Clinical approach to the patient with refractory atopic dermatitis.
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ABSTRACT:
SUBMITTER: Izadi N
PROVIDER: S-EPMC8564861 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Genetic predisposition, epidermal barrier disruption, and dysregulation of the immune system are some of the critical components of AD. An impaired skin barrier may be the initial step in the development of the atopic march as well as AD, which leads to further skin inflammation and allergic sensitization. Type 2 cytokines as well as interleukin 17 and interleukin 22 contribute to skin barrier dysfunction and the development of AD. New insights into the pathophysiology of AD have focused on epidermal lipid profiles, neuroimmune interactions, and microbial dysbiosis. Newer therapeutic strategies focus on improving skin barrier function and targeting polarized immune pathways found in AD. Further understanding of AD pathophysiology will allow us to achieve a more precision medicine approach to the prevention and the treatment of AD.
| S-EPMC6399565 | biostudies-literature
Project description:BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease that affects children and adults. Poor treatment adherence in AD requires interventions to promote self-management; patient education in chronic diseases is key to self-management. Many international AD management guidelines published to date include a recommendation for educating patients as part of their treatment but there are no formal recommendations on how to deliver this knowledge. MAIN: We performed a scoping review to map the existing literature on patient education practices in AD and to highlight the clinical need for improved patient education in AD. The literature search was performed with the online databases MEDLINE, Embase, Grey Matters, ClinicalTrails.gov and the International Clinical Trials Registry Platform (ICTRP). The search strategy yielded 388 articles. Of the 388 articles screened, 16 studies met the eligibility criteria, and the quantitative data was summarized by narrative synthesis. The majority of studies were randomized controlled trials conducted in Europe, Asia and North America. Since 2002, there have been limited studies evaluating patient education in the treatment of AD. Frequent education methods used included group-based educational programs, educational pamphlets, individual consultations and online resources. Education was most commonly directed at caregivers and their children. Only one study compared the efficacy of different education methods. In all included studies, the heterogenous nature of outcome measures and study design limited the consistency of results. Despite the heterogeneity of studies, patient education was shown to improve quality of life (QoL), disease severity and psychological outcomes in AD patients.ConclusionThis scoping review highlights that patient education is effective in a variety of domains relevant to AD treatment. Further comparative studies and randomized trials with longer-term follow-up are needed to provide validated and consistent patient education recommendations for AD; these may depend on age and population.
| S-EPMC10576377 | biostudies-literature
Project description:Severe refractory atopic dermatitis (AD) is a chronic, debilitating condition that is associated with elevated serum immunoglobulin E (IgE) levels. Thymic stromal lymphopoietin (TSLP), thymus and activation-regulated chemokine (TARC) and OX40 ligand (OX40L) are important immunologic factors involved in the pathogenesis of AD. Omalizumab, an anti-IgE antibody indicated for use in allergic asthma, is implicated in regulating allergen presentation by dendritic cells and the T cell response during the effector phases of allergic disease. We investigated if anti-IgE therapy modulates the allergen-specific responses mediated by the TSLP pathway in young patients with severe refractory AD.This was a randomized, double-blind, placebo-controlled study of 8 patients between the ages of 4 and 22 years (mean = 11.6 years) with severe refractory AD (clinical trials.gov NCT01678092). Serum IgE ranged from 218 to 1,890 (mean = 1,068 IU/ml). Subjects received omalizumab (n = 4) or placebo (n = 4) every 2-4 weeks over 24 weeks using a regimen extrapolated from the package insert. TSLP, TARC, OX40L and other cytokines involved in AD were measured by using cytometric bead arrays.All patients receiving omalizumab had strikingly decreased levels of TSLP, OX40L, TARC (involved in Th2 polarization) and interleukin (IL)-9 compared to placebo. In addition, there was a marked increase in IL-10, a tolerogenic cytokine, in the omalizumab-treated group. Patients on anti-IgE therapy had an improvement in clinical outcomes as measured by the SCORAD system; however, these effects were comparable to improvements in the control group.Anti-IgE therapy with omalizumab decreases levels of cytokines that are involved in Th2 polarization and allergic inflammation, including TSLP, TARC and OX40L.
