Chronic urticaria: Standard management and patient education

INTRODUCTION

Chronic urticaria (CU) is defined by the presence of urticaria (hives) on most days of the week for a duration of longer than six weeks. The prevalence of this disorder is up to 1 percent of the general population in the United States and is believed similar around the world [1]. Associated angioedema occurs in about 40 percent of patients with CU and usually affects the lips, cheeks, periorbital areas of the face, extremities, and genitals [2].

The management of CU in most patients as well as counseling of individuals with this disorder will be discussed here. Treatment of CU that is refractory to standard management and the diagnosis, pathogenesis, and prognosis of CU are presented separately. (See "Chronic urticaria: Treatment of refractory symptoms" and "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history".)

Disorders involving isolated angioedema, urticarial vasculitis, and specific physical forms of CU (such as delayed-pressure urticaria, cholinergic urticaria, or cold urticaria) are discussed separately. (See "An overview of angioedema: Pathogenesis and causes" and "Urticarial vasculitis" and "Physical urticarias" and "Cold urticaria".)

Terminology — In this review, the term CU refers to patients with isolated chronic idiopathic urticaria (CIU), as well as those with both urticaria and angioedema.

Chronic urticaria and chronic idiopathic urticaria — The terms "chronic urticaria" and "chronic idiopathic urticaria" are used interchangeably in this review and in the medical literature. These terms refer to CU in which appearance of lesions is not triggered by consistent or identifiable factors. However, physical urticaria syndromes are variably included in CU. Physical urticarias are disorders in which urticaria is induced by one or more environmental stimuli, such as heat, cold, pressure applied to the skin, exercise, water, vibration, and sunlight. The inclusion of physical urticaria in the definition of CU is based upon the observation that some patients with CU have symptoms triggered by a physical stimulus on some occasions, while most of the symptoms are spontaneous.

                               

