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![The immunologic pathogenesis of atopic dermatitis and the corresponding major targets for the emerging therapies. Adapted from reference 5 with permission [5]](publication/342569142/figure/fig1/AS:962697260695555@1606536321533/The-immunologic-pathogenesis-of-atopic-dermatitis-and-the-corresponding-major-targets-for.png)
The immunologic pathogenesis of atopic dermatitis and the corresponding major targets for the emerging therapies. Adapted from reference 5 with permission [5]
Source publication
Atopic dermatitis (AD) is generally considered a T helper type 2–dominated disease. Pediatric AD is usually less severe than adult AD, but it may present as moderate to severe lesions that are inadequately managed by current modalities including emollients/moisturizers, topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), and even...
Citations
... To explore this further, we stained mast cells with toluidine blue (TB) and observed a significant reduction in mast cell numbers after IL-38 knockout ( Figure 3F). In AD-lesions, the production of TSLP, a critical activator of Th2 inflammation [39], as well as Th2-related cytokines such as IL-4, IL-5, and IL-13 can enhance AD progression [40]. Furthermore, the production of cytokines such as CC17 [41], IFN-γ [42] and IL-17 [43] adds to the development of AD. ...
... important cause of the disrupted skin barrier, leading to local inflammation and related immune responses. 8 Atopic dermatitis develops due to a complex interplay of factors, which encompass genetic elements, an ineffective epidermal barrier, and type-2 dominant cutaneous inflammation. Individuals who have a genetic mutation in the filaggrin (FLG) gene have an increased susceptibility to AD. Filaggrin is a protein that is involved in the structure of the skin barrier. ...
Atopic dermatitis (AD) is a very common skin disease caused by inflammatory reactions, in which the main symptoms of severe itching and recurrent eczema diminish quality of life. As epidermal barrier function and the immune system play a critical role in atopic dermatitis, promoting IgE-mediated sensitization can be the main targets of AD treatment. The goal of AD treatment should be to eliminate the symptoms and obtain longterm eczema control with a multi-step approach adapted to the severity of the disease. Basic management for all patients comprises the use of moisturisers and avoiding triggers. While topical therapy is effective for most children diagnosed with AD, there may also be children who require systemic therapy. The aim of this paper was to present an extensive review of the systemic agents commonly used in childhood atopic dermatitis which mainly target cutaneous inflammation.
... The severity of the disease can range from mild to severe disease that is difficult to control [1,2]. AD is characterized by dryness and lichenification and is often accompanied by a combination of pruritic erythema, excoriations, and serous exudate [3][4][5]. AD affects between 10% and 20% [6] of the pediatric population worldwide and has increased in developed countries in recent decades. Fifty to 60% of patients diagnosed with AD experience symptoms before the age of 1 year [3,6,7]. ...
Atopic dermatitis (AD) is a chronic disease that occurs mainly in children. Topical corticosteroids are the main treatment for mild to moderate AD, although they can induce side effects. The efficacy and tolerability of xyloglucan and pea protein (XG-PP) was compared with hydrocortisone in pediatric patients with AD as a steroid-sparing solution.
A prospective, multicenter, comparative study enrolled 42 patients (age 0.5–12 years) with mild-to-moderate AD, assigned 1:1 to XG-PP or hydrocortisone ointment. Treatments were applied twice daily for 14 consecutive days and assessed at baseline, day 8, and day 15. Efficacy endpoints were AD Severity Index (ADSI) score, Scoring Atopic Dermatitis (SCORAD) index, and Patient-Oriented Eczema Measure (POEM). Tolerability was assessed by the occurrence of adverse events (AEs).
Both treatments significantly improved ADSI mean score from baseline to day 15; in the XG-PP arm, ADSI score decreased from 10.55 to 4.15 (p = 0.00001), and in the hydrocortisone arm, from 10.65 to 4.30 (p = 0.0001). In the XG-PP arm, the mean SCORAD score decreased from 65.86 to 30.26 (p = 0.00001) and in the hydrocortisone arm from 68.84 to 31.19 (p = 0.0001) at day 15. An overall decrease from moderate to mild AD for both arms (p = 0.0001) was observed with POEM. For all the three indexes evaluated, no statistical significant differences between the study arms evolution from baseline to day 8 or to day 15 were found. No AEs were reported.
XG-PP provided a comparable efficacy to hydrocortisone ointment in managing AD, thus representing a safe and effective steroid-sparing alternative in pediatric patients with AD.
Retrospectively registered on 24 November 2021 in the ISRCTN registry: 11118799.
... However, due to the many adverse reactions and poor patient compliance, these treatments cannot be widely promoted and applied. Systemic immunosuppressants are usually not recommended for adolescent AD patients by the current guidelines due to their toxicities (Chu, 2021). In the past few years, two novel systemic therapies have been applied to the treatment of AD: one is antibody against the type 2 inflammation pathway, and the other is the small molecules that inhibit the type 2 pathway and other cytokine signaling. ...
