Severe Atopic Dermatitis In Children Research Articles

The effects of ciclosporin and methotrexate on kidney function in the treatment of severe atopic dermatitis in children - results from the TREAT trial.

Ciclosporin (CyA) and methotrexate (MTX) are both frequently prescribed drugs for the treatment of atopic dermatitis in children and young people (CYP). Both can affect renal function and frequent blood monitoring is standard to monitor safety. We show that both CyA and MTX are not associated with decreased renal function and are safe and effective as a treatment for AD in CYP.

Dupilumab Efficacy and Safety in Severe Atopic Dermatitis in Children under 6 Years of Age: Two Clinical Cases

Background. Atopic dermatitis (AD) manifests during the first year of life in majority of all cases. The early disease onset is associated with the development of comorbid atopic conditions within the «atopic march» phenomenon. The AD pathogenesis is associated with genetic predisposition, epidermal barrier dysfunction, and immune dysregulation. T2-inflammation specifically determines the entire immune cascade of inflammatory reactions, and, thus, dictates the need of early drug intervention to modify the disease course. Clinical case description. This article presents two clinical cases of severe AD in children under 6 years of age. The treatment of both cases included genetically engineered biologic drug dupilumab. Continuous therapy for 4–5 months made it possible to relieve the skin manifestations of the disease.Conclusion. AD, manifesting in infancy, is associated with high risk of developing other atopic spectrum diseases in older age. The timely onset of biological therapy allows us to affect immune dysregulation, and thereby to prevent the comorbid atopic conditions development.

Moderate to severe atopic dermatitis in children: focus on systemic Th2 cytokine receptor antagonists and Janus kinase inhibitors.

Atopic dermatitis (AD) is a lifelong disease that markedly impairs quality of life. AD is considered a starting point of the "atopic march," which begins at a young age and may progress to systemic allergic diseases. Moreover, it is strongly associated with comorbid allergic and inflammatory diseases including arthritis and inflammatory bowel disease. Understanding the pathogenesis of AD is essential for the development of targeted therapies. Epidermal barrier dysfunction, immune deviation toward a T helper 2 proinflammatory profile, and microbiome dysbiosis play important roles via complex interactions. The systemic involvement of type 2 inflammation, wheather acute or chronic, and whether extrinsic or intrinsic, is evident in any type of AD. Studies on AD endotypes with unique biological mechanisms have been conducted according to clinical phenotypes, such as race or age, but the endotype for each phenotype, or endophenotype, has not yet been clearly identified. Therefore, AD is still being treated according to severity rather than endotype. Infancy-onset and severe AD are known risk factors leading to atopic march. In addition, up to 40% of adult AD are cases of infancy-onset AD that persist into adulthood, and these are often accompanied by other allergic diseases. Therefore, early intervention strategies to identify high-risk infants and young children, repair an impaired skin barrier, and control systemic inflamation may improve long-term outcomes in AD patients. However, to the best of our knowledge, no study has evaluated the effectiveness of early intervention on atopic march using systemic therapy in high-risk infants. This narrative review addresses the latest knowledge of systemic treatment, including Th2 cytokine receptor antagonists and Janus kinase inhibitors, for children with moderate to severe AD that is refractory to topical treatment.

Emerging Systemic Treatments for Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease which results from a complex, multifaceted interaction between environmental factors in genetically predisposed patients. Epidermal barrier impairment, alteration of the cutaneous microbiota, effect of external antigens, neurosensory dysfunction, and inflammatory and immune dysregulation all play a pivotal role in inducing and maintaining AD lesions. AD significantly impacts the patient's quality of life and general well-being and is often associated with anxiety and/or depressive symptoms. Classical treatment options include topical corticosteroids and calcineurin inhibitors, phototherapy, and systemic immunosuppression with oral corticosteroids, cyclosporine, methotrexate, and azathioprine in more severe cases. A turning point in facing AD was accomplished when the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor α subunit, led to its approval for the treatment of moderate-to-severe or severe AD in children, adolescents, and adults. Subsequently, a more extensive understanding of AD etiology and pathogenesis has allowed the development of several topical and systemic novel therapy options. Most of these drugs are monoclonal antibodies which interfere with the type2 inflammatory cascade, especially its key cytokines IL-4 and IL-13, or its downstream Janus kinase signaling pathway. However, considering the relevance of other subtypes of Thelper (Th) cells, such as Th1 and Th22, and the important role of specific cytokines (IL-31) in generating pruritus, the horizon of potential therapeutic targets has widened extremely. In this review, we aim to present the most promising systemicagents currently under investigation and illustrate the most significant aspects of their efficacy, safety, and tolerability.

