麻豆传媒

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Atopic dermatitis is associated with a large negative impact on health-related quality of life (HRQoL) and is the leading contributor to disability-adjusted life years (DALYs) of all skin dermatoses globally. Individuals in resource-rich countries, as well as women and children throughout the world, are vulnerable.

A 2021 , which reflects the burden of atopic dermatitis in 195 countries, showed that children from the ages of 1 and 5 years had the highest number of DALYs, and that women of all ages and across all regions had consistently higher DALYs compared with men.

"This suggests that atopic dermatitis may be considered a chronic systemic disorder, with significant physical and psychosocial impairments," the authors said.

Patients with atopic dermatitis are at risk of developing asthma, allergic rhinitis, and food allergies -- the atopic comorbidities commonly referred to as the "allergic triad." Less is known about the associations between atopic dermatitis and non-allergic conditions such as sleep disturbance, insomnia, and anxiety and depression.

"Understanding these non-allergic co-morbidities has the potential to improve patient outcomes and to help mitigate the cost and burdens associated with these conditions," said Amy S. Paller, MD, professor of pediatrics and the Walter J. Hamlin chair and professor of dermatology at Northwestern University Feinberg School of Medicine in Chicago, and co-authors in a 2018 . "The consequences of atopic dermatitis reach beyond the skin and past childhood."

In addition to disease severity, a 2022 analysis of survey data from 1,056 adults showed that time spent managing atopic dermatitis as well as comorbid depression were also strongly associated with disease burden. "This analysis highlights the multidimensional burden of atopic dermatitis in adults and emphasizes the need for more effective treatment strategies," the authors wrote in .

The impact of atopic dermatitis on health-related quality of life (HRQoL) appears to be just as substantial in children, if not more. The 2022 observational PEDIatric STudy in Atopic Dermatitis (), led by Paller, showed that the real-world disease burden among 732 children younger than 12 with moderate to severe disease was significant, reflecting "a major unmet need for effective disease control." When compared with other chronic diseases in children ages 5-16, generalized atopic dermatitis had the second-largest impact on HRQoL, after cerebral palsy.

Sleep Disturbance

Sleep disturbance is driven primarily by intense night-time itch, one of the most distressing manifestations of atopic dermatitis. Up to 80% of children and 90% of adults with atopic dermatitis have difficulty falling asleep and staying asleep. Comorbid sleep disturbance is associated with fatigue, daytime drowsiness, impaired performance at work or at school, and an increased risk of anxiety and depression. In children, sleep disturbances have also been linked to hyperactivity and inattention, and stunted growth.

"Many patients will be sleep deprived from the non-stop itching," said Jashin J. (Jay) Wu, MD, a dermatologist in Irvine, California, who is founder and CEO of the Dermatology Research and Education Foundation. "It's important to ask the patient how they are sleeping, and if not well, this is an indication for a systemic therapy," he told 麻豆传媒.

In terms of treatment, "the highest-yield interventions for sleep disturbance are those that achieve better control of the underlying signs and symptoms of atopic dermatitis," said Jonathan Silverberg, MD, PhD, MPH, of George Washington University School of Medicine and Health Sciences in Washington, D.C. Even so, "some patients require additional therapies to address concomitant sleep disturbances."

Effect on Patients and Other Family Members

Sleep disturbance is also a significant driver of poor quality of life in the parents and other family members of children with atopic dermatitis. A 2020 revealed that during disease flares, 86% of parents reported losing up to 2.6 hours of sleep per night, and that parental sleep disturbance was maintained throughout childhood, especially by mothers. The net effect: exhaustion, interpersonal conflict, and reduced happiness.

"The terrible burden of atopic dermatitis on the child and the family with respect to sleep and basically the time commitment to management of the disease is huge," Paller told 麻豆传媒.

Sleep assessment is important in patients with atopic dermatitis, said Wilfred R. Pigeon, PhD, a sleep specialist and professor of psychiatry and public health sciences at the University of Rochester Medical Center in New York.

Validated self-report measures of sleep or clinical interview questions can be used to measure the effects of atopic dermatitis treatment on sleep, and as the basis of a referral to sleep medicine. Objective measurement of sleep is required to diagnose sleep apnea.

Despite limited data on the treatment of sleep disorders in children or adults with atopic dermatitis, clinical practice guidelines for the two most common sleep disorders -- insomnia disorder and sleep apnea -- can be applied to most patients, Pigeon told 麻豆传媒. "Given the bi-directional relationship between sleep and atopic dermatitis, and sleep and itch, it is likely that improvement in one domain would lead to improvements in the other."

In adults and children with sleep apnea, the recommended first-line treatment is positive airway pressure when more conservative measures such as weight loss have failed or aren't indicated. In adults with insomnia, cognitive-behavioral therapy is recommended, and may be helpful in some adolescents, although teens should first be assessed for circadian rhythm disorder, Pigeon said.

