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Exacerbating Factors in Chronic Spontaneous Urticaria

  • Urticaria and Atopic Dermatitis (M Furue and T Nakahara, Section Editors)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Abstract

Purpose of review

Chronic spontaneous urticaria (CSU) is frequently associated with autoimmunity and is often exacerbated by several factors. These include stress, infections, colourings and preservatives in pre-packaged foods, as well as deficiency of vitamin D3 and iron. While chronic underlying infection and mental and emotional stress have been known to precede the onset of CSU, it is now clear that they can also aggravate the severity of the symptoms and perpetuate the condition. It is unclear how gastrointestinal dysbiosis affects CSU. Vitamin D3, however, can increase T regulatory function which can control a tendency to autoimmunity and inflammation. In this review, we discuss the different factors that can exacerbate established CSU, prolong the duration of the condition and encourage the need for second and third line therapy.

Recent findings

While the precise molecular mechanism by which the above factors worsen CSU is unclear, there is some evidence that the Mas-related G protein–coupled X2 receptor (MRGPRX2) may be involved. This shows increased expression on the mast cells of patients with CSU and can be stimulated by anti-microbial host defence peptides, neuropeptides released during stress, major basic protein, eosinophil peroxidase and several peptidergic drugs. Several of these agents acting in concert may overcome the threshold for mast cell activation leading to CSU.

Summary

CSU is a complex condition with multiple subthreshold aetiological factors frequently converging to effect mast cell activation. Effective treatment of CSU should involve the use of anti-histamines, intermittent steroids and anti-IgE therapy. Depending on the clinical history, the ‘talking therapies’ that reduce stress and anxiety, vitamin D3 and iron supplementation, correction of intestinal dysbiosis and treatment of any chronic infection should also be considered.

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Data availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Abbreviations

CGRP:

Calcitonin gene–related peptide

CSU:

Chronic spontaneous urticaria

IL:

Interleukin

IFN:

Interferon

MRGPRX2:

Mas-related G protein–coupled X2 receptor

Th:

T helper cells

TNF:

Tumour necrosis factor

Tregs:

T regulatory cells

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Balp M-M, Vietri J, Tian H, Isherwood G. The impact of chronic urticaria from the patient’s perspective: a survey in five European countries. Patient. 2015;8:551–8. https://doi.org/10.1007/s40271-015-0145-9.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lapi F, Cassano N, Pegoraro V, et al. Epidemiology of chronic spontaneous urticaria: results from a nationwide, population-based study in Italy. Br J Dermatol. 2016;174:996–1004. https://doi.org/10.1111/bjd.14470.

    Article  CAS  PubMed  Google Scholar 

  3. Dionigi PCL, Menezes MCS, Forte WCN. A prospective ten-year follow-up of patients with chronic urticaria. Allergol Immunopathol (Madr). 2016;44:286–91. https://doi.org/10.1016/j.aller.2015.10.004.

    Article  CAS  Google Scholar 

  4. Chen Q, Zhong H, Chen WC, et al. Different expression patterns of plasma Th1-, Th2-, Th17- and Th22-related cytokines correlate with serum autoreactivity and allergen sensitivity in chronic spontaneous urticaria. J Eur Acad Dermatol Venereol. 2018;32:441–8. https://doi.org/10.1111/jdv.14541.

    Article  CAS  PubMed  Google Scholar 

  5. Lopes A, Machado D, Pedreiro S, Henriques A, Silva I, Tavares B, et al. Different frequencies of Tc17/Tc1 and Th17/Th1 cells in chronic spontaneous urticaria. Int Arch Allergy Immunol. 2013;161:155–62. https://doi.org/10.1159/000345401.

    Article  CAS  PubMed  Google Scholar 

  6. Dos Santos JC, Azor MH, Nojima VY, et al. Increased circulating pro-inflammatory cytokines and imbalanced regulatory T-cell cytokines production in chronic idiopathic urticaria. Int Immunopharmacol. 2008;8:1433–40. https://doi.org/10.1016/j.intimp.2008.05.016.

    Article  CAS  PubMed  Google Scholar 

  7. • Bansal CJ, Bansal AS. Stress, pseudoallergens, autoimmunity, infection and inflammation in chronic spontaneous urticaria. Allergy, Asthma Clin Immunol. 2019;15:1–11. https://doi.org/10.1186/s13223-019-0372-z Wide ranging review on the different factors that can affect CSU.