| S-EPMC4161454 | biostudies-literature
Project description:IntroductionThe diagnosis and management of atopic dermatitis (AD) is extensively addressed in detailed clinical guidelines. However, the high heterogeneity regarding presentation and progression and the increasingly broad therapeutic landscape suggest a complex real-world scenario, leading to multiple trajectories of AD patients.MethodsUsing a Delphi methodology for assessing the degree of consensus, we explored the views of a panel of dermatologists regarding the patients' trajectory through the diagnosis (block 1), treatment (block 2), and long-term management (block 3) of AD. Based on a systematic search of the literature, a scientific committee prepared a questionnaire of relevant items that were rated on a 10-point scale (from "totally agree" to "totally disagree") by a panel of dermatologists attending patients with AD in the hospital setting. Consensus was established based on predefined rules.ResultsThe final questionnaire included 58 items and was answered by 17 dermatologists. Overall, consensus was reached on 22 items (37.9%), each of which was a consensus for agreement. The consensus rates in blocks 1, 2, and 3 were 22.7%, 19.0%, and 86%, respectively.ConclusionsOur analysis revealed a remarkable lack of consensus on various aspects of the routine diagnosis and treatment of AD. These findings suggest the presence of unmet needs or limited implementation of guidelines for the management of AD and encourage further research to explore the causes of this low consensus on the management of AD in the real-world setting.
| S-EPMC8484426 | biostudies-literature
Project description:Atopic dermatitis (AD) is a common chronic, pruritic inflammatory skin disease that profoundly impacts patients' quality of life. As the first FDA-approved topical JAK inhibitor, ruxolitinib 1.5% cream represents a novel therapeutic topical agent for the treatment of AD. The objective of this review is to summarize the efficacy and safety of ruxolitinib cream in patients with AD based on the available evidence. Overall, ruxolitinib cream demonstrated high efficacy and a favorable safety profile for treating atopic dermatitis.
| S-EPMC9617518 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2-deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information.
| S-EPMC2883413 | biostudies-literature
Project description:BackgroundThe purpose of this study was to gather information on the current assessment and management of patients with moderate-to-severe AD in routine daily practice.MethodsA cross-sectional two-round Delphi survey with the participation of dermatologists and allergologists throughout Spain was conducted. They completed a 46-item questionnaire, and consensus was defined when responses of ≥80% of participants coincided in the categories of a 5-point Likert scale for that item.ResultsA total of 105 specialists (aged 40-59 years) completed the two rounds. Participants agreed regarding the consideration of AD as a multifaceted disease and the differences in clinical presentation of AD according to the patient's age. It is recommendable to perform a skin biopsy to exclude early stage T-cell cutaneous lymphoma, psoriasis, or dermatitis herpetiformis, among others (99.1%). Also, consensus was reached regarding the use of the SCORAD index to quantify the severity of the disease (86.7%), the use of wet wraps to increase the effect of topical corticosteroids (90.4%), the usefulness of proactive treatment during follow-up (85.6%) and tacrolimus ointment (91.2%) to reduce new flares, and the fact that crisaborole is not the treatment of choice for severe AD (92.4%). AD was not considered a contraindication for immunotherapy in patients with allergic respiratory diseases (92.4%). In patients with severe AD, the use of immune response modifier drugs (97.6%) or phototherapy (92.8%) does not sufficiently cover their treatment needs. Consensus was also obtained regarding the role of the new biologic drugs (93.6%) targeting cytokines involved in the Th2 inflammatory pathway (92.0%) and the potential role of dupilumab as first-line treatment (90.4%) in moderate-to-severe AD patients.ConclusionThis study contributes a reference framework to the care of AD patients. There is no diagnostic test or biomarkers to direct treatment or to assess the severity of the disease, and many therapeutic challenges remain.
