Severe Atopic Dermatitis In Children Research Articles

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

Cyclosporine-A for severe childhood atopic dermatitis: clinical experience on efficacy and safety profile

Background/aim: Management of atopic dermatitis (AD) in children is still challenging. The aim of this study was to evaluate the efficacy and safety profile of cyclosporine-A (CsA) treatment in children with severe and recalcitrant AD. Materials and methods: Medical records of 43 children followed between January 2010 and December 2015 and treated with systemic CsA were evaluated retrospectively. Treatment efficacy was assessed according to the physician's global assessment (PGA) score. According to the treatment response, patients were grouped as nonresponder, moderate responder, or good responder. Effects of the variables on treatment response were evaluated by analysis of variance (ANOVA). The safety profile of CsA was assessed by clinical and laboratory findings at each visit. Results: The median initial dose of CsA was 3 mg/kg daily, ranging between 2.5 and 5 mg/kg daily. The mean duration of CsA therapy was 4.9 ± 4.24 months. Seventeen patients (39.5%) achieved good response in a treatment period of 3 to 14 months. After discontinuation of CsA, of the 17 patients, relapse was observed in 4 (23.5%). Moderate response was observed in 12 (27.9%) patients; however, 14 (32.6) patients did not respond to the treatment. Five patients reported mild side effects. Conclusion: Low-dose CsA seems to be an effective and safe treatment option for severe and recalcitrant AD in children.

IgG response against Staphylococcus aureus is associated with severe atopic dermatitis in children.

An altered immune response against Staphylococcus aureus might contribute to inflammation and barrier damage in atopic dermatitis (AD). To profile IgG antibodies against 55 S. aureus antigens in sera of children with mild-to-severe AD and to evaluate the association between IgG levels and disease severity. In this cross-sectional study, we included children with AD from two interventional study cohorts, the Shared Medical Appointment (SMA) cohort (n = 131) and the older DAVOS cohort (n = 76). AD severity was assessed using the Self-Administered Eczema Area and Severity Index (SA-EASI) and levels of thymus and activation-regulated chemokine (TARC) in serum. IgG antibody levels against 55 S. aureus antigens were quantified simultaneously using a Luminex assay. Pair-wise correlations were calculated between the 55 IgG levels using the Spearman rank correlation test. Linear regression analysis was performed to test for associations between 55 IgG levels and SA-EASI and TARC, adjusting for age, sex and S. aureus colonization. In the SMA cohort, 16 antigens were associated with SA-EASI and 12 with TARC (10 overlapping antigens; P-values 0·001-0·044). The associated IgG antibodies targeted mainly secreted proteins with immunomodulatory functions. In the DAVOS study, IgG levels against only four and one S. aureus antigen(s) were associated with SA-EASI and TARC, respectively (no overlap). In young children, severity of AD is associated with an IgG response directed against S. aureus antigens with mainly immunomodulatory functions. These findings encourage further evaluation of the role of S. aureus in the pathogenesis of AD.

A short period of breastfeeding in infancy, excessive house cleaning, absence of older sibling, and passive smoking are related to more severe atopic dermatitis in children.

Atopic dermatitis (AD) is one of the most common, chronic or chronically relapsing inflammatory skin diseases that affect children. Multiple genetic and environmental factors appear to regulate the pathogenesis of AD. Our aim was to investigate the possible association between family, social, dieting, atopic and environmental factors and the severity of AD evaluated by SCORAD scores in children. The study group included 100 children with AD who attended a paediatric dermatology outpatient clinic with a median age of 18.5 months. The diagnosis of AD was established on the basis of the clinical criteria according to the American Dermatology Society, while the SCORAD score was used to evaluate disease severity. Multivariate linear regression analysis disclosed that excessive cleanliness (p<0.001), RAST level greater than 0.7KU/l (p<0.001), breastfeeding for less than two months (p=0.001), and the absence of an older sibling (p=0.049) were statistically significant independent determinants for high SCORAD scores. Multivariate logistic regression analysis showed that excessive cleanliness (p<0.001) was the strongest independent risk factor for severe AD (SCORAD>36) (aOR: 59.4; 95%CI: 10.9-322.6). RAST level greater than 0.7KU/l (aOR: 7.9; 95%CI: 1.5-41.0; p=0.014) and severe passive smoking (aOR: 4.6; 95%CI: 1.0-22.1; p=0.050) also showed a significant independent, but clearly weaker, association with severe AD. A short duration of breastfeeding, absence of older siblings, parental passive smoking, food allergens along with aeroallergens, and excessive cleanliness should be considered as negative prognostic factors, leading to a higher SCORAD score in children with AD.