    Article  Google Scholar 

  8. Augey F, Gunera-Saad N, Bensaid B, et al. Chronic spontaneous urticaria is not an allergic disease. Eur J Dermatol. 2011;21:349–53. https://doi.org/10.1684/ejd.2011.1285.

    Article  PubMed  Google Scholar 

  9. Rosman Y, Hershko AY, Meir-Shafrir K, Kedem R, Lachover-Roth I, Mekori YA, et al. Characterization of chronic urticaria and associated conditions in a large population of adolescents. J Am Acad Dermatol. 2019;81:129–35. https://doi.org/10.1016/j.jaad.2019.02.034.

    Article  PubMed  Google Scholar 

  10. Wöhrl S. NSAID hypersensitivity – recommendations for diagnostic work up and patient management. Allergo J Int. 2018;27:114–21. https://doi.org/10.1007/s40629-018-0064-0.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Thong BY-H. Nonsteroidal anti-inflammatory drug hypersensitivity in the Asia-Pacific. Asia Pac Allergy. 2018;8. https://doi.org/10.5415/apallergy.2018.8.e38.

  12. • Akoglu G, Atakan N, Cakır B, Kalayci O, Hayran M. Effects of low pseudoallergen diet on urticarial activity and leukotriene levels in chronic urticaria. Arch Dermatol Res. 2012;304:257–62. https://doi.org/10.1007/s00403-011-1203-3 This article proposes an important mechanism by which certain pseudoallergens may affect CSU.

    Article  CAS  PubMed  Google Scholar 

  13. • Magerl M, Pisarevskaja D, Scheufele R, et al. Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial. Allergy. 2010;65:78–83. https://doi.org/10.1111/j.1398-9995.2009.02130.x Good article on the importance of pseudoallergens in CSU.

    Article  CAS  PubMed  Google Scholar 

  14. Siebenhaar F, Melde A, Magerl M, et al. Histamine intolerance in patients with chronic spontaneous urticaria. J Eur Acad Dermatol Venereol. 2016;30:1774–7. https://doi.org/10.1111/jdv.13778.

    Article  CAS  PubMed  Google Scholar 

  15. • Cornillier H, Giraudeau B, Samimi M, Munck S, Hacard F, Jonville-Bera AP, et al. Effect of diet in chronic spontaneous Urticaria: a systematic review. Acta Derm Venereol. 2019;99:127–32. https://doi.org/10.2340/00015555-3015 Many patients with CSU are adamant that their skin condition is worsened by certain foods. As conventional allergy tests are negative and the relationshop between specific foods and CSU is inconsistent, there is doubt regarding this relationship. This article is helpful in understanding some of these controversies.

    Article  PubMed  Google Scholar 

  16. Henz BM, Zuberbier T. Most chronic urticaria is food-dependent, and not idiopathic. Exp Dermatol. 1998;7:139–42. https://doi.org/10.1111/j.1600-0625.1998.tb00314.x.

    Article  CAS  PubMed  Google Scholar 

  17. Rajan JP, Simon RA, Bosso JV. Prevalence of sensitivity to food and drug additives in patients with chronic idiopathic urticaria. J Allergy Clin Immunol Pract. 2014;2:168–71. https://doi.org/10.1016/j.jaip.2013.10.002.

    Article  PubMed  Google Scholar 

  18. • Buhner S, Reese I, Kuehl F, et al. Pseudoallergic reactions in chronic urticaria are associated with altered gastroduodenal permeability. Allergy. 2004;59:1118–23. https://doi.org/10.1111/j.1398-9995.2004.00631.x The role of pseudoallergens in CSU has always been controversial, but this article provides an interesting basis for how they may aggravate and perhaps initiate urticaria.

    Article  CAS  PubMed  Google Scholar 

  19. Son JH, Chung BY, Kim HO, et al. A histamine-free diet is helpful for treatment of adult patients with chronic spontaneous urticaria. Ann Dermatol. 2018;30:164–72. https://doi.org/10.5021/ad.2018.30.2.164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kolkhir P, Borzova E, Grattan C, et al. Autoimmune comorbidity in chronic spontaneous urticaria: a systematic review. Autoimmun Rev. 2017;16:1196–208. https://doi.org/10.1016/j.autrev.2017.10.003.

    Article  PubMed  Google Scholar 

  21. Najib U, Bajwa ZH, Ostro MG, et al. A retrospective review of clinical presentation, thyroid autoimmunity, laboratory characteristics, and therapies used in patients with chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2009;103:496–501. https://doi.org/10.1016/S1081-1206(10)60266-9.

    Article  PubMed  Google Scholar 

  22. Sugiyama A, Nishie H, Takeuchi S, et al. Hashimoto’s disease is a frequent comorbidity and an exacerbating factor of chronic spontaneous urticaria. Allergol Immunopathol (Madr). 2015;43:249–53. https://doi.org/10.1016/j.aller.2014.02.007.

    Article  CAS  Google Scholar 

  23. • Confino-Cohen R, Chodick G, Shalev V, et al. Chronic urticaria and autoimmunity: associations found in a large population study. J Allergy Clin Immunol. 2012;129:1307–13. https://doi.org/10.1016/j.jaci.2012.01.043 Good review article summarising the different sorts of autoimmunity in CSU.

    Article  PubMed  Google Scholar 

  24. Kumaran MS, Mangal S, Narang T, et al. Autologous serum and plasma skin tests in chronic spontaneous urticaria: a reappraisal. Indian Dermatol Online J. 2017;8:94–9. https://doi.org/10.4103/2229-5178.202266.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Magen E, Zueva E, Mishal J, et al. The clinical and laboratory characteristics of acute spontaneous urticaria and its progression to chronic spontaneous urticaria. Allergy Asthma Proc. 2016;37:394–9. https://doi.org/10.2500/aap.2016.37.3971.

    Article  CAS  PubMed  Google Scholar 

  26. Boonpiyathad T, Sangasapaviliya A. Autologous serum and plasma skin test to predict 2-year outcome in chronic spontaneous urticaria. Asia Pac Allergy. 2016;6:226–35. https://doi.org/10.5415/apallergy.2016.6.4.226.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ulambayar B, Chen Y-H, Ban G-Y, et al. Detection of circulating IgG autoantibody to FcεRIα in sera from chronic spontaneous urticaria patients. J Microbiol Immunol Infect. Published Online First: 14 November 2017. https://doi.org/10.1016/j.jmii.2017.10.003

  28. Kolkhir P, Metz M, Altrichter S, et al. Comorbidity of chronic spontaneous urticaria and autoimmune thyroid diseases: a systematic review. Allergy Eur J Allergy Clin Immunol. 2017;72:1440–60. https://doi.org/10.1111/all.13182.

    Article  CAS  Google Scholar 

  29. • Altrichter S, Peter H-J, Pisarevskaja D, et al. IgE mediated autoallergy against thyroid peroxidase--a novel pathomechanism of chronic spontaneous urticaria? PLoS One. 2011;6:e14794. https://doi.org/10.1371/journal.pone.0014794 One of the early articles indicating the presence of anti-TPO IgE antibodies in CSU and how these could mediate mast cell activation and degranulation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Dreyfus DH. Serological evidence that activation of ubiquitous human herpesvirus-6 (HHV-6) plays a role in chronic idiopathic/spontaneous urticaria (CIU). Clin Exp Immunol. 2016;183:230–8. https://doi.org/10.1111/cei.12704.

    Article  CAS  PubMed  Google Scholar 

  31. • Imbalzano E, Casciaro M, Quartuccio S, et al. Association between urticaria and virus infections: a systematic review. Allergy Asthma Proc. 2016;37:18–22. https://doi.org/10.2500/aap.2016.37.3915 Good review article on viruses and CSU.

    Article  PubMed  Google Scholar 

  32. Calado G, Loureiro G, Machado D, et al. Streptococcal tonsillitis as a cause of urticaria: tonsillitis and urticaria. Allergol Immunopathol (Madr). 2012;40:341–5. https://doi.org/10.1016/j.aller.2011.06.008.

    Article  CAS  Google Scholar 

  33. Godse KV, Zawar V. Chronic urticaria associated with tinea infection and success with antifungal therapy--a report of four cases. Int J Infect Dis. 2010;14(Suppl 3):e364–5. https://doi.org/10.1016/j.ijid.2009.12.005.

