Impact of Long-term Stability on Mental Health in Adults with Atopic Dermatitis: A Cohort Study with Unsupervised Cluster Analysis
DOI:
https://doi.org/10.2340/actadv.v105.43071Keywords:
anxiety, atopic dermatitis, depression, flares, long-term outcomes, disease severityAbstract
Atopic dermatitis (AD) is a heterogeneous disease characterized by unpredictable flares, potentially leading to impaired mental health. Adult patients with a dermatologist-verified AD diagnosis received after their 18th birthday were grouped according to patient-reported flare activity between 2018 and 2023. The k-means clustering algorithm was used in combination with dynamic time warping and barycenter averaging. Clusters were analysed according to current levels of anxiety and depression and severity across the 4 time points. The clustering method divided the 262 patients into 4 groups. Cluster 1 was characterized by a disease course with an average of < 6 annual flares, a median (interquartile range) anxiety and depression score of 3.0 (1.0–6.3), and 1.0 (0.0–4.0), respectively. Clusters 2 and 3 were characterized by annual flares ranging from 4 to 16 and anxiety scores of 6.0 (3.0–8.5) and 4.0 (2.0–7.0) and depression scores of 3.0 (1.0–6.0) and 2.0 (1.0–5.0), respectively. Cluster 4 was characterized by an unstable disease course with an average of ≥ 14 yearly flares, and anxiety and depression scores similar to cluster 2. Patients characterized by an unstable moderate disease course were more burdened compared with patients with a stable disease course (p = 0.03). This emphasizes the importance of long-term flare patterns in clinical decision-making.
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Garmhausen D, Hagemann T, Bieber T, Dimitriou I, Fimmers R, Diepgen T, et al. Characterization of different courses of atopic dermatitis in adolescent and adult patients. Allergy Eur J Allergy Clin Immunol 2013; 68: 498–506. DOI: https://doi.org/10.1111/all.12112
Bao Q, Chen L, Lu Z, Ma Y, Guo L, Zhang S, et al. Association between eczema and risk of depression: A systematic review and meta-analysis of 188,495 participants. J Affect Disord 2018; 238: 458–464. DOI: https://doi.org/10.1016/j.jad.2018.05.007
Yaghmaie P, Koudelka CW, Simpson EL. Mental health comorbidity in patients with atopic dermatitis. J Allergy Clin Immunol 2013; 131: 428–433. DOI: https://doi.org/10.1016/j.jaci.2012.10.041
Thyssen JP, Hamann CR, Linneberg A, Dantoft TM, Skov L, Gislason GH, et al. Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide. Allergy Eur J Allergy Clin Immunol 2018; 73: 214–220. DOI: https://doi.org/10.1111/all.13231
Vittrup I, Andersen YMF, Droitcourt C, Skov L, Egeberg A, Fenton MC, et al. Association between hospital-diagnosed atopic dermatitis and psychiatric disorders and medication use in childhood. Br J Dermatol 2021; 185: 91–100. DOI: https://doi.org/10.1111/bjd.19817
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: 448-456.e30. DOI: https://doi.org/10.1016/j.jaad.2018.03.017
Hanifin JM, Rajka G. Diagnostic features of AD. Acta Derm Venereol 1980; Suppl 92: 44–47. DOI: https://doi.org/10.2340/00015555924447
Williams HC, Burney PG, Pembroke AC, Hay RJ. The U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation. Br J Dermatol 1994; 131: 406–416. DOI: https://doi.org/10.1111/j.1365-2133.1994.tb08532.x
Larsen FS, Diepgen T, Svensson Å. The occurrence of atopic dermatitis in North Europe: an international questionnaire study. J Am Acad Dermatol 1996; 34: 760–764. DOI: https://doi.org/10.1016/S0190-9622(96)90009-2