Management of severe atopic dermatitis in children

Management of severe atopic dermatitis in children

Efficacy of wet-wrap treatment for 13 cases of severe childhood atopic dermatitis: a clinical observation

Objective To evaluate the efficacy and safety of wet-wrap treatment (WWT) for severe childhood atopic dermatitis (AD) . Methods A total of 13 children with severe AD were enrolled from Department of Dermatology of Beijing Children′s Hospital between September 2016 and March 2017, whose diagnosis was based on the Williams′ diagnostic criteria and SCORing atopic dermatitis (SCORAD) score was more than 50. These patients received WWT daily for 3 - 5 days. The changes of SCORAD and visual analog scale (VAS) scores before and after treatment were evaluated. Moreover, 3 patients with symmetrical skin lesions on bilateral limbs were selected, and received WWT (WWT group) and traditional topical treatment (control group) on the bilateral limbs respectively for 3 days. After the treatment, the severity of local skin lesions on the bilateral limbs were evaluated and compared. Results Before the treatment, the SCORAD and VAS scores of the 13 patients were 60.2 ± 9.7 and 7.3 ± 1.8 respectively. Three to five days after the WWT, the SCORAD and VAS scores significantly decreased to 24.7 ± 5.8 and 2.4 ± 1.0 respectively (t = 15.128, 9.385 respectively, P < 0.001) . Of the 13 patients, 12 achieved a more than 50% improvement in SCORAD. After 3-day treatment with WWT in the 3 patients, the severity score of skin lesions was significantly lower in the WWT group than in the control group (t = 7.0, P < 0.05) . Mild adverse reactions to WWT occurred, and 3 patients reported discomfort induced by wetness during the treatment. Conclusion WWT shows rapid efficacy and less adverse reactions in the treatment of severe childhood AD, and its therapeutic effect is superior to that of traditional topical treatment. Key words: Dermatitis, atopic; Child; Treatment outcome; Wet-wrap treatment

Cyclosporine A for severe atopic dermatitis in children. efficacy and safety in a retrospective study of 63 patients.

Cyclosporine A (CSA) is an immunosuppressant agent widely used in severe atopic dermatitis (AD). However, experience in children is limited. To assess the efficacy and adverse events of CSA therapy in children. Retrospective study of children with severe AD treated with CSA between January 2009 and December 2015. Data from 63 patients were collected. Mean age at the beginning of treatment was 8.4 years (±3.6). The median starting dose was 4.27 (±0.61) mg/kg/day. After 4 weeks of treatment, the outcome was excellent in 35% of cases, good in 29% and poor in 36% of the patients. The response was better in patients without eosinophilia (P < 0.05). The median duration of treatment was 4.6 months (range 1.5-21.6). Side-effects were frequent but mild, being more common in patients after longer treatment periods (P < 0.05). Mean time of follow-up was 19.4 months (±12.7). Prolonged remission (>6 months) was observed in 13 patients (20%). This is a retrospective review. The follow-up period is limited. Our data confirm that CSA is efficacious and acts rapidly in the majority of children with severe AD. CSA therapy can provide sustained remission in some patients. CSA seems to be well tolerated in children, but strict monitoring is mandatory.

Potential preventive effects of proactive therapy on sensitization in moderate to severe childhood atopic dermatitis: A randomized, investigator-blinded, controlled study.

