Severe Atopic Dermatitis Research Articles

Changes in the composition of molecular species of covalently bound and free ceramides [EOS], and their correlation with disease severity in atopic dermatitis.

Ceramides are major constituents of stratum corneum (SC) intercellular lipids involved in skin barrier function. The ratio of molecular species of ceramides and their correlation with disease severity was examined in patients with atopic dermatitis (AD). Thirty-eight patients with AD and 32 healthy controls (HCs) were assessed for transepidermal water loss, SC collection and clinical assessment. The ceramide content of different molecular species in the samples was quantified using high-performance liquid chromatography coupled with tandem mass spectrometry. Unsaturated acyl chains of both covalently bound and free ceramides [EOS] were higher in AD lesional skin than those in AD non-lesional or normal HC skin. The proportion of unsaturated acyl chains (C30:1, C32:1 and C34:1) was higher than other ceramide molecular species among covalently bound and free ceramides [EOS] in patients with AD. The proportion of unsaturated acyl chains in covalently bound ceramides was positively correlated with transepidermal water loss (r = 0.600) when considering the total number of non-lesional and lesional skin. Additionally, thymus and activation-regulated chemokine (TARC) showed a positive correlation with unsaturated acyl chains proportion in AD non-lesional (r = 0.676) and lesional (r = 0.503) skin. Our study is the first to show the increase in unsaturated acyl chains of both covalently bound and free ceramides [EOS] in lesional and non-lesional skin in AD for each molecular species. This increase is associated with dryness and impaired barrier function, which correlates with TARC levels, a marker for the degree of type 2 inflammation. We speculate that type 2 inflammation exacerbation leads to abnormal epidermal lipid metabolism in the skin of patients with AD.

Serum 25-Hydroxyvitamin D Level Might Be a Useful Indicator of Disease Severity in Obese Children With Atopic Dermatitis: A Case-Control Study

Objective: To assess the relationship between the severity of atopic dermatitis (AD) in children of varying weight categories and their serum 25-hydroxyvitamin D [25(OH)D] levels. Methods: The study population comprised 899 patients with AD and 854 age- and sex-matched controls. The Mann-Whitney U test and Kruskal-Wallis H tests were used to assess differences between groups, and Spearman correlation analysis was used to test correlation. Results: The 25(OH)D level in the AD group was M (Q 25, Q 75), 24.0 (19.7, 28.4) ng/mL, which was significantly lower than the control group (26.4 [23.6, 29.9] ng/mL; Z = −3.34, P = 0.001). 25(OH)D levels in children with AD were negatively correlated with body mass index (r = −0.30, P < 0.001), Severity scoring of Atopic Dermatitis (SCORAD; r = −0.14, P < 0.001), total immunoglobulin E (r = −0.13, P < 0.001), and eosinophil (r = −0.08, P = 0.017). There were statistically significant differences in 25(OH)D (H = 18.46, P < 0.001), total immunoglobulin E (H = 9.13, P = 0.010), eosinophil (H = 67.17, P < 0.001), and SCORAD (H = 10.49, P = 0.005) among groups with different body mass index classification. The 25(OH)D levels were 22.3 (17.5, 27.1) ng/mL in the overweight AD group and 22.3 (17.6, 25.7) ng/mL in the obese AD group, which were significantly lower than those in the normal-weight AD group (24.7 [20.4, 25.5] ng/mL; P = 0.003, P = 0.004). 25(OH)D levels were negatively correlated with SCORAD in obese AD patients (r = −0.25, P = 0.010). Conclusion: Vitamin D insufficient or deficient is obvious in children AD patients. The 25(OH)D levels in the overweight/obese AD group are significantly lower than those in the normal-weight AD group. Vitamin D level is negatively correlated with SCORAD in obese children with AD.

Practical Use of Upadacitinib in Patients with Severe Atopic Dermatitis in a Real-World Setting: A Systematic Review.

Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies. Of these, 214 were excluded after reviewing their titles and abstracts. We then conducted a full-text review of 25 studies, of which 17 met our inclusion criteria and were therefore included in our systematic review. The analysis of real-world studies showed high effectiveness of upadacitinib, in terms of both clinical signs and subjective symptoms, in different patient populations, including those resistant to other treatments. No new significant safety concerns have emerged as compared to randomized clinical trials.

