Stressful life events, psychiatric comorbidities and serum neuromediator levels in patients with chronic spontaneous urticaria treated with omalizumab
Main Article Content
Keywords
spontaneous urticaria, omalizumab, stress, psychopathology, neuromediators
Abstract
Introduction: Many chronic spontaneous urticaria (CSU) patients have highly stressful life events and exhibit psychiatric comorbidities. Emotional stress can cause or exacerbate urticaria symptoms by causing mast cell degranulation via neuromediators.
Objectives: To investigate the frequency of stressful life events and compare psychiatric comorbidities and serum neuromediator levels in patients with CSU who responded to omalizumab with healthy controls.
Methods: In this cross-sectional study, we included 42 patients with CSU who received at least 6 months of omalizumab treatment and a control group of 42 healthy controls. Stressful life events were evaluated with the Life Events Checklist for DSM-5 (LEC-5). The Depression Anxiety Stress Scale-42 (DASS-42) was used to evaluate depression, anxiety and stress levels. Serum nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and substance P (SP) levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique.
Results: Twenty-six (62%) patients reported at least one stressful life event a median of 3.5 months before the onset of CSU. There were no significant differences in all three variables in the DASS subscales between the patient and control groups. Serum NGF levels were found to be significantly lower in patients with CSU (p <0.001), whereas CGRP levels were found to be significantly higher (p <0.001). There was no significant difference for SP.
Conclusions: The psychological status of patients with CSU who benefited from omalizumab was similar to that of healthy controls. Omalizumab may affect stress-related neuromediator levels.
References
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13. Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol. 2018;40(3):249–59. 10.1007/s00281-018-0675-z
14. Church MK, Kolkhir P, Metz M, Maurer M. The role and relevance of mast cells in urticaria. Immunol Rev. 2018;282(1):232–47. 10.1111/imr.12632
15. Babina M, Guhl S, Artuc M, Zuberbier T. Allergic FcɛRI-and pseudo-allergic MRGPRX 2-triggered mast cell activation routes are independent and inversely regulated by SCF. Allergy. 2018;73(1):256-60. 10.1111/all.13301
16. Bilgel NG, Bayram N. Turkish version of the depression anxiety stress scale (DASS-42): Psychometric properties. Noro Psikiyatr Ars. 2010;48(3):118–26. 10.4274/npa.5344
17. Boysan M, Guzel Ozdemir P, Ozdemir O, Selvi Y, Yilmaz E, Kaya N. Psychometric properties of the Turkish version of the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, (PCL-5). Psychiatry Clin Psychopharmacol. 2017;27(3):300–10. 10.1080/24750573.2017.1342769
18. Can PK, Etikan P, Degirmentepe EN, Kocaturk E. Depression scores change significantly after omalizumab treatment in patients with chronic spontaneous urticaria. Asian Pac J Allergy Immunol. 2021;10 (Online ahead of print). 10.12932/AP-180920-0965
19. Diluvio L, Piccolo A, Marasco F, Vollono L, Lanna C, Chiaramonte B, et al. Improving of psychological status and inflammatory biomarkers during omalizumab for chronic spontaneous urticaria. Future Science OA. 2020;6(9):FSO618. 10.2144/fsoa-2020-0087
20. Patella V, Zunno R, Florio G, Palmieri M, Palmieri S, Brancaccio R. Omalizumab improves perceived stress, anxiety, and depression in chronic spontaneous urticaria. J Allergy Clin Immunol Pract. 2021;9(3):1402–4. 10.1016/j.jaip.2020.11.026
21. Uzer F, Ozbudak O. Benefits of omalizumab on anxiety and depression in patients with severe asthma. Casp J Intern Med.. 2018;9(3):228–31. 10.22088/cjim.9.3.228
22. Fava GA, Perini GI, Santonastaso P, Fornasa CV. Life events and psychological distress in dermatologic disorders: Psoriasis, chronic urticaria and fungal infections. Br J Med Psychol. 1980;53(3):277–82. 10.1111/j.2044-8341.1980.tb02551.x
23. Chung MC, Symons C, Gilliam J, Kaminski ER. Posttraumatic stress disorder, emotional suppression and psychiatric co-morbidity in patients with chronic idiopathic urticaria: A moderated mediation analysis. J Mental Health. 2018;27(5):442–9. 10.1080/09638237.2018.1437601
24. Yang H-Y, Sun C-C, Wu Y-C, Wang J-D. Stress, insomnia, and chronic idiopathic urticaria–A case-control study. J Formos Med Assoc. 2005;104(4):254–63. https://www.ncbi.nlm.nih.gov/pubmed/15909063
25. Tat TS. Higher levels of depression and anxiety in patients with chronic urticaria. Med Sci Monit. 2019;25:115. 10.12659/MSM.912362
26. Konstantinou GN, Konstantinou GN. Psychological stress and chronic urticaria: A neuro-immuno-cutaneous crosstalk. A systematic review of the existing evidence. Clin Ther. 2020;42(5):771–82. 10.1016/j.clinthera.2020.03.010
27. Skaper SD. Nerve growth factor: A neuroimmune crosstalk mediator for all seasons. Immunology. 2017;151(1):1–15. 10.1111/imm.12717
28. Peters EM, Liezmann C, Spatz K, Daniltchenko M, Joachim R, Gimenez-Rivera A, et al. Nerve growth factor partially recovers inflamed skin from stress-induced worsening in allergic inflammation. J Invest Dermatol. 2011;131(3):735–43. 10.1038/jid.2010.317
29. Bonini S, Lambiase A, Angelucci F, Magrini L, Manni L, Aloe L. Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma. Proc Natl Acad Sci U S A . 1996;93(20):1095560. 10.1073/pnas.93.20.10955
30. Xiang Z, Nilsson G. IgE receptor-mediated release of nerve growth factor by mast cells. Clin Exp Allergy. 2000;30(10): 1379–86. 10.1046/j.1365-2222.2000.00906.x
31. Kimata H. Exposure to road traffic enhances allergic skin wheal responses and increases plasma neuropeptides and neurotrophins in patients with atopic eczema/dermatitis syndrome. Int J Hyg Environ Health. 2004;207(1):45–9. 10.1078/1438-4639-00261
32. Kimata H. Enhancement of allergic skin wheal responses by microwave radiation from mobile phones in patients with atopic eczema/dermatitis syndrome. Int Arch Allergy Immunol. 2002;129(4):348–50. 10.1159/000067592
33. Kimata H. Enhancement of allergic skin wheal responses in patients with atopic eczema/dermatitis syndrome by playing video games or by a frequently ringing mobile phone. Eur J Clin Invest. 2003;33(6):513–17. 10.1046/j.1365-2362.2003.01177.x
34. Borici-Mazi R, Kouridakis S, Kontou-Fili K. Cutaneous responses to substance P and calcitonin gene-related peptide in chronic urticaria: The effect of cetirizine and dimethindene. Allergy. 1999;54(1):46–56. 10.1034/j.1398-9995.1999.00726.x
35. Kay A, Ying S, Ardelean E, Mlynek A, Kita H, Clark P, et al. Calcitonin gene-related peptide and vascular endothelial growth factor are expressed in lesional but not uninvolved skin in chronic spontaneous urticaria. Clin Exp Allergy. 2014;44(8):1053–60. 10.1111/cea.12348