    Article  PubMed  Google Scholar 

  34. Kolkhir P, Balakirski G, Merk HF, et al. Chronic spontaneous urticaria and internal parasites--a systematic review. Allergy. 2016;71:308–22. https://doi.org/10.1111/all.12818.

    Article  CAS  PubMed  Google Scholar 

  35. Kohli S, Mahajan VK, Rana BS, et al. Clinicoepidemiologic features of chronic urticaria in patients with versus without subclinical Helicobacter pylori infection: a cross-sectional study of 150 patients. Int Arch Allergy Immunol. 2018;175:114–20. https://doi.org/10.1159/000485893.

    Article  CAS  PubMed  Google Scholar 

  36. Tan R-J, Sun H-Q, Zhang W, et al. A 21–35 kDa mixed protein component from Helicobacter pylori activates mast cells effectively in chronic spontaneous urticaria. Helicobacter. 2016;21:565–74. https://doi.org/10.1111/hel.12312.

    Article  CAS  PubMed  Google Scholar 

  37. • Desai A, Jung M-Y, Olivera A, et al. IL-6 promotes an increase in human mast cell numbers and reactivity through suppression of suppressor of cytokine signaling 3. J Allergy Clin Immunol. 2016;137:1863–1871.e6. https://doi.org/10.1016/j.jaci.2015.09.059 This report provides the basis for how inflammation can increase mast cell activity and is important in understanding how CSU activity is increased whenever inflammation of diverse aetiology coexists.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hong GU, Ro JY, Bae Y, et al. Association of TG2 from mast cells and chronic spontaneous urticaria pathogenesis. Ann Allergy Asthma Immunol. 2016;117:290–7. https://doi.org/10.1016/j.anai.2016.06.026.

    Article  CAS  PubMed  Google Scholar 

  39. Minnei F, Wetzels C, De Hertogh G, et al. Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa. Virchows Arch. 2006;448:262–8. https://doi.org/10.1007/s00428-005-0111-3.

    Article  PubMed  Google Scholar 

  40. Rezazadeh A, Shahabi S, Bagheri M, et al. The protective effect of Lactobacillus and Bifidobacterium as the gut microbiota members against chronic urticaria. Int Immunopharmacol. 2018;59:168–73. https://doi.org/10.1016/j.intimp.2018.04.007.

    Article  CAS  PubMed  Google Scholar 

  41. Nettis E, Di Leo E, Pastore A, et al. Probiotics and refractory chronic spontaneous urticaria. Eur Ann Allergy Clin Immunol. 2016;48:182–7 http://www.ncbi.nlm.nih.gov/pubmed/27608474 (accessed 4 Jan 2020).

    CAS  PubMed  Google Scholar 

  42. • Staubach P, Dechene M, Metz M, et al. High prevalence of mental disorders and emotional distress in patients with chronic spontaneous urticaria. Acta Derm Venereol. 2011;91:557–61. https://doi.org/10.2340/00015555-1109 Stress is increased in people with CSU, and this is one of the first reports to try to properly document and quantify stress in those with CSU.

    Article  PubMed  Google Scholar 

  43. Vestergaard C, Deleuran M. Chronic spontaneous urticaria: latest developments in aetiology, diagnosis and therapy. Ther Adv Chronic Dis. 2015;6:304–13. https://doi.org/10.1177/2040622315603951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Vietri J, Turner SJ, Tian H, et al. Effect of chronic urticaria on US patients: analysis of the National Health and Wellness Survey. Ann Allergy Asthma Immunol. 2015;115:306–11. https://doi.org/10.1016/j.anai.2015.06.030.

    Article  PubMed  Google Scholar 

  45. Tat TS. Higher levels of depression and anxiety in patients with chronic urticaria. Med Sci Monit. 2019;25:115–20. https://doi.org/10.12659/MSM.912362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yang H-Y, Sun C-C, Wu Y-C, et al. Stress, insomnia, and chronic idiopathic urticaria--a case-control study. J Formos Med Assoc. 2005;104:254–63 http://www.ncbi.nlm.nih.gov/pubmed/15909063 (accessed 4 Jan 2020).