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2014. | This topic last updated: Dec 4, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Kaplan AP. Clinical practice. Chronic urticaria and angioedema. N Engl J Med 2002; 346:175.
  2. Goldsobel AB, Rohr AS, Siegel SC, et al. Efficacy of doxepin in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol 1986; 78:867.
  3. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol 2014; 133:1270.
  4. Powell RJ, Du Toit GL, Siddique N, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy 2007; 37:631.
  5. Maurer M, Magerl M, Metz M, Zuberbier T. Revisions to the international guidelines on the diagnosis and therapy of chronic urticaria. J Dtsch Dermatol Ges 2013.
  6. Hide M, Hiragun T, Japanese Dermatological Association. Japanese guidelines for diagnosis and treatment of urticaria in comparison with other countries. Allergol Int 2012; 61:517.
  7. Chow SK. Management of chronic urticaria in Asia: 2010 AADV consensus guidelines. Asia Pac Allergy 2012; 2:149.
  8. Tedeschi A, Girolomoni G, Asero R, AAITO Committee for Chronic Urticaria and Pruritus Guidelines. AAITO Position paper. Chronic urticaria: diagnostic workup and treatment. Eur Ann Allergy Clin Immunol 2007; 39:225.
  9. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy 2014; 69:868.
  10. Kozel MM, Mekkes JR, Bossuyt PM, Bos JD. Natural course of physical and chronic urticaria and angioedema in 220 patients. J Am Acad Dermatol 2001; 45:387.
  11. Zuberbier T, Chantraine-Hess S, Hartmann K, Czarnetzki BM. Pseudoallergen-free diet in the treatment of chronic urticaria. A prospective study. Acta Derm Venereol 1995; 75:484.
  12. 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.
  13. Kaplan AP. What the first 10,000 patients with chronic urticaria have taught me: a personal journey. J Allergy Clin Immunol 2009; 123:713.
  14. Zuberbier T, Bindslev-Jensen C, Canonica W, et al. EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of urticaria. Allergy 2006; 61:316.
  15. Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy 2009; 64:1427.
  16. Kavosh ER, Khan DA. Second-generation H1-antihistamines in chronic urticaria: an evidence-based review. Am J Clin Dermatol 2011; 12:361.
  17. Humphreys F, Hunter JA. The characteristics of urticaria in 390 patients. Br J Dermatol 1998; 138:635.
  18. Staevska M, Popov TA, Kralimarkova T, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol 2010; 125:676.
  19. Nelson HS, Reynolds R, Mason J. Fexofenadine HCl is safe and effective for treatment of chronic idiopathic urticaria. Ann Allergy Asthma Immunol 2000; 84:517.
  20. Ring J, Hein R, Gauger A, et al. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study. Int J Dermatol 2001; 40:72.
  21. Ortonne JP, Grob JJ, Auquier P, Dreyfus I. Efficacy and safety of desloratadine in adults with chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Clin Dermatol 2007; 8:37.
  22. Kamide R, Niimura M, Ueda H, et al. Clinical evaluation of ketotifen for chronic urticaria: multicenter double-blind comparative study with clemastine. Ann Allergy 1989; 62:322.
  23. Grob JJ, Lachapelle JM. Non-sedating antihistamines in the treatment of chronic idiopathic urticaria using patient-reported outcomes. Curr Med Res Opin 2008; 24:2423.
  24. Kalivas J, Breneman D, Tharp M, et al. Urticaria: clinical efficacy of cetirizine in comparison with hydroxyzine and placebo. J Allergy Clin Immunol 1990; 86:1014.
  25. Belaich S, Bruttmann G, DeGreef H, et al. Comparative effects of loratadine and terfenadine in the treatment of chronic idiopathic urticaria. Ann Allergy 1990; 64:191.
  26. Potter PC, Kapp A, Maurer M, et al. Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients. Allergy 2009; 64:596.
  27. Purohit A, Melac M, Pauli G, Frossard N. Comparative activity of cetirizine and desloratadine on histamine-induced wheal-and-flare responses during 24 hours. Ann Allergy Asthma Immunol 2004; 92:635.
  28. Handa S, Dogra S, Kumar B. Comparative efficacy of cetirizine and fexofenadine in the treatment of chronic idiopathic urticaria. J Dermatolog Treat 2004; 15:55.
  29. Garg G, Thami GP. Comparative efficacy of cetirizine and levocetirizine in chronic idiopathic urticaria. J Dermatolog Treat 2007; 18:23.
  30. Maiti R, Jaida J, Raghavendra BN, et al. Rupatadine and levocetirizine in chronic idiopathic urticaria: a comparative study of efficacy and safety. J Drugs Dermatol 2011; 10:1444.
  31. Dakhale GN, Shinde AT, Mahatme MS, et al. Clinical effectiveness and safety of cetirizine versus rupatadine in chronic spontaneous urticaria: a randomized, double-blind, 6-week trial. Int J Dermatol 2014; 53:643.
  32. Ortonne JP. Chronic urticaria: a comparison of management guidelines. Expert Opin Pharmacother 2011; 12:2683.
