A Multicenter Study on the Prevalence of Clinical Patterns and Clinical Phenotypes in Adult Atopic Dermatitis

Nettis, Eustachio; Ortoncelli, Michela; Pellacani, Giovanni; Foti, Caterina; Leo, Elisabetta; Patruno, Cataldo; Rongioletti, Franco; Argenziano, Giuseppe; Ferrucci, Silvia; Macchia, Luigi; Napolitano, Maddalena; Ribero, Simone; Bonzano, Laura; Romita, Paolo; Bona, Danilo Di; Bennardo, Luigi; Piras, Viviana; Calabrese, Giulia; Tavecchio, Simona; Detoraki, C; Carbonara, Monica; Fabbrocini, Gabriella

doi:10.18176/jiaci.0519

Cited by 46 publications

(51 citation statements)

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“…Atopic dermatitis (AD) is a recurrent dermatitis with a high susceptibility to irritants and allergens, which is characterized clinically by severe dry skin even in nonlesional skin [ 1 , 2 ]. The nonlesional AD dry skin is thought to be a prerequisite factor for the easily provoked itching that results in accelerating the cutaneous permeability of many foreign substances due to the subsequent scratching, as has been called ‘scratch dermatitis’.…”

Section: Skin Characteristics and Barrier/water Reservoir Functionmentioning

confidence: 99%

Cutting Edge of the Pathogenesis of Atopic Dermatitis: Sphingomyelin Deacylase, the Enzyme Involved in Its Ceramide Deficiency, Plays a Pivotal Role

Imokawa

2021

IJMS

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Atopic dermatitis (AD) is characterized clinically by severe dry skin and functionally by both a cutaneous barrier disruption and an impaired water-holding capacity in the stratum corneum (SC) even in the nonlesional skin. The combination of the disrupted barrier and water-holding functions in nonlesional skin is closely linked to the disease severity of AD, which suggests that the barrier abnormality as well as the water deficiency are elicited as a result of the induced dermatitis and subsequently trigger the recurrence of dermatitis. These functional abnormalities of the SC are mainly attributable to significantly decreased levels of total ceramides and the altered ceramide profile in the SC. Clinical studies using a synthetic pseudo-ceramide (pCer) that can function as a natural ceramide have indicated the superior clinical efficacy of pCer and, more importantly, have shown that the ceramide deficiency rather than changes in the ceramide profile in the SC of AD patients plays a central role in the pathogenesis of AD. Clinical studies of infants with AD have shown that the barrier disruption due to the ceramide deficiency is not inherent and is essentially dependent on postinflammatory events in those infants. Consistently, the recovery of trans-epidermal water loss after tape-stripping occurs at a significantly slower rate only at 1 day post-tape-stripping in AD skin compared with healthy control (HC) skin. This resembles the recovery pattern observed in Niemann–Pick disease, which is caused by an acid sphingomyelinase (aSMase) deficiency. Further, comparison of ceramide levels in the SC between before and after tape-stripping revealed that whereas ceramide levels in HC skin are significantly upregulated at 4 days post-tape-stripping, their ceramide levels remain substantially unchanged at 4 days post-tape-stripping. Taken together, the sum of these findings strongly suggests that an impaired homeostasis of a ceramide-generating process may be associated with these abnormalities. We have discovered a novel enzyme, sphingomyelin (SM) deacylase, which cleaves the N-acyl linkage of SM and glucosylceramide (GCer). The activity of SM deacylase is significantly increased in AD lesional epidermis as well as in the involved and uninvolved SC of AD skin, but not in the skin of patients with contact dermatitis or chronic eczema, compared with HC skin. SM deacylase competes with aSMase and -glucocerebrosidase (BGCase) to hydrolyze their common substrates, SM and GCer, to yield their lysoforms sphingosylphosphorylcholine (SPC) and glucosylsphingosine (GSP), respectively, instead of ceramide. Consistently, those reaction products (SPC and GSP) accumulate to a greater extent in the involved and uninvolved SC of AD skin compared with chronic eczema or contact dermatitis skin as well as HC skin. Successive chromatographies were used to purify SM deacylase to homogeneity with a single band of ≈43 kDa and with an enrichment of >14,000-fold. Analysis of a protein spot with SM deacylase activity separated by 2D-SDS-PAGE using MALDI-TOF MS/MS allowed its amino acid sequence to be determined and to identify it as the β-subunit of acid ceramidase (aCDase), an enzyme consisting of α- and β-subunits linked by amino-bonds and a single S-S bond. Western blotting of samples treated with 2-mercaptoethanol revealed that whereas recombinant human aCDase was recognized by antibodies to the α-subunit at ≈56 and ≈13 kDa and the β-subunit at ≈43 kDa, the purified SM deacylase was detectable only by the antibody to the β-subunit at ≈43 kDa. Breaking the S-S bond of recombinant human aCDase with dithiothreitol elicited the activity of SM deacylase with an apparent size of ≈40 kDa upon gel chromatography in contrast to aCDase activity with an apparent size of ≈50 kDa in untreated recombinant human aCDase. These results provide new insights into the essential role of SM deacylase as the β-subunit aCDase that causes the ceramide deficiency in AD skin.