Proactive therapy for atopic dermatitis (AD) effectively prevents exacerbation. However, its role in preventing subsequent sensitization to allergens has not been prospectively studied. We investigated whether proactive therapy for AD can effectively impact immunological parameters in a randomized, investigator-blinded, parallel group study. Thirty patients aged 3 months to 7 years with moderate to severe AD who had undergone an AD educational program were allocated to a proactive treatment group or a reactive treatment group. During the disease control period, patients in the proactive group performed intermittent preventive application of topical corticosteroid for 1 year. Changes in the severity scoring, quality of life measures and immunological parameters (serum thymus and activation regulated chemokine [TARC], total immunoglobulin E [IgE] and house dust mite-specific IgE levels) were evaluated and compared between the proactive and reactive treatment groups. Although the average topical corticosteroid ointment use per day in both groups was not significantly different, the severity and quality of life scores were significantly lower in the proactive group than in the reactive group at the final visit. In addition, compared with baseline levels, serum TARC levels remained significantly lower during proactive therapy, while house dust mite-specific IgE levels were significantly increased only in the reactive group. The results suggest that in addition to controlling the severity of AD, intermittent preventive administration of topical corticosteroids may prevent an increase in aeroallergen-specific IgE levels in patients with childhood AD. The use of TARC levels as a biomarker for AD remission is also supported.

Systemic Agents for Severe Atopic Dermatitis in Children.

Atopic dermatitis (AD), or eczema, is a chronic inflammatory skin condition characterized by relapsing pruritic, scaly, erythematous papules and plaques frequently associated with superinfection. The lifelong prevalence of AD is over 20 % in affluent countries. When a child with severe AD is not responding to optimized topical therapy including phototherapy, and relevant triggers cannot be identified or avoided, systemic therapy should be considered. If studies show early aggressive intervention can prevent one from advancing along the atopic march, and relevant triggers such as food allergies cannot be either identified or avoided, systemic therapy may also play a prophylactic role. Though the majority of evidence exists in adult populations, four systemic non-specific immunosuppressive or immunomodulatory drugs have demonstrated efficacy in AD and are used in most patients requiring this level of intervention regardless of age: cyclosporine, mycophenolate mofetil, methotrexate, and azathioprine. This article reviews the use of these medications as well as several promising targeted therapies currently in development including dupilumab and apremilast. We briefly cover several other systemic interventions that have been studied in children with atopic dermatitis.

Long-term use of a 4% sodium cromoglicate cutaneous emulsion in the treatment of moderate to severe atopic dermatitis in children

Introduction: Sodium cromoglicate (SCG), a chromone with anti-inflammatory, anti-itch and anti-allergic properties. We report a long-term study of a 4% aqueous solution of SCG in children with moderate to severe atopic dermatitis (AD). Materials and methods: Children aged 1 to 12 years with AD were entered into a 12-week randomised clinical trial (RCT), followed by 12 months open treatment with known 4% SCG emulsion (Altocrom®). Primary endpoint was change in SCORAD score. Secondary endpoints included symptom severity, Quality of Life, concomitant treatment usage, global assessments. Results: One hundred and seventy-seven subjects entered, 118 treated with 4% SCG emulsion and 59 with vehicle: 128 completed 12 months in open study. SCORAD score reduced during RCT by −15.3 (−33%) on 4% SCG emulsion and −18.0 (−39%) on vehicle: p = 0.2331. After 12 months reduction was 56%. No secondary endpoint showed differences between treatments during RCT. Thirty-two subjects reported treatment related events during RCT and open trial. Eleven (7%) reported application site discomfort. Most were reported as mild and most resolved without intervention and the study drug was stopped in one case only. Conclusions: SCG 4% cutaneous emulsion was well tolerated in children treated for 15 months.

The adverse effect profile of oral azathioprine in pediatric atopic dermatitis, and recommendations for monitoring