Rare FLG mutation associated with severe atopy

Background: The prevalence of atopic disease, which consists of conditions such as atopic dermatitis, allergies, and asthma, has been on the rise in recent decades. In children, atopic dermatitis often acts as an initial manifestation of atopic disease and frequently precedes the development of food allergies, asthma, and allergic rhinitis. Mutations in the FLG gene, encoding the fillagrin precursor profillagrin, serve as a genetic risk factor for these diseases. Approximately 25%–50% of individuals with atopic dermatitis carry FLG mutations. It has been proposed that FLG mutations exhibit variations specific to different populations, indicating distinct patterns within each population. Severe allergic symptoms could indicate the presence of an underlying immunodeficiency or immune dysregulation and in patients with severe, early-onset, or simultaneous allergic conditions, these could be suggestive of an underlying Primary Atopic Disorder. Specifically, the allergic triad characterized by elevated IgE levels, eosinophilia, and eczema is a common feature in various inborn errors of immunity that could be mistakenly diagnosed as severe allergic conditions. Method: Our patient’s medical record was analyzed retrospectively, including her medical history, as well as results from immune laboratory tests and genetic analyses. Results: We present a 9-year-old female of mixed ethnicity with a history severe eczematous rash diagnosed with atopic dermatitis. Whole exome sequencing analysis revealed an initially novel heterozygous variant in the FLG gene (NM_002016: EXON3:c.C2218T: p.R740X). Conclusion: Healthcare providers caring for patients with atopic dermatitis and recurrent staphlococcus infections should be aware of the significant link between filaggrin gene mutations and the development of severe, persistent atopic dermatitis that begins in childhood, as well as its association with recurring staphlococcus infections. Additionally, they should keep in mind that certain inborn errors of immunity may predominantly manifest as severe and treatment-resistant atopic disorders. Statement of novelty: We have identified a rare variant in the FLG gene associated with severe atopic dermatitis and allergies.

Off-label use of Baricitinib improves moderate and severe atopic dermatitis in China through inhibiting MAPK and PI3K/Akt/mTOR pathway via targeting JAK-STAT signaling of CD4+ cells.

As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD.

Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research: aninterdisciplinary perspective.

More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts.

Establishment of clinical criteria for the diagnosis of adverse food reactions in dogs with atopic dermatitis.

Diagnosis of canine adverse food reactions (AFRs) is based on vague criteria, such as '>50% improvement' during elimination diet trial (EDT) followed by 'deterioration' during provocation test (PT). The objective of the study was to use predefined criteria to evaluate response during EDT [i.e., Owner Global Assessment of Treatment Efficacy (OGATE) = good-to-excellent] and relapse during PT [i.e., Owner Global Assessment of Challenge Deterioration (OGACD) = moderate-to-severe and/or >100% increase of lesional (Canine Atopic Dermatitis Extent and Severity Index, 4th iteration, CADESI-04) and/or of pruritus (pruritus Visual Analog Scale, PVAS) scores]. Twenty-nine dogs with atopic dermatitis. An extensively hydrolysed diet was fed to all dogs followed, in seven of 11 nonresponders, by a second home-made novel-protein EDT. Dogs responding to either EDT were challenged with their previous diet. Thirteen (44.8%) dogs were diagnosed with AFRs: at the end of EDT, their OGATE was good (9 of 13; 69.2%) or excellent (four of 13; 30.8%), and both CADESI-04 (46.7%) and PVAS (71.1%) had decreased significantly; at the end of PT, OGACD was moderate or severe in 12 of 13 (92.3%) dogs, and both CADESI-04 (127.9%) and PVAS (181.8%) had increased significantly. Of the 16 dogs without AFRs, 6 (37.5%) responded to the commercial (n = 5) or home-made (n = 1) diet [OGATE = good (three of six) or excellent (three of six)], with significant concurrent reduction of CADESI-04 and nonsignificant reduction of PVAS, yet they did not relapse during PT. The proposed (predefined) criteria for the evaluation of response during EDT and deterioration during PT seem reliable and are easily applicable in clinical practice and research.

Alterations in gut microbiome associated with severity of atopic dermatitis in infants.

