History

Pruritus (itching) and rash are the primary manifestations of urticaria, and permanent hyperpigmentation or hypopigmentation is rare.

Lesions commonly last 20 minutes to 3 hours, disappear, and then reappear in other skin areas. An entire episode of urticaria often lasts 24-48 hours; individual lesions usually fade within 24 hours or so, but new lesions may be developing continuously. Rarely, acute urticaria can last 3-6 weeks.^[29]Scars do not develop.

With delayed pressure urticaria, lesions may last as long as 48 hours. The lesions of urticarial vasculitis, which are palpable and purpuric, may last for several days or more and may lead to residual hyperpigmented changes.^[30]

Typical lesions described by patients are edematous pink or red wheals of variable size and shape that are pruritic.^[31]The lesions are often described as welts or hives, including pressure-induced hives, which can occur with elastic or tight clothing, as shown in the images below.^[32]Patients may report a painful or burning sensation; such lesions are often associated with angioedema.^[33]Pruritus of nonlesional skin may also occur.

Photograph of dermographism.

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Pressure urticaria (dermatographia) developed after strokes.

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Acute urticaria associated with dermatographism.

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Determining whether the lesions have an allergic (IgE) or nonallergic (non-IgE) basis is helpful in the management of the patient. A complete thorough medical and travel history is important to provide clues to urticaria resulting from a new infectious or medical problem. Questions asked to determine possible allergic and nonallergic causes include the following:

Are the hives associated with any foods? Have any new foods been added to the diet?
Is the patient taking any regular medications, or have any new medicines been started? In particular, ask about aspirin, NSAIDs, antibiotics, over-the-counter (OTC) medications, herbs, and supplements.
Does the patient have any recent or chronic infections?
Are the hives caused by any physical stimuli (eg, heat, cold, pressure, vibration)?
Does the patient have any chronic medical conditions?
Is the urticaria associated with any substances that are inhaled or come in contact with the skin (which may occur in an occupational setting)?
Is the urticaria associated with insect bites or stings?

Physical Examination

If any features of anaphylaxis (eg, hypotension, respiratory distress, stridor, gastrointestinal distress, swallowing problems, joint swelling, joint pain) are present, immediate medical intervention should occur.

Assess for any features of angioedema (deep tissue or submucosal edema).^[34]Angioedema appears as swellings of the tissues, with indistinct borders around the eyelids and lips. Swellings may also appear on the face, trunk, genitalia, and extremities. The face, hands, and feet are involved in 85% of patients. As many as 50% of children who have urticaria exhibit angioedema with swelling of the hands and feet. Hereditary angioedema (C1 inhibitor deficiency) accounts for only 0.4% of cases of angioedema but is associated with a high mortality rate.

Lesions of urticaria can be polymorphic and vary from several millimeters to large, continuous edematous plaques that have smooth surfaces with polycyclic curved borders. The lesions do not have scales but show an intense erythema in the newest areas, with a trailing clearing region in older areas. The central clearing can cause a target configuration in expanding plaques. The advancing border shows a discrete edge followed by a faint, trailing, diffuse border.

Look for any atypical skin lesions. Lesions that are purpuric, nonblanchable, and palpable are characteristic of urticarial vasculitis. These lesions may leave residual pigmented changes. Tiny pinpoint hives are characteristic of cholinergic urticaria.^[35]

Edema can be observed by slightly stretching the skin to demonstrate whitish centers. Occasionally, large annular urticarial lesions as large as 30 cm in diameter with polycystic borders are observed.

Examine for dermographism, as it is often observed in conjunction with urticaria. Itching, erythema, and a raised wheal occur in areas that are scratched or stroked with a blunt object, such as a tongue blade.^[36]The examiner can use the end of a tongue blade or similar blunt object to scratch the patient's skin and observe the area over the next 5-15 minutes for the development of whealing with erythema, as shown in the following image.

Photograph of dermographism.

