Severe Cases Of Atopic Dermatitis Research Articles

Monoclonal Antibodies: Current Advancements and Future Potential for Atopic Dermatitis Therapy.

Atopic Dermatitis (AD) is an inflammatory skin condition with a severe itch. The topical therapy using corticosteroids is not sufficient for the effective therapy of moderate to severe cases of AD. The investigation and development of immunological targetspecific human monoclonal antibodies have changed the paradigm for the therapy of moderate to severe cases of AD. The establishment of target-specific, tolerable, and efficacious human monoclonal antibodies might lead to the better management of moderate to severe cases of AD. The scientific literature available in databases, such as Pubmed and Clinicaltrial.gov, was searched and discussed for available clinical therapeutic information. The present review has discussed the potential immunological targets of specific monoclonal antibodies developed and approved or which are under investigation in clinical trials. The development of targeted monoclonal antibodies can improve the understanding of the role of different immunological pathways and biomarkers in AD and become the future of AD treatment.

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.

Treatments for atopic dermatitis.

Atopic dermatitis usually develops in childhood, but can occur in adults. Management involves drug and non-drug treatments to clear the skin. Not all patients with atopic dermatitis have allergies. Most patients have trigger factors that can be avoided. All patients should use soap substitutes and bath oils. Moisturisers are important for improving the condition of the skin. Topical corticosteroids are the main drug treatment. The choice of corticosteroid depends largely on the site of the atopic dermatitis. Topical calcineurin inhibitors can be considered for sensitive sites such as the face where potent topical corticosteroids are potentially harmful. Adjunctive treatments given during flares of dermatitis include bleach baths and wet dressings. Antihistamines may help to relieve itch. Phototherapy may be considered by a specialist for adults if there is inadequate response to treatment. Severe cases of atopic dermatitis may require systemic treatment. Immunosuppressants, such as ciclosporin, have been used and now dupilumab and upadacitinib are available for severe chronic atopic dermatitis.

Quality of life in children with atopic dermatitis aged 13–17 years

Purpose. To study the quality of life of children aged 13–17 years with atopic dermatitis, depending on the sex of the child, the severity of the disease.Material and methods. 350 children aged 13–17 with atopic dermatitis (observation group) and 350 children of the same age of I– II health groups, without allergic diseases (comparison group) were examined. The quality of life of children and their parents was studied using a general questionnaire, Pediatric Quality of Life Inventory — PedsQL™4.0 (Varni J. et al., USA, 2001).Results. The quality of life of children with atopic dermatitis aged 13–17 years is reduced in all respects in comparison with their healthy peers. Atopic dermatitis had the greatest negative impact on such areas of the child’s life as emotional, school, and social functioning. The quality of life in children aged 13–17 years with severe cases of atopic dermatitis was significantly more impaired in girls, compared with boys. Parents rated the quality of life of their children higher than the children themselves.Conclusion. A significant decrease in emotional, school, and social functioning in the structure of the components of the quality of life of children aged 13–17 years with atopic dermatitis indicates the need for timely diagnosis of these disorders and their correction.

DEVELOPING AN INFANT ATOPIC DERMATITIS SCORECARD FOR PEDIATRIC CLINICIANS

<h3>Introduction</h3> Accurate diagnosis and categorization of infant atopic dermatitis (AD) is necessary for assessing risk prior to early peanut introduction. AD assessment tools were primarily developed for research purposes and not for clinical use. Objective:To develop an infant AD scorecard with a focus on diverse skin tones to assist pediatric clinicians with AD assessments. <h3>Methods</h3> Parents of children with AD diagnosis were contacted and consented to provide high-resolution standardized photographs of their infant's AD lesions. Two dermatologists reviewed all images and determined AD severity using the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD). An instructional video about AD and how to use the scorecard was developed and presented to pediatric clinicians. <h3>Results</h3> Overall, photographs of 13 children were obtained: 6 children were photographed by research staff and 7 provided images of their infants using the same standardized photographic protocol. Two pediatric dermatologists evaluated 58 infant's images, with 84% agreement on first-pass severity categorization. Of these, 14 images were selected representing 2 White, 2 Black, 1 mixed race, and 2 Hispanic/LatinX infants. These images were used to develop the final scorecard which included 5 mild, 5 moderate, and 4 severe cases of AD. Overall, 189 pediatricians completed an educational module on AD categorization and vIGA-AD scorecard. Initial feedback surveys (N=14) 64.3% reported the training was "very effective." Observation of utilization and effectiveness of the scorecard and training is ongoing. <h3>Conclusion</h3> Development of an infant AD scorecard can assist pediatric providers in assessing peanut allergy risk prior to early introduction.

Reducing costs in atopic dermatitis.

Atopic dermatitis (AD) is a common relapsing inflammatory skin condition associated with a high economic burden due to its chronicity and multitude of direct and indirect treatment costs. AD disproportionately impacts children and minority populations, and treatment choices are cost-prohibitive for many patients. Our objective was to describe the treatment and management of AD from a cost-conscious perspective. A review of the literature was conducted with PubMed using the following keywords: AD, cost, medications, treatment, management, efficacy, adherence, education, and prophylactic. The use of moisturizers prophylactically in high-risk infants who have yet to develop AD may reduce incidence of disease and associated costs. Increasing patient medication adherence and moisturizing between flares also reduces costs in AD. The use of corticosteroids as the first-line treatment is efficacious and cost-effective for mild cases of AD, however, in severe cases of AD corticosteroids alone are not sufficient. Systemic biologics are necessary in some patients with severe cases of AD; however, they are associated with high costs. Phototherapy, through portable home units, tanning beds, and natural sunlight are cost-effective alternatives. Effective management of AD improves with education programs for both the patient and their family, reducing long-term costs in the management of this disease. Reducing AD treatment costs requires consideration of prophylactic therapies, patient education, and should differ based on the severity of disease. A multifaceted approach to AD treatment reduces costs and health-care barriers.

(Invited) Flock -Flare Clock: Passive Sweat-Based Eczematous Flare Detection System

Point-of-need platforms that work with sweat offer the advantage of self-monitoring for chronic diseases. Sweat based platform offer benefits in areas like comfort, functionality, and provide real time analysis of biomarker fluctuations in the body. For chronic conditions like Atopic Dermatitis, evaluating the severity of the disease on a case-by-case basis can help with providing an effective treatment plan. Sweat contains biomarkers like interleukin-31 and cortisol, which are biomarkers for atopic dermatitis (AD) and circadian disruption that is associated with the itching symptom of the disease. This portable detection technology is aimed at bridging the gap between assessing the severity of the disease and providing a patient-centric treatment plan. The research is envisioned to work as a wearable that can predict flares based on the biomarker levels and help with management of severe cases of AD, especially in pediatric populations.FLOCK (flare clock) system is a novel platform that comprises of a nanoporous membrane based multilayer stack that works with passively secreted sweat. It is designed to capture eczema severity and circadian disruption caused due to its symptoms. This is aimed to be a wearable designed for efficient management of the flaring associated with Atopic Dermatitis (AD). The work presents the development of an eczematous flare tracker that detects IL-31 and cortisol levels to create an AD management platform. The platform uses electrochemical detection for tracking these biomarkers in sweat. It is sensitive to IL-31 levels in various flare-based formulations tested through simulated sweating with a detection limit of 50 pg/mL and range 50-1000 pg/mL. On-body study highlights the ability of the wearable platform to track the rise and fall in the biomarkers’ levels. These levels are well correlated to salivary levels and commercial gold standard techniques (r>0.8, R2 >0.95).

Rapid response to dupilumab treatment in children with moderate-to-severe atopic dermatitis: A case series.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by itch and clinical heterogeneity regarding the age of onset, morphology, distribution, and severity of lesions. Severe AD has a significant impact on the quality of life of affected children and their caregivers. Children with moderate‐severe AD inadequately controlled with topical therapy have limited treatment options, such as systemic corticosteroids or phototherapy, often prescribed as off‐label treatments, often with unfavorable benefit‐to‐risk ratio adverse events. Dupilumab is a fully human monoclonal antibody with proven effectiveness and a relatively safe adverse effect profile in patients with type 2 inflammatory diseases, including AD. We report three pediatric cases of severe AD successfully treated with dupilumab.

Relationship of Substance P with the Degree of Atopic Dermatitis Severity.

