Childhood atopic dermatitis is associated with cognitive dysfunction

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Childhood atopic dermatitis is associated with cognitive dysfunction: A National Health Interview Survey study from 2008 to 2018 - PubMed

<p>In a nationally representative sample of the US population, a statistically significant and positive association between childhood AD and atopic disease with cognitive dysfunction was identified (P < .001). Furthermore, a dimorphic relationship with developmental delays was identified between...

pubmed.ncbi.nlm.nih.gov

Background: Atopic dermatitis (AD) is a common inflammatory skin disease in children and adults. Little is known regarding the association of childhood AD with cognitive dysfunction.

Objective: To evaluate the association of AD and cognitive dysfunction, including memory impairment, developmental delays and attention deficit (hyperactivity) disorder in US children (age <18 years).

Methods: Data was analyzed from the National Health Interview Survey 2008 to 2018, which used a multistage, clustered, cross-sectional design.

Results: The prevalences of cognitive dysfunction, such as memory impairment (0.87% vs 0.42%), developmental delays (6.96% vs 3.87%), and attention deficit (hyperactivity) disorder (10.78% vs 8.10%), were higher in children with vs without AD. In multivariable logistic regression models adjusting for age, sex, race, region, socioeconomic factors, allergic conditions, and mental health, childhood AD was associated with higher odds of memory impairment (adjusted odds ratio [95% confidence interval]: 1.84 [1.34-2.51]), developmental delays (1.54 [1.40-1.70]), and attention deficit (hyperactivity) disorder (1.31 [1.20-1.42]) compared with children without AD. Childhood atopic disease (defined as comorbid AD, asthma, allergic rhinitis, and food allergies) further increased the prevalence of developmental delays to 13.44% (2.10 [1.20-3.70]) in boys but not in girls.

Conclusion: In a nationally representative sample of the US population, a statistically significant and positive association between childhood AD and atopic disease with cognitive dysfunction was identified (P < .001). Furthermore, a dimorphic relationship with developmental delays was identified between sexes.

 

[hei]

They have sinced published a review:

TH2 sensitization in the skin-gut-brain axis: How early-life Th2-mediated inflammation may negatively perpetuate developmental and psychologic abnormalities - PubMed

We recently reported children with comorbid atopic dermatitis (AD), asthma, allergic rhinitis, and food allergies displaying a 2.7-fold increase in developmental delays.² To this end, we hypothesize unregulated increases in T helper-2 (Th2)-driven inflammation, such as those seen in...

pubmed.ncbi.nlm.nih.gov

TH2 sensitization in the skin-gut-brain axis: How early-life Th2-mediated inflammation may negatively perpetuate developmental and psychologic abnormalities​

Abstract
We recently reported children with comorbid atopic dermatitis (AD), asthma, allergic rhinitis, and food allergies displaying a 2.7-fold increase in developmental delays.2 To this end, we hypothesize unregulated increases in T helper-2 (Th2)-driven inflammation, such as those seen in atopic diseases, can exert deleterious effects on the developing brain. Recognizing that available information is incomplete and that many potential associations are not firmly established, we speculate these effects underlie the association between Th2 sensitization and cognitive dysfunction in children. In this review, we explore the role of Th2 sensitization in the skin-gut-brain axis and explain how it can lead to reduced connectivity and transmission in the developing brain. With a focus on AD, we explore the association between Th2 sensitization and developmental abnormalities such as developmental delays, memory impairment, autism spectrum disorder (ASD), and epilepsy/seizures. As such, we review the available literature to examine the impact of increased IL-4 exposure in early life on the brain. We explore the possible association between Th2 sensitization and psychologic dysfunction such as attention-deficit/hyperactivity disorder (ADHD), depression, anxiety, and suicidal ideation. We also examine the impact that increased exposure to glucocorticoids and neurotrophins in early life exerts on the developing brain. Last, we discuss future directions for the advancement of our knowledge as a scientific community including possible interventions to reduce developmental and psychologic aberrations in children.

4 EARLY-LIFE Th2 SENSITIZATION LEADS TO DEVELOPMENTAL AND PSYCHOLOGIC CONSEQUENCES—FOCUS ON AD​

4.1 Early-life overexposure to IL-4 alters the developing brain and is associated with developmental consequences​

Atopic dermatitis is associated with developmental consequences including autism spectrum disorder (ASD), developmental delays, memory impairment, speech disorders, and seizures/epilepsy (Table 1). The hippocampus is a key structure within the brain specialized in learning and memory. Many publications have reported the detrimental influence that exaggerated immune cell responses (neurotrophins and cytokines triggered by peripheral challenges) can exert on learning and memory.10 Of the aforementioned conditions, the pathophysiology underlying ASD has been most extensively studied. Children with ASD have elevated pro-inflammatory cytokines in the blood and brain.16 The inflammation leads to microglial and astrocyte activation, resulting in synaptic deficits, hypomyelination, and altered functional connectivity between brain regions.16, 23

Although IL-4 is notorious for its antiinflammatory properties, more data are surfacing that highlight the contributory role of IL-4 in both anti- and pro-inflammatory states depending on dose, timing, and duration.24 Using mouse models, early-life overexposure to IL-4 is reported to reduce myelination and lead to cognitive impairment and developmental delays.25 These effects are blocked with IL-4 neutralization.25 Additionally, IL-4 overexpression is a key feature in the epileptic brain as postmortem astrocytes derived from epileptic brains characteristically express high levels of Il-4Rα.24

The FDA recently approved dupilumab for patients aged 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled by topical prescriptions or when those therapies are not advisable. The association between AD and developmental aberrations brings into question whether we should consider administering dupilumab in younger age-groups, in an effort to intervene prior to developmental disruptions. Both preclinical and clinical trials are needed to investigate the impact that IL-4 blockage would pose on brain development in children of all ages.

4.2 Early-life overexposure to glucocorticoids and neurotrophins alters the developing brain and is associated with psychologic consequences​

AD is associated with psychologic aberrations including ADD/ADHD, anxiety, depression, and suicidality (Table 2). The saturation of pro-inflammatory microglia in white matter areas is associated with hypomyelination, reducing neurotransmission. Both upregulations of microglia and alterations to the white matter microstructure are often observed in mood disorders.26, 27 Using diffusion tensor imaging, white matter alterations have also been observed in ADHD and correlate with symptom severity in children.23

Corticotrophin-induced AD aggravation also promotes a loss of Treg function and IL-10 production, both of which clinically correlate with anxiety levels of AD patients.28 The upregulation of corticotrophin-releasing hormone (CRH) and IL-4 in the absence of IL-10 reduces synaptic plasticity and induces the overexpression of neurotrophins. Although brain-derived neurotrophic factor (BDNF) is commonly regarded as a positive regulator of synaptic plasticity, alterations in synaptic plasticity and overexpression of BDNF signaling are implicated as the basis of many mood disorders.29 Neurotrophins such as nerve growth factor (NGF) and BDNF are elevated in children with AD.30 BDNF levels correlate with disease severity as well as itch and are decreased with treatment of AD.30 High peripheral BDNF if overexpressed is negatively correlated with intelligence, behavioral problems, and clinical symptoms of neurodevelopmental disorders such as intellectual disability in preschool children.31 This information emphasizes the delicate balance needed to maintain efficient and effective connectivity and transmission in the developing brain. Resolution of dysregulated brain connectivity may also underlie the effectiveness of antidepressants in the treatment of AD.32

 

[aliml]

They have sinced published a review:

TH2 sensitization in the skin-gut-brain axis: How early-life Th2-mediated inflammation may negatively perpetuate developmental and psychologic abnormalities - PubMed

We recently reported children with comorbid atopic dermatitis (AD), asthma, allergic rhinitis, and food allergies displaying a 2.7-fold increase in developmental delays.² To this end, we hypothesize unregulated increases in T helper-2 (Th2)-driven inflammation, such as those seen in...