Atopic dermatitis (AD) often arises in infancy, and gut microbial dysbiosis is associated with the development of AD. However, less is known about specific changes in early-life gut microbiome associated with AD and AD severity. This study aims to reveal the gut microbial composition and function profiles associated with the severity of AD in infants. Sixty-two infants (mean [SD] age, 4.7[1.9] months) with different severities of AD were enrolled and divided into three groups (mild, moderate and severe) according to the Scoring Atopic Dermatitis (SCORAD) index. The profiles of gut microbial composition and function were analysed by sequencing 16S ribosomal RNA amplicons. Quality of life on children and the family was evaluated using published questionnaires. Decreased levels of Clostridium sensu stricto, Collinsella and increased level of Parabacteroides presented in the severe AD group compared with the mild AD group after adjusting potential confounders (p < 0.05). There were strong positive correlations between the Scoring Atopic Dermatitis (SCORAD) index and the relative abundance (RA) of Bacteroides and functional pathways for metabolism of sphingolipids and glycosphingolipids (p < 0.05). The SCORAD index was negatively correlated with the RA of Clostridium sensu stricto (p < 0.05), and was also positively correlated with the index of quality of life on children and the family (p < 0.05). Discrepancies in gut microbial composition and functional pathways were observed in infants with mild-to-severe AD. Alterations in butyrate-producing bacteria (Clostridium sensu stricto), sphingolipid-producing bacteria (Parabacteroides, Bacteroides), and related functional pathways were associated with the severity of AD infants.

Unraveling Atopic Dermatitis: Insights into Pathophysiology, Therapeutic Advances, and Future Perspectives.

Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% of children are affected by this serious skin condition, which is painful for the sufferers. Recent research has connected the environment, genetics, the skin barrier, drugs, psychological factors, and the immune system to the onset and severity of AD. The causes and consequences of AD and its cellular and molecular origins are reviewed in this paper. The exploration of interleukins and their influence on the immunological pathway in AD has been facilitated by using relevant biomarkers in clinical trials. This approach enables the identification of novel therapeutic modalities, fostering the potential for targeted translational research within the realm of personalized medicine. This review focuses on AD's pathophysiology and the ever-changing therapeutic landscape. Beyond the plethora of biologic medications in various stages of approval or development, a range of non-biologic targeted therapies, specifically small molecules, have emerged. These include Janus kinase (JAK) inhibitors like Baricitinib, Upadacitinib, and Abrocitinib, thus expanding the spectrum of therapeutic options. This review also addresses the latest clinical efficacy data and elucidates the scientific rationale behind each targeted treatment for atopic dermatitis.

Research Trends on Atopic Dermatitis an Autoimmune Disease and Exercise

PURPOSE: Autoimmune diseases attack the organs and tissues of the body because of abnormalities in the immune system, causing health issues such as inflammation and atopic dermatitis. Atopic dermatitis is a chronic inflammatory skin disease with a multifactorial pathogenesis that presents with an itchy, dry dermis. Atopic dermatitis can be alleviated or worsened by environmental factors, and studies have reported that exercise has various effects on atopic dermatitis.METHODS: This review collected and analyzed data on the effects of exercise and atopic dermatitis from previous studies obtained through online databases and search engines, including PubMed, Web of Science, and Google Scholar.RESULTS: Moderate exercise has a positive effect on the health of patients with atopic dermatitis. During moderate- and high-intensity exercise, the thickness of the dermis and epidermis of atopic skin, serum immunoglobulin (Ig)E levels, and cytokine levels decreased. However, conflicting results showed that high-intensity swimming exercises increased the severity of atopic dermatitis. Additionally, patients with atopic dermatitis and lower physical activity levels showed increased disease severity.CONCLUSION: These results indicate that several exercises have therapeutic potential against atopic diseases. Further studies are required to investigate the effects of exercise on atopic dermatitis, including the limitations.

