Itch in Atopic Dermatitis

Kido‐Nakahara, Makiko; Furue, Masutaka; Ulzii, Dugarmaa; Nakahara, Takeshi

doi:10.1016/j.iac.2016.08.007

Cited by 60 publications

(85 citation statements)

References 46 publications

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“…It affects developing as well as developed countries and is associated with significant morbidity, including a significantly higher prevalence of sleep and mood disorders . Reduction in quality of life is associated with intractable pruritis and is proportional to disease severity . AD in infancy is also an independent risk factor for the development of other allergic diseases later in life, including food allergy, asthma and allergic rhinitis …”

Section: Introductionmentioning

confidence: 99%

Zinc and atopic dermatitis: a systematic review and meta‐analysis

Gray

Dhana

Stein

et al. 2019

Acad Dermatol Venereol

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Zinc plays a central role in skin integrity via barrier and immune mechanisms and may also be relevant in the pathogenesis of atopic dermatitis (AD). However, little is known about the relationship between zinc and AD. We performed a systematic review to determine (i) the association between zinc levels or zinc deficiency and AD and (ii) the efficacy of oral zinc supplementation in the treatment of AD. We searched PubMed, Scopus, Web of Science and article references for observational studies on zinc levels or zinc deficiency in participants with AD vs. controls and for randomized control trials (RCTs) on zinc supplementation in AD. For observational studies, we calculated pooled standardized mean differences (SMDs) or odds ratios (ORs) along with 95% confidence intervals (CIs) using a random effects model. We included 14 observational studies and two RCTs. The pooled SMD demonstrated significantly lower serum (SMD 0.66, 95% CI 0.21–1.10, P = 0.004), hair (SMD 0.95, 95% CI 0.38–1.52, P = 0.001) and erythrocyte (SMD 0.95, 95% CI 0.38–1.52, P = 0.001) zinc levels in participants with AD compared to controls. Pooled unadjusted data from three studies showed a non‐significant increased odds of AD in those with zinc deficiency compared with those without zinc deficiency (OR = 1.50, 95% CI 0.71–3.16, P = 0.28). One RCT of oral zinc supplementation among AD patients with zinc deficiency showed improvement in extent and severity of AD, while another RCT among all AD patients showed no significant improvement. All the studies were of low or moderate quality. We conclude that low serum, hair and erythrocyte zinc levels are associated with AD. However, the poor quality of included studies makes interpretation of these results problematic. High‐quality observational studies are needed to confirm the association between low zinc levels and AD, and RCTs are required to evaluate the merit of zinc supplementation for the treatment or prevention of AD.

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Section: Introductionmentioning

confidence: 99%

Zinc and atopic dermatitis: a systematic review and meta‐analysis

Gray

Dhana

Stein

et al. 2019

Acad Dermatol Venereol

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“…Itch or pruritus is one of the most irritating symptoms that characterizes AD and can significantly impair the quality of life of affected individuals . Pruritus in AD is the result of a complex interplay between many factors.…”

Section: Pruritus In Admentioning

confidence: 99%

“…However, pruritus in AD is not controlled well by anti‐histamines, suggesting that other itch mediators exist. In addition to histamine and its receptors, the H1 and H4 receptors, several other pruritogens are reported to be increased/involved in AD such as proteases (including tryptase, dust mites, and S. aureus ); substance P; IL‐31; TSLP; and endothelin‐1 …”

Section: Pruritus In Admentioning

confidence: 99%

“…However, a study based on functional magnetic resonance imaging with arterial spin labeling demonstrated an increase in the activation of the anterior cingulate cortex and dorsolateral prefrontal cortex in human subjects with AD compared with healthy controls . This result suggests that individuals with AD are centrally sensitized Importantly, cognitive and affective processes play a pivotal role in the interpretation and perception of pruritus . For example, several psychotropic drugs, including anti‐depressants, can attenuate the itch severity in some patients with AD …”

Section: Pruritus In Admentioning

confidence: 99%

“…Itch or pruritus is one of the most irritating symptoms that characterizes AD and can significantly impair the quality of life of affected individuals. 161 Pruritus in AD is the result of a complex interplay between many factors. Although the exact pathogenesis remains unknown, recent studies have shown that the hyperinnervation of the epidermis, an increase in several itch mediators/pruritogens, and the central sensitization of itch are evident in AD.…”