More targeted anti-inflammatory treatments for atopic dermatitis, such as dupilumab (Dupixent), approved for the systemic treatment of moderate to severe atopic dermatitis in patients age 6 and up, may also improve sleep problems, Pigeon said. The exception to this may be insomnia, however: "Once insomnia becomes chronic, it tends to need direct intervention in order to resolve," he noted.

New therapies for atopic dermatitis, particularly dupilumab, "have revolutionized how we can treat severe disease early on in young children who are not responding to topical steroids," Paller said. "When you can turn around the itch, when you can turn around the atopic dermatitis, and reduce the burden of not being able to sleep at night, it can be life-changing."

Many physicians caring for children with atopic dermatitis don't ask the parents about sleep, however, said Karan Lal, DO, MS, a pediatrician and dermatologist in New York City. "It is the one question that truly changes my management beyond topical steroids," he told 麻豆传媒.

"Oral antihistamines are often prescribed to help with itch, but in my experience, medications such as dupilumab, methotrexate, cyclosporine, and the JAK [Janus kinase] inhibitors control the underlying inflammation without the need for antihistamines. My go-to is making sure that parents of young children are bathing, moisturizing, using the topical steroids, and giving their child the anti-inflammatory, if prescribed, to promote better sleep hygiene," Lal explained.

New evidence also indicates that insomnia plays a crucial role in predisposing patients with atopic dermatitis to anxiety and depression, which in turn increase the risk of insomnia, creating a "pathological circle."

A 2023 in 57 adults showed that insomnia accounted for about 82% of both the relationship between atopic eczema severity and depression, and the effect of disease severity on anxiety symptoms.

"Early interventions focused on treating sleep disturbances could indirectly be beneficial on the mental health of patients with atopic dermatitis, counteracting the onset and exacerbation of anxiety and depression disorders," the researchers concluded.

Mood Disorders

How common are mood disorders in atopic dermatitis? A 2018 revealed that almost 1 in 6 patients with atopic dermatitis had clinical depression, 1 in 4 had depressive symptoms, and 1 in 8 had suicidal ideation. Disease severity was associated with markedly worse mental health.

"Depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with atopic dermatitis," the researchers wrote. "Because atopic dermatitis disease improvement appears to reduce these risks, this should be a priority."

Instead, a U.S. population-based study of 2,893 adults demonstrated that the mental health comorbidities associated with atopic dermatitis often go undiagnosed. In spite of "dramatically higher rates of anxiety and depression" in participants with atopic dermatitis, many reported no diagnosis of either mood disorder.

"It is important for clinicians to recognize that virtually all patients with moderate‐to‐severe atopic dermatitis have symptoms of anxiety and depression," Silverberg and co-authors wrote in the . "We recommend that clinicians incorporate assessment of mental health symptoms in clinical practice to determine disease burden and screen for patients with symptoms of anxiety and depression."

In an interview, Silverberg noted that improvement of atopic dermatitis symptoms often results in improvement of comorbid depression and anxiety. "We already have data for dupilumab and the JAK inhibitors that show improvements of HADS [Hospital Anxiety and Depression Scale] scores and other patient-reported outcome measures of mental health," he said.

"Better long-term control of atopic dermatitis appears to be beneficial for reducing itch, sleep disturbance, and depression and anxiety," agreed Lawrence Eichenfield, MD, of the University of California San Diego School of Medicine.

"It is important to consider recording the extent and severity of atopic dermatitis in moderate to severe disease, as this helps with evaluations over time, and of asking about itch, sleep disturbance, and the life impact of atopic dermatitis on the individual and family," he told 麻豆传媒.

At Seattle Children's Hospital, routine screening for depression and suicidality is conducted every 30 days in all patients older than age 12. "This is important for all pre-adolescent and adolescent patients, but it is particularly important for kids with atopic dermatitis, especially those with severe disease," said Robert Sidbury, MD, MPH, chief of the Division of Dermatology and professor of pediatrics at the University of Washington School of Medicine.

Read previous installments in this series:

Part 1: Atopic Dermatitis: Reasons for Optimism

Part 2: Atopic Dermatitis: The Latest on Diagnosis and Assessment

Part 3: The Many Ways to Measure the Severity of Atopic Dermatitis

Part 4: Case Study: Why Is This Young Boy's Atopic Dermatitis So Resistant to Treatment?

Part 5: Atopic Dermatitis Has Myriad Life-Altering Comorbidities

Part 6: Topical Therapies for Adult Atopic Dermatitis

Part 7: Improving Treatment Adherence in Atopic Dermatitis

Part 8: Case Study: Sudden Appearance of Painful Pustules in Patient With Eczema