As in Atopic Dermatitis, Nonlesional Skin in Allergic Contact Dermatitis Displays Abnormalities in Barrier Function and Ceramide Content

Kim, Donghye; Lee, Noo Ri; Park, Sang Yeon; Jun, Moo-Jin; Lee, Kyohoon; Kim, Sunki; Park, Chang Seo; Liu, Kwang-Hyeon; Choi, Eung Ho

doi:10.1016/j.jid.2016.10.034

Cited by 34 publications

(32 citation statements)

References 16 publications

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“…Ceramides in human SC have been assigned to 12 distinct groups based upon their fatty acid and sphingoid base structures , as shown in Supplementary Figure S4. In the skin of patients with AD, Ishikawa et al (2010) used normal-phase liquid chromatographyeelectrospray ionization mass spectrometry to demonstrate that the levels of endogenous ceramides are significantly downregulated in lesional SC, which is consistent with previous studies using other analytical methods (Arikawa et al, 2002;Choi and Maibach, 2005;Di Nardo et al, 1998;Imokawa et al, 1991a;Ishibashi et al, 2003;Ishikawa et al, 2010;Jungersted et al, 2010;Kim et al, 2017;Okamoto et al, 2003; lengths (<40 total carbons) are expressed at higher levels than in healthy skin. Janssens et al (2012) also reported that the relative ratio (but not quantitative levels) of ceramides with smaller chain lengths is distinctly decreased in the SC of AD skin, which is mainly associated with aberrant lipid organization and an impaired skin barrier function.…”

Section: Discussionsupporting

confidence: 56%

“…Atopic dermatitis (AD) is a recurrent dermatitis with a high susceptibility to itching, irritants, and allergens even in nonlesional skin, which is characterized clinically by severe dry skin and functionally by cutaneous barrier disruption and impaired water-holding function. Many studies have shown that the barrier-disrupted dry skin of patients with AD is mainly attributable to significantly decreased levels of ceramides in the stratum corneum (SC) (Arikawa et al, 2002;Choi and Maibach, 2005;Di Nardo et al, 1998;Imokawa et al, 1991a;Ishibashi et al, 2003;Ishikawa et al, 2010;Jungersted et al, 2010;Kim et al, 2017;Okamoto et al, 2003;. That mechanism is based on evidence that ceramide can function as a water reservoir (Imokawa and Hattori, 1985;Imokawa et al, 1991b) and also as a permeability barrier because of the formation of multilayered lamellar structures with other lipids, such as cholesterol ester and fatty acids, between the SC layers (Holleran et al, 1994a(Holleran et al, , 1994b(Holleran et al, , 1993(Holleran et al, , 1991a(Holleran et al, , 1991b.…”

Section: Introductionmentioning

confidence: 99%

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Treatment with Synthetic Pseudoceramide Improves Atopic Skin, Switching the Ceramide Profile to a Healthy Skin Phenotype

Ishida

Takahashi

Bito

et al. 2020

Journal of Investigative Dermatology

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Little is known about the pathophysiological linkages between altered ceramide profiles in the stratum corneum (SC) of patients with atopic dermatitis and their impaired skin barrier and water-holding functions. We studied those characteristics following topical treatment with a designed synthetic pseudoceramide (pCer) and analyzed that pathophysiological linkage by microanalyzing ceramides using normal phase liquid chromatographyeelectrospray ionization mass spectrometry. Four weeks of treatment with pCer significantly reduced skin symptoms, accompanied by significant decreases in transepidermal water loss and increases in water content. In the SC ceramide profiles, ceramides containing nonhydroxy fatty acids and 6hydroxysphingosines (Cer[NH]) and ceramides containing nonhydroxy fatty acids and phytosphingosines (Cer[NP]) increased, whereas ceramides containing nonhydroxy fatty acids and sphingosines (Cer[NS]) and ceramides containing a-hydroxy fatty acids and sphingosines (Cer[AS]) decreased, with larger alkyl chain lengths in Cer[NS], distinctly representing a switch from an atopic dermatitis to a healthy skin phenotype. The level of pCer that penetrated into the SC was significantly correlated with the SC water content but not with transepidermal water loss. The level and the average carbon chain length of Cer[NS] were closely correlated with the pCer level in the SC. These findings indicate that the penetrated pCer contributes to shift the ceramide profile from an atopic dermatitis to a healthy skin phenotype. Taken together, the observed clinical efficacy of treatment with pCer provides a deep insight into the pathogenesis of atopic dermatitis as a ceramide-deficient disease.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Treatment with Synthetic Pseudoceramide Improves Atopic Skin, Switching the Ceramide Profile to a Healthy Skin Phenotype

Ishida

Takahashi

Bito

et al. 2020

Journal of Investigative Dermatology

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“…It has been shown that in the skin of psoriasis and atopic dermatitis patients, ceramide AS is increased compared to healthy skin [10]. In contrast, another paper described a reduction in ceramide AS in nonlesional skin from allergic contact dermatitis patients, along with reduced barrier recovery rate after acute disruption by tape stripping [26].…”

Section: Discussionmentioning

confidence: 99%

Gentiana lutea Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes

et al. 2020

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Gentiana lutea is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that Gentiana lutea extract (GE) also modulates the lipid metabolism of human keratinocytes in vitro and in vivo. In the present study, we investigated the role of GE on ceramide synthesis in human primary keratinocytes (HPKs) and psoriasis-like keratinocytes. We could demonstrate that GE increased the concentrations of glucosylceramides and the ceramide AS/AdS subclass without affecting the overall ceramide content in HPKs. The expression of ceramide synthase 3 (CERS3) and elongases (ELOVL1 and 4) was reduced in psoriasis lesions compared to healthy skin. Psoriasis-like HPKs, generated by stimulating HPKs with cytokines that are involved in the pathogenesis of psoriasis (IL-17, TNF-α, IL-22 and IFN-γ) showed increased levels of IL-6, IL-8 and increased expression of DEFB4A, as well as decreased expression of ELOVL4. The treatment with GE partly rescued the reduced expression of ELOVL4 in psoriasis-like HPKs and augmented CERS3 expression. This study has shown that GE modulates ceramide synthesis in keratinocytes. Therefore, GE might be a novel topical treatment for skin diseases with an altered lipid composition such as psoriasis.

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“…As low ceramide levels have been associated with greater sensitivity to SLSinduced ICD [39], the compromised ceramide profile seen in AD patients is likely to predispose them to greater risk of ICD. Recent research has also suggested that ACD skin may display similar barrier abnormalities to AD, a finding that warrants further investigation [40]. A holistic approach to optimize management -how do we treat CD and restore the skin barrier in practice?…”

Section: Classification Of CDmentioning

confidence: 99%

Best practices, new perspectives and the perfect emollient: optimizing the management of contact dermatitis

Lachapelle

Giménez‐Arnau

Metz

et al. 2017

Journal of Dermatological Treatment

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Contact dermatitis (CD) is caused by environmental agents, irritants, and allergens that penetrate the epidermis and lead to inflammation. An intact skin barrier prevents penetration and is important in maintaining healthy skin. Classical diagnosis of CD is made using the patch test, and traditional treatment strategies for CD promote skin barrier integrity and resolve the inflammatory component of the condition. This can be achieved by using emollient-based therapy, which is most important for skin barrier repair, and in addition to topical glucocorticosteroids, which are used in severe cases of CD and are most effective in reducing inflammation. Preventative measures, such as irritant and allergen avoidance in the workplace, also play a pivotal role in effective CD management. Moreover, CD management necessitates a holistic approach that incorporates prevention, barrier repair, and inflammatory resolution to ensure optimized efficacy. It is also important to consider potential barriers to optimal management when evaluating individuals with CD, such as limited patient education or poor access to care. Finally, key literature and our own clinical practice experience have highlighted the value of patient preference, as well as safety, efficacy and simplicity, in building the perfect emollient.

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As in Atopic Dermatitis, Nonlesional Skin in Allergic Contact Dermatitis Displays Abnormalities in Barrier Function and Ceramide Content

Cited by 34 publications

References 16 publications

Treatment with Synthetic Pseudoceramide Improves Atopic Skin, Switching the Ceramide Profile to a Healthy Skin Phenotype

Treatment with Synthetic Pseudoceramide Improves Atopic Skin, Switching the Ceramide Profile to a Healthy Skin Phenotype

Gentiana lutea Extract Modulates Ceramide Synthesis in Primary and Psoriasis-Like Keratinocytes

Best practices, new perspectives and the perfect emollient: optimizing the management of contact dermatitis

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