EE13 Cost-Utility Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Children and Adolescents in Portugal

Atopic dermatitis (AD) is a chronic, systemic, type-2 inflammatory disease caused by an increased production/signaling of IL-4/IL-13 associated with long-term negative effects and variable disease course. Dupilumab is the first-in-class targeted therapy (anti-IL4/IL-13) approved and reimbursed in Portugal for the treatment of children/adolescent with AD. We aimed to evaluate cost-utility of dupilumab versus best supportive care (BSC) in children/adolescents (6-17 years) with severe AD candidates for systemic therapy in Portugal.

Systemic treatment for severe atopic dermatitis in children: a case series.

Atopic dermatitis (AD) is children's most frequent chronic inflammatory skin disease. In most patients, this condition is controlled with topical treatments; however, some patients with severe AD do not respond to these treatments, requiring systemic therapy. There is insufficient information about the ideal dose, time of use, clinical response, and safety of systemic therapy in children with severe AD. This study described the clinical characteristics of patients with severe AD who required systemic treatment, drugs used, their clinical course, adverse effects, and associated complications. We conducted a retrospective review of the records of pediatric patients with severe AD treated in the Dermatology Clinic, Instituto Nacional de Pediatría (2000 to 2018), who required systemic treatment for more than 3 months. We included 21 patients. The mean age at disease onset was 3.31 years. The drugs used were methotrexate (57.1%), thalidomide (38%), prednisone (42.8%), azathioprine (19%), mycophenolate mofetil (9.5%), cyclosporine (4.7%), and systemic steroids as bridging therapy (42.8%). Adverse effects were mild and were observed in two patients (9.5%) treated with methotrexate and mycophenolate mofetil. Methotrexate was the most frequently used drug in > 50% of the patients, and most patients attained remission. Cyclosporine, azathioprine, and mycophenolate mofetil were also effective. Side effects were mild and infrequent. Comparative studies of systemic treatments for severe AD in the pediatric population are necessary.

Cost-Utility Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Children and Adolescents in Italy

BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a chronic, multifactorial, inflammatory condition characterized by a significant impact on patients’ quality of life. Dupilumab is reimbursed by the Italian Medicines Agency (AIFA) for the treatment of adolescent and adult patients with severe AD (according to AIFA registry criteria). Recently, dupilumab has been reimbursed in the treatment of children with severe AD. The objective of this analysis was to estimate the incremental cost-utility ratio (ICUR) of dupilumab compared to current supportive care (SC), for the treatment of severe AD in children (6-11 years) and adolescents (12-17 years) in Italy.MATERIALS AND METHODS: Cost-effectiveness analysis was conducted using a 1-year decision tree followed by a Markov model over a lifetime period. The base case analysis was performed on the overall population of the LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914) studies, adopting the National Health Service (NHS) perspective. The following costs were considered: acquisition of treatment, management of disease, adverse events and complications. The robustness of the model was tested through sensitivity analysis. In addition, a scenario analysis adopting the social perspective was performed.RESULTS: In the base case, over a lifetime, dupilumab was more effective than SC in both children and adolescents (+2.44 and +1.62 quality-adjusted life years—QALYs, respectively). The introduction of dupilumab generated an increase in treatment costs (+€ 64,800 and +€ 52,853 € for children and adolescents, respectively), partially offset by a decrease in the costs of disease management and complications. Incremental cost-utility ratios (ICURs) were € 21,189 per QALY gained, for children, and € 26,569 per QALY gained, for adolescents. In both cases, the ICUR was lower than the willingness to pay threshold considered in Italy (€ 50,000 per QALY gained). Both the deterministic and probabilistic sensitivity analysis confirmed the robustness of the base case results. Finally, the scenario analysis, adopting the social perspective, showed coherent results compared to the base case.DISCUSSION: Dupilumab is a cost-effective option for the treatment of children and adolescents with severe AD eligible for systemic treatment in Italy compared to SC, from both the NHS and social perspective, confirming the results obtained in the adult population.