BackgroundAzathioprine is efficacious in the treatment of severe childhood atopic dermatitis; however, robust data on adverse effects in this population are lacking.ObjectiveWe sought to assess adverse effects of azathioprine treatment in a pediatric atopic dermatitis cohort, and make recommendations for monitoring based on these data.MethodsBlood test results for all 82 children prescribed oral azathioprine for atopic dermatitis in our department between 2010 and 2012 were collated prospectively, and clinical notes were reviewed retrospectively.ResultsMean age at commencing azathioprine was 8.3 years (SEM 0.4). Mean maximum doses were 2.4 mg/kg (SEM 0.1) and 1.5 mg/kg (SEM 0.1) for normal and reduced serum thiopurine-S-methyltransferase levels, respectively. Adverse effects on blood indices occurred in 34 of 82 patients (41%), with pronounced effects in 18 of 82 (22%) after a median time of 0.4 years. Two patients stopped therapy as a result of abnormal blood indices. Clinical adverse effects occurred in 16 of 82 (20%), two resulting in cessation of therapy. Incidence of adverse effects was unaffected by age, sex, thiopurine-S-methyltransferase level, and drug dose on multivariate regression.LimitationsComparison with other studies is limited by varying definitions of adverse effects.ConclusionOral azathioprine was associated with few pronounced adverse effects for the duration of use and dosage in this cohort. Recommendations for monitoring are made.

Systemic Treatment of Severe Atopic Dermatitis in Children and Adults

Most patients with atopic dermatitis (AD) can control their skin disease with emollients combined with topical immunosuppressive therapy, ultraviolet (UV) therapy or both. Unfortunately, though, a small group of children and adults is not sufficiently treated with any combination of these therapies. This group includes the patients with the most recalcitrant phenotype who have severe AD, with frequent major exacerbations or chronic localised AD lesions like eyelid eczema. They can be a challenge to treat, and systemic treatment is the next step to induce and maintain disease control. It is crucial when planning systemic therapy that treatment be tailored to the unique patient. Systemic treatment of severe AD in both young and old is a delicate matter, and special care should be taken to monitor possible side effects. Some patients respond well to one medication but not to others, and predicting the effect of a medication for the individual patient is not possible. Therefore, some patients have to try several systemic immunosuppressants before they obtain sufficient control of the disease.

Is phototherapy useful in the treatment of atopic dermatitis in asian children? A 5-year report from singapore.

The goal of the current study was to review a cohort of Asian children with atopic dermatitis (AD) treated using phototherapy at a tertiary dermatologic center in Singapore. We performed a retrospective review of patients younger than 16years old with a clinical diagnosis of AD treated with phototherapy at the National Skin Center, Singapore, over a 5-year period from 2004 to 2008. Twenty-five patients were identified who were ages 7 to 15years at the time they underwent phototherapy, with equal sex distribution. The duration of disease ranged from 2 to 14years. Most patients had extensive disease involving more than 70% of their body surface area. Fifteen patients were treated with narrowband ultraviolet B (NBUVB) phototherapy, with 10 (66%) showing improvement of symptoms. The duration of therapy was 3 to 30months (mean 11mos), with a mean of 60 treatment sessions (range 12-104). Nine patients were treated with combined ultraviolet A (UVA) and NBUVB phototherapy. Five patients (55%) improved, with four having good response and one having mild improvement. The duration of therapy was 1-6months (mean 3.6mos), with an average of 22 treatment sessions (range 10-44). Two patients underwent combined UVA/broad-band UVB (BBUVB) phototherapy. Both had worsening of disease requiring cessation of treatment. Phototherapy is a useful adjunct in the treatment of moderate to severe AD in children. More than half of the patients treated with NBUVB or combined UVA and NBUVB improved with phototherapy, but the usefulness of combined UVA and BBUVB requires further evaluation.

Effects of probiotics for the treatment of atopic dermatitis: a meta-analysis of randomized controlled trials

BackgroundThe effects of probiotics on the treatment of atopic dermatitis (AD) are inconclusive. ObjectiveTo determine the clinical effect of probiotics in the management of AD overall and in different age groups. MethodsA comprehensive search of databases through December 2013 was performed. For this meta-analysis, randomized controlled trials measuring the treatment effects of probiotics or synbiotics in patients diagnosed with AD were included. The primary outcome was a difference in Scoring of Atopic Dermatitis (SCORAD) values between the treatment and placebo groups overall and in different age populations. ResultsTwenty-five randomized controlled trials (n = 1,599) were available for this meta-analysis. Significant differences in SCORAD values favoring probiotics over the control were observed overall (mean −4.51, 95% confidence interval −6.78 to −2.24), in children 1 to 18 years old (−5.74, 95% confidence interval −7.27 to −4.20), and in adults (−8.26, 95% confidence interval −13.28 to −3.25). However, the effectiveness of probiotics in infants (<1 year old) with AD was not proved. The effect of synbiotic use was not significantly different from that of probiotic use. Treatment with a mixture of different bacterial species or of Lactobacillus species showed greater benefit than did treatment with Bifidobacterium species alone. ConclusionThe overall result of this meta-analysis suggests that probiotics could be an option for the treatment of AD, especially for moderate to severe AD in children and adults. However, no evidence was found supporting the beneficial role of probiotics in infants.

