described successful use of acitretin in managing severe pustular psoriasis in infants. Isolated case reports describe the use of infliximab, adalimumab, and isotretinoin.
Induction of remission with cyclosporine can be maintained with acitretin later on. A report has described using acitretin 1 mg/kg/day in pustular psoriasis recalcitrant to methotrexate and cyclosporine with good results. Subsequently, the dose of acitretin was reduced to 0.5 mg/kg/day and twice-weekly NB-UVB was added to maintain the results. In severe disease, acitretin can be started from 1 mg/kg/day and can be combined with prednisone if metabolic and hemodynamic disturbances ensue. Skeletal toxicity remains a concern and serial skeletal X-rays are recommended every 6 months, though large studies have revealed no skeletal abnormalities in children aged 6 months–16 years who were administered acitretin.
The indications for use of biologics in adult patients include severe disease, intolerance or resistance to phototherapy and nonbiologic systemic therapies. Being relatively new, the experience with the use of biologics in pediatric psoriasis is limited, though many of them have been employed successfully in treating juvenile inflammatory arthritis and Crohn's disease. Recent recommendations from an Italian expert group for the treatment of severe psoriasis in children do not approve conventional systemic therapies such as cyclosporine, methotrexate, and acitretin for the treatment of severe psoriasis in pediatric population in view of limited evidence and significant risk of adverse effects. These guidelines recommend using adalimumab, etanercept, and ustekinumab for severe disease in pediatric patients. The same group has recommended adalimumab as a first-line treatment modality for severe psoriasis in children >4 years of age, and etanercept and ustekinumab as the second-line treatment options for children >6 years and >12 years of age, respectively. Use of infliximab in pediatric psoriasis is limited to case reports only, although it has been approved for use in pediatric Crohn's disease. Etanercept is the only biologic approved for pediatric usage in European union, and has not been approved in the USA yet.
Secukinumab is an IL-17A inhibitor human monoclonal antibody that has recently been approved as a first-line treatment for moderate-to-severe adult plaque psoriasis in Europe. There is a recent report of recalcitrant chronic erythrodermic psoriasis in a 13-year-old boy, who was successfully induced and maintained in remission over an year using secukinumab.
In a study assessing systemic treatments in 27 pediatric patients having psoriasis, methotrexate was the most frequently prescribed systemic agent (70%), followed by etanercept (59%). Clearance rates were highest on biologic medications (67% for etanercept and adalimumab and 33% for ustekinumab). Phototherapy, cyclosporine, and methotrexate were less effective in clearing psoriasis. The most common adverse events were sunburn for patients on NB-UVB phototherapy (14%), gastrointestinal intolerance and minor infections for patients on methotrexate (16% each), and minor infections for patients on etanercept (25%) and adalimumab (33%). The most common reasons for discontinuation were secondary failure (38% for etanercept and 33% for adalimumab) or lack of response (37% for methotrexate and 33% for cyclosporine). A recent retrospective review concluded that biologics seem to be safe and effective in managing severe pediatric psoriasis, though more safety data need to be generated.
Overall, due to rarity of childhood pustular psoriasis, there is a lack of structured research. Combination therapies are employed in almost 50% of the children with generalized pustular psoriasis in order to provide optimum disease control. Moreover, though literature describes the regimens employed to induce remission, the treatment and maintenance for long-term disease control is usually not mentioned in detail. Pustular psoriasis in children has a more favorable course as compared to adults. The response to treatment is good and remission lasts longer as compared to adults.
| Conclusion|| |
Management of pediatric psoriasis is challenging with no official published guidelines and treatment algorithms that include children. The psychosocial impact can be tremendous in all spheres of life and therefore needs large-scale prospective studies assessing the needs of this population.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
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| ||Current Drug Delivery. 2020; 17(1): 52 |
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