New and developing therapies for atopic dermatitis

Hajar, Tamar; Gontijo, João Renato Vianna; Hanifin, Jon M.

doi:10.1590/abd1806-4841.20187682

Cited by 60 publications

(62 citation statements)

References 27 publications

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“…This is an exciting time for developments in the treatment of AD as the first biological medication (dupilumab) has been approved by the U.S. Food and Drug Administration, and more biological and small molecule medications are in the pipeline. [76][77][78] However, adult clinical trials traditionally enrol only patients aged 18-65 years, thus excluding a large proportion of the elderly. Further studies and clearer guidelines for treating AD in the elderly need to be developed.…”

Section: Diagnosis and Managementmentioning

confidence: 99%

Atopic dermatitis in the elderly: a review of clinical and pathophysiological hallmarks

2019

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Summary Background Atopic dermatitis (AD) is a multifactorial and complex disease, characterized by an impaired skin barrier function and abnormal immune response. Many elderly patients present with pruritus and xerosis to dermatology, allergy and primary care clinics, and there is a lack of information available to clinicians regarding the proper diagnosis and management of these patients. Although the elderly are described as having a distinct presentation of AD and important comorbidities, most investigations and clinical care guidelines pertaining to AD do not include patients aged 60 years and older as a separate group from younger adults. Objectives To summarize current information on pathophysiology, diagnosis and management of AD in the elderly population and identify areas of insufficient information to be explored in future investigations. Methods We carried out a systematic review of published literature, which assessed changes in the skin barrier and immune function with ageing and current information available for physicians to use in the diagnosis and treatment of AD in elderly patients. Results Many age‐related changes overlap with key hallmarks observed in AD, most notably a decline in skin barrier function, dysregulation of the innate immune system, and skewing of adaptive immunity to a type‐2 T helper cell response, in addition to increased Staphylococcus aureus infection. Conclusions While general physiological alterations with ageing overlap with key features of AD, a research gap exists regarding specific ageing‐related changes in AD disease development. More knowledge about AD in the elderly is needed to establish firm diagnostic and treatment methodologies. What's already known about this topic? Atopic dermatitis (AD) is a common inflammatory skin disease that causes significant burden worldwide. Recently, elderly patients have been considered a subgroup of patients with distinct AD manifestation. Limited studies have characterized the clinical presentation and role of IgE‐mediated allergy in elderly patients with AD. What does this study add? This review offers a summary of age‐related skin and immune alterations that correspond to pathogenic changes noted in patients with AD. The role of itch, environmental factors and skin microbiota in AD disease presentation in ageing patients is explored.

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Section: Diagnosis and Managementmentioning

confidence: 99%

Atopic dermatitis in the elderly: a review of clinical and pathophysiological hallmarks

2019

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“…1) The underlying mechanism of AD involves activation of the inflammatory cytokine transcription factor nuclear factor kappa B (NF-κB) in the epidermis and dermis, which leads to chronic skin inflammation and failure of the stratum corneum barrier. 2) The main symptom of AD is severe itchy eczema., which diminishes the patient's QOL. Topical corticosteroids are the most common AD therapy; however, long-term corticosteroid use can create dependency, weaken the immune system, and cause skin thinning and darkening.…”

Section: Introductionmentioning

confidence: 99%

Anti-RelA siRNA-Encapsulated Flexible Liposome with Tight Junction-Opening Peptide as a Non-invasive Topical Therapeutic for Atopic Dermatitis