Dupilumab in the treatment of severe adopic dermatitis and respiratory allergy: a case report

The use of biological targeted therapy for allergic diseases has significantly increased the effectiveness of the treatment of patients with atopic dermatitis, bronchial asthma, and combined allergopathology. Dupilumab, a monoclonal antibody drug that blocks signaling from IL-4 and IL-13, is one of the options for biological therapy aimed at modifying the Th2 immune response. The article discusses current ideas about the pathogenesis of allergic Th2-dependent inflammation, about the key mechanisms of the formation of atopic dermatosis and its role in inducing the progressive course of atopy. A clinical example of successful treatment of an 8-year-old child with severe atopic dermatitis, moderate partially controlled bronchial asthma, allergic rhinitis, and multisensitization to food and pollen allergens is given. The use of biological targeted therapy with dupilumab made it possible to achieve sustainable remission in the course of atopic dermatitis and bronchial asthma. The SCORAD index, which was 66.8 points before dupilumab treatment, decreased to 8.9 points. Immunobiological therapy with an IL-4Rα inhibitor, dupilumab, is indicated for patients with moderate to severe allergic diseases when it is not possible to achieve adequate control with standard treatment methods. The presented clinical case of the use of the drug contributes to the study of the clinical efficacy and safety of dupilumab during its long-term use.

Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

Is Dupilumab a chance for patients with moderate to severe atopic dermatitis? Literature review

Introduction: Atopic dermatitis is an inflammatory disease which can significantly affect quality of life of patients. Especially severe forms of this disease are challenging to treat and for a long time forms of treatment have been limited. Because of that- it is crucial to find new ways of treatment which can be registered and impove moderate and severe dermatitis.&#x0D; Aim of study: Fundament purpose of this literature review is focusing on effectiveness, safety, side effects or different potential medical applications of Dupilumab. The main question, which is formulated in the title- is Dupilumab a chance for patients with moderate to severe atopic dermatitis?&#x0D; State of knowledge: Nowadays Dupilumab is well known drug and a lot of trials and analysis focus on efficacy, safety in treatment of moderate and severe dermatitis. The development of Dupilumab and different potential, clinical applications is also a chance for other groups of patients- for example patients with asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis.&#x0D; Conclusion: Dupilumab is definitely a relevant and essential element of treatment therapy for patients with moderate to severe atopic dermatitis. There were many analysis and researches which confirmed effectiveness, safety level and described Dupilumab impact on many different parameteres and scales focused on symptoms and life quality of patients during treatment with Dupilumab.

Treatment and referral patterns of patients with atopic dermatitis from the Danish primary care system to the tertiary care system

AbstractBackgroundPatients with atopic dermatitis (AD) are mostly managed by general practitioners (GPs) and practicing dermatologists (PDs) in Denmark. In cases of severe and refractory AD, the primary physician can refer the patient to a specialised dermatology department.ObjectivesAim of the study was to investigate treatment at the time of referral to a specialised dermatology department and the cause stated by the GP in a Danish cohort of AD patients referred to the Department of Dermatology, Aarhus University Hospital from 2019 to 2021.MethodsOne hundred and thirty cases were randomly selected via diagnosis codes for AD. Information regarding the cause for referral and treatment given at time of referral was obtained from medical records. 18 cases were excluded due to missing referral in the patients' medical records, other diagnosis than AD or treatment initiation before 2019. The final cohort consisted of 112 cases. Differences between patients referred from GP and PD were analysed with Fisher's exact test.ResultsMost cases were referred by PDs (45.5%) and GPs (24.1%). GPs primarily referred due to acute flare‐ups in need of treatment (40.7%), and PDs due to lacking disease control (64.7%), (p‐values &lt; 0.0018). GPs generally included more descriptive information in their referrals than PDs, however, only the difference in mentioning sleep disturbance was significant (p‐value = 0.0144). Topical corticosteroids were the preferred treatments before referral regardless of the referring doctor, with no statistical differences. Topical calcineurin inhibitors were significantly more used among PD‐referred patients compared to GP‐referred patients (p‐value = 0.0018). Systemic therapy was initiated in 45 patients (40.2%) at the tertiary hospital with no differences between referral from either GPs or PDs.ConclusionsThe study identified few differences in the referral pattern of AD to a tertiary treatment center from GPs and PDs. No major deviations from Danish guidelines were found.

Patient Preferences in the Treatment of Moderate-to-severe Atopic Dermatitis.