    PubMed  Google Scholar 

  47. Dyke SM, Carey BS, Kaminski ER. Effect of stress on basophil function in chronic idiopathic urticaria. Clin Exp Allergy. 2007:071101015606002-??? https://doi.org/10.1111/j.1365-2222.2007.02864.x This provides the basis for understanding how CSU is affected by stress and via basophil irritability.

  48. • Kumagai M, Nagano M, Suzuki H, et al. Effects of stress memory by fear conditioning on nerve-mast cell circuit in skin. J Dermatol. 2011;38:553–61. https://doi.org/10.1111/j.1346-8138.2010.01045.x This article is important in understanding how stress can affect mast cell function and is helpful in managing patients with CSU and other conditions such as eczema.

    Article  PubMed  Google Scholar 

  49. Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol. 2018;40:249–59. https://doi.org/10.1007/s00281-018-0675-z.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Lotti T, D’Erme AM, Hercogová J. The role of neuropeptides in the control of regional immunity. Clin Dermatol. 2014;32:633–45. https://doi.org/10.1016/j.clindermatol.2014.04.011.

    Article  PubMed  Google Scholar 

  51. Ding W, Stohl LL, Xu L, et al. Calcitonin gene-related peptide-exposed endothelial cells bias antigen presentation to CD4+ T cells toward a Th17 response. J Immunol. 2016;196:2181–94. https://doi.org/10.4049/jimmunol.1500303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144(Pt A):138–45. https://doi.org/10.1016/j.jsbmb.2013.11.003.

    Article  CAS  PubMed  Google Scholar 

  53. Alhassan Mohammed H, Saboor-Yaraghi AA, Mirshafiey A, et al. Immunomodulatory and immunosuppressive roles of 1α,25(OH)2D3 in autoimmune diseases. Scand J Immunol. 2017;85:95–103. https://doi.org/10.1111/sji.12512.

    Article  CAS  PubMed  Google Scholar 

  54. Kivity S, Agmon-Levin N, Zisappl M, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011;8:243–7. https://doi.org/10.1038/cmi.2010.73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hall SC, Agrawal DK. Vitamin D and bronchial asthma: an overview of data from the past 5 years. Clin Ther. 2017;39:917–29. https://doi.org/10.1016/j.clinthera.2017.04.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ardesia M, Ferlazzo G, Fries W. Vitamin D and inflammatory bowel disease. Biomed Res Int. 2015;2015:470805. https://doi.org/10.1155/2015/470805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Movahedi M, Tavakol M, Hirbod-Mobarakeh A, et al. Vitamin D deficiency in chronic idiopathic urticaria. Iran J Allergy Asthma Immunol. 2015;14:222–7 http://www.ncbi.nlm.nih.gov/pubmed/25780889 (accessed 4 Jan 2020).

    PubMed  Google Scholar 

  58. Rather S, Keen A, Sajad P. Serum levels of 25-hydroxyvitamin D in chronic urticaria and its association with disease activity: a case control study. Indian Dermatol Online J. 2018;9:170–4. https://doi.org/10.4103/idoj.IDOJ_74_17.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Woo YR, Jung KE, Koo DW, et al. Vitamin D as a marker for disease severity in chronic urticaria and its possible role in pathogenesis. Ann Dermatol. 2015;27:423–30. https://doi.org/10.5021/ad.2015.27.4.423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Oguz Topal I, Kocaturk E, Gungor S, et al. Does replacement of vitamin D reduce the symptom scores and improve quality of life in patients with chronic urticaria? J Dermatolog Treat. 2016;27:163–6. https://doi.org/10.3109/09546634.2015.1079297.

    Article  CAS  PubMed  Google Scholar 

  61. Rasool R, Masoodi KZ, Shera IA, et al. Chronic urticaria merits serum vitamin D evaluation and supplementation; a randomized case control study. World Allergy Organ J. 2015;8:15. https://doi.org/10.1186/s40413-015-0066-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Guarneri F, Guarneri C, Cannavò SP. Oral iron therapy and chronic idiopathic urticaria: Sideropenic urticaria? Dermatol Ther. 2014;27:223–6. https://doi.org/10.1111/dth.12122.

    Article  PubMed  Google Scholar 

  63. Wu CH, Eren E, Ardern-Jones MR, et al. Association between micronutrient levels and chronic spontaneous urticaria. Biomed Res Int. 2015;2015. https://doi.org/10.1155/2015/926167.

