News & Trends

10/31/2018

AD Differs Significantly Between African American and European American Patients

A recent study found significant differences in the molecular profile of lesions from African American patients with atopic dermatitis (AD) compared with European American patients. The results from this study could help explain differences in severity and lack of response to current therapies among African American patients, as well as improve treatment options among this patient population.

While African Americans are disproportionately affected by AD, with a high prevalence of this skin condition and unique therapeutic challenges, molecular profiling used to develop targeted therapies for AD are derived mainly from European American patients, the researchers noted. In the study, the researchers sought to characterize the global molecular profile of AD among African American patients compared with European American patients and healthy controls. RNA sequencing with real-time polymerase chain reaction validation and immunohistochemistry studies were used to assess lesional and nonlesional skin of African American and European American patients with AD and compared with healthy controls. 

 Compared with AD lesions from European American patients,   AD lesions from African American patients were characterized by greater infiltration of dendritic cells and marked by high-affinity IgE receptor (FcεR1+). Although both cohorts with AD showed similarly robust upregulation of Th2-related and Th22-related markers (IL- 22, S100A8/9/12), African American patients with AD had decreased expression of innate immune (tumor necrosis factor, IL-1β), Th1-related (IFN-γ, MX1, IL-12RB1), and Th-17-related markers (IL-23p19, IL-36G, CXCL1) compared with European American patients. 

In addition, Th2 (IL-13), Th22-related products (IL-22, S100A8/9/12) and serum IgE were significantly correlated with clinical severity, based on SCORing Atopic Dermatitis (SCORAD) scores, among African American patients. Among European American patients with AD, filaggrin was exclusively downregulated. Both AD cohorts had downregulated loricrin, which was negatively correlated with SCORAD scores among African American patients. 

“The molecular phenotype of African American AD skin is characterized by attenuated Th1 and Th17 but similar Th2/Th22-skewing to European American AD,” the researchers concluded. “Our data encourages a personalized medicine approach accounting for phenotype-specific characteristics in future development of targeted therapeutics and clinical trial design for AD.” 

Reference

Sanyal RD, Pavel AB, Glickman J, et al. Atopic dermatitis in African American patients is TH2/TH22-skewed with TH1/TH17 attenuation [published online September 14, 2018]. Ann Allergy Asthma Immunol. doi:10.1016/j.anai.2018.08.024

AD Linked to Mental Health Disorders, Suicide

Atopic dermatitis (AD) was associated with depression and anxiety, as well as suicidal ideation, according to the findings of a recent study.

The researchers conducted a meta-analysis to determine the magnitude of the association between AD and depression, anxiety, and suicidal behavior using studies on PubMed, Embase, and PyschINFO. 

AD was significantly associated with depression (pooled odds ratio [OR], 2.19; 95% CI, 1.87-2.57) and anxiety (pooled OR, 2.19; 95% CI, 1.75-2.73). Among children, AD was associated with depression, but few data were available for anxiety. In addition, a positive association was found between AD and suicidal ideation among adults and adolescents (pooled OR, 4.32; 95% CI, 1.93-9.66). While only a few studies assessed the risk of completed suicide among patients with AD, the majority showed a positive association between the skin condition and completed suicide. 

“Depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD,” the researchers concluded. “Because AD disease improvement appears to reduce these risks, this should be a priority.” 

Reference

Rønnstad ATM, Halling-Overgaard AS, Hamann CR, Skov L, Egeberg A, Thyssen JP. Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis. J Am Acad Dermatol. 2018;79(3): 448-456.e30.

Atopic Dermatitis Linked to High Disease Burden

A new study designed to explore the relationship between atopic dermatitis (AD) severity, comorbidities, and quality of life (QoL) found that AD was commonly linked to limited lifestyle (51.3%), avoidance of social interaction (39.1%), and impacted activities (43.3%).1

Researchers analyzed data from a cross-sectional, population-based study of 602 adults, sampled from the GfK Knowledge Panel. AD severity was assessed using self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring AD (POSCORAD), POSCORAD-itch and sleep. QoL was assessed using the short-form (SF)-12 mental and physical health scores and Dermatology Life Quality Index (DLQI).

Adults with AD were more likely to report having fair/poor overall health (25.8% vs 15.8%), being somewhat/very dissatisfied with life (16.7% vs 11.4%), have a lower weighted mean SF-12 mental score (45.9 vs. 50.9) and physical scores (53.0 vs 53.5), and higher DLQI (4.9 vs 1.1). 

AD severity was correlated to significant stepwise decreases on overall health, life satisfaction, and mental health and increases of DLQI scores. Physical health scores were only associated with moderate AD.

The most burdensome symptoms reported were itch (54%), excessive dryness or scaling (19%), and red or inflamed skin (7%). Skin pain and sleep disturbances were also mentioned.

