Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.
References
[1]
Lönndahl, L., Abdelhadi, S., Holst, M., Lonne-Rahm, S., Nordlind, K. and Johansson, B. (2023) Psychological Stress and Atopic Dermatitis: A Focus Group Study. Annals of Dermatology, 35, 342-347. https://doi.org/10.5021/ad.22.035
[2]
Hughes, O., Shelton, K.H., Penny, H. and Thompson, A.R. (2022) Parent and Child Experience of Skin Conditions: Relevance for the Provision of Mindfulness-Based Interventions. British Journal of Dermatology, 188, 514-523. https://doi.org/10.1093/bjd/ljac129
[3]
Pondeljak, N. and Lugović-Mihić, L. (2020) Stress-induced Interaction of Skin Immune Cells, Hormones, and Neurotransmitters. Clinical Therapeutics, 42, 757-770. https://doi.org/10.1016/j.clinthera.2020.03.008
[4]
Chu, D.K., Schneider, L., Asiniwasis, R.N., Boguniewicz, M., De Benedetto, A., Ellison, K., et al. (2024) Atopic Dermatitis (Eczema) Guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE and Institute of Medicine-Based Recommendations. Annals of Allergy, Asthma & Immunology, 132, 274-312. https://doi.org/10.1016/j.anai.2023.11.009
[5]
Guilloteau, K., Paris, I., Pedretti, N., Boniface, K., Juchaux, F., Huguier, V., et al. (2010) Skin Inflammation Induced by the Synergistic Action of IL-17A, IL-22, Oncostatin M, Il-1α, and TNF-Α Recapitulates Some Features of Psoriasis. The Journal of Immunology, 184, 5263-5270. https://doi.org/10.4049/jimmunol.0902464
[6]
Cay, M., Ucar, C., Senol, D., et al. (2018) Effect of Increase in Cortisol Level Due to Stress in Healthy Young Individuals on Dynamic and Static Balance Scores. Northern Clinics of İstanbul, 5, 295-301. https://doi.org/10.14744/nci.2017.42103
[7]
Herman, J.P., McKlveen, J.M., Ghosal, S., et al. (2016) Regulation of the Hypothalamic-Pituitary Adrenocortical Stress Response. Comprehensive Physiology, 6, 603-621. https://doi.org/10.1002/cphy.c150015
[8]
Spindler, M., Palombo, M., Zhang, H. and Thiel, C.M. (2023) Dysfunction of the Hypothalamic-Pituitary Adrenal Axis and Its Influence on Aging: The Role of the Hypothalamus. Scientific Reports, 13, Article No. 6866. https://doi.org/10.1038/s41598-023-33922-5
[9]
Arndt, J., Smith, N. and Tausk, F. (2008) Stress and Atopic Dermatitis. Current Allergy and Asthma Reports, 8, 312-317. https://doi.org/10.1007/s11882-008-0050-6
[10]
Soares, S., Rocha, V., Kelly-Irving, M., Stringhini, S. and Fraga, S. (2021) Adverse Childhood Events and Health Biomarkers: A Systematic Review. Frontiers in Public Health, 9, Article 649825. https://doi.org/10.3389/fpubh.2021.649825
[11]
Nehring, S.M., Goyal, A. and Patel, B.C. (2023) C Reactive Protein. StatPearls Publishing.