Objective: This study aims to investigate the safety and efficacy of abrocitinib in treating moderate-to-severe AD in adolescents and adults.
Methods: Pubmed, Cochrane, Embase, and Web of science data base were searched from inception to 9 August 2022. All randomized controlled trials (RCTs) evaluating the efficacy and safety of abrocitinib in moderate to severe AD were included in the meta-analysis.
Results: This meta-analysis comprised 7 studies and found that 100 mg or 200 mg of abrocitinib significantly improved IGA {[RR = 2.44, 95% CI (1.93–3.08)] [RR = 3.16, 95% CI (2.52–3.96)]} and EASI-75{[RR = 2.18, 95%CI (1.78–2.67)] [RR = 3.04, 95%CI (2.22–4.16)]} responses compared to placebo. Following that, the population was divided into adolescent and adult groups. The abrocitinib improved IGA, EASI-75 responses, and it was still superior to placebo in both the adolescent and the adult groups. PP-NRS4 response index demonstrated that abrocitinib had a greater effect than placebo at 100 mg [RR = 2.22, 95% CI 1.80–2.72] and 200 mg [RR = 3.28, 95% CI 2.59–4.17]. Abrocitinib improved PSAAD, POEM, DLQI, CDLQI, and HADS more than a placebo.
Conclusion: In conclusion, this meta-analysis preliminarily demonstrated that abrocitinib had higher efficacy and safety in the treatment of moderate-to-severe AD in adolescents and adults. In addition, abrocitinib could rapidly relieve itching, and effectively improve symptoms and signs, with a greater effect at the dosage of 200 mg than 100 mg.
... Relatedly, several phase II trials have demonstrated this drug's utility in the treatment of pruritus in patients with moderate-to-severe AD. Improvements were noted in the pruritus visual analog scale (VAS) and EASI scores in comparison with the placebo group [24]. In 2021, a 16-week phase III RCT was conducted to further assess the efficacy and safety of nemolizumab. ...
Purpose of Review
Biologics and small molecule inhibitors (SMIs) are a rapidly growing class of highly efficacious therapies in the treatment of chronic immunologic and allergic conditions. With precision targeting of inflammatory signaling molecules, these new agents selectively modulate the immune system to treat a variety of conditions. Dermatologic diseases, including atopic dermatitis and psoriasis, are of particular interest due to the growing number of new biologics and SMIs in recent years. This review serves to summarize and evaluate the recent literature regarding biologics and SMIs.
Recent Findings
Currently approved biologics for AD achieve clear or almost clear skin in less than 40% of patients treated. Several biologics that are still under investigation for AD have shown better efficacy in phase III trials with similar safety profiles. Recently approved SMIs for AD also demonstrate a high degree of efficacy, but safety profiles may limit their use. Psoriasis has several highly efficacious biologics on the market; however, only one SMI is currently available. Additional SMIs for psoriasis have completed phase III trials and demonstrated high efficacy.
Summary
This article evaluates recent literature on biologics and small molecule inhibitors for AD and psoriasis.
... With the increasing number of potential treatment options for young people with AE, it becomes more important to assess effectiveness in ways important to young people. 24 In addition to measuring patient-reported symptoms and quality of life, patients and professionals recently agreed that longterm control should be a core outcome for all AE trials. 9 The added value of capturing young people's own reported outcomes is known in paediatrics and is underlined by the US Food and Drug Administration. ...
Background:
Recap of atopic eczema (RECAP) is a patient-reported outcome measure (PROM) assessing eczema control. This instrument has been developed and validated in the UK. There is a self-reported and a proxy-reported version in English, Dutch and German. However, it is unclear whether the self-reported version shows adequate content validity when completed by young people (8-16 years) in these languages.
Objectives:
To assess the content validity (comprehensibility, relevance and comprehensiveness) of the English, German and Dutch versions of the self-reported RECAP in young people with atopic eczema and to identify the most appropriate age cut-off for self-completion.
Methods:
We conducted 23 semi-structured cognitive interviews with young people from 8 to 16 years, using the "think-aloud" method. In Germany and the Netherlands, participants were recruited in dermatology clinics and in the UK through social media and existing mailing lists. Interviews were audio recorded, transcribed verbatim and analysed in the three languages, using a problem-focused coding manual. Transcripts were coded by two independent reviewers in each country. Themes were translated into English and compared across the three countries.
Results:
Significant age-related comprehensibility issues with the last three items of the questionnaire occurred with young people aged 8 to 11 years, causing difficulties completing RECAP without help. However, older children had only minor problems and were able to complete the questionnaire by themselves. The self-reported version of RECAP has sufficient content validity for self-completion in young people aged 12 years and above. However, the German version with some translational adaptations may be appropriate for children from the age of 8 years. There may be some situations, where the proxy-version is needed for older children too.