“Those with moderate or severe eczema were less likely to report itch or excessive dryness or scaling as their most burdensome symptoms,” said Jonathan I. Silverberg, MD, PhD, MPH, lead author of the study, in a press statement. “A higher proportion of that group reported blisters or bumps, sleep disturbance, pain, and open sores or oozing as their most burdensome symptoms. In addition, a high percentage of all those surveyed considered themselves to only have fair (25%) or poor (15%) overall health and reported being somewhat (16%) or very (11%) dissatisfied with life compared to those who do not have eczema.”2

Researchers noted that AD was associated with worse quality of life scores compared to other chronic diseases, including heart disease, diabetes, and high blood pressure. 

“These data support the heavy burden that moderate and severe AD place on patients,” the researchers concluded. “We recommend that clinicians incorporate quality of life assessments in clinical practice to determine disease-burden, identify patients requiring step-up treatment of their skin disease, and potentially screen for patients with mental health disturbances.” 

References

1. Silverberg JI, Gelfand JM, Margolis DJ, et al. Patient-burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018;121(3):340-347.

2. Study shows painful eczema symptoms negatively impact quality of life [press release]. Arlington Heights, IL: American College of Allergy, Asthma, & Immunology; July 16, 2018. https://acaai.org/news/study-shows-painful-eczema-symptoms-negatively-impact-quality-life. Accessed September 23, 2018. 

Inadequate Disease Control More Common With Moderate to Severe AD

Inadequate control of atopic dermatitis (AD) was common among patients with moderate to severe disease and was associated with greater disease burden, according to the findings of a recent study. 

The cross-sectional study included 1519 participants with AD enrolled in 6 academic medical centers in the United States. Participants were stratified by AD severity as mild (n=689) or moderate to severe (n=830) using the Patient-Oriented SCORing Atopic Dermatitis (PR-SCORAD). Additionally, participants with moderate to severe AD receiving systemic immunomodulators and/or phototherapy were categorized as having adequate or inadequate disease control. 

Validated measures and stand-alone questions that assessed itch, pain, sleep, anxiety and depression, and health-related quality of life were used to assess patient-reported burden of AD and disease control, which were compared between groups. 

Compared with participants with mild AD, those with moderate to severe AD reported more severe itching and pain, greater adverse effects on sleep, higher prevalence of anxiety and depression, and greater impairment in health-related quality of life. 

A total of 103 participants with moderate to severe AD had inadequate disease control despite treatment with systemic immunomodulators or phototherapy. They reported higher burdens of itch and sleep symptoms compared with those with controlled disease. Participants with inadequately controlled AD despite treatment experienced itchy skin on more days during the week and a higher proportion experienced itch that lasted more than half a day. In addition, trouble sleeping, more frequent sleep disturbances, and greater need for over-the-counter sleep medications were reported by more participants with inadequately controlled AD compared with those with disease control. 

“For patients with moderate to severe dermatitis, there is a need for more effective therapies and for greater incorporation of the patient’s perspective into clinical assessment,” the researchers concluded. 

Reference

Simpson EL, Guttman-Yassky E, Margolis DJ, et al. Association of inadequately controlled disease and disease severity with patient-reported disease burden in adults with atopic dermatitis JAMA Dermatol. 2018;154(8):903-912.

Dupilumab Improves Symptoms of Pain/Discomfort

A recent study found that dupilumab (Dupixent) improved symptoms of pain and discomfort among patients with moderate to severe atopic dermatitis (AD). 

In the study, researchers analyzed data from 3 phase 3 trials on symptoms of pain and discomfort and the efficacy of dupilumab at relieving pain among participants with moderate to severe AD (LIBERTY AD SOLO 1 and 2, LIBTERTY AD CHRONOS, and LIBERTY AD CAFÉ). In SOLO 1 and 2, participants were randomized to receive subcutaneous dupilumab 300 mg every week, every 2 weeks, or placebo for 16 weeks. Participants in CAFÉ and CHRONOS were randomized to concomitant topical corticosteroids and dupilumab every week or every 2 weeks or topical corticosteroid and placebo for 16 weeks or 52 weeks, respectively. Perceived pain/discomfort was reported as either “no problem,” “some problems,” or “extreme problems” in the EuroQol five dimensions questionnaire on pain/discomfort dimension.

In pooled data of all studies, 80% of participants reported some or extreme pain/discomfort at baseline. Among those who reported some or extreme pain/discomfort at baseline, a high proportion of participants who received dupilumab reported no pain after 16 weeks of treatment compared with placebo and placebo combined with topical corticosteroids. This response was maintained through 52 weeks of treatment in CHRONOS. All trials had similar rates of adverse events.

“There is a high burden related to pain/discomfort in moderate to severe AD participants,” the researchers concluded. “Dupilumab monotherapy or with concomitant topical corticosteroids improved symptoms of pain/discomfort in moderate to severe AD participants consistently across multiple trials.” n

Reference

Simpson E, Silverberg JI, Eckert L, et al. LB1520 Dupilumab improves symptoms of pain/discomfort in moderate-to-severe atopic dermatitis: EuroQol five dimensions questionnaire (EQ-5D) phase 3 clinical trials results. J Investig Dermatol. 2018;138(9): B9.