36. Tedeschi A, Lorini M, Asero R. No evidence of increased serum substance P levels in chronic urticaria patients with and without demonstrable circulating vasoactive factors. Clin Exp Dermatol. 2005;30(2):171–5. 10.1111/j.1365-2230.2005.01732.x
37. Zheng W, Wang J, Zhu W, Xu C, He S. Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: Induction of histamine release and basophil accumulation by substance P. Cell Biol Toxicol. 2016;32(3):217–28. 10.1007/s10565-016-9330-4
38. Metz M, Krull C, Hawro T, Saluja R, Groffik A, Stanger C, et al. Substance P is upregulated in the serum of patients with chronic spontaneous urticaria. J Invest Dermatol. 2014;134(11):2833–6. 10.1038/jid.2014.226
39. Basak P, Erturan I, Yuksel O, Kazanoglu O, Vural H. Evaluation of serum neuropeptide levels in patients with chronic urticaria. Indian J Dermatol Venereol Leprol. 2014;80(5):483. 10.4103/0378-6323.140345
40. Başak PY, Vural H, Kazanoglu OO, Erturan I, Buyukbayram HI. Effects of loratadine and cetirizine on serum levels of neuropeptides in patients with chronic urticaria. Int J Dermatol. 2014;53(12):1526–30. 10.1111/ijd.12590
2. Kaplan A, Greaves M. Pathogenesis of chronic urticaria. Clin Exp Allergy. 2009;39(6):777–87. 10.1111/j.1365-2222.2009.03256.x
3. Türk M, Carneiro-Leão L, Kolkhir P, Bonnekoh H, Buttgereit T, Maurer M. How to treat patients with chronic spontaneous urticaria with omalizumab: Questions and answers. J Allergy Clin Immunol Pract. 2020;8(1):113–24. 10.1016/j.jaip.2019.07.021
4. Maurer M, Eyerich K, Eyerich S, Ferrer M, Gutermuth J, Hartmann K, et al. Urticaria: Collegium internationale allergologicum (CIA) update 2020. Int Arch Allergy Immunol. 2020;181(5):321–33. 10.1159/000507218
5. Bernstein JA, Kavati A, Tharp MD, Ortiz B, MacDonald K, Denhaerynck K, et al. Effectiveness of omalizumab in adolescent and adult patients with chronic idiopathic/spontaneous urticaria: A systematic review of ‘real-world’ evidence. Expert Opin Biol Ther. 2018;18(4):425–48. 10.1080/14712598.2018.1438406
6. Akdaş E, Adışen E, Öztaş MO, Aksakal AB, İlter N, Gülekon A. Real-life clinical practice with omalizumab in 134 patients with refractory chronic spontaneous urticaria: A single-center experience. An Bras Dermatol. 2023;98(2):240–2. 10.1016/j.abd.2022.06.003
7. Konstantinou GN, Konstantinou GN. Psychiatric comorbidity in chronic urticaria patients: A systematic review and meta-analysis. Clin Transl Allergy. 2019;9(1):1–12. 10.1186/s13601-019-0278-3
8. Joachim RA, Kuhlmei A, Dinh Q, Handjiski B, Fischer T, Peters EM, et al. Neuronal plasticity of the “brain–skin connection”: Stress-triggered up-regulation of neuropeptides in dorsal root ganglia and skin via nerve growth factor-dependent pathways. J Mol Med. 2007;85(12):1369–78. 10.1007/s00109-007-0236-8
9. Zhang Y, Zhang H, Jiang B, Tong X, Yan S, Lu J. Current views on neuropeptides in atopic dermatitis. Exp Dermatol. 2021;30(11):1588–97. 10.1111/exd.14382
10. Ayasse MT, Buddenkotte J, Alam M, Steinhoff M. Role of neuroimmune circuits and pruritus in psoriasis. Exp Dermatol. 2020;29(4):414–26. 10.1111/exd.14071
11. Williams KA, Roh YS, Brown I, Sutaria N, Bakhshi P, Choi J, et al. Pathophysiology, diagnosis, and pharmacological treatment of prurigo nodularis. Expert Rev Clin Pharmacol. 2021;14(1):67–77. 10.1080/17512433.2021.1852080
12. Arck PC, Slominski A, Theoharides TC, Peters EM, Paus R. Neuroimmunology of stress: Skin takes center stage. J Invest Dermatol. 2006;126(8):1697–704. 10.1038/sj.jid.5700104
13. Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol. 2018;40(3):249–59. 10.1007/s00281-018-0675-z
