Psychosocial and mental impact of alopecia areata: Analysis of the Danish Skin Cohort.

IMPORTANCE: Alopecia areata (AA) carries a psychological burden for patients beyond hair loss. However, quality-of-life measurement tools such as EQ-5D used in clinical trials may not adequately capture the burden of AA, the perceived stigmatization or the psychosocial impact of AA. OBJECTIVE: To investigate the potential association between disease severity and the degree of social isolation, perceived stigmatization, anxiety and depression, alcohol consumption and work absenteeism using multiple PRO measures in patients with AA. DESIGN, SETTING AND PARTICIPANTS: Using the Danish Skin Cohort, the study included adult patients diagnosed with AA. The study included multiple PRO measures, including Skindex-16, EQ-5D-5L, Work Productivity and Activity Impairment (WPAI), Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and the Alopecia Areata Symptom Impact Scale (AASIS). The questionnaires were dispatched to the patients in January 2023. The severity of AA was determined based on scalp involvement using a modified Alopecia Areata Scale. Multiple multivariate linear regressions were conducted using Skindex-16, AASIS and WPAI, while multivariate logistic regressions were applied to HADS, AUDIT-C and EQ-5D-5L. RESULTS: A total of 376 patients were included, of which 177 (47%) had severe disease, 41 (11%) had moderate disease, 94 (25%) had mild disease, and 64 (17%) were in remission. The median age of patients was 55 (IQR, 47-66 years) and most were female (70%). Skindex-16 and AASIS were the only PRO measures able to distinguish between severity. For these scores, moderate and severe diseases, female sex, and involvement of eyebrows increased the score and negatively impacted patient quality of life. CONCLUSION AND RELEVANCE: The results indicate the importance of using the proper tool for the intended measurement of quality of life and that factors such as the severity of AA, as well as female sex and involvement of the eyebrows, may potentially increase the psychosocial burden of AA.

The Association Between Fatigue and Adult Atopic Dermatitis: A Cross-Sectional Study.

Background: There is currently limited insight into the broader impact of atopic dermatitis (AD) on mental health. Although studies indicate that AD patients may experience fatigue, no study has so far examined fatigue in more granular detail, for example, occurrence of general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue, or correlated fatigue measures with AD severity and symptoms intensity. Objectives: To examine fatigue subtypes and their prevalence in adults with AD, as well as their possible association with AD severity. Methods: A survey was conducted in adults with AD who had been managed in a hospital setting. The Patient-Oriented SCORing Atopic Dermatitis was used to determine AD severity. Patient reported outcomes, including multidimensional fatigue inventory, were included. Results: Data from 2729 adults with AD were analyzed. The total and individual fatigue scores increased consistently with lower socioeconomic scores, higher AD severity, Dermatology Life Quality Index, itch, pain, and sleep scores. Increased fatigue scores were associated with AD severity in adjusted analyses. Conclusions: Among adults with AD, fatigue scores increased with disease severity as well as intensity of AD symptoms. Fatigue is a hitherto underappreciated symptom of AD that clinicians should be cognizant about.

The protease inhibitor cystatin C down-regulates the release of IL-ß and TNF-α in lipopolysaccharide activated monocytes.

Human cystatin C, a member of the cysteine proteinase-inhibitory family, is produced by all nucleated cells and has important roles in regulating natural immunity. Nematode homologs to human cystatin C have been shown to have anti-inflammatory effects on monocytes and to reduce colitis in mice. In Crohn's disease, pathogenic activated monocytes help drive inflammatory processes via the release of proinflammatory cytokines and chemokines. In particular, tumor necrosis factor-α-producing inflammatory monocytes have a central role in the intestinal inflammation in patients with Crohn's disease. We investigated the potential of human cystatin C to regulate pathogenic activated monocytes and its potential as an Immunomodulator in Crohn's disease. We found that cystatin C significantly decreased the lipopolysaccharide-stimulated release and expression of interleukin-1ß and tumor necrosis factor-α in monocyte and peripheral blood mononuclear cell cultures from healthy donors, whereas interleukin-6 and interleukin-8 levels were unchanged. A similar reduction of interleukin-1ß and tumor necrosis factor-α was also seen in peripheral blood mononuclear cell cultures from patients with Crohn's disease, and in particular, tumor necrosis factor-α was reduced in supernatants from lamina propria cell cultures from patients with Crohn's disease. Further investigation revealed that cystatin C was internalized by monocytes via an active endocytic process, decreased phosphorylation of the mitogen-activated protein kinase pathway extracellular signal-regulated kinase-1/2, and altered surface marker expression. The ability of cystatin C to modulate the cytokine expression of monocytes, together with its protease-inhibitory function, indicates that modulation of the local cystatin C expression could be an option in future Crohn's disease therapy.