  33. Church DS, Baiardini I, Staevska M, et al. The effectiveness of antihistamines in up to four-times conventional doses on urticarial discomfort and quality of life in difficult to treat urticaria. Abstract 1501, Warsaw XXVIII EAACI Congress, 2009.
  34. Asero R. Chronic unremitting urticaria: is the use of antihistamines above the licensed dose effective? A preliminary study of cetirizine at licensed and above-licensed doses. Clin Exp Dermatol 2007; 32:34.
  35. Kameyoshi Y, Tanaka T, Mihara S, et al. Increasing the dose of cetirizine may lead to better control of chronic idiopathic urticaria: an open study of 21 patients. Br J Dermatol 2007; 157:803.
  36. Finn AF Jr, Kaplan AP, Fretwell R, et al. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol 1999; 104:1071.
  37. Grob JJ, Auquier P, Dreyfus I, Ortonne JP. How to prescribe antihistamines for chronic idiopathic urticaria: desloratadine daily vs PRN and quality of life. Allergy 2009; 64:605.
  38. 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.
  39. Schweitzer PK, Muehlbach MJ, Walsh JK. Sleepiness and performance during three-day administration of cetirizine or diphenhydramine. J Allergy Clin Immunol 1994; 94:716.
  40. Hindmarch I, Johnson S, Meadows R, et al. The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare. Curr Med Res Opin 2001; 17:241.
  41. Verster JC, Volkerts ER, van Oosterwijck AW, et al. Acute and subchronic effects of levocetirizine and diphenhydramine on memory functioning, psychomotor performance, and mood. J Allergy Clin Immunol 2003; 111:623.
  42. Khan DA. Chronic urticaria: diagnosis and management. Allergy Asthma Proc 2008; 29:439.
  43. Staevska M, Gugutkova M, Lazarova C, et al. Night-time sedating H1 -antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial. Br J Dermatol 2014; 171:148.
  44. Fedorowicz Z, van Zuuren EJ, Hu N. Histamine H2-receptor antagonists for urticaria. Cochrane Database Syst Rev 2012; 3:CD008596.
  45. Monroe EW, Cohen SH, Kalbfleisch J, Schulz CI. Combined H1 and H2 antihistamine therapy in chronic urticaria. Arch Dermatol 1981; 117:404.
  46. Wan KS. Efficacy of leukotriene receptor antagonist with an anti-H1 receptor antagonist for treatment of chronic idiopathic urticaria. J Dermatolog Treat 2009; 20:194.
  47. Bleehen SS, Thomas SE, Greaves MW, et al. Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: a multi-centre randomized double-blind study. Br J Dermatol 1987; 117:81.
  48. Harvey RP, Wegs J, Schocket AL. A controlled trial of therapy in chronic urticaria. J Allergy Clin Immunol 1981; 68:262.
  49. Jáuregui I, Ferrer M, Montoro J, et al. Antihistamines in the treatment of chronic urticaria. J Investig Allergol Clin Immunol 2007; 17 Suppl 2:41.
  50. Salo OP, Kauppinen K, Männistö PT. Cimetidine increases the plasma concentration of hydroxyzine. Acta Derm Venereol 1986; 66:349.
  51. Simons FE, Sussman GL, Simons KJ. Effect of the H2-antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H1-antagonists hydroxyzine and cetirizine in patients with chronic urticaria. J Allergy Clin Immunol 1995; 95:685.
  52. Paul E, Bödeker RH. Treatment of chronic urticaria with terfenadine and ranitidine. A randomized double-blind study in 45 patients. Eur J Clin Pharmacol 1986; 31:277.
  53. Sharpe GR, Shuster S. In dermographic urticaria H2 receptor antagonists have a small but therapeutically irrelevant additional effect compared with H1 antagonists alone. Br J Dermatol 1993; 129:575.
  54. Ellingsen AR, Thestrup-Pedersen K. Treatment of chronic idiopathic urticaria with topical steroids. An open trial. Acta Derm Venereol 1996; 76:43.
  55. 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.
  56. Maxwell DL, Atkinson BA, Spur BW, et al. Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects. J Allergy Clin Immunol 1990; 86:759.
  57. Bisgaard H. Vascular effects of leukotriene D4 in human skin. J Invest Dermatol 1987; 88:109.
  58. Wedi B, Novacovic V, Koerner M, Kapp A. Chronic urticaria serum induces histamine release, leukotriene production, and basophil CD63 surface expression--inhibitory effects ofanti-inflammatory drugs. J Allergy Clin Immunol 2000; 105:552.
  59. Mora PM, González Pérez Mdel C, Jiménez Villarruel M, et al. [Therapeutic options in idiopathic chronic urticaria]. Rev Alerg Mex 2005; 52:77.
  60. Erbagci Z. The leukotriene receptor antagonist montelukast in the treatment of chronic idiopathic urticaria: a single-blind, placebo-controlled, crossover clinical study. J Allergy Clin Immunol 2002; 110:484.
  61. Ellis MH. Successful treatment of chronic urticaria with leukotriene antagonists. J Allergy Clin Immunol 1998; 102:876.