[12]
Jishna, P. and Dominic, S. (2023) Acute Phase Reactants: Relevance in Dermatology. Indian Dermatology Online Journal, 14, 1-8. https://doi.org/10.4103/idoj.idoj_174_21
[13]
Adelantado-Renau, M., Beltran-Valls, M.R., Mota, J. and Moliner-Urdiales, D. (2020) Circulating Inflammatory Biomarkers and Academic Performance in Adolescents: DADOS Study. PLOS ONE, 15, e0242016. https://doi.org/10.1371/journal.pone.0242016
[14]
Camara, M.L., Corrigan, F., Jaehne, E.J., Jawahar, M.C., Anscomb, H., Koerner, H., et al. (2013) TNF-α and Its Receptors Modulate Complex Behaviours and Neurotrophins in Transgenic Mice. Psychoneuroendocrinology, 38, 3102-3114. https://doi.org/10.1016/j.psyneuen.2013.09.010
[15]
Esteban-Cornejo, I., Martinez-Gomez, D., Gómez-Martínez, S., del Campo-Vecino, J., Fernández-Santos, J., Castro-Piñero, J., et al. (2016) Inflammatory Biomarkers and Academic Performance in Youth. The up & down Study. Brain, Behavior, and Immunity, 54, 122-127. https://doi.org/10.1016/j.bbi.2016.01.010
[16]
Herberth, G., Röder, S., Bockelbrink, A., Schäfer, T., Borte, M., Herbarth, O., et al. (2018) Stressful Life Events in Childhood and Allergic Sensitization. Allergologie select, 2, 1-9. https://doi.org/10.5414/alx01275e
[17]
Lacey, R.E., Pinto Pereira, S.M., Li, L. and Danese, A. (2020) Adverse Childhood Experiences and Adult Inflammation: Single Adversity, Cumulative Risk and Latent Class Approaches. Brain, Behavior, and Immunity, 87, 820-830. https://doi.org/10.1016/j.bbi.2020.03.017
[18]
Flouri, E., Francesconi, M., Midouhas, E. and Lewis, G. (2020) Prenatal and Childhood Adverse Life Events, Inflammation and Depressive Symptoms across Adolescence. Journal of Affective Disorders, 260, 577-582. https://doi.org/10.1016/j.jad.2019.09.024
[19]
Buske-Kirschbaum, A. and Hellhammer, D.H. (2003) Endocrine and Immune Responses to Stress in Chronic Inflammatory Skin Disorders. Annals of the New York Academy of Sciences, 992, 231-240. https://doi.org/10.1111/j.1749-6632.2003.tb03153.x
[20]
Pavlovic, S., Daniltchenko, M., Tobin, D.J., Hagen, E., Hunt, S.P., Klapp, B.F. and Peters, E.M. (2008) Further Exploring the Brain–Skin Connection: Stress Worsens Dermatitis via Substance P-Dependent Neurogenic Inflammation in Mice. Journal of Investigative Dermatology, 128, 434-446. https://doi.org/10.1038/sj.jid.5701102
[21]
Brenninkmeijer, E.E.A., Legierse, C.M., Sillevis Smitt, J.H., Last, B.F., Grootenhuis, M.A. and Bos, J.D. (2009) The Course of Life of Patients with Childhood Atopic Dermatitis. Pediatric Dermatology, 26, 14-22. https://doi.org/10.1111/j.1525-1470.2008.00745.x
[22]
Vasiadi, M., Therianou, A., Sideri, K., Smyrnioti, M., Sismanopoulos, N., Delivanis, D.A. and Theoharides, T.C. (2012) Increased Serum CRH Levels with Decreased Skin CRHR-1 Gene Expression in Psoriasis and Atopic Dermatitis. Journal of Allergy and Clinical Immunology, 129, 1410-1413. https://doi.org/10.1016/j.jaci.2012.01.056
[23]
Akamine, A.A., Rusch, G.D.S., Nisihara, R. and Skare, T.L. (2021) Adverse Childhood Experiences in Patients with Psoriasis. Trends in Psychiatry and Psychotherapy, 44, e20210251. https://doi.org/10.47626/2237-6089-2021-0251
[24]
Kellum, C.E., King, M.A., Cruz-Ojeda, F. and Pollock, J. (2022) Early Life Stress (ELS) Accelerates Autoimmunity and Synergistically Increases Risk for Cardiovascular Disease (CVD) in the Pristane-Induced Model of Systemic Lupus Erythematosus (SLE) in Mice. The FASEB Journal, 36. https://doi.org/10.1096/fasebj.2022.36.s1.r4763