Atopic dermatitis is a chronic, inflammatory skin disease. A variety of systemic treatments are available for patients with moderate-to-severe atopic dermatitis. The efficacy, safety and administration profile of these treatments vary, and determining the optimal treatment strategy may require weighing the benefits and drawbacks of therapies with diverse characteristics. This study used an online discrete choice experiment survey to investigate treatment preferences among adults with atopic dermatitis from Denmark, France, the UK, or Canada. Participants were identified through existing online panels. The survey included questions regarding different treatment attributes, defined based on currently approved treatments for moderate to severe atopic dermatitis. Treatment preferences were measured as the relative importance of different treatment attributes. A total of 713 respondents met the inclusion criteria and completed the survey. The discrete choice experiment identified a significant preference for avoiding the risk of severe adverse events, and for oral pill every day compared with biweekly injections. The time to full effect was not rated as being important. These findings suggest that patients with moderate-to-severe atopic dermatitis prioritize safety as most important, followed by ease of administration in their treatment preferences, while time to full effect and monitoring requirements were the least important attributes.

Decreased skin colonization with Malassezia spp. and increased skin colonization with Candida spp. in patients with severe atopic dermatitis.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which patients are sensitized towards a plethora of allergens. The hosts fungal microbiota, the mycobiota, that is believed to be altered in patients suffering from AD acts as such an allergen. The correlation context of specific sensitization, changes in mycobiota and its impact on disease severity however remains poorly understood. We aim to enhance the understanding of the specific sensitization towards the mycobiota in AD patients in relation to their fungal skin colonization. Sensitization pattern towards the Malassezia spp. and Candida albicans of 16 AD patients and 14 healthy controls (HC) were analyzed with the newly developed multiplex-assay ALEX2® and the established singleplex-assay ImmunoCAP®. We compared these findings with the fungal skin colonization analyzed by DNA sequencing of the internal transcribed spacer region 1 (ITS1). Sensitization in general and towards Malassezia spp. and C. albicans is increased in AD patients compared to HC with a quantitative difference in severe AD when compared to mild to moderate AD. Further we saw an association between sensitization towards and skin colonization with Candida spp. yet a negative correlation between sensitization towards and skin colonization with Malassezia spp. We conclude that AD in general and severe AD in particular is associated with increased sensitization towards the hosts own mycobiota. There is positive correlation in Candida spp. skin colonization and negative in Malassezia spp. skin colonization when compared to AD, AD severity as well as to specific sensitization patterns.

Impact of Atopic Dermatitis on Quality of Life of Caregivers: A Systematic Review and Meta-Analysis.

Abstracts: Background: Atopic dermatitis (AD) is a chronic dermatological condition that affects both patients and their caregivers. Aims: To summarize evidence on the impact of AD on the quality of life (QoL) of caregiver. Methods: Observational studies were searched for in Medline, Embase, Cochrane Library, SCOPUS, and CINAHL databases up till March 1, 2023. Results: Seventy studies with a total of 33,291 study participants were identified. The Dermatitis Family Index (DFI) questionnaire featured in 29 studies and was chosen for further meta-analysis. The pooled DFI for all studies was 9.35 (95% confidence interval [CI] 6.94-11.76). For individual components, the highest component scores were for 1.24 for expenditure (95% CI 0.80-1.69), followed by 1.14 for emotions (95% CI 0.77-1.50), as well as sleep 1.12 (95% CI 0.71-1.54) and exhaustion 1.12 (95% CI 0.76-1.48). Meta-analysis on the effect of patient QoL on family QoL was conducted on 15 studies, with a pooled Spearman's rank coefficient using Infants' Dermatitis Quality of Life Index (IDQoL) was 0.632 (95% CI 0.558-0.707), whereas that using Children's Dermatology Life Quality Index (CDLQI) was 0.624 (95% CI 0.507-0.741). For the 17 studies correlating AD severity with family QoL, a pooled Spearman's rank coefficient of 0.425 (95% CI 0.330-0.521) was obtained. Conclusions: AD is associated with significant negative impacts on caregiver QoL, particularly in family finance, caregiver burnout, and sleep impairment. This was consistently affected by AD severity and patient QoL in all studies examining this association.

