Atopic Dermatitis: A Qualitative Study on the Burdens of Living with Itchiness.

Objective: We sought to understand the consequences itchiness has on daily life that may not be immediately obvious in clinical assessments for patients with atopic dermatitis (AD). Methods: Focus groups and interviews involving 21 patients with AD and 12 family members examined aspects of the effects of itchiness on health-related quality of life (HRQL). Investigators conducted a thematic analysis where two researchers independently coded the narratives and arrived at a consensus on major themes. Results: Five themes emerged from our discussions. 1) Miserable experience: Itchiness was difficult to control and cease. 2) Physical damage: Damage to skin and hair occurred from scratching to alleviate the itchiness. 3) Effects on daily activities: Itchiness could affect everything participants did, including how they dressed, used make-up, and slept. 4) Effects on social activities and relationships: The discomfort and embarrassment from scratching in public and others' reactions hindered participants' social lives. 5) Emotional consequences: Various emotional responses to itchiness were reported, including embarrassment, depression, and irritation. Limitations: Though qualitative research provides a level of detail not often found in quantitative analyses, this study design is limited by small sample size and generalizability. Conclusion: Understanding these challenges can help clinicians open deeper conversations with their patients to learn more about what patients need from their dermatologic care. While itchiness from AD is well-known, this study shows that its effects on HRQL are not minimal and that patients may need further care for the consequences of this symptom.

Quality of Life Among Family of Patients with Atopic Dermatitis and Psoriasis.

BACKGROUND: Chronic inflammatory skin diseases like atopic dermatitis (AD) and psoriasis can severely impact patients' quality of life (QOL). However, the effect of these diseases can diminish the QOL of patients' family members as well. The objective of this study was to understand the impact on QOL for family members of patients diagnosed with AD or psoriasis. METHODS: We conducted focus groups and interviews with 23 individuals; 12 had a family member with AD, and 11 had a family member with psoriasis. After investigators independently coded the transcripts, thematic analysis was conducted. RESULTS: Three major themes emerged: (1) lifestyle consequences-many daily activities for family members, including but not limited to leisure activities, sleep, and cleaning, were affected by AD or psoriasis; (2) emotional consequences-family members felt frustrated, worried, or embarrassed, among other concerns, because of their loved ones' AD or psoriasis; (3) relationships-relationships between family members and their loved ones with AD or psoriasis could become strained, and though family members might try to be sympathetic, doing so could be difficult because of their lack of understanding of how these diseases feel and personally affect their loved ones. CONCLUSIONS: This study highlights the impacts of AD and psoriasis on the whole family. Clinicians should be mindful of the effects on QOL not only for patients but also for family members who live with and care about these patients. Especially when family members assist with treatments, it is important to understand family members' experiences when making treatment decisions.

Neuroinflammatory disease disrupts the blood-CNS barrier via crosstalk between proinflammatory and endothelial-to-mesenchymal-transition signaling.

Breakdown of the blood-central nervous system barrier (BCNSB) is a hallmark of many neuroinflammatory disorders, such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), we show that endothelial-to-mesenchymal transition (EndoMT) occurs in the CNS before the onset of clinical symptoms and plays a major role in the breakdown of BCNSB function. EndoMT can be induced by an IL-1ß-stimulated signaling pathway in which activation of the small GTPase ADP ribosylation factor 6 (ARF6) leads to crosstalk with the activin receptor-like kinase (ALK)-SMAD1/5 pathway. Inhibiting the activation of ARF6 both prevents and reverses EndoMT, stabilizes BCNSB function, reduces demyelination, and attenuates symptoms even after the establishment of severe EAE, without immunocompromising the host. Pan-inhibition of ALKs also reduces disease severity in the EAE model. Therefore, multiple components of the IL-1ß-ARF6-ALK-SMAD1/5 pathway could be targeted for the treatment of a variety of neuroinflammatory disorders.

The Disruptiveness of Itchiness from Psoriasis: A Qualitative Study of the Impact of a Single Symptom on Quality of Life.