  64. Darlenski R, Kazandjieva J, Zuberbier T, et al. Chronic urticaria as a systemic disease. Clin Dermatol. 2014;32:420–3. https://doi.org/10.1016/j.clindermatol.2013.11.009.

    Article  PubMed  Google Scholar 

  65. Kitsioulis NA, Papadopoulos NG, Kostoudi S, et al. Assessment of atopic dermatitis as a risk factor for chronic spontaneous urticaria in a pediatric population. Allergy Asthma Proc. 2018;39:445–8. https://doi.org/10.2500/aap.2018.39.4166.

    Article  PubMed  Google Scholar 

  66. Zuberbier T, Balke M, Worm M, et al. Epidemiology of urticaria: a representative cross-sectional population survey. Clin Exp Dermatol. 2010;35:869–73. https://doi.org/10.1111/j.1365-2230.2010.03840.x.

  67. Weller K, Ardelean E, Scholz E, et al. Can on-demand non-sedating antihistamines improve urticaria symptoms? A double-blind, randomized, single-dose study. Acta Derm Venereol. 2013;93:168–74. https://doi.org/10.2340/00015555-1434.

  68. Asero R, Ferrucci S, Casazza G, et al. Total IgE and atopic status in patients with severe chronic spontaneous urticaria unresponsive to omalizumab treatment. Allergy. 2019;74:1561–3. https://doi.org/10.1111/all.13754.

    Article  PubMed  Google Scholar 

  69. Kasperska-Zajac A, Brzoza Z, Rogala B. Sex hormones and urticaria. J Dermatol Sci. 2008;52:79–86. https://doi.org/10.1016/j.jdermsci.2008.04.002.

    Article  CAS  PubMed  Google Scholar 

  70. Kasperska Zając A, Zamlynski J. Chronic urticaria and irregular menstrual cycle: a case report of effective therapy with oral contraception. J Dermatolog Treat. 2012;23:159–60. https://doi.org/10.3109/09546634.2010.499933.

    Article  PubMed  Google Scholar 

  71. Wingate-Saul L, Rymer J, Greaves MW. Chronic urticaria due to autoreactivity to progesterone. Clin Exp Dermatol. 2015;40:644–6. https://doi.org/10.1111/ced.12632.

    Article  CAS  PubMed  Google Scholar 

  72. Assad S, Khan HH, Ghazanfar H, et al. Role of sex hormone levels and psychological stress in the pathogenesis of autoimmune diseases. Cureus. 2017;9:e1315. https://doi.org/10.7759/cureus.1315.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Faresjö M. The link between psychological stress and autoimmune response in children. Crit Rev Immunol. 2015;35:117–34. https://doi.org/10.1615/critrevimmunol.2015013255.

    Article  PubMed  Google Scholar 

  74. Carlsson E, Frostell A, Ludvigsson J, et al. Psychological stress in children may alter the immune response. J Immunol. 2014;192:2071–81. https://doi.org/10.4049/jimmunol.1301713.

    Article  CAS  PubMed  Google Scholar 

  75. Sepa A, Ludvigsson J. Psychological stress and the risk of diabetes-related autoimmunity: a review article. Neuroimmunomodulation. 2006;13:301–8. https://doi.org/10.1159/000104858.

    Article  CAS  PubMed  Google Scholar 

  76. Vita R, Lapa D, Trimarchi F, et al. Certain HLA alleles are associated with stress-triggered Graves’ disease and influence its course. Endocrine. 2017;55:93–100. https://doi.org/10.1007/s12020-016-0909-6.

    Article  CAS  PubMed  Google Scholar 

  77. Welsh CJ, Steelman AJ, Mi W, et al. Effects of stress on the immune response to Theiler’s virus – implications for virus-induced autoimmunity. Neuroimmunomodulation. 2010;17:169–72. https://doi.org/10.1159/000258715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Morandi E, Jagessar SA, ‘t Hart BA, et al. EBV infection empowers human B cells for autoimmunity: role of autophagy and relevance to multiple sclerosis. J Immunol. 2017;199:435–48. https://doi.org/10.4049/jimmunol.1700178.