pubmed.ncbi.nlm.nih.gov

TH2 sensitization in the skin-gut-brain axis: How early-life Th2-mediated inflammation may negatively perpetuate developmental and psychologic abnormalities​

Abstract
We recently reported children with comorbid atopic dermatitis (AD), asthma, allergic rhinitis, and food allergies displaying a 2.7-fold increase in developmental delays.2 To this end, we hypothesize unregulated increases in T helper-2 (Th2)-driven inflammation, such as those seen in atopic diseases, can exert deleterious effects on the developing brain. Recognizing that available information is incomplete and that many potential associations are not firmly established, we speculate these effects underlie the association between Th2 sensitization and cognitive dysfunction in children. In this review, we explore the role of Th2 sensitization in the skin-gut-brain axis and explain how it can lead to reduced connectivity and transmission in the developing brain. With a focus on AD, we explore the association between Th2 sensitization and developmental abnormalities such as developmental delays, memory impairment, autism spectrum disorder (ASD), and epilepsy/seizures. As such, we review the available literature to examine the impact of increased IL-4 exposure in early life on the brain. We explore the possible association between Th2 sensitization and psychologic dysfunction such as attention-deficit/hyperactivity disorder (ADHD), depression, anxiety, and suicidal ideation. We also examine the impact that increased exposure to glucocorticoids and neurotrophins in early life exerts on the developing brain. Last, we discuss future directions for the advancement of our knowledge as a scientific community including possible interventions to reduce developmental and psychologic aberrations in children.

The Following Have Been Associated With Th2 Dominance:

• IgE-related allergies, which are immediate and can be measured by skin scratch tests [57]
• Seasonal allergies
• Airway constriction
• Asthma
• Nasal drip
• Mucus
• Eczema (Dermatitis)
• Hay fever (Allergic rhinitis)
• Increased stomach acidity or GERD
• Excess histamine or what some people call “histamine intolerance”
• Hives (Urticaria)
• Chronic Fatigue Syndrome [58]
• Autism [59]
• Uveitis, Grave’s disease, Sjogren’s, Oral Lichen Planus, SLE (also Th1 dominant) [60, 61, 62, 63]

Are You Th1 or Th2 Dominant? Effects + Immune Response - SelfHacked

Is your immune system dominated by Th1 or Th2? Many health problems and lifestyle factors are said to affect this balance: learn more here.

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Top Factors That Lower Th2:

1. Sun/UVB light [1] – UVB decreases IFNy in Th1 dominance but increases it in Th2 dominance. So it’s balancing. It also decreases IgE responses. UVA in the sun also decreases Th2 dominance [2].
2. Probiotics… Decreases Th2: L Reuteri [3] (probiotic), L. Plantarum [4] (probiotic), L. salivarius [4] (probiotic), L. lactis [4] (probiotic)… Increases Th1: S Boulardii? [5], L. Sporogenes, L Acidophilus [6], L casei [7], Lactobacillus rhamnosus GG [8], Lactobacillus paracasei [9], Lactobacillus salivarius [9], B Longum [10], L Brevis [11], L fermentum [12].
3. NAC/Glutathione sufficiency decreases Th2 [13] and increases Th1 [14].
4. Licorice -18/β-glycyrrhetinic acid+LicoA [15, 16]. Glycyrrhizin increases IFNy and decreases the Th2 response [17, 18].
5. Gynostemma [19]. This is a Th1 immune stimulant and reduces allergies. Gynostemma is recommended also because it’s a powerful mitochondrial enhancer.
6. Ginger or juice the root [20, 21]. Recommended because it has anecdotal support in addition to the research, but also because you can get it everywhere, it has a long history of use and for its multitude of other benefits.
7. Reishi [22]
8. Tinospora [23]. This has a clinical trial backing it, with some anecdotal support.
9. Quercetin [24]
10. Astragalus [25] Decreases Th2 and increases Th1.

Tips on Rebalancing an Elevated Th2 Immune System - SelfHacked

People with Th2 dominance may be prone to allergies. Read on to learn what to eat & avoid to control Th2 and balance your immune system.

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