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The remainder of the physical examination should be used to investigate any suspicions that were raised by the history.

Staging

According to a study, the cutaneous biopsy of urticaria lesions may be divided into the following categories, as the response to treatment could be different:

Class 1 - A mixture of perivascular dermal inflammatory infiltrates composed of lymphocytes, monocytes, and neutrophils, eosinophils, or both
Class 2 - Inflammatory infiltrate chiefly composed of neutrophils^[37]
Class 3 - Inflammatory infiltrate mainly composed of eosinophils

Differential Diagnoses

Frigas E, Park MA. Acute urticaria and angioedema: diagnostic and treatment considerations. Am J Clin Dermatol. 2009. 10(4):239-50. [Medline].
Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP, Greaves MW. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med. 1993 Jun 3. 328(22):1599-604. [Medline].
Zuberbier T, Maurer M. Urticaria: current opinions about etiology, diagnosis and therapy. Acta Derm Venereol. 2007. 87(3):196-205. [Medline].
Kaplan AP, Joseph K, Maykut RJ, Geba GP, Zeldin RK. Treatment of chronic autoimmune urticaria with omalizumab. J Allergy Clin Immunol. 2008 Sep. 122(3):569-73. [Medline].
Criado PR, Criado RF, Takakura CF, Pagliari C, de Carvalho JF, Sotto MN, et al. Ultrastructure of vascular permeability in urticaria. Isr Med Assoc J. 2013 Apr. 15(4):173-7. [Medline].
Viola M, Quaratino D, Gaeta F, Rumi G, Caruso C, Romano A. Cross-reactive reactions to nonsteroidal anti-inflammatory drugs. Curr Pharm Des. 2008. 14(27):2826-32. [Medline].
Kalogeromitros D, Kempuraj D, Katsarou-Katsari A, Gregoriou S, Makris M, Boucher W, et al. Theophylline as "add-on" therapy in patients with delayed pressure urticaria: a prospective self-controlled study. Int J Immunopathol Pharmacol. 2005 Jul-Sep. 18(3):595-602. [Medline].
[Guideline] Magerl M, Borzova E, Giménez-Arnau A, Grattan CE, Lawlor F, Mathelier-Fusade P, et al. The definition and diagnostic testing of physical and cholinergic urticarias--EAACI/GA2LEN/EDF/UNEV consensus panel recommendations. Allergy. 2009 Dec. 64(12):1715-21. [Medline].
Tong LJ, Balakrishnan G, Kochan JP, Kinét JP, Kaplan AP. Assessment of autoimmunity in patients with chronic urticaria. J Allergy Clin Immunol. 1997 Apr. 99(4):461-5. [Medline].
Cardinale F, Mangini F, Berardi M, Sterpeta Loffredo M, Chinellato I, Dellino A, et al. [Intolerance to food additives: an update]. Minerva Pediatr. 2008 Dec. 60(6):1401-9. [Medline].
Sheikh J. Advances in the treatment of chronic urticaria. Immunol Allergy Clin North Am. 2004 May. 24(2):317-34, vii-viii. [Medline].
Schuller DE. Acute urticaria in children: causes and an aggressive diagnostic approach. Postgrad Med. 1982 Aug. 72(2):179-85. [Medline].
Wedi B, Raap U, Wieczorek D, Kapp A. Urticaria and infections. Allergy Asthma Clin Immunol. 2009 Dec 1. 5(1):10. [Medline]. [Full Text].
Kaplan AP. What the first 10,000 patients with chronic urticaria have taught me: a personal journey. J Allergy Clin Immunol. 2009 Mar. 123(3):713-7. [Medline].
Valsecchi R, Pigatto P. Chronic urticaria and Helicobacter pylori. Acta Derm Venereol. 1998 Nov. 78(6):440-2. [Medline].
Ozkaya-Bayazit E, Demir K, Ozgüroglu E, Kaymakoglu S, Ozarmagan G. Helicobacter pylori eradication in patients with chronic urticaria. