Materials and methods

Patient-level data were obtained within the framework of a multicenter nationwide cross-sectional study of atopic dermatitis. Colombian patients older than 12 years or foreigners residing for more than 15 years in the country with a clinical diagnosis of moderate to severe atopic dermatitis were included. Patients with any mental disability were excluded.

Patients attended different health provider institutions, hospitals, and dermatology private practice offices in six different Colombian regions: northwest (main city: Barranquilla), northeast (main city: Bucaramanga), central area (main cities: Bogotá, Medellín, Armenia); southwest (main city: Cali). Informed consent was obtained from all adult patients or from all children and their parents or guardians.

The data presented in this study included two visits: One initial visit (initial) performed before the COVID-19 pandemic (until February 2020), for which epidemiologic features have already been published ¹², and a second visit, performed at the end of 2020 until the first semester of 2021. At both inperson visits, all trained investigators assessed sociodemographic information and data related to disease distribution, severity (applying BSA, EASI, SCORAD, and POEM scales), and the impact of atopic dermatitis on quality of life using the DLQI, EQ-5D and Skindex-29.

Itching intensity was measured with the visual analog scale (VAS) categorized according to Reich et al.¹³, as follows: 0 = no pruritus, > 0 to < 4 points = mild pruritus, ≥ 4 to < 7 points = moderate pruritus, ≥ 7 to < 9 points = severe pruritus, and ≥ 9 points = very severe pruritus. Sleep disturbance was also evaluated with the visual analog scale (VAS). The percentage of BSA involved was classified as clear (0%), mild (> 0.1 to < 16%), moderate (16 to < 40%), and severe (40 to 100%), as previously described ¹⁴. The EASI strata were categorized as follows: 0 = clear; 0.1 to 1 = almost clear; 1.1 to 7 = mild; 7.1 to 21 = moderate; 21.1 to 50 = severe; 50.1 to 72 = very severe as previously described ¹⁵. The SCORAD strata were classified as clear-mild = 0 to 28.9, moderate = 29 to 48.9, and severe = 49 to 103, according to Chopra et al.¹⁶. POEM is a seven-item questionnaire that measures the frequency of child symptoms, including itch, bleeding, sleep disturbance, weeping or oozing, and flaking, cracked, and dry skin. Each question was scored from 0 = ‘No days’ to 4 = ‘Every day’ for a maximum score of 28. The severity banding for the POEM score was classified as previously described by Charman et al.¹⁷: 0 - 2 = clear/almost clear, 3 - 7 = mild, 8 -16 = moderate, 17 - 24 = severe, and 25 - 28 = very severe atopic eczema.

For measuring the quality of life, we used the EQ-5D, a standardized generic instrument consisting of two parts: EQ-VAS records the respondents’ self-rated health on a visual analogue scale, from 0 to 100 (worst to best imaginable health state). Health status was measured considering the following dimensions: Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each health dimension has three response levels: ‘no problems’, ‘some problems’, and ‘extreme problems’. EQ-5D reflects the current general health status. Other quality-of-life instruments used were the Colombian-Spanish dermatology life quality index (DLQI) and the Colombian- validated version of Skindex-29. The DLQI is a 10-question survey: scores range from 0 to 30, with higher scores indicating worse quality of life. DLQI scoring was classified according to Hongbo et al.¹⁸ as follows: 0 - 1 = ‘no effect at all on patient’s life’, 2 - 5 = ‘small effect on patient’s life’, 6 - 10 = ‘moderate effect on patient’s life’, 11 - 20 = ‘very large effect on patient’s life’, 21 - 30 = ‘extremely large effect on patient’s life’. The Colombian version of Skindex-29 has 29 questions split into three domains: Symptoms, emotions, and functioning, with a higher score also indicating a worse quality of life. Skindex-29 cutoffs for mild (≥ 20), moderate (≥ 30), and severe (≥ 40) impairment were those suggested by Prinsen et al¹⁹.

The assessment of the quality of life and the disease severity correlation was an a priori secondary objective of the study in patients who fulfilled the two in-person visits.

Results

From 212 patients enrolled, only 139 patients (65.5%); 57 (41%) men and 82 (59%) women completed the follow-up visit. Non-responders had similar sociodemographic features to responders (data not shown). Patients' characteristics are summarized in table 1.

The sociodemographic characteristics of the included patients at baseline had previously been published ¹². The mean study duration per patient (time between the initial and the follow-up visit) was 16 months (SD ± 3; range: 13 - 21 months). Most patients (76 %) started therapy with topical or systemic drugs after the initial visit.