POSA50 Cost-Effectiveness Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Adolescent and Children Patients in Italy

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory systemic condition. Recently, dupilumab has been reimbursed by Italian Medicines Agency (AIFA) for the treatment of adolescents (according to the AIFA registry criteria) and adults with severe AD. Furthermore, it has been authorized by European Medicines Agency in children with severe AD. The objective of this analysis was to estimate the incremental cost-effectiveness ratio (ICER) of dupilumab versus current supportive care (SC), for the treatment of severe AD in children (6-11 years) and adolescents (12-17 years) in Italy.

Tapinarof Cream 1% Once Daily for the Treatment of Moderate to Severe Atopic Dermatitis in Children and Adults: The Pivotal Phase 3 ADORING Clinical Program

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27406 Dupilumab improves signs and symptoms of severe atopic dermatitis in children aged 6–11 years with and without comorbid asthma

Background: Atopic dermatitis (AD), a chronic inflammatory skin disease, frequently occurs with atopic comorbidities, including asthma. Dupilumab inhibits interleukin-4 and interleukin-13 signaling and is approved for treating multiple type 2 inflammatory diseases, including AD and asthma. Here, we evaluate the efficacy of dupilumab with concomitant topical corticosteroids (TCS) in severe AD in children with and without comorbid asthma.

Dupilumab Improves Signs And Symptoms Of Severe Atopic Dermatitis In Children Aged 6–11 Years With And Without Comorbid Asthma

Atopic dermatitis (AD) is a chronic inflammatory skin disease that frequently occurs with atopic comorbidities, including asthma. Dupilumab inhibits interleukin (IL)-4 and IL-13 signaling and is approved for treating multiple type 2 inflammatory diseases, including AD and asthma. Here, we evaluate the efficacy of dupilumab with concomitant topical corticosteroids (TCS) for severe AD in children with and without comorbid asthma.

Dupilumab Improves Signs And Symptoms Of Severe Atopic Dermatitis In Children Aged 6–11 Years With And Without Comorbid Allergic Rhinitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease that frequently occurs with atopic comorbidities, including allergic rhinitis (AR). Dupilumab inhibits signaling of interleukin (IL)-4 and IL-13 – key drivers of type 2-mediated inflammation in multiple diseases, including AD and AR. This subgroup analysis evaluated the efficacy of dupilumab with concomitant topical corticosteroids (TCS) for severe AD in children with and without comorbid AR.

Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis (the ADAPT Randomized Clinical Trial)

S Chan, V Cornelius, S Cro, JI Harper, G Lack. JAMA Pediatr. 2020;174(1):29–37 Currently, systemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. The use of anti-IgE medication (omalizumab) has been employed for multiple forms of atopic diseases such as severe asthma and in conjunction with oral immunotherapy during trials to treat food allergy. However, no large randomized studies in childhood atopic dermatitis have been published. The objective of this study was to determine the effectiveness of omalizumab in treating severe atopic dermatitis in children. Eligible participants were children and adolescents aged 4 to 19 years of age who had severe eczema (with objective Scoring Atopic Dermatitis [SCORAD] index >40) that was unresponsive to optimum topical or systemic therapy and were living in the London, UK area. The Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT) was a single-center, double-blind, …

Disease severity and trigger factors in Danish children with atopic dermatitis: a nationwide study.

Atopic dermatitis (AD) is a prevalent chronically relapsing inflammatory skin disease of childhood. However, little is known about self-reported trigger factors, impact on daily life and factors associated with AD severity. A nationwide questionnaire study of children in Denmark with hospital-diagnosed AD in the time period 2014-2018. The web-based questionnaire was completed by the legal parents. AD severity was assessed using Patient-Oriented Eczema Measure (POEM) tool. Of 3438 invited parents, 1343 (39%) completed the questionnaire. Factors associated with severe AD were onset during the first 6months of life, onset of AD on multiple body regions, a history of hay fever, female sex and low maternal educational level. Staying home from daycare or school due to AD, concentration problems and sleep disturbances in the child were more frequently reported by parents to children with severe AD. Overall, 90% reported at least one AD trigger factor, and all were more frequently reported in children with severe AD. The three most commonly reported trigger factors were cold weather (51.9%), chlorinated water (35.7%) and warm weather (30.2%). We identified factors associated with severe AD in childhood, the impact on daily life, as well as the most common self-reported triggers of AD. These findings may be valuable in clinical practice to inform about prognosis and educate families about trigger avoidance.

PECULIARITIES OF CLINICAL PASSING OF ATOPIC DERMATITIS AND VITAMIN D EXCHANGE IN EARLY CHILDREN

The article is devoted to the study of features of clinical course of atopic dermatitis and vitamin D exchange in young children conducted by us by estimation of severity of atopic dermatitis depending on the value of SCORAD index, determination of 25(OH)D concentration in serum of children by immunochemical method with chemocentric analysis according to the classification approved by experts of the international endocrinological society. In the examination of 188 young children, two groups were formed on the basis of the Lviv City Children's Clinical Hospital. Children from 1 month to 1 year of age with manifestations of atopic dermatitis (n = 120), who were born full-term and had no birth defects, metabolic disorders, severe perinatal CNS lesions formed the main group. The comparison group consisted of 68 healthy young children without chronic diseases. All children had atopic dermatitis in the main group and were classified by severity (depending on the SCORAD index): children with mild severity – 31 (26 %), moderate 47 (39 %), and severe 42 (35 %). As a result of the study, we found a association between the severity of clinical manifestations of atopic dermatitis and the level of vitamin D in the serum. Comparative analysis of the severity of atopic dermatitis, depending on the level of vitamin D in the serum, showed that with severe atopic dermatitis in children of the main group, the level of 25(OH)D was significantly lower compared to its indicators in children with moderate to severe (P < 0.05). Serum vitamin D levels are significantly lower in all forms of atopic dermatitis severity and correlate significantly with the overall SCORAD severity score, erythema intensity, excoriation, itching, and sleep disturbances. The scientific data on the presence of feedback correlation (r = –0,48; P < 0,05) between the development of atopic dermatitis in children and their level of 25(OH)D in serum were added. Our findings suggest that there is a need for a differentiated approach to treating early-stage atopic dermatitis of varying severity, a personalized therapeutic approach to choosing a vitamin D supplementation, given the level of 25(OH)D in the serum.

Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis

Systemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. Despite the efficacy of anti-IgE medication (omalizumab) in the treatment of atopy, no large randomized studies in childhood atopic dermatitis have been published. To determine the effectiveness of omalizumab in treating severe atopic dermatitis in children. The Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT) was a 24-week single-center, double-blind, placebo-controlled randomized clinical trial with a 24-week follow-up. Conducted from November 20, 2014, to August 31, 2017, at Guy's and St Thomas' Hospital NHS Foundation Trust and King's College London in the United Kingdom, this trial recruited participants after a screening visit. Eligible participants (n = 62) were aged 4 to 19 years and had severe eczema (with objective Scoring Atopic Dermatitis [SCORAD] index >40) that was unresponsive to optimum therapy. Statistical analysis was conducted using the intention-to-treat principle. Subcutaneous omalizumab or placebo for 24 weeks. The drug manufacturer's dosing tables were used to determine the dosage based on total IgE (30-1500 IU/mL) and body weight (in kilograms) at randomization. Objective SCORAD index after 24 weeks of treatment. In total, 62 children (mean [SD] age, 10.3 [4.2] years; 32 (52%) were male) were randomized to either omalizumab (n = 30) or placebo (n = 32). Five participants withdrew from treatment (4 [13%] from the placebo group, and 1 [3%] from the omalizumab group). Follow-up attendance was 97% at week 24 and 98% at week 48. After adjustment for baseline objective SCORAD index, age, and IgE level, the mean difference in objective SCORAD index improvement between groups at week 24 was -6.9 (95% CI, -12.2 to -1.5; P = .01), significantly favoring omalizumab therapy and reflecting the results in other assessments of atopic dermatitis severity. Improved quality-of-life scores were seen in the omalizumab group, as measured by the Children's Dermatology Life Quality Index/Dermatology Life Quality Index (-3.5; 95% CI, -6.4 to -0.5) and Pediatric Allergic Disease Quality of Life Questionnaire score (-0.5; 95% CI, -0.9 to -0.0). Improvements in disease severity occurred despite lower potent topical corticosteroid use in the omalizumab group compared with the placebo group (median [interquartile range (IQR)] percentage of body surface area covered, 16% [10%-46%] vs 31% [14%-55%]; median [IQR] number of days of use, 109 [34-164] days vs 161 [82-171] days). This randomized clinical trial found that omalizumab significantly reduced atopic dermatitis severity and improved quality of life in a pediatric population with atopy and severe eczema despite highly elevated total IgE levels at baseline. The result was associated with a potent topical corticosteroid sparing effect and may suggest that omalizumab is a treatment option for difficult-to-manage severe eczema in children with atopy. ClinicalTrials.gov identifier: NCT02300701.

Monitoring trough levels in cyclosporine for atopic dermatitis: A systematic review.

Cyclosporine is a useful immunosuppressive agent for achieving disease control in moderate to severe atopic dermatitis in children and adults. However, it carries the potential for nephrotoxicity. Monitoring of drug levels is performed in other patient groups, such as transplant recipients, but is not commonplace in the management of atopic dermatitis. To investigate levels of nephrotoxicity associated with cyclosporine use in atopic dermatitis and assess potential correlation with trough levels of cyclosporine. An electronic search was conducted on MEDLINE, EMBASE, and Cochrane databases for randomized controlled trials and cohort studies assessing the safety profile of cyclosporine compared to placebo or other atopic dermatitis treatments, in adult and pediatric atopic dermatitis patients from 1966 to May 2019. Studies that did not assess renal toxicity were excluded from analysis. Thirty-eight trials were included for analysis, excluding 11 that did not assess renal toxicity. Descriptive statistical analysis only was performed, due to the high heterogeneity between study methodologies. Significant renal toxicity was seen in 0%-9% of pediatric participants. Monitoring of trough cyclosporine levels was performed in only 10 of the studies, and their correlation to toxicity or disease activity was not explored. There is limited evidence in atopic dermatitis regarding trough level monitoring of cyclosporine. Currently, the practice is not commonplace, particularly in pediatrics, and this is reflected in trial methodology. Monitoring may be useful in specific pediatric groups, such as those on multiple concurrent medications, patients with hepatic or renal dysfunction and non-responders to therapy.

Omalizumab as an adjuvant therapy for treating severe atopic dermatitis in children. A serie of cases.

Atopic dermatitis (AD) is a chronic skin disease that affects 5-20% of children. This disease compromises the quality of life. Omalizumab offers a promising role in the treatment of severe atopic dermatitis. To share our experience with the use of omalizumab for treating severe AD in children. A retrospective review of the cases of pediatric patients with severe atopic dermatitis who were treated with omalizumab as an adjuvant therapy in an outside allergy service. Patients under 18 who had been treated for at least 6 months were included. 19 patients were included. At the beginning of the study, all patients reported a compromise of life quality of 8/10 or more on a analogue scale. A majority of patients had previously received either systemic steroids or other immunosuppressive therapies without obtaining symptom control. At maximum treatment time, the obtained SCORAD scores revealed that the disease in 85.7% of the patients was mild/moderate while, in 14% of the patients, the disease was severe. The Children's Dermatological Life Quality Index (CDLQI) was consistent with the SCORAD scores. From the beginning of treatment to the last visit to the doctor's office, no patient required systemic steroid therapy. Omalizumab appears promising for treating severe atopic dermatitis in pediatric patients. That results shows that omalizubam improves the quality of life, also decreases the severity of the disease and the need for systemic steroid and immunosuppressive therapy, which decreases the side effects that are caused by these medications.

Severe Childhood Atopic Dermatitis : Epidemiological and Clinical Features, and Associated Factors in Brazzaville (Congo)

Severe Childhood Atopic Dermatitis : Epidemiological and Clinical Features, and Associated Factors in Brazzaville (Congo)

Modern principles of anti-inflammatory therapy of moderate and severe atopic dermatitisin children

Modern principles of anti-inflammatory therapy of moderate and severe atopic dermatitisin children