[25]
Humphreys, K.L. (2019) Understanding the Link between Early Adversity and Disease—Stress, Immunity, and Prevention. Brain, Behavior, and Immunity, 78, 1-2. https://doi.org/10.1016/j.bbi.2018.12.019
[26]
Coffman, J.A., Burman, M.A. and Duboué, E.R. (2022) Editorial: Early Life Stress and Developmental Programming of Immune and Nervous System Responsivity. Frontiers in Cell and Developmental Biology, 10, Article 897251. https://doi.org/10.3389/fcell.2022.897251
[27]
Wintermann, G., Bierling, A.L., Peters, E.M.J., Abraham, S., Beissert, S. and Weidner, K. (2022) Childhood Trauma and Psychosocial Stress Affect Treatment Outcome in Patients with Psoriasis Starting a New Treatment Episode. Frontiers in Psychiatry, 13, Article 848708. https://doi.org/10.3389/fpsyt.2022.848708
[28]
Rønnstad, A.T.M., Halling-Overgaard, A., Hamann, C.R., Skov, L., Egeberg, A. and Thyssen, J.P. (2018) Association of Atopic Dermatitis with Depression, Anxiety, and Suicidal Ideation in Children and Adults: A Systematic Review and Meta-Analysis. Journal of the American Academy of Dermatology, 79, 448-456.e30. https://doi.org/10.1016/j.jaad.2018.03.017
[29]
Peters, E.M.J., Liezmann, C., Klapp, B.F. and Kruse, J. (2012) The Neuroimmune Connection Interferes with Tissue Regeneration and Chronic Inflammatory Disease in the Skin. Annals of the New York Academy of Sciences, 1262, 118-126. https://doi.org/10.1111/j.1749-6632.2012.06647.x
[30]
Revankar, R.R., Revankar, N.R., Balogh, E.A., Patel, H.A., Kaplan, S.G. and Feldman, S.R. (2022) Cognitive Behavior Therapy as Dermatological Treatment: A Narrative Review. International Journal of Women’s Dermatology, 8, e068. https://doi.org/10.1097/jw9.0000000000000068
[31]
Kaundinya, T., El-Behaedi, S., Bilimoria, S. and Choi, J.N. (2023) Characterization of Online Support Group Resources for Patients with Dermatologic Conditions. Archives of Dermatological Research, 315, 1547-1552. https://doi.org/10.1007/s00403-023-02528-2
[32]
Datta, D., Sarkar, R. and Podder, I. (2021) Parental Stress and Quality of Life in Chronic Childhood Dermatoses: A Review. The Journal of Clinical and Aesthetic Dermatology, 14, S19-S23.
[33]
Montgomery, K. and Thompson, A.R. (2018) The Potential Role of Mindfulness in Psychosocial Support for Dermatology Patients. Clinics in Dermatology, 36, 743-747. https://doi.org/10.1016/j.clindermatol.2018.08.010
[34]
Sarti, M.G. (1998) Biofeedback in Dermatology. Clinics in Dermatology, 16, 711-714. https://doi.org/10.1016/s0738-081x(98)00052-2
[35]
Schmeer, K.K. and Yoon, A. (2016) Socioeconomic Status Inequalities in Low-Grade Inflammation during Childhood. Archives of Disease in Childhood, 101, 1043-1047. https://doi.org/10.1136/archdischild-2016-310837
[36]
Xerfan, E.M.S., Andersen, M.L., Facina, A.S., Tufik, S. and Tomimori, J. (2021) Sleep Loss and the Skin: Possible Effects of This Stressful State on Cutaneous Regeneration during Nocturnal Dermatological Treatment and Related Pathways. Dermatologic Therapy, 35, e15226. https://doi.org/10.1111/dth.15226
[37]
Weerdmeester, J., van Rooij, M.M., Engels, R.C. and Granic, I. (2020) An Integrative Model for the Effectiveness of Biofeedback Interventions for Anxiety Regulation: Viewpoint. Journal of Medical Internet Research, 22, e14958. https://doi.org/10.2196/14958