Ibaraki

Kanazawa

Kurano

et al. 2019

Biological & Pharmaceutical Bulletin

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Small interfering RNA (siRNA) has been proposed as a novel treatment for atopic dermatitis (AD) because it suppresses sequence-specific mRNA expression. Indeed siRNA-based therapy achieves an almost complete cure with fewer side effects than currently available treatments. However, the tight junctions in the granular layer of the epidermis in the atopic skin are barriers to siRNA delivery. We previously reported the potential clinical utility of AT1002, a peptide that opens tight junctions. In the present study, we evaluated a topical siRNA-based therapy for AD using AT1002 in combination with a flexible liposome. The 1,2-dioleoylsn-glycero-3-phosphoethanolamine (DOPE)/cholesteryl hemisuccinate (CHEMS) liposome was chosen as a carrier for siRNA because of its highly flexible structure and permeability. We prepared siRNA-encapsulated DOPE/CHEMS liposomes and examined their physical properties, safety, uptake into RAW264.7 cells, and topical application in healthy and AD-affected skin. We then assessed the efficacy of anti-nuclear factorkappa B (NF-κB) (RelA) siRNA (siRelA)-encapsulated DOPE/CHEMS liposomes with AT1002 in AD model mice. The siRNA-DOPE/CHEMS liposomes were absorbed significantly better than siRNA alone and they enhanced siRNA skin penetration without toxicity. Moreover, siRelA-DOPE/CHEMS liposomes with AT1002 alleviated AD symptoms and reduced the levels of inflammatory cytokines in AD model mice. Therefore, the combination of AT1002 and DOPE/CHEMS liposomes could be a dermally applied RNA interference therapeutic system for effective RNA delivery and AD treatment.

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“…Among these drugs category, the fully humanized monocolonal antibody targeting IL-4 and IL-13 Dupilumab, has demonstrated to be effective in treating symptoms of adult patients with severe AD in a dose dependent manner. 11,12 Phototherapy is an effective treatment modality in patients with acute, severe exacerbation of AD. Many studies described beneficial effects of either UVB or UVA administration or combined UVA/UVB radiation in AD.…”

Section: Introductionmentioning

confidence: 99%

‘High dose’ vs. ‘medium dose’ UVA1 phototherapy in italian patients with severe atopic dermatitis

Pacifico

Iacovelli

Damiani

et al. 2018

Acad Dermatol Venereol

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Background The current evidences attest UVA1 phototherapy as effective in the treatment of severe atopic dermatitis (AD). Furthermore, in this indication, 'medium dose' is as effective as 'high dose' regimen. To date, a randomized comparison study evaluating the effectiveness as well as safety of different UVA1 protocols in different skin types in the treatment of adult patients with severe AD is still lacking.Objective The aim of the present study was to compare the safety and the efficacy of medium and high dose UVA1 either in fair or in dark skin types.Methods Twenty-seven adult patients with severe AD were consecutively included in a randomized, controlled, open, two arms trial Severity of AD was determined by means of SCORAD index and clinical improvement was also monitored.A total of 13 out of 27 patients were treated with high dose (130 J/cm 2 ) UVA1 protocol while 14 out of 27 patients received medium dose (60 J/cm 2 ) UVA1 protocol. Phototherapy was performed five times weekly up to 3 weeks. Before and after UVA1 treatment each patient was evaluated for skin pigmentation through Melanin Index (MI) quantitative evaluation.Results Skin status improved in all patients resulting in a reduction of SCORAD index in all groups. Our results demonstrated that among patients with darker skin types and higher MI, high dose UVA1 was significantly more effective than medium dose (P < 0.0001) while within the groups with skin type II, no significant differences between high and medium dose protocols were observed. ConclusionOur study, confirms previous observations that UVA1 phototherapy should be considered among the first approaches in the treatment of patients with severe generalized AD and also demonstrates that in darker skin types, high dose UVA1 phototherapy is more effective than medium dose in the treatment of adult patients with severe AD.JEADV 2019, 33, 718-724 720 A. Pacifico et al.

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New and developing therapies for atopic dermatitis

Cited by 60 publications

References 27 publications

Atopic dermatitis in the elderly: a review of clinical and pathophysiological hallmarks

Atopic dermatitis in the elderly: a review of clinical and pathophysiological hallmarks

Anti-RelA siRNA-Encapsulated Flexible Liposome with Tight Junction-Opening Peptide as a Non-invasive Topical Therapeutic for Atopic Dermatitis

‘High dose’ vs. ‘medium dose’ UVA1 phototherapy in italian patients with severe atopic dermatitis

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