Section: Pruritus In Admentioning

confidence: 99%

See 2 more Smart Citations

The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis

Otsuka

Nomura

Rerknimitr

et al. 2017

Immunological Reviews

118

101

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Atopic dermatitis (AD) is a chronic skin disorder characterized by pruritus and recurrent eczematous lesions that are accompanied by T-helper (Th)2-dominated inflammation. AD Etiology is not yet completely understood, but it is multifactorial. Moreover, the disease is characterized by complex interactions between genetic and environmental factors, such as skin barrier dysfunctions, allergy/immunity, and pruritus. For example, filaggrin is a key protein involved in skin barrier function. Th2 cells produce interleukin (IL)-31, which provokes pruritus, and other Th2 cytokines decrease filaggrin expression by keratinocytes. Dupilumab has recently been developed for AD treatment; its mechanism of action is to bind to IL-4 receptor α and inhibit downstream signaling induced by IL-4 and IL-13. This review summarizes the etiopathogenesis of AD and provides the rationale for selecting a novel targeted therapy.

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Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

et al. 2020

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IMPORTANCE Interleukin 13 (IL-13) is a central pathogenic mediator driving multiple features of atopic dermatitis (AD) pathophysiology.OBJECTIVE To evaluate the efficacy and safety of lebrikizumab, a novel, high-affinity, monoclonal antibody targeting IL-13 that selectively prevents formation of the IL-13Rα1/IL-4Rα heterodimer receptor signaling complex, in adults with moderate to severe AD. DESIGN, SETTING, AND PARTICIPANTSA phase 2b, double-blind, placebo-controlled, dose-ranging randomized clinical trial of lebrikizumab injections every 4 weeks or every 2 weeks was conducted from January 23, 2018, to May 23, 2019, at 57 US centers. Participants were adults 18 years or older with moderate to severe AD.INTERVENTIONS Patients were randomized 2:3:3:3 to placebo every 2 weeks or to subcutaneous injections of lebrikizumab at the following doses: 125 mg every 4 weeks (250-mg loading dose [LD]), 250 mg every 4 weeks (500-mg LD), or 250 mg every 2 weeks (500-mg LD at baseline and week 2). MAIN OUTCOMES AND MEASURESThe primary end point was percentage change in the Eczema Area and Severity Index (EASI) (baseline to week 16). Secondary end points for week 16 included proportion of patients achieving Investigator's Global Assessment score of 0 or 1 (IGA 0/1); EASI improvement of at least 50%, 75%, or 90% from baseline; percentage change in the pruritus numeric rating scale (NRS) score; and pruritus NRS score improvement of at least 4 points. Safety assessments included treatment-emergent adverse events.RESULTS A total of 280 patients (mean [SD] age, 39.3 [17.5] years; 166 [59.3%] female) were randomized to placebo (n = 52) or to lebrikizumab at doses of 125 mg every 4 weeks (n = 73), 250 mg every 4 weeks (n = 80), or 250 mg every 2 weeks (n = 75). Compared with placebo (EASI least squares mean [SD] percentage change, −41.1% [56.5%]), lebrikizumab groups showed dose-dependent, statistically significant improvement in the primary end point vs placebo at week 16: 125 mg every 4 weeks (−62.3% [37.3%], P = .02), 250 mg every 4 weeks (−69.2% [38.3%], P = .002), and 250 mg every 2 weeks (−72.1% [37.2%], P < .001). Differences vs placebo-treated patients (2 of 44 [4.5%]) in pruritus NRS improvement of at least 4 points were seen as early as day 2 in the high-dose lebrikizumab group (9 of 59 [15.3%]). Treatment-emergent adverse events were reported in 24 of 52 placebo patients (46.2%) and in lebrikizumab patients as follows: 42 of 73 (57.5%) for 125 mg every 4 weeks, 39 of 80 (48.8%) for 250 mg every 4 weeks, and 46 of 75 (61.3%) for 250 mg every 2 weeks; most were mild to moderate and did not lead to discontinuation. Low rates of injection-site reactions (1 of 52 [1.9%] in the placebo group vs 13 of 228 [5.7%] in all lebrikizumab groups), herpesvirus infections (2 [3.8%] vs 8 [3.5%]), and conjunctivitis (0% vs 6 [2.6%]) were reported.CONCLUSIONS AND RELEVANCE During 16 weeks of treatment, lebrikizumab provided rapid, dose-dependent efficacy across a broad range of clinical manifestations in adult patients with moderate to severe ...

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Itch in Atopic Dermatitis

Cited by 60 publications

References 46 publications

Zinc and atopic dermatitis: a systematic review and meta‐analysis

Zinc and atopic dermatitis: a systematic review and meta‐analysis

The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis

Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

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