    Article  CAS  PubMed  Google Scholar 

  79. Nagata K, Kumata K, Nakayama Y, et al. Epstein–Barr virus lytic reactivation activates B cells polyclonally and induces activation-induced cytidine deaminase expression: a mechanism underlying autoimmunity and its contribution to Graves’ disease. Viral Immunol. 2017;30:240–9. https://doi.org/10.1089/vim.2016.0179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Rodiño-Janeiro BK, Alonso-Cotoner C, Pigrau M, et al. Role of corticotropin-releasing factor in gastrointestinal permeability. J Neurogastroenterol Motil. 2015;21:33–50. https://doi.org/10.5056/jnm14084.

    Article  PubMed  PubMed Central  Google Scholar 

  81. •• Fujisawa D, Kashiwakura J, Kita H, et al. Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria. J Allergy Clin Immunol. 2014;134:622–633.e9. https://doi.org/10.1016/j.jaci.2014.05.004 Very important early article documenting alteration of the Mas-related G protein coupled receptor X2 gene and protein in the skin in people with CSU.

    Article  CAS  PubMed  Google Scholar 

  82. • Ali H. Emerging roles for MAS-related G protein-coupled receptor-X2 in host defense peptide, opioid, and neuropeptide-mediated inflammatory reactions. In: Advances in immunology; 2017. p. 123–62. https://doi.org/10.1016/bs.ai.2017.06.002. Good summary of the different factors that can alter expression of the Mas-related G protein–coupled receptor X2. This provides the basis for understanding how CSU varies with everyday factors such as infection and inflammation etc.

    Chapter  Google Scholar 

  83. • Subramanian H, Gupta K, Ali H. Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol. 2016;138:700–10. https://doi.org/10.1016/j.jaci.2016.04.051 Good summary of the different factors that can alter expression of the Mas-related G protein–coupled receptor X2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Olivera A, Beaven MA, Metcalfe DD. Mast cells signal their importance in health and disease. J Allergy Clin Immunol. 2018;142:381–93. https://doi.org/10.1016/j.jaci.2018.01.034.

    Article  CAS  PubMed  Google Scholar 

  85. • Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73:1393–414. https://doi.org/10.1111/all.13397 Important article detailing the different sorts of urticaria and how it is diagnosed and managed with an evidence-based approach.

    Article  CAS  PubMed  Google Scholar 

  86. Magen E, Delgado J-S. Helicobacter pylori and skin autoimmune diseases. World J Gastroenterol. 2014;20:1510. https://doi.org/10.3748/wjg.v20.i6.1510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kim DH, Sung NH, Lee AY. Effect of levothyroxine treatment on clinical symptoms in hypothyroid patients with chronic urticaria and thyroid autoimmunity. Ann Dermatol. 2016;28:199. https://doi.org/10.5021/ad.2016.28.2.199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kim S, Baek S, Shin B, et al. Influence of initial treatment modality on long-term control of chronic idiopathic urticaria. PLoS One. 2013;8:e69345. https://doi.org/10.1371/journal.pone.0069345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lindsay K, Goulding J, Solomon M, et al. Treating chronic spontaneous urticaria using a brief ‘whole person’ treatment approach: a proof-of-concept study. Clin Transl Allergy. 2015;5:40. https://doi.org/10.1186/s13601-015-0082-7.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Frimley Health NHS Trust, Portsmouth Road, Frimley, Camberley, Surrey, GU16 7UJ, UK

    Rhea A. Bansal MBBS, MRCP

  2. St Anthony’s Hospital, London Road, Cheam, Sutton, SM3 9DW, UK

    Amolak S. Bansal DM, FRCP, FRCPath

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  1. Rhea A. Bansal MBBS, MRCP
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  2. Amolak S. Bansal DM, FRCP, FRCPath
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Conceptualisation by RAB and ASB. RAB wrote the first draft. Both authors have reviewed the manuscript prior to submission.

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Correspondence to Amolak S. Bansal DM, FRCP, FRCPath.

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Rhea Bansal declares that she has no conflict of interest. Amolak Bansal declares that he has no conflict of interest.

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This article is part of the Topical Collection on Urticaria and Atopic Dermatitis

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Bansal, R.A., Bansal, A.S. Exacerbating Factors in Chronic Spontaneous Urticaria. Curr Treat Options Allergy 7, 142–154 (2020). https://doi.org/10.1007/s40521-020-00254-y

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