Abstract
BackgroundSkin barrier dysfunction plays a key role in atopic dermatitis (AD). This impairment is related to altered composition and metabolism of epidermal sphingolipids and a deficiency of ceramides. Glycosaminoglycans (GAGs), and especially hyaluronic acid, could be useful in the management of AD. This study aimed to evaluate the effects of a novel topical treatment consisting of sphingolipids and GAGs extracts in dogs with AD. This formulation is different from previously tested products because the sphingolipid extract contained high amounts of sphingomyelin, a precursor of ceramides, and this has been shown to enhance endogenous synthesis of ceramides and to increase lamellar-related structures in vitro. Thus, it was hypothesized that this formulation could improve clinical disease and skin barrier function in patients with AD.ResultsTwelve house dust mite (HDM) allergic atopic beagle dogs were randomized into two groups: control (n = 6; no treatment) or treatment (n = 6; topical sphingolipids and GAGs twice weekly for 8 weeks). Dogs were challenged with allergen twice weekly and the severity of dermatitis was scored using the canine atopic dermatitis and extent severity index (CADESI-03) once weekly. Skin barrier function (measurement of transepidermal water loss) and severity of pruritus (both pruritus visual analog scale [PVAS] and pruritus timed episodes) were assessed at 0, 4 and 8 weeks of treatment. Assessments were done by personnel unaware of group allocation. Complete blood count, serum biochemistry and stratum corneum (SC) lipidomics analyses were done at baseline and at week 8.Compared to baseline, significant increases in CADESI (P = 0.0003) and PVAS (P = 0.041) were observed only in the control group, and SC polyunsaturated fatty acids increased significantly only with treatment (P = 0.039). Compared to control, treatment group had a significantly lower CADESI after 1 week (P = 0.0078) and a significantly lower PVAS after 8 weeks (P = 0.0448). Treatment was well tolerated.ConclusionsIn this study in dogs with AD, a new topical formulation containing sphingomyelin-rich sphingolipids plus GAGs extracts attenuated the clinical worsening induced by HDM, supporting its use in atopic patients, either as an adjunctive treatment or used as monotherapy in certain cases.
Highlights
Skin barrier dysfunction plays a key role in atopic dermatitis (AD)
A canine model of AD in which high IgE atopic beagles are sensitized by epicutaneous application of house dust mites (HDM) [4] results in immunologic and clinical changes similar to those observed in dogs and humans with naturally-occurring AD [3]
The topical application of lipid-based formulations aimed at improving stratum corneum (SC) defects in AD has been investigated in several studies and, they had some positive effects, they appear to be insufficient as monotherapy [21,22,23,24,25,26,27,28,29,30,31]
Summary
Skin barrier dysfunction plays a key role in atopic dermatitis (AD) This impairment is related to altered composition and metabolism of epidermal sphingolipids and a deficiency of ceramides. Canine atopic dermatitis (AD) is a genetically predisposed inflammatory and pruritic skin disease with characteristic clinical features associated with IgE antibodies most commonly directed against environmental allergens [1]. This condition is very similar to its human counterpart in many aspects, the use of dogs for investigating the pathogenesis of AD as well as for testing new therapies [2, 3]. The topical application of lipid-based formulations aimed at improving SC defects in AD has been investigated in several studies and, they had some positive effects, they appear to be insufficient as monotherapy [21,22,23,24,25,26,27,28,29,30,31]
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