IntroductionAtopic dermatitis (AD) is a chronic inflammatory skin disease that starts during childhood with a varied course. Itching or incessant itching in severe cases, sleep disturbance, and infection-prone skin are the typical symptoms of this disease. Substance P is postulated to have an important role in AD. Increasing levels of substance P in AD induce the release of IFN-γ, IL-4, tumor necrosis factor-α (TNF-α), and IL-10 from peripheral blood mononuclear leukocytes, inducing an itching response.MethodsThis study is a cross-sectional study that aims to analyze the relationship between serum substance P levels and AD severity in children using Score of AD (SCORAD), and to determine the mean serum substance P levels and severity of AD in patients with AD. This study also aims to find out the correlation of substance P levels with the SCORAD values.ResultsForty-six children (29 males; 17 females) with a mean age of 10.35 years (standard deviation (SD) = 4.01) were diagnosed with AD. The SCORAD index assessment was conducted to analyze AD (mean value, 23.15; SD = 9.42), and mild AD obtained the highest degree. The level of substance P was also examined (mean value, 300.88; SD = 127.55).DiscussionThis study did not find a significant relationship between substance P levels and AD severity (p-value = 0.880), and there was no significant correlation between substance P levels and SCORAD values (p-value = 0.233; r = −0.179). The limitations of this study include a small number of cases, no control group, and we only found two cases of severe AD. To generalize the results, further studies with wide range population and AD severity might be done in the future.

Effects of Hyperbaric Oxygen Therapy in Children with Severe Atopic Dermatitis.

In the course of atopic dermatitis (AD), the overactivity of the immune system, associated with predominant Th2 lymphocyte responses, is observed, which leads to an increased inflammatory reaction. Cases of a severe course of atopic dermatitis lead to the search for new therapeutic options. The aim of this study was to assess the effects of hyperbaric oxygen therapy (HBOT) treatment for severe cases of AD in children. A total of 15 children with severe AD underwent therapy. The influence of HBOT on the clinical course of AD and immunomodulatory effect of the therapy was analyzed by the SCORAD and objective SCORAD (oSCORAD) scales and by determining the serum concentration of immunological parameters (blood: nTreg lymphocytes, CD4+CD25highCD127-FOXP3+, NKT lymphocytes CD3+, CD16/56+, and serum: total IgE, cytokines IL-4, IL-6, and IL-10, before and after the 30-day treatment cycle). The study showed a significant effect of the therapy on the improvement of the skin condition. In all children, a reduction in the extent and intensity of skin lesions, reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification after HBOT was observed. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after therapy. In all children, a statistically significant decrease in the serum level of IgE was observed. However, no statistically significant changes in the blood levels of IL-4, IL-6 and IL-10, as well as the percentage of CD4+CD25highCD127−FOXP3+ Treg and NKT lymphocytes, were found. In conclusion, the use of hyperbaric therapy has a positive impact on treatment results in children with a severe course of atopic dermatitis.

The Role of Toll-Like Cell Receptor 2 (Arg753gln) Polymorphism in Allergen Sensitization and Disease Severity in Atopic Dermatitis Patients

Background: Variations in Toll-like receptor 2 (TLR2) encoding gene have been associated with atopic conditions. Objective: The present work aims to analyze single nucleotide polymorphism (SNP) of TLR2 gene Arg753Gln in atopic dermatitis (AD) and its association with allergen sensitization and disease severity. Methodology: 110 AD patients and 75 healthy controls were enrolled and subjected to genotyping of TLR2 gene Arg753Gln by restriction enzyme analysis and allergy investigations. Results: TLR2 Arg753Gln SNP was significantly more frequent in the patients (48%) in comparison to the healthy group (32%) (0R= 1.7). Individuals with the G/A genotype were at a higher risk for AD development by two times. Inhalant allergens specific IgE were distinguished in 80 % of patients with TLR2 gene polymorphism. Conclusion: GA genotype of TLR2 gene is more dominant in severe cases of atopic dermatitis and associated with sensitization to certain inhalant allergens as house dust mites and pollens.

12828 Mycophenolate mofetil and atopic dermatitis: Systematic review and meta-analysis

Background: For severe cases of atopic dermatitis, systemic or potent agents may be required for control of disease. There have been some reports of treatment efficacy of off-label use of mycophenolate mofetil (MMF) in patients with refractory atopic dermatitis who are unresponsive or have developed adverse effects to initial systemic immunosuppressant agents.