14. Church MK, Kolkhir P, Metz M, Maurer M. The role and relevance of mast cells in urticaria. Immunol Rev. 2018;282(1):232–47. 10.1111/imr.12632
15. Babina M, Guhl S, Artuc M, Zuberbier T. Allergic FcɛRI-and pseudo-allergic MRGPRX 2-triggered mast cell activation routes are independent and inversely regulated by SCF. Allergy. 2018;73(1):256-60. 10.1111/all.13301
16. Bilgel NG, Bayram N. Turkish version of the depression anxiety stress scale (DASS-42): Psychometric properties. Noro Psikiyatr Ars. 2010;48(3):118–26. 10.4274/npa.5344
17. Boysan M, Guzel Ozdemir P, Ozdemir O, Selvi Y, Yilmaz E, Kaya N. Psychometric properties of the Turkish version of the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, (PCL-5). Psychiatry Clin Psychopharmacol. 2017;27(3):300–10. 10.1080/24750573.2017.1342769
18. Can PK, Etikan P, Degirmentepe EN, Kocaturk E. Depression scores change significantly after omalizumab treatment in patients with chronic spontaneous urticaria. Asian Pac J Allergy Immunol. 2021;10 (Online ahead of print). 10.12932/AP-180920-0965
19. Diluvio L, Piccolo A, Marasco F, Vollono L, Lanna C, Chiaramonte B, et al. Improving of psychological status and inflammatory biomarkers during omalizumab for chronic spontaneous urticaria. Future Science OA. 2020;6(9):FSO618. 10.2144/fsoa-2020-0087
20. Patella V, Zunno R, Florio G, Palmieri M, Palmieri S, Brancaccio R. Omalizumab improves perceived stress, anxiety, and depression in chronic spontaneous urticaria. J Allergy Clin Immunol Pract. 2021;9(3):1402–4. 10.1016/j.jaip.2020.11.026
21. Uzer F, Ozbudak O. Benefits of omalizumab on anxiety and depression in patients with severe asthma. Casp J Intern Med.. 2018;9(3):228–31. 10.22088/cjim.9.3.228
22. Fava GA, Perini GI, Santonastaso P, Fornasa CV. Life events and psychological distress in dermatologic disorders: Psoriasis, chronic urticaria and fungal infections. Br J Med Psychol. 1980;53(3):277–82. 10.1111/j.2044-8341.1980.tb02551.x
23. Chung MC, Symons C, Gilliam J, Kaminski ER. Posttraumatic stress disorder, emotional suppression and psychiatric co-morbidity in patients with chronic idiopathic urticaria: A moderated mediation analysis. J Mental Health. 2018;27(5):442–9. 10.1080/09638237.2018.1437601
24. Yang H-Y, Sun C-C, Wu Y-C, Wang J-D. Stress, insomnia, and chronic idiopathic urticaria–A case-control study. J Formos Med Assoc. 2005;104(4):254–63. https://www.ncbi.nlm.nih.gov/pubmed/15909063
25. Tat TS. Higher levels of depression and anxiety in patients with chronic urticaria. Med Sci Monit. 2019;25:115. 10.12659/MSM.912362
26. Konstantinou GN, Konstantinou GN. Psychological stress and chronic urticaria: A neuro-immuno-cutaneous crosstalk. A systematic review of the existing evidence. Clin Ther. 2020;42(5):771–82. 10.1016/j.clinthera.2020.03.010
27. Skaper SD. Nerve growth factor: A neuroimmune crosstalk mediator for all seasons. Immunology. 2017;151(1):1–15. 10.1111/imm.12717
28. Peters EM, Liezmann C, Spatz K, Daniltchenko M, Joachim R, Gimenez-Rivera A, et al. Nerve growth factor partially recovers inflamed skin from stress-induced worsening in allergic inflammation. J Invest Dermatol. 2011;131(3):735–43. 10.1038/jid.2010.317
29. Bonini S, Lambiase A, Angelucci F, Magrini L, Manni L, Aloe L. Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma. Proc Natl Acad Sci U S A . 1996;93(20):1095560. 10.1073/pnas.93.20.10955