Commentary: Methotrexate and ciclosporin in the treatment of severe eczema in children

Funding sources: None. Conflicts of interest: None declared. Severe and persistent childhood atopic dermatitis (AD) has a dramatic impact on quality of life. If AD remains poorly controlled after appropriate and well‐adhered‐to topical regimens have been exhausted, including assessment of immediate and delayed allergies and infective aggravations (bacterial, viral and fungal pathogens),1 what is the next option on the treatment menu? Narrowband phototherapy is often an attractive option. When other treatments have been exhausted, paediatric dermatologists not infrequently find themselves offering advice and choices to families considering systemic therapy. Clearly, any treatment offered must be both effective and safe, not just in the immediate term but, especially in a paediatric population, in the long term too. What evidential basis do we have to inform and guide parental and child choice? The truth is that direct evidence is hard to find, as primary data from properly conducted clinical trials of systemic therapies in severe childhood AD are very few, and thus we often must extrapolate backwards from adult studies or from the use of these drugs in childhood for other indications. Neither situation is ideal: in the first instance due to the very different pharmacokinetic and dynamic considerations in children, and in the second for the obvious disease‐specific variations in response to therapy. As a subspecialty, paediatric dermatology has not succeeded in exploring, in a robust and systematic way, the best options in this clinical scenario. In this setting any new evidence is very welcome and is worth examining closely to see whether it can substantiate a change in clinical practice. Current therapeutic choices in this situation include ciclosporin, azathioprine and methotrexate. Ciclosporin is licensed for use in over 16 year olds and remains the systemic therapy of first choice in most of Europe.2 Azathioprine has been widely used in the U.K., but recent reports of late side‐effects with this drug have understandably given cause for concern on safely grounds;3 these include skin cancer, hepatosplenic T‐cell lymphoma and progressive multifocal leucoencephalopathy, albeit in other disease settings and often in conjunction with other immune‐modifying drugs.

Methotrexate vs. ciclosporin in the treatment of severe atopic dermatitis in children: author response

Methotrexate vs. ciclosporin in the treatment of severe atopic dermatitis in children: author response

Methotrexate vs. ciclosporin in the treatment of severe atopic dermatitis in children: a critical appraisal

El-Khalawany et al. (Eur J Pediatr 2012; 172: 351-6) aimed to compare the efficacy and safety of methotrexate vs. ciclosporin in the treatment of children with severe atopic eczema. This multicentre, parallel group (ratio 1 : 1), randomized controlled trial was conducted in a secondary care setting in Egypt. Children with severe atopic eczema were randomly assigned to receive either methotrexate (7.5 mg weekly) or ciclosporin (2.5 mg kg(-1) daily) for 12 weeks, followed by a 12-week follow-up period. Eczema severity was measured using the SCORing of Atopic Dermatitis (SCORAD) index. The authors also recorded the number of patients on each therapy experiencing adverse effects. The primary outcome was the mean change in SCORAD after 12 weeks of treatment. Forty patients with a mean age of 11.6 ± 1.52 years were included in the trial. At week 12, patients in the methotrexate group had a mean ± SD absolute reduction in SCORAD of 26.25 ± 7.03, compared with 25.02 ± 8.21 in the ciclosporin group (P = 0.93). Both drugs were associated with minor adverse effects, none of which necessitated changing the treatment regimen. El-Khalawany et al. conclude that both methotrexate and ciclosporin in low doses are clinically effective, relatively safe, and well tolerated as treatments for severe atopic eczema in children.