Atopic dermatitis and its relation to food allergy.

To present the most recent evidence on atopic dermatitis and its relation to food allergy. Atopic dermatitis is a chronic inflammatory disorder of the skin characterized by impaired skin barrier because of multifactorial causes including genetic factors, immune dysregulation, and skin microbiome dysbiosis. Infants with temporary skin barrier disruption and/or persistent atopic dermatitis are particularly at risk of developing food allergy (during the so-called atopic march), with up to half of patients demonstrating positive food-specific IgE and one-third of severe cases of atopic dermatitis having positive symptoms on oral food challenge. A high proportion of children with atopic dermatitis exhibit asymptomatic sensitization to foods, and skin testing to identify potential food triggers is not recommended unless the patient has a history suggestive of food allergy and/or moderate-to-severe atopic dermatitis unresponsive to optimal topical care. Indeed, indiscriminate testing can lead to a high proportion of false-positive tests and harmful dietary evictions. Promising strategies to prevent food allergy in children with atopic dermatitis include early skincare with emollients and treatment with topical steroid, and early introduction of highly allergenic foods. Further studies are required to identify risk factors for atopic dermatitis to help prevent the development of food allergy in this high-risk population.

Trends in Atopic Dermatitis-From Standard Pharmacotherapy to Novel Drug Delivery Systems.

Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by robust burning and eczematous lacerations in diverse portions of the body. AD affects about 20% of both offspring and adults worldwide. The pathophysiology of AD combines environmental, hereditary, and immunological aspects, together with skin barrier dysfunction. The procedures used to prevent the disease are the everyday usage of creams to support the restoration of the epidermal barrier. The classical treatments include the use of topical corticosteroids as a first-line therapy, but also calcineurin inhibitors, antihistamines, antibiotics, phototherapy, and also immunosuppressant drugs in severe cases of AD. Topical drug delivery to deeper skin layers is a difficult task due to the skin anatomic barrier, which limits deeper penetration of drugs. Groundbreaking drug delivery systems, based on nanoparticles (NPs), have received much attention due to their ability to improve solubility, bioavailability, diffusion, targeting to specific types of cells, and limiting the secondary effects of the drugs employed in the treatment of AD. Even so, additional studies are still required to recognize the toxicological characteristics and long-term safety of NPs. This review discusses the current classical pharmacotherapy of AD against new nanoparticle skin delivery systems and their toxicologic risks.

Mycophenolate mofetil and atopic dermatitis: systematic review and meta-analysis

Background: For severe cases of atopic dermatitis, systemic or potent agents may be required for control of disease. There have been some reports of treatment efficacy of off-label use of mycophenolate mofetil (MMF) in patients with refractory atopic dermatitis or have developed adverse effects to initial systemic agents.Methods: Electronic searches were performed using six databases from their inception to April 2019. Data were extracted and analyzed according to predefined clinical endpoints.Results: From 140 cases, the mean age was 38.21 ± 22.8 years. There were 52.9% males and 47.1% females. The average number of failed agents was 3.5 ± 1.2. 77.6% reported partial or full remission. Relapses occurred in 8.2% of cases. The average time for initial effects was 6.8 ± 7 weeks. There was a significant reduction in pre to post SCORAD scores by 18 points (p = .0002). More males had complications compared to females. Prolonged duration of treatment ≥1 year was associated with herpes infections.Conclusions: In summary, the current evidence to date is low-quality in nature but is promising regarding the efficacy and safety of MMF for adult and pediatric atopic dermatitis. There should be ongoing monitoring for infections that may develop on long term therapy.

Lack of omalizumab efficacy in severe atopic dermatitis with extremely elevated IgE levels: two case reports and a literature review

The authors present two cases of severe atopic dermatitis with extremely elevated IgE levels treated with omalizumab. The effect of this treatment was completely unconvincing in both patients, most likely because of extremely elevated IgE values, which could not be eliminated by omalizumab. Our observation is consistent with earlier published literature reporting that omalizumab as a treatment for atopic dermatitis seems to work better in patients with lower levels of IgE antibodies.

