A randomized trial of a barrier lipid replacement strategy for the prevention of atopic dermatitis and allergic sensitization: the
            <scp>PEBBLES</scp>
            pilot study

Lowe, Adrian J.; Su, John; Allen, Katrina J.; Abramson, M; Cranswick, Noel; Robertson, Colin F.; Forster, Della; Varigos, George; Hamilton, Simone; Kennedy, Rachel; Axelrad, Christine; Tang, Mimi L.K.; Dharmage, Shyamali C.

doi:10.1111/bjd.15747

Cited by 140 publications

(159 citation statements)

References 9 publications

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“…This approach seems prudent, since coapplication of moisturizers under nursing supervision have been shown to reduce reliance on topical steroids in AD management [27, 28]. Recent studies, however, show that some commonly employed moisturizers can harm the skin if they are deployed in settings where the barrier is already compromised [28], as is certainly the case in AD. Here, we will compare the key differences between ubiquitous, over-the-counter moisturizers and preparations formulated specifically to correct the biochemical abnormalities in AD.…”

Section: The Role Of Brt In Admentioning

confidence: 99%

Moisturizers versus Current and Next-Generation Barrier Repair Therapy for the Management of Atopic Dermatitis

Elias¹,

Wakefield²,

Man³

2018

Skin Pharmacol Physiol

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We compare here the principal characteristics of over-the-counter moisturizers with physiologic lipid-based barrier repair therapy. Moisturizers are standard ancillary therapy for anti-inflammatory skin disorders, like atopic dermatitis (AD), and can attenuate the emergence of AD, the initial step in the “atopic march.” But not all moisturizers are beneficial; some can make skin function worse, and can even induce inflammation, possibly accounting for the frequent occurrence of “sensitive skin” in women. In contrast, physiologic lipid-based barrier repair therapy, if comprised of the 3 key stratum corneum lipids, in sufficient quantities and at an appropriate molar ratio, can correct the barrier abnormality and reduce inflammation in AD, and perhaps in other inflammatory dermatoses.

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Section: The Role Of Brt In Admentioning

confidence: 99%

Moisturizers versus Current and Next-Generation Barrier Repair Therapy for the Management of Atopic Dermatitis

Elias¹,

Wakefield²,

Man³

2018

Skin Pharmacol Physiol

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“…Even if having an FLG null mutation, a study reported that there is no increased risk of developing asthma without eczema . In other words, early intervention and maintenance therapy by repairing the skin barrier using emollients and topical corticosteroids may be important for young children, even with FLG null mutations, to prevent progression to asthma and rhinitis.…”

Section: Discussionmentioning

confidence: 99%

Palmar hyperlinearity in early childhood atopic dermatitis is associated with filaggrin mutation and sensitization to egg

Fukuie

Yasuoka

Fujiyama

et al. 2019

Pediatric Dermatology

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Background/Objectives Palmar hyperlinearity is a typical clinical feature of Filaggrin gene (FLG) null mutations. There are reports of FLG mutations and allergic sensitization; however, reports on the relationship between palmar hyperlinearity to sensitization are limited. This study aimed to examine the association between palmar hyperlinearity and sensitization in atopic dermatitis (AD) children. Methods This cross‐sectional, case‐control study included children ˂ 6 years old with moderate‐severe AD whose parents consented for mutation analysis and photographic documentation. Each child underwent genotyping to detect the eight most prevalent FLG mutations in the Japanese population: R501X, 3321delA, S1695X, Q1701X, S2554X, S2889X, S3296X, and K4022X. Clinical features and parameters including egg‐specific IgE were examined, and palm photographs were evaluated by 12 trained dermatologists blinded to genotyping results. Results Of the 57 patients (age range, 2 months to 5 years; median, 22 months), 16 were heterozygotes and three were compound heterozygotes. Palmar hyperlinearity, as recognized by more than two‐thirds of dermatologists, was significantly associated with FLG mutation (P = 0.002, OR = 6.98, 95% CI = 2.1‐23.7), and this association was observed especially in children over 2 years. Cross‐shaped crease of the thenar eminence, as known in previous reports, also demonstrated significant correlation with FLG mutation. When the children were divided according to the presence or absence of palmar hyperlinearity, the egg white–specific IgE was significantly higher in the hyperlinearity group (55.9 vs 18.3 IU/mL, P < 0.05). Conclusions Palmar hyperlinearity indicates possible inherited barrier abnormalities of the skin in early childhood. Its identification may help to predict a more accurate prognosis, such as sensitization.

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“…Several clinical studies have demonstrated the efficacy of this ceramide‐dominant formulation as stand‐alone therapy, even in moderate‐to‐severe AD . More recently, it has also demonstrated efficacy in blocking the progression of the atopic march from AD to food allergies . These attributes include its low pH (=5), which in itself is anti‐inflammatory by several mechanisms (Figure ), including (i) inactivation of potentially damaging KLKs that both compromise SC structural integrity and block activation of the plasminogen activator receptor 2 (PAR2); (ii) inhibition of pathogen colonization and attendant, superantigen‐initiated inflammation; and (iii) activation of two key lipid‐processing enzymes, β‐glucocerebrosidase and acidic sphingomyelinase, which generate the ceramides required to form the lamellar membranes that mediate the permeability barrier and contribute to antimicrobial defense …”

Section: How Barrier Repair Therapy Can Be Anti‐inflammatory In Admentioning

confidence: 99%

Primary role of barrier dysfunction in the pathogenesis of atopic dermatitis

Elias

2018

Experimental Dermatology

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Based upon the efficacy of recently developed biologics, the pathogenesis of atopic dermatitis (AD) is being attributed once again to the prominent inflammation that occurs in this disorder. Yet, molecular genetics has clearly shown that the aetiology of AD can be attributed to mutations in stratum corneum structural proteins that impact epidermal barrier function, while inflammation instead emerges as a downstream consequence of a sustained, barrier-driven cytokine cascade. Although several different mutations that compromise barrier function are associated with AD, all of these mutations compromise either the contents or secretion of epidermal lamellar bodies. Therapies directed at specific immune participants, though effective temporarily, inevitably are followed by "rebound flares," just as occur following glucocorticoid therapy. While occlusive moisturizers dampen inflammation, they do not address the underlying lipid biochemical abnormality in AD, which can be corrected more specifically with topical, physiologic lipid-based forms of barrier repair therapy (BRT). Accordingly, BRT has been shown to be as effective as topical, mid-potency steroids for the treatment of moderate-to-severe paediatric AD.

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A randomized trial of a barrier lipid replacement strategy for the prevention of atopic dermatitis and allergic sensitization: the PEBBLES pilot study

Cited by 140 publications

References 9 publications

Moisturizers versus Current and Next-Generation Barrier Repair Therapy for the Management of Atopic Dermatitis

Moisturizers versus Current and Next-Generation Barrier Repair Therapy for the Management of Atopic Dermatitis

Palmar hyperlinearity in early childhood atopic dermatitis is associated with filaggrin mutation and sensitization to egg

Primary role of barrier dysfunction in the pathogenesis of atopic dermatitis

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