| S-EPMC7166259 | biostudies-literature
Project description:Atopic Dermatitis (AD) is the most common inflammatory skin disease and characterized by a deficient epidermal barrier and cutaneous inflammation. Genetic studies suggest a key role of keratinocytes in AD pathogenesis, but the alterations in the proteome that occur in the entire epidermis have not been defined. Employing a pressure-cycling technology-data-independent acquisition (PCT-DIA) approach, we performed quantitative proteomics of epidermis from healthy volunteers and lesional and non-lesional skin of AD patients. Results were validated by targeted proteomics using parallel reaction monitoring mass spectrometry or by immunofluorescence staining. The identified proteins reflect the strong inflammation in lesional skin and the defect in keratinocyte differentiation and epidermal stratification. Most importantly, they reveal impaired activation of the NRF2-antioxidant pathway and reduced abundance of mitochondrial proteins involved in key metabolic pathways in the epidermis. These results provide insight into the molecular alterations in the epidermis of AD patients and identify novel targets for pharmaceutical intervention.
2022-10-04 | PXD025431 | Pride
Project description:A 29-year-old male, with chronic atopic dermatitis (AD), presented with a 2-week history of fatigue, pyrexia and weight loss. Examination showed eczematous patches with lichenified papules, erosions on the right shin and a new murmur. Blood cultures isolated methicillin-sensitive Staphylococcus aureus. Transthoracic echocardiography showed vegetation on the tricuspid valve (TV) that was adherent to the septal leaflet. He was treated for infective endocarditis, attributed to poorly controlled AD, with intravenous Flucloxacillin. Due to ongoing sepsis and pulmonary septic emboli, Clindamycin was added. He underwent TV repair; the septal leaflet was excised, and the remnant two leaflets were brought together with a ring. His patent foramen ovale was closed. His skin was treated with topical steroids and emollients. Right-sided endocarditis of an intact TV is uncommon in a non-intravenous drug user. Therefore, this novel case portrays the importance of aggressively managing AD as it is a risk factor for significant systemic infections.
| S-EPMC7376984 | biostudies-literature
Project description:BackgroundSeveral patient-reported outcomes have been used to assess the burden of atopic dermatitis (AD). Some are disease specific, such as the Patient-Oriented Eczema Measure (POEM), while others pertain to itch, for example the numerical rating scale (NRS)-itch, ItchyQoL and 5-D itch, or dermatological disease in general, for example the Dermatology Life Quality Index (DLQI). Development of severity strata is essential for proper interpretability of these assessments.ObjectivesTo confirm previously developed strata for POEM, DLQI and raw ItchyQoL, and develop strata for the NRS-itch, mean ItchyQoL and 5-D itch scale for use in adults with AD.MethodsSelf-administered questionnaires were completed by 210 adults with AD in a dermatology practice setting. Strata were selected using an anchoring approach based on patient-reported disease severity.ResultsWe confirmed the existing strata for POEM (mild 0-7, moderate 8-16, severe 17-28; κ = 0·440), DLQI (mild 0-5, moderate 6-10, severe 11-30; κ = 0·398) and NRS-itch (mild 0-3, moderate 4-6, severe 7-10; κ = 0·499). However, the preferred band for raw ItchyQoL was mild 22-58, moderate 59-74 and severe 75-110 (κ = 0·379) and for mean ItchyQoL, mild 1-2·9, moderate 3·0-3·9, severe 4·0-5·0 (κ = 0·374). The preferred band for 5-D itch scale was mild 0-11, moderate 12-17 and severe 18-25 (κ = 0·331).ConclusionsExisting strata for POEM and DLQI performed well in adult AD. Previously reported strata for visual analogue scale-itch performed best for NRS-itch. We identified banding for the raw ItchyQoL for our AD population that varies slightly from the banding published for a more heterogeneous population. Finally, we proposed strata for mean ItchyQoL and 5-D itch scale in adult AD.
| S-EPMC5906166 | biostudies-literature