Cost per NNT for upadacitinib in the treatment of patients with moderate-severe atopic dermatitis in Italy

Background: Targeted systemic therapies, including abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib, are new treatments for moderate to severe atopic dermatitis (AD). We evaluated the efficacy and the costs of these targeted systemic therapies in the treatment of adult patients with moderate to severe AD. Methods: The clinical efficacy was assessed considering the results of a previous network meta-analysis (NMA). The analysis involved five therapies approved in Italy for the treatment of moderate to severe AD: abrocitinib (ABR), baricitinib (BAR), dupilumab (DUP), tralokinumab (TRA) and upadacitinib (UPA). According to the NMA, the cost of the treatment was based on the number of administrations dispensed at 16 weeks and the clinical efficacy was measured by the number needed to treat (NNT) compared to placebo using the improvement ≥ 75% (EASI-75) or ≥ 90 (EASI-90) from baseline of the eczema area and severity index (EASI). Only the ex-factory price of the targeted systemic therapies was considered. The cost per NNT was adopted as a cost-effectiveness indicator. Results: At 16 weeks, the cost per NNT based on EASI-75 was lower for UPA 15 mg (€ 6,384.00) compared to BAR 4 mg (€ 11,619.73) and 2 mg (€ 14,524.66), ABR 100 mg (€ 16,265.22), DUP 300 mg (€ 16,115.04) and TRA 300 mg (€ 31,710.24). UPA 15 (€ 8,512.00) also showed the lower cost per NNT based on EASI-90 at 16 weeks compared to BAR 4 mg (€ 14,788.75) and 2 mg (€ 20,862.70), ABR 100 mg (€ 25,922.69), DUP 300 mg (€ 25,992.00) and TRA 300 mg (€ 41,067.36). Conclusions: The findings show that upadacitinib is the most cost-effective option (cost per NNT) for the treatment of moderate to severe atopic dermatitis.

Efficacy and safety of crisaborole ointment in pediatric atopic dermatitis: A 4-week open-label study

Objectives: Managing mild-to-moderate atopic dermatitis (AD) often necessitates topical therapies, and one such recently introduced option is crisaborole ointment. This study sets out to assess the efficacy and safety of crisaborole ointment in pediatric cases of AD over four weeks. Material and Methods: Nineteen children between 2 and 16 years old with mild-to-moderate AD were enrolled and treated with crisaborole ointment twice daily in affected areas for 30 days. The primary objective was to appraise the shift in the investigator’s static global assessment (ISGA) scores (0–4) every week for the four-week follow-up. The severity of pruritus score (SPS) was another secondary objective. Furthermore, individual indicators of clinical signs that included erythema, exudation, excoriation, induration/papulation, and lichenification, were examined with subjective scores (0–3). Children’s dermatology quality of life index (CDLQI) was employed to study the quality of life. Results: Following four weeks of crisaborole ointment treatment, the average ISGA score declined from 2.58 ± 0.61 to 0.95 ± 0.78, signifying a substantial reduction in AD severity (P &lt; 0.001). The SPS score also decreased from a mean of 2.32 ± 0.478 to 0.84 ± 0.60 (P &lt; 0.001), underscoring a significant reduction in itching. Moreover, individual markers for clinical signs of AD, including erythema, exudation, excoriation, induration/papulation, and lichenification, all exhibited statistically significant improvement. Crisaborole ointment was well tolerated. Only 6 of the 19 patients reported a localized burning sensation, which was manageable. No patient needed to be withdrawn during the study period. The CDLQI showed a substantial drop in scores, decreasing from an average of 13.79 ± 3.57 at the commencement to 6.74 ± 1.97 (P &lt; 0.001). Furthermore, 14 out of 19 patients met the study’s primary goal, achieving at least a 2-point reduction in ISGA along with the attainment of clear or nearly clear skin (ISGA 0–1). Conclusion: Our study found crisaborole ointment significantly improved pediatric AD symptoms and was well-tolerated. The only adverse event was localized burning in a few patients. Further, research is needed for validation.

Upadacitinib improves symptoms of concomitant allergic rhinitis or allergic asthma in patients with severe atopic dermatitis: A 16-week multicentre retrospective study.

Upadacitinib improves symptoms of concomitant allergic rhinitis or allergic asthma in patients with severe atopic dermatitis: A 16-week multicentre retrospective study.