Average disease severity at the initial visit was moderate, assessed by the BSA, EASI, SCORAD, and POEM scores, and it improved at the follow-up visit (table 2). All before and after comparisons of disease severity scales were statistically significant (p < 0.001; Student t test for dependent variables).

Discussion

In this multicenter observational study, we found patients with overall moderate disease but considerable quality of life impairment at the initial visit. In addition, our results indicate that disease activity correlated better with the quality-of-life measurements when the disease was less severe. These findings differ from other studies performed in adults with atopic dermatitis that have described a good correlation between atopic dermatitis severity and the quality of life ^21,22.

Interestingly, our study results are similar to the ones reported by Haeck et al.²³ when they compared BSA (“rule of nines”) and SCORAD with DLQI as the disease improved. Like the authors of the previous study, we do not have a clear explanation for this finding. We were expecting a better correlation of disease severity indices with Skindex-29 as this scale was formally validated in our country ^24,25 and per se includes items for evaluating anger, selfimage, and anxiety. However, it could be that the patient’s age is influencing these results, possibly because the adult has resigned himself more than a child or their parents to cope with the disease.

Our study included adolescent and adult patients with atopic dermatitis from several Colombian regions who were assessed in person by experienced dermatologists, assuring an in-depth characterization of the disease and an objective evaluation of the impact the disease exerts on the quality of life.

Patients' mean age was 29.1 years, a very relevant finding previously reported ¹² not only because our population belonged to the contributive social security, meaning people with a formal job in Colombia, but also because at this age, individual productivity and labor could be more affected by any disease. We also found a female preponderance, also reported in other studies describing that atopic dermatitis is more frequent in females during adolescence and thereafter ^26,27. Most of our patients were single, suggesting a possible interference of the disease in social relationships.

This study assessed atopic dermatitis disease severity and quality of life impairment with all the main instruments used in clinical practice or multicenter clinical trials. Disease severity was moderate which indirectly relates to the need for emollients, topical therapy, and systemic agents. When correlations of disease severity indices were evaluated, SCORAD strongly correlated with EASI (0.65), and BSA strongly correlated with SCORAD and EASI, a finding in line with Chopra et al.²⁸, but that could be explained by the important severity of the disease in this study since EASI is considered a poorer measurer when assessing patients with more limited disease ²⁸.

Regarding the quality of life, moderate to severe impairment was found at the initial visit (before starting treatment in most participants), confirming the impact the disease exerts on patients. In fact, at the follow-up visit, the Skindex-29 symptoms domain score remained severe, and the emotional domain continued to be notably affected, suggesting two scenarios: that even after the therapy, the atopic patient remains affected, or that Skindex-29 could be a better tool than the other quality of life scales since it continues showing affectation despite disease improvement.

With regard to the moderate to important magnitude of the effect at the initial of the study versus the follow-up, we found a more realistic effect of therapy among our atopic dermatitis patients as Cohen's D test does not depend on sample size ²⁹. This finding suggests that treatment initiation in our patients significantly improved their quality of life and disease severity scores (table 5).

Overall, POEM showed strong correlations with the most used quality of life measurements (DLQI, EQ-5D), but particularly with the symptoms and emotions domains of Skindex-29. This finding is relevant because few studies in atopic dermatitis have reported POEM to measure the quality of life (most studies focused mainly on DLQI) ³⁰. Also, POEM was recommended by the HOME International Consensus Group as the preferred assessment tool for atopic dermatitis symptoms in clinical trials ³¹.

The strengths of this study rely on a representative Colombian population sample and the fact that all outcomes were verified in person by dermatologists, diminishing the survey biases of previous studies. The limitations involved a probable selection bias because not all patients in the study completed the two visits. Statistical limitations included the scarce observation number explaining some unexpected low correlations, and correlation tests do not allow drawing conclusions about the causal relationships among the measured variables, however, from a clinical point of view, it is expected that the greater the severity of the disease, the lower the quality of life.

In conclusion, patients with atopic dermatitis experience a substantial burden in quality of life, calling for any clinician (general practitioner, pediatrician, or dermatologist) to consider this outcome in all patient evaluations in all visits. In addition, our findings indicate that disease activity correlates better with quality-of-life measurements when the disease is less severe after starting therapy, suggesting the need to evaluate the psychometric properties of some quality of life (i.e., DLQI) or disease severity scales (i.e., SCORAD and EASI). Although age may be influencing its occurrence, future analytical studies are required to determine the role of age and other factors besides disease activity. Finally, POEM and Skindex-29 seem to be optimal for establishing disease severity and quality of life in adults with atopic dermatitis.