New aspects in systemic treatment of atopic dermatitis

In severe cases of atopic dermatitis (AD) systemic treatment is indicated. So far, cyclosporine and systemic glucocorticosteroids represented the only systemic treatment options approved for the indications of AD in Germany; however, from clinical practice there is increasing evidence for beneficial therapeutic effects in AD by other immunosuppressive or immunomodulatory substances, such as mycophenolate, methotrexate, alitretinoin and ustekinumab. Beyond this, ongoing research activities focus on abetter understanding of genetic and immunological aspects of this chronic inflammatory skin disease. Regarding treatment with mycophenolate, genetic polymorphisms in AD patients could be identified that might predict responsiveness to this medication. Moreover, several new substances specifically targeting inflammation in AD are currently being studied and the first promising treatment effects on skin condition and pruritic symptoms of AD could be observed. As an exceptional result of this development in September 2017 in Europe and therefore in Germany the first biologic as first-line treatment was approved for the indication of moderate to severe AD in adults. Dupilumab is ahuman monoclonal IgG4 antibody that blocks asubunit of the interleukin (IL)-4 and IL-13 receptors, thus inhibiting the proinflammatory effects of these cytokines. Furthermore, the cytokine IL-13 itself, the IL-31 receptor, which is of particular relevance for pruritus in AD, the histamine-4-receptor and Janus kinases represent further promising targets currently being investigated in clinical trials for the treatment of AD.

Atopic Dermatitis in Cameroon: Quality of Life and Psychiatric Comorbidities among Affected Children and Adolescents Running Head: Atopic Dermatitis and Psychiatric Impairments

Background: The dearth of Cameroonian data on the quality of life (QoL) of patients with atopic dermatitis (AD) prompted this study which aimed to assess the impact of AD on QoL of affected children and adolescents as well as their families, and seek existence of psychiatric comorbidity (depression and anxiety). Methods: We conducted a cross-sectional study from February to May 2015 in Yaounde, Cameroon. Patients aged 0-16 years, diagnosed with AD by a dermatologist, and whose parents/guardians had given consent were included. Standardized scores and scales were used to assess the severity of the disease, the QoL of patients and families, as well as the presence of depression or anxiety. Results: A total of 53 children were recruited. The median age was 60 months. There were 23 cases of severe AD, 21 of moderate AD and 9 of mild AD. QoL was impaired in 94.3% of cases, moderate in 20 subjects, high in 8 patients and extreme in 2 patients. QoL of the family was impaired in 88.7% of cases, moderate in 16 and high in 7 families. The higher the severity of AD, the more QoL of patients was impaired (r=0,475; p<0.0001), as well as that of families (r=0,365; p=0.007). Alteration in patients’ QoL was linked with that of families (r=0.527; p<0.0001). There were 5 teenagers with mild depression, 2 with mild anxiety, and 1 with moderate anxiety. Conclusion: AD alters the QoL of children and their families.

Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis

Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis

Atopic dermatitis in older adults: A viewpoint from geriatric dermatology.

Atopic dermatitis (AD) in older adults represents a newly defined subgroup of AD. The prevalence of elderly AD is approximately 1-3% among elderly populations in industrialized countries. Elderly patients with AD show some common clinical characteristics, such as a male predominance, a lower incidence of lichenified eczema at the elbow and knee folds, and particular patterns of onset and clinical course. Both immunoglobulin (Ig)E-allergic and non-IgE-allergic types are observed in elderly AD. Elderly patients with IgE-allergic AD show high rates of positivity for specific IgE antibodies against house dust mites, associations with IgE allergic and asthmatic complications, histopathological features with a predominance of IgE-mediated allergic inflammation in the lesional skin, and a significantly lower incidence of malignancy as compared with control subjects. The etiology of elderly AD might be associated with immunosenescence, age-related changes to the sex hormone milieu, age-related barrier dysfunctions in the skin and gut, functional disturbance of sweat production, and environmental stimuli in the lifestyle of elderly individuals. Powerful anti-inflammatory treatments, such as oral corticosteroids, might be required together with standard treatments to manage moderate to severe cases of elderly AD. Finally, most elderly patients with AD reach the end of life with this disease, which should now be considered a lifelong allergic disease.