Conclusions:
The self-reported version of RECAP is appropriate for use from the age of 12 years. The proxy-version can be used in children younger than 12 years. Other measurement properties should be further investigated.
... In recent years, considerable progress has been made in understanding the etiopathogenesis of atopic dermatitis. e main triggering and/or aggravating agents have been identified, and new perspectives with the application of precision medicine and emerging therapeutics have brought encouraging results [31]. Recent studies indicate a substantial increase in the prevalence of AD [32] and point to its complexity related to genetic predisposition, phenotypic and molecular variations, and immune status. ...
... e guidelines 6 Dermatology Research and Practice recommend dietary restrictions based on allergic skin testing and specific IgE research consistent with a clinical history of cause and effect [9,18,19,22,25], and approximately 77% of experts agree with this recommendation. e guidelines differ regarding the environmental control of aeroallergens for patients with AD. e BAAI/BPS and JTF [18,31] guidelines note that approaches to reduce contact with aeroallergens should only be adopted in highly sensitive patients with moderate to severe chronic symptoms [19,25], and most of the participants indicated this recommendation. ...
Objectives. Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease, with a vast drug arsenal and guidelines available for its management and diagnosis and different medical specialties engaged in providing care. is study aimed to outline the therapeutic and diagnostic approaches to the AD of allergists, dermatologists, and pediatricians and verify whether they are compliant with the guidelines. Methods. A cross-sectional study using an electronic questionnaire administered through the SurveyMonkey ® platform was disclosed by participating medical societies to their medical associates. Results. Of the 1,473 participating physicians, the use of moisturizers as part of AD treatment was observed among pediatricians (91.9%), dermatologists (97.5%), and allergists (100%; p � 0.07). e preference for the use of new emollients was lower among pedi-atricians (57%) than dermatologists (75.9%) and allergists (71.4%; p < 0.001). e prevalence of wet-wrap therapy was lower among dermatologists (16.3%) than allergists (51%; p < 0.001). e recommendation of proactive treatment with topical cor-ticosteroids was more frequently reported by allergists (65.3%) than pediatricians (43.3%) and dermatologists (40.8%; p < 0.001), and the same trend was observed in relation to proactive treatment using calcineurin inhibitors. e use of oral anti-histamines to control pruritus was mainly considered by pediatricians (69.2%) and dermatologists (59.2% p < 0.001). Clinical experience with systemic immunomodulating agents was greater among allergists (77.5%) and dermatologists (60.8%; p < 0.001), with cyclo-sporine being the most cited systemic immunomodulating agent. Environmental control of aeroallergens was recommended by pediatricians (89.8%), dermatologists (86.9%), and allergists (100%; p � 0.01). Conclusion. ere were differences in the therapeutic and diagnostic approaches to AD used by allergists, dermatologists, and pediatricians and those recommended by the guidelines, especially regarding the use of wet-wrap therapy, proactive treatment with topical corticosteroids or calcineurin inhibitors, prescription of anti-histamines, recommendation of phototherapy, and control of aeroallergens.
... Recently, the anti-IL-13 mAb tralokinumab has shown a positive benefit/risk profile and has also been approved for use in adults with AD in Europe [20]. Moreover, several phase 2/3 trials evaluating the efficacy and safety profile of other therapeutic alternatives, such as the mAbs lebrikizumab and nemolizumab, are currently ongoing [21,22]. ...
Introduction:
As research continues, new drugs will no doubt be added to the current pool of treatments for moderate-to-severe atopic dermatitis (AD). This raises the need for studies to determine prescriber preferences for different pharmacological options and the factors that influence their choice of treatment. Here we aim to explore physician preferences in the systemic treatment of moderate-to-severe AD, identify the sociodemographic characteristics that can influence physician preferences, and evaluate their satisfaction with current AD therapies.
Methods:
A discrete-choice experiment (DCE) survey was administered to physicians treating patients with AD in Spain. Results were analyzed using a conditional logit model to estimate the relative importance of each attribute and the maximum risk accepted to achieve therapeutic benefit.
Results:
A total of 28 respondents completed the DCE survey (67.9% female, mean age 45.9 years). Participants identified objective clinical efficacy and risk of severe adverse events (AEs) as the most important attributes, followed by improvement in sleep and pruritus and faster onset of action from the start of the treatment. Respondents gave less importance to mode of administration and therapeutic benefit in other atopic conditions. Respondents were willing to accept an increased risk of severe AEs and mild-to-moderate AEs leading to treatment discontinuation due to intolerance in order to obtain improvements in efficacy, sleep, and pruritus, and long-term clinical benefit.
Conclusion:
Our findings can help prescribers choose the most appropriate systemic AD therapy.