  62. Asero R. Leukotriene receptor antagonists may prevent NSAID-induced exacerbations in patients with chronic urticaria. Ann Allergy Asthma Immunol 2000; 85:156.
  63. Pérez C, Sánchez-Borges M, Capriles E. Pretreatment with montelukast blocks NSAID-induced urticaria and angioedema. J Allergy Clin Immunol 2001; 108:1060.
  64. Serrano C, Valero A, Picado C. Usefulness of montelukast to prevent adverse reactions to COX-2 selective inhibitors: a case report. J Investig Allergol Clin Immunol 2005; 15:156.
  65. Pacor ML, Di Lorenzo G, Corrocher R. Efficacy of leukotriene receptor antagonist in chronic urticaria. A double-blind, placebo-controlled comparison of treatment with montelukast and cetirizine in patients with chronic urticaria with intolerance to food additive and/or acetylsalicylic acid. Clin Exp Allergy 2001; 31:1607.
  66. Rodríguez del Río P, González-Gutiérrez ML, Sánchez-López J, et al. Urticaria caused by antihistamines: report of 5 cases. J Investig Allergol Clin Immunol 2009; 19:317.
  67. Catelain A, Freymond N, Queuille E, Nicolas JF. [Urticaria paradoxically aggraved by H1 antihistamines]. Ann Dermatol Venereol 2004; 131:451.
  68. Nettis E, Dambra P, D'Oronzio L, et al. Comparison of montelukast and fexofenadine for chronic idiopathic urticaria. Arch Dermatol 2001; 137:99.
  69. Nettis E, Colanardi MC, Paradiso MT, Ferrannini A. Desloratadine in combination with montelukast in the treatment of chronic urticaria: a randomized, double-blind, placebo-controlled study. Clin Exp Allergy 2004; 34:1401.
  70. Godse KV. Oral montelukast monotherapy is ineffective in chronic idiopathic urticaria: a comparison with oral cetirizine. Indian J Dermatol Venereol Leprol 2006; 72:312.
  71. Kosnik M, Subic T. Add-on montelukast in antihistamine-resistant chronic idiopathic urticaria. Respir Med 2011; 105 Suppl 1:S84.
  72. Di Lorenzo G, Pacor ML, Mansueto P, et al. Randomized placebo-controlled trial comparing desloratadine and montelukast in monotherapy and desloratadine plus montelukast in combined therapy for chronic idiopathic urticaria. J Allergy Clin Immunol 2004; 114:619.
  73. Reimers A, Pichler C, Helbling A, et al. Zafirlukast has no beneficial effects in the treatment of chronic urticaria. Clin Exp Allergy 2002; 32:1763.
  74. Bagenstose SE, Levin L, Bernstein JA. The addition of zafirlukast to cetirizine improves the treatment of chronic urticaria in patients with positive autologous serum skin test results. J Allergy Clin Immunol 2004; 113:134.
  75. Ohnishi-Inoue Y, Mitsuya K, Horio T. Aspirin-sensitive urticaria: provocation with a leukotriene receptor antagonist. Br J Dermatol 1998; 138:483.
  76. Kotturi MF, Carlow DA, Lee JC, et al. Identification and functional characterization of voltage-dependent calcium channels in T lymphocytes. J Biol Chem 2003; 278:46949.
  77. Kim YY, Holgate ST, Church MK. Inhibition of histamine release from dispersed human lung and tonsillar mast cells by nicardipine and nifedipine. Br J Clin Pharmacol 1985; 19:631.
  78. Bressler RB, Sowell K, Huston DP. Therapy of chronic idiopathic urticaria with nifedipine: demonstration of beneficial effect in a double-blinded, placebo-controlled, crossover trial. J Allergy Clin Immunol 1989; 83:756.
  79. Leznoff A, Josse RG, Denburg J, Dolovich J. Association of chronic urticaria and angioedema with thyroid autoimmunity. Arch Dermatol 1983; 119:636.
  80. Doutre MS. Chronic urticaria and thyroid auto-immunity. Clin Rev Allergy Immunol 2006; 30:31.
  81. 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.
  82. Rumbyrt JS, Katz JL, Schocket AL. Resolution of chronic urticaria in patients with thyroid autoimmunity. J Allergy Clin Immunol 1995; 96:901.
  83. Dreyfus DH, Schocket AL, Milgrom H. Steroid-resistant chronic urticaria associated with anti-thyroid microsomal antibodies in a nine-year-old boy. J Pediatr 1996; 128:576.
  84. Gaig P, García-Ortega P, Enrique E, Richart C. Successful treatment of chronic idiopathic urticaria associated with thyroid autoimmunity. J Investig Allergol Clin Immunol 2000; 10:342.
  85. Monge C, Demarco P, Burman KD, Wartofsky L. Autoimmune thyroid disease and chronic urticaria. Clin Endocrinol (Oxf) 2007; 67:473.
  86. Kirkpatrick CH. A mechanism for urticaria/angioedema in patients with thyroid disease. J Allergy Clin Immunol 2012; 130:988.
  87. Kisakol G, Kaya A, Gonen S, Tunc R. Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism. Endocr J 2003; 50:657.
  88. Källén B. Use of antihistamine drugs in early pregnancy and delivery outcome. J Matern Fetal Neonatal Med 2002; 11:146.
  89. Weller K, Groffik A, Church MK, et al. Development and validation of the Urticaria Control Test: a patient-reported outcome instrument for assessing urticaria control. J Allergy Clin Immunol 2014; 133:1365.