30. Xiang Z, Nilsson G. IgE receptor-mediated release of nerve growth factor by mast cells. Clin Exp Allergy. 2000;30(10): 1379–86. 10.1046/j.1365-2222.2000.00906.x
31. Kimata H. Exposure to road traffic enhances allergic skin wheal responses and increases plasma neuropeptides and neurotrophins in patients with atopic eczema/dermatitis syndrome. Int J Hyg Environ Health. 2004;207(1):45–9. 10.1078/1438-4639-00261
32. Kimata H. Enhancement of allergic skin wheal responses by microwave radiation from mobile phones in patients with atopic eczema/dermatitis syndrome. Int Arch Allergy Immunol. 2002;129(4):348–50. 10.1159/000067592
33. Kimata H. Enhancement of allergic skin wheal responses in patients with atopic eczema/dermatitis syndrome by playing video games or by a frequently ringing mobile phone. Eur J Clin Invest. 2003;33(6):513–17. 10.1046/j.1365-2362.2003.01177.x
34. Borici-Mazi R, Kouridakis S, Kontou-Fili K. Cutaneous responses to substance P and calcitonin gene-related peptide in chronic urticaria: The effect of cetirizine and dimethindene. Allergy. 1999;54(1):46–56. 10.1034/j.1398-9995.1999.00726.x
35. Kay A, Ying S, Ardelean E, Mlynek A, Kita H, Clark P, et al. Calcitonin gene-related peptide and vascular endothelial growth factor are expressed in lesional but not uninvolved skin in chronic spontaneous urticaria. Clin Exp Allergy. 2014;44(8):1053–60. 10.1111/cea.12348
36. Tedeschi A, Lorini M, Asero R. No evidence of increased serum substance P levels in chronic urticaria patients with and without demonstrable circulating vasoactive factors. Clin Exp Dermatol. 2005;30(2):171–5. 10.1111/j.1365-2230.2005.01732.x
37. Zheng W, Wang J, Zhu W, Xu C, He S. Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: Induction of histamine release and basophil accumulation by substance P. Cell Biol Toxicol. 2016;32(3):217–28. 10.1007/s10565-016-9330-4
38. Metz M, Krull C, Hawro T, Saluja R, Groffik A, Stanger C, et al. Substance P is upregulated in the serum of patients with chronic spontaneous urticaria. J Invest Dermatol. 2014;134(11):2833–6. 10.1038/jid.2014.226
39. Basak P, Erturan I, Yuksel O, Kazanoglu O, Vural H. Evaluation of serum neuropeptide levels in patients with chronic urticaria. Indian J Dermatol Venereol Leprol. 2014;80(5):483. 10.4103/0378-6323.140345
40. Başak PY, Vural H, Kazanoglu OO, Erturan I, Buyukbayram HI. Effects of loratadine and cetirizine on serum levels of neuropeptides in patients with chronic urticaria. Int J Dermatol. 2014;53(12):1526–30. 10.1111/ijd.12590
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May 1, 2024
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Akdaş, E., Gülekon, A., Deveci Bulut, T. S., Gülbahar, Özlem, Öztürk, M., Başaran, A. S., & Coşar, B. (2024). Stressful life events, psychiatric comorbidities and serum neuromediator levels in patients with chronic spontaneous urticaria treated with omalizumab. Allergologia Et Immunopathologia, 52(3), 1-7. https://doi.org/10.15586/aei.v52i3.1015
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Author Biography
Ayla Gülekon, Department of Dermatovenereology, Faculty of Medicine, Gazi University, Ankara, Turkey.
How to Cite
Akdaş, E., Gülekon, A., Deveci Bulut, T. S., Gülbahar, Özlem, Öztürk, M., Başaran, A. S., & Coşar, B. (2024). Stressful life events, psychiatric comorbidities and serum neuromediator levels in patients with chronic spontaneous urticaria treated with omalizumab. Allergologia Et Immunopathologia, 52(3), 1-7. https://doi.org/10.15586/aei.v52i3.1015