... 7 Many patients seek medical care in emergency rooms due to acute flares or complications. 8 Many countries have developed or adopted guidelines for diagnosing and treating AD. 9,[10][11][12][13][14][15][16] However, these guidelines are not familiar to all practitioners who may treat AD, and many clinics do not use established sets of diagnostic criteria developed to aid diagnosis. [17][18][19] In addition, clinics may not always use established instruments to assess disease severity. ...
Atopic dermatitis (AD) is frequently misdiagnosed and undertreated, resulting in increased morbidity. In 2019, the Atopic Dermatitis Quality of Care Initiative was launched globally to investigate barriers to AD care and note good practice interventions to improve care. The initiative included a literature review to define the challenges in AD and a survey of 32 AD centers to define good practice interventions. One topic studied was best practices for clinical assessment and diagnosis. The literature review revealed the primary gaps included difficulty differentiating AD from other skin disorders, diagnosing atypical AD, staging AD severity in individual patients, and delays in assessment and treatment due to referral time lag. The best clinical practices used by leading AD centers included the use of validated diagnostic criteria, established AD scoring tools including patient-reported outcome measures and electronic health records (EHR), the formation of multidisciplinary teams (MDTs), and improved communication between health care providers (HCPs) and patients. Most centers worked with patient advocacy groups and implemented educational programs for HCPs. AD centers are overcoming issues in AD care. Educating health care providers and the public, using screening surveys, using established guidelines, and communicating with MCTs and patients through EHRs are the most frequently used strategies.
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... Standard treatment modalities for the management of these patients are centered around the use of topical anti-inflammatory preparations and moisturization of the skin, but patients with severe disease may require phototherapy or systemic treatment [18]. Based on the growing understanding of the pathomechanisms of AD, several biologics and small molecules targeting various AD-related pathways are being investigated in clinical trials [19]. Among these, dupilumab, a monoclonal antibody directed against the interleukin-4 receptor subunit α (IL-4Rα) of IL-4 and IL-13 receptors, is the only biologic therapy that is Food and Drug Administration approved for the treatment of moderate-to-severe AD in patients 6 years and older, with consistent long-term efficacy and safety trial data. ...
... In a comparative study on a cohort of 58 adult patient affected by CU, bilastine 20 mg daily was found to be less-sedative and more effective long-term treatment compared to levocetirizine 5 mg daily in term of UAS7 reduction at the end of treatment (UAS score mean change of −31.6 ± 1.5 during bilastine 20 mg therapy compared to mean change of −27.4 ± 1.7 during levocetirizine 5 mg daily), but with similar effect on improvement of QoL and urticarial-induced global discomfort in a follow-up period of 42 days. Both drugs statistically improved patients' QoL with comparable results: 94,8% of patients reported large to very large effect of chronic spontaneous urticaria (CSU) on QoL (DLQI score [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] in contrast to 8.6% of patient who referred small to moderate impairment of their QoL (DLQI 0-10) at the end of the study. In addition, longterm administration of levocetirizine 5 mg daily was associated with greater onset of somnolence compared to bilastine 20 mg daily (63% Vs 12.9%) [137]. ...
Allergic and immunologic skin diseases negatively impact the quality of life (QoL) of affected patients with detrimental consequences. Nonetheless, in everyday clinical practice the evaluation of QoL is often overlooked. Considering the increasing prevalence of atopic dermatitis, allergic contact dermatitis, hereditary angioedema, cutaneous mastocytosis, and urticaria, it is essential to determine the effects of allergic and immunologic skin diseases on QoL. A joint meeting (GET TOGETHER 2021) of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to summarize the features of the main QoL tools used in these diseases and to describe the extent of QoL impairment as well as the impact of treatments on QoL, particularly biologic therapies. The assessment of QoL in patients with allergic and immunologic skin diseases relies on generic, organ-specific and disease-specific questionnaires. While generic and organ-specific questionnaires allow comparison between different diseases, disease-specific questionnaires are designed and validated for specific cohorts: the QoL Index for Atopic Dermatitis (QoLIAD) and the Childhood Atopic Dermatitis Impact Scale (CADIS) in atopic dermatitis, the ACD-11 in allergic contact dermatitis, the Angioedema QoL Questionnaire (AE-QoL) and the Hereditary Angioedema QoL questionnaire (HAE-QoL) in hereditary angioedema, the Mastocytosis QoL Questionnaires (MCQoL e MQLQ) in cutaneous mastocytosis, and the Chronic Urticaria QoL questionnaire (CU-Q2oL) in urticaria. Among the many factors that variably contribute to QoL impairment, pruritus can represent the leading cause of patient discomfort. Biologic therapies significantly ameliorate QoL in atopic dermatitis, hereditary angioedema, mastocytosis and chronic urticaria. In general, adequate management strategies are essential for improving QoL in patients with allergic and immunologic skin diseases.