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Section: Skin Characteristics and Barrier/water Reservoir Functionmentioning

confidence: 99%

Cutting Edge of the Pathogenesis of Atopic Dermatitis: Sphingomyelin Deacylase, the Enzyme Involved in Its Ceramide Deficiency, Plays a Pivotal Role

Imokawa

2021

IJMS

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“…AD is one of the most common chronic inflammatory skin disease affecting up to 14.3% of adults, with 63.3% of these cases first appearing before 18 years of age. 1 Patients' disease burden is important with high rate of discomfort, less confidence in daily life activities and psycho-social distress. The introduction of dupilumab changed the natural history of this disease, drastically improving AD manifestations and therefore quality of life.…”

Section: Effects Of Lockdown On Health Of Patients With Severe Atopicmentioning

confidence: 99%

“…Benign skin reactions are a common adverse event when using ixekizumab. In a meta-analysis of phase III studies, ixekizumab appears to have had the highest rate of skin reactions among all anti-IL-17 and IL-12-IL-23 agents, 1 affecting approximately 25-30% of treated patients. 2 A severe type III hypersensitivity resulting in serum sickness-like reaction has been described.…”

Section: Immediate Hypersensitivity Reaction To Ixekizumab In a Patiementioning

confidence: 99%

Effects of lockdown on health of patients with severe atopic dermatitis treated with dupilumab

Ferrucci

Tavecchio

Favale

et al. 2020

Acad Dermatol Venereol

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use of dupilumab as treatment for severe adult atopic dermatitis (AD) increased over time since its introduction in September 2018, due to its established efficacy. AD is one of the most common chronic inflammatory skin disease affecting up to 14.3% of adults, with 63,3% of these cases first appearing before 18 years of age. Patients’ disease burden is important with high rate of discomfort, less confidence in daily life activities and psycho‐social distress. The introduction of dupilumab changed the natural history of this disease, drastically improving AD manifestations and therefore quality of life.

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“…It is characterized by an impaired skin barrier, skin lesions, and intense pruritus, which lower the individual’s quality of life [ 2 ]. As the most common inflammatory skin disease, AD affects 15–30% of children and almost 14.3% of adults [ 3 ]. The high incidence of AD causes substantial social and financial burdens on society [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways

Gil

Hong

2021

IJMS

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Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by an impaired skin barrier and intense itchiness, which decreases the individual’s quality of life. No fully effective therapeutic agents have prevailed for AD due to an insufficient grasp of the complex etiology. Ellagic acid (EA), a natural compound, has anti-inflammatory properties in chronic diseases. The effects of EA on AD have not yet been explored. The present study investigated the effects of EA on TNF-α/IFN-γ-stimulated HaCaT keratinocytes and house dust mite-induced AD-like skin lesions in NC/Nga mice. Treatment with EA suppressed inflammatory responses in keratinocytes by regulating critical inflammatory signaling pathways, such as mitogen-activated protein kinases and signal transducers and activators of transcription. In vivo studies using a DfE-induced AD mouse model showed the effects of EA administration through ameliorated skin lesions via decremented histological inflammatory reactions. These results suggest that EA could be a potential therapeutic alternative for the treatment of AD by inhibiting inflammatory signaling pathways.

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A Multicenter Study on the Prevalence of Clinical Patterns and Clinical Phenotypes in Adult Atopic Dermatitis

Cited by 46 publications

References 0 publications

Cutting Edge of the Pathogenesis of Atopic Dermatitis: Sphingomyelin Deacylase, the Enzyme Involved in Its Ceramide Deficiency, Plays a Pivotal Role

Cutting Edge of the Pathogenesis of Atopic Dermatitis: Sphingomyelin Deacylase, the Enzyme Involved in Its Ceramide Deficiency, Plays a Pivotal Role

Effects of lockdown on health of patients with severe atopic dermatitis treated with dupilumab

Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways

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