BACKGROUND: Pruritus is the most common symptom of psoriasis, with a significant impact on patient quality of life. In spite of this, the severity, persistence, and overall impact of itchiness has only been rarely formally assessed during standard psoriasis clinic visits. Objectives: We sought to understand the far-reaching impacts of itchiness on the lives of those with psoriasis and their families. METHODS: We conducted a qualitative study with five focus groups and 10 semi-structured interviews from August 2018 to January 2019. We enrolled 25 individuals with a diagnosis of at least moderate plaque psoriasis and 11 family members (primarily significant others). Views and experiences were analyzed thematically via content analysis. RESULTS: Itchiness considerably impacts those with plaque psoriasis and their families. Our narrative analysis produced three main themes relating to itchiness: the triggers of itchiness, including climate, emotions, and behaviors; the physical consequences of itchiness, including disruption of emotional well-being, sleep disturbance, and daily activities; and the prevention and treatment strategies used to alleviate itchiness. CONCLUSION: Itchiness impacts the quality of life in those with psoriasis and their family members. We strongly urge clinicians to inquire about and monitor the severity and impact of itchiness in psoriasis patients.

Effects of Pain From Atopic Dermatitis: Interview and Focus Group Study With Patients and Their Families.

BACKGROUND: Pain is an underappreciated symptom of atopic dermatitis that can affect the health-related quality of life (HRQL) of patients. OBJECTIVE: The aim of this study is to understand the effect of pain on patients with atopic dermatitis and their family members and to recognize how this symptom affects HRQL. METHODS: We conducted focus groups and interviews with patients with atopic dermatitis and their family members. Researchers independently coded the transcripts and reached a consensus on the major themes. RESULTS: A total of 33 adult participants, consisting of 21 patients with atopic dermatitis (median age 47 years, range 22-77) and 12 family members (median age 50, range 22-72), attended either focus groups (23/33, 70%) or interviews (10/33, 30%), where we assessed their experiences of pain. Four themes emerged in our study. Itchiness and pain can be intertwined: pain was often caused by or otherwise associated with itchiness and could result from open sores and excoriated skin. Characteristics of pain: pain was most often described as burning. Other descriptors included mild, persistent discomfort; stinging; and stabbing. Effects of pain: pain negatively affected various aspects of daily life, including choice of clothing, sleep, social activities, and relationships. The location of painful areas could also limit physical activity, including sex. Pain management: pain from atopic dermatitis could be managed to varying degrees with different over-the-counter and prescription treatments. Systemic agents that cleared the skin also resolved the pain associated with atopic dermatitis. CONCLUSIONS: Pain can be a significant factor in the HRQL of patients with atopic dermatitis and should be considered by clinicians when caring for patients with atopic dermatitis.

Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic retinopathy.

The devastating sequelae of diabetes mellitus include microvascular permeability, which results in retinopathy. Despite clinical and scientific advances, there remains a need for new approaches to treat retinopathy. Here, we have presented a possible treatment strategy, whereby targeting the small GTPase ARF6 alters VEGFR2 trafficking and reverses signs of pathology in 4 animal models that represent features of diabetic retinopathy and in a fifth model of ocular pathological angiogenesis. Specifically, we determined that the same signaling pathway utilizes distinct GEFs to sequentially activate ARF6, and these GEFs exert distinct but complementary effects on VEGFR2 trafficking and signal transduction. ARF6 activation was independently regulated by 2 different ARF GEFs - ARNO and GEP100. Interaction between VEGFR2 and ARNO activated ARF6 and stimulated VEGFR2 internalization, whereas a VEGFR2 interaction with GEP100 activated ARF6 to promote VEGFR2 recycling via coreceptor binding. Intervening in either pathway inhibited VEGFR2 signal output. Finally, using a combination of in vitro, cellular, genetic, and pharmacologic techniques, we demonstrated that ARF6 is pivotal in VEGFR2 trafficking and that targeting ARF6-mediated VEGFR2 trafficking has potential as a therapeutic approach for retinal vascular diseases such as diabetic retinopathy.