Williams H, Robertson C, Stewart A, Aït-Khaled N, Anabwani G, Anderson R, et al. Worldwide variations in the prevalence of symptoms of atopic eczema in the international study of asthma and allergies in childhood. J Allergy Clin Immunol 1999; 103: 125–138. DOI: https://doi.org/10.1016/S0091-6749(99)70536-1
Nymand L, Nielsen M-L, Vittrup I, Halling A-S, Francis Thomsen S, Egeberg A, et al. Atopic dermatitis phenotypes based on cluster analysis of the Danish Skin Cohort. Br J Dermatol 2024; 190: 207–215. DOI: https://doi.org/10.1093/bjd/ljad401
Zuberbier T, Orlow SJ, Paller AS, Taïeb A, Allen R, Hernanz-Hermosa JM, et al. Patient perspectives on the management of atopic dermatitis. J Allergy Clin Immunol 2006; 118: 226–232. DOI: https://doi.org/10.1016/j.jaci.2006.02.031
Egeberg A, Andersen YMF, Thyssen JP. Prevalence and characteristics of psoriasis in Denmark: findings from the Danish skin cohort. BMJ Open 2019; 9: 1–7. DOI: https://doi.org/10.1136/bmjopen-2018-028116
Wollenberg A, Christen-Zäch S, Taieb A, Paul C, Thyssen JP, de Bruin-Weller M, et al. ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children. J Eur Acad Dermatol Venereol 2020; 34: 2717–2744. DOI: https://doi.org/10.1111/jdv.16892
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19: 210–216. DOI: https://doi.org/10.1111/j.1365-2230.1994.tb01167.x
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67: 361–370. DOI: https://doi.org/10.1111/j.1600-0447.1983.tb09716.x
Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. The REDCap consortium: building an international
community of software platform partners. J Biomed Inform 2019; 95: 103208. DOI: https://doi.org/10.1016/j.jbi.2019.103208
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap): a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377–381. DOI: https://doi.org/10.1016/j.jbi.2008.08.010
Petitjean F, Ketterlin A, Gançarski P. A global averaging method for dynamic time warping, with applications to clustering. Pattern Recognit 2011; 44: 678–693. DOI: https://doi.org/10.1016/j.patcog.2010.09.013
Rousseeuw PJ. Silhouettes: a graphical aid to the interpretation and validation of cluster analysis. J Comput Appl Math 1987; 20: 53–65. DOI: https://doi.org/10.1016/0377-0427(87)90125-7
Tavenard R, Faouzi J, Vandewiele G, Divo F, Androz G, Holtz C, et al. Tslearn, a machine learning toolkit for time series data. J Mach Learn Res 2020; 21: 1–6.
Santamaria-Babí LF. Atopic dermatitis pathogenesis: lessons from immunology. Dermatol Pract Concept 2022; 12: e2022152. DOI: https://doi.org/10.5826/dpc.1201a152
Fania L, Moretta G, Antonelli F, Scala E, Abeni D, Albanesi C, et al. Multiple roles for cytokines in atopic dermatitis: from pathogenic mediators to endotype-specific biomarkers to therapeutic targets. Int J Mol Sci 2022; 23. DOI: https://doi.org/10.3390/ijms23052684
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010; 67: 446–457. DOI: https://doi.org/10.1016/j.biopsych.2009.09.033
Savva M, Papadopoulos NG, Gregoriou S, Katsarou S, Papapostolou N, Makris M, et al. Recent advancements in the atopic dermatitis mechanism. Front Biosci (Landmark Ed) 2024; 29: 84. DOI: https://doi.org/10.31083/j.fbl2902084
Dalgard FJ, Gieler U, Tomas-Aragones L, Lien L, Poot F, Jemec GBE, et al. The psychological burden of skin diseases: a cross-sectional multicenter study among dermatological out-patients in 13 European countries. J Invest Dermatol 2015; 135: 984–991. DOI: https://doi.org/10.1038/jid.2014.530
