Disease management of atopic dermatitis: an updated practice parameter

Leung, Donald Y.M.; Nicklas, Richard A.; Li, James T.; Bernstein, I. Leonard; Blessing-Moore, Joann; Boguniewicz, Mark; Chapman, Jean A.; Khan, David A.; Lang, David M.; Lee, Rufus E.; Portnoy, Jay M.; Schuller, Diane E.; Spector, Sheldon L.; Tilles, Stephen A.

doi:10.1016/s1081-1206(10)61385-3

Cited by 118 publications

(104 citation statements)

References 115 publications

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“…В связи с этим достижение раннего контроля тече-ния АтД может замедлить его трансформацию в другие аллергические болезни. Кроме того, адекватное лечение АтД существенно улучшает качество жизни больных [1][2][3]. В то же время неправильная и неоптимальная терапия приводит к более частым обострениям АтД и потребности в сильных ТГК либо в других иммуносупрессантах с более высокими рисками токсичности [1][2][3][4].…”

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“…Кроме того, адекватное лечение АтД существенно улучшает качество жизни больных [1][2][3]. В то же время неправильная и неоптимальная терапия приводит к более частым обострениям АтД и потребности в сильных ТГК либо в других иммуносупрессантах с более высокими рисками токсичности [1][2][3][4]. Этому в большин-стве случаев способствуют, например, недооценка со сто-роны врачей и пациентов роли эмолентов; увлеченность, в частности российских врачей, мыслью о необходимости непременно лечить «дисбактериоз кишечника» и назна-чать энтеросорбенты, антигистаминные препараты и т. п. Во всех случаях эффективность и последствия терапии, а также расходы на лечение будут зависеть также от точ-ности диагноза АтД.…”

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“…Для обоих патогенетических путей развития АтД дефект эпидермального барьера функции кожи признан наи-более характерным и значимым звеном [1][2][3][4][5]. C другой стороны, не менее сложные иммунологические процессы активации Т лимфоцитов, дисбаланс врожденной и адап-тивной иммунной системы до конца не изучены.…”

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“…[3]. Общепризнанные рекомендации включают меры, направленные на исклю-чение/уменьшение контакта с различными триггерами (табл.…”

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“…Общепризнанные рекомендации включают меры, направленные на исклю-чение/уменьшение контакта с различными триггерами (табл. ), уход за кожей (постоянное очищение/увлажне-ние), а также лечение зуда и хронического воспаления противовоспалительными препаратами в зависимости от степени тяжести, локализации очагов поражения кожи, а также ассоциированных с АтД кожных инфекций [1][2][3][4].…”

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Atopic Dermatitis: New Aspects of Treatment

Мачарадзе¹

2013

Vopr. sovr. pediatr.

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В недавно опубликованном исследовании, отвечая на вопрос: «Кто и как лечит атопический дерматит у младенцев в США?», врачи сообщили, что чаще всего таких детей педиатры направляют к дерматологу (52,4% случаев) и реже -к аллергологу (32%), особенно при средней/тяжелой форме болезни [1]. Дальнейший анализ показал существенные различия и в лечении атопического дерматита (АтД): педиатры (59%) и аллер-гологи (61,5%) на первое место ставили диету (в основ-ном таким детям назначали соевое молоко) отдельно или в сочетании с эмолентами, тогда как дерматоло-ги предпочитали фармакологическое вмешательство с использованием топических глюкокортикоидов (ТГК). По заключению ученых, у детей в возрасте до 36 мес

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Atopic Dermatitis: New Aspects of Treatment

Мачарадзе¹

2013

Vopr. sovr. pediatr.

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Clinical Trial of Human Umbilical Cord Blood-Derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies

et al. 2016

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Mesenchymal stem cells (MSCs) have been proven to be therapeutically effective against atopic dermatitis (AD) in preclinical studies. However, the safety and efficacy of MSCs against AD have not yet been investigated in a clinical study. To establish the safety and efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) in AD, 34 adult patients with moderate-tosevere AD were enrolled in two phase trials with a follow-up for 1 month and 3 months, respectively. Patients were randomly allocated to receive low dose (2.5 3 10 7 ) or high dose (5.0 3 10 7 ) of hUCB-MSCs subcutaneously. An Eczema Area and Severity Index (EASI) score, Investigator's Global Assessment (IGA) score, Severity Scoring for Atopic Dermatitis (SCORAD) score, adverse effect assessments, and serum biomarker levels were evaluated as end points. A single treatment of hUCB-MSCs resulted in dose-dependent improvements in AD manifestation. Fifty-five percent of patients in high dose hUCB-MSC-treated group showed a 50% reduction in the EASI score. The IGA score and SCORAD score decreased by 33% and 50%, respectively, in high dose-treated group. Particularly, the administration of high dose hUCB-MSCs reduced the pruritus score by 58%. The serum IgE levels and number of blood eosinophils were downregulated by the treatment. No serious adverse events occurred, and none of the patients discontinued the trial due to adverse events. This is the first report to demonstrate a marked improvement of AD features with cell therapeutics. These data suggest that the infusion of hUCB-MSCs might be an effective therapy for patients with moderate-to-severe AD. STEM CELLS 2017;35:248-255 SIGNIFICANCE STATEMENTAtopic dermatitis (AD) is a chronic and relapsing skin disease which has become a major public health issue. The current clinical therapy against AD has been reported to be limited in its efficacy and often accompanied by side effects. In this study, we report the efficacy and safety of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in patients with moderate-to-severe atopic dermatitis (AD) as a promising alternative therapy. This first-in-class clinical study shows that single subcutaneous injection of hUCB-MSCs improves disease symptoms based on the evaluation of various parameters including EASI, IGA, and SCORAD score without noteworthy adverse events.

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TGF-β secreted by human umbilical cord blood-derived mesenchymal stem cells ameliorates atopic dermatitis by inhibiting secretion of TNF-α and IgE

Park

Lee

et al. 2020

Stem Cells

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Human mesenchymal stem cells (MSCs) are promising therapeutics for autoimmune diseases due to their immunomodulatory effects. In particular, human umbilical cord blood-derived MSCs (hUCB-MSCs) have a prominent therapeutic effect on atopic dermatitis (AD). However, the underlying mechanism is unclear. This study investigated the role of transforming growth factor-beta (TGF-β) in the therapeutic effect of hUCB-MSCs on AD. Small interfering RNA (siRNA)-mediated depletion of TGF-β disrupted the therapeutic effect of hUCB-MSCs in a mouse model of AD by attenuating the beneficial changes in histopathology, mast cell infiltration, tumor necrosis factor-alpha (TNF-α) expression, and the serum IgE level. To confirm that hUCB-MSCs regulate secretion of TNF-α, we investigated whether they inhibit TNF-α secretion by activated LAD2 cells. Coculture with hUCB-MSCs significantly inhibited secretion of TNF-α by LAD2 cells. However, this effect was abolished by siRNA-mediated depletion of TGF-β in hUCB-MSCs. TNF-α expression in activated LAD2 cells was regulated by the extracellular signal-related kinase signaling pathway and was suppressed by TGF-β secreted from hUCB-MSCs. In addition, TGF-β secreted by hUCB-MSCs inhibited maturation of B cells. Taken together, our findings suggest that TGF-β plays a key role in the therapeutic effect of hUCB-MSCs on AD by regulating TNF-α in mast cells and maturation of B cells.atopic dermatitis, IgE, mast cells, transforming growth factor-beta, tumor necrosis factoralpha, umbilical cord blood-derived mesenchymal stem cells | INTRODUCTIONAtopic dermatitis (AD) is a chronic allergic skin disorder associated with a delayed-type hypersensitivity reaction. The occurrence of AD is associated with various factors such as genetic predisposition, environmental factors, and immunological abnormalities. AD is classified as type 1 hypersensitivity according to the Gell and Coombs classification and is characterized by an allergic reaction triggered via Th2 signaling; however, the pathogenesis of AD is complex and not fully understood. [1][2][3][4][5] AD was recently found to be a much more heterogeneous disease than previously thought, with additional activation of the Th22, Th17/interleukin (IL)-23, and Th1 cytokine pathways depending on the disease subtype. 6 Hwan hee Park, Seunghee Lee, and Yeonsil Yu contributed equally to this work.

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Disease management of atopic dermatitis: an updated practice parameter

Cited by 118 publications

References 115 publications

Atopic Dermatitis: New Aspects of Treatment

Atopic Dermatitis: New Aspects of Treatment

Clinical Trial of Human Umbilical Cord Blood-Derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies

TGF-β secreted by human umbilical cord blood-derived mesenchymal stem cells ameliorates atopic dermatitis by inhibiting secretion of TNF-α and IgE

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