Marron SE, Tomas-Aragones L, Navarro-Lopez J, Gieler U, Kupfer J, Dalgard FJ, et al. The psychosocial burden of hand eczema: data from a European dermatological multicentre study. Contact Dermatitis 2018; 78: 406–412. DOI: https://doi.org/10.1111/cod.12973
Brenaut E, Halvorsen JA, Dalgard FJ, Lien L, Balieva F, Sampogna F, et al. The self-assessed psychological comorbidities of prurigo in European patients: a multicentre study in 13 countries. J Eur Acad Dermatol Venereol 2019; 33: 157–162. DOI: https://doi.org/10.1111/jdv.15145
Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale: an updated literature review. J Psychosom Res 2002; 52: 69–77. DOI: https://doi.org/10.1016/S0022-3999(01)00296-3
Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U.S. adults. Br J Dermatol 2019; 181: 554–565. DOI: https://doi.org/10.1111/bjd.17683
Barbarot S, Rogers NK, Abuabara K, Aubert H, Chalmers J, Flohr C, et al. Strategies used for measuring long-term control in atopic dermatitis trials: a systematic review. J Am Acad Dermatol 2016; 75: 1038–1044. DOI: https://doi.org/10.1016/j.jaad.2016.05.043
Langan SM, Thomas KS, Williams HC. What is meant by a “flare” in atopic dermatitis? Arch Dermatol 2006; 142: 1190–1196. DOI: https://doi.org/10.1001/archderm.142.9.1190
Langan SM, Schmitt J, Williams HC, Smith S, Thomas KS. How are eczema ‘flares’ defined? A systematic review and recommendation for future studies. Br J Dermatol 2014; 170: 548–556. DOI: https://doi.org/10.1111/bjd.12747
Nielsen M-L, Nymand LK, Domenech Pena A, Du Jardin KG, Kasujee I, Thomsen SF, et al. Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: a Danish population-based study. J Eur Acad Dermatol Venereol 2025; 39: 301–307. DOI: https://doi.org/10.1111/jdv.20160
Dainty KN, Thibau IJC, Amog K, Drucker AM, Wyke M, Begolka WS. Towards a patient-centred definition for atopic dermatitis flare: a qualitative study of adults with atopic dermatitis. Br J Dermatol 2024; 191: 82–91.
https://doi.org/10.1093/bjd/ljae037 DOI: https://doi.org/10.1093/bjd/ljae037
Drucker AM, Thibau IJC, Mantell B, Dainty KN, Wyke M, Smith Begolka W. Consensus on a patient-centered definition of atopic dermatitis flare. JAMA Dermatol 2024; 160: 1099–1106. DOI: https://doi.org/10.1001/jamadermatol.2024.3054
Howells LM, Chalmers JR, Gran S, Ahmed A, Apfelbacher C, Burton T, et al. Development and initial testing of a new instrument to measure the experience of eczema control in adults and children: Recap of atopic eczema (RECAP). Br J Dermatol 2020; 183: 524–536. DOI: https://doi.org/10.1111/bjd.18780
Pascal C, Maucort-Boulch D, Gilibert S, Bottigioli D, Verdu V, Jaulent C, et al. Therapeutic management of adults with atopic dermatitis: comparison with psoriasis and chronic urticaria. J Eur Acad Dermatol Venereol 2020; 34: 2339–2345. DOI: https://doi.org/10.1111/jdv.16329
Kleyn CE, Barbarot S, Reed C, Losi S, von Arx LB, Robert C, et al. Burden of moderate to severe atopic dermatitis in adults from France, Italy, and the UK: patient-reported outcomes and treatment patterns. Dermatol Ther (Heidelb) 2022; 12: 1947–1965. DOI: https://doi.org/10.1007/s13555-022-00777-z
Nymand LK, Andersen YMF, Thyssen JP, Egeberg A. Limitations of using questionnaires for assessing the prevalence of psoriasis and atopic dermatitis among adults. JAMA Dermatol 2021; 157: 971–977. DOI: https://doi.org/10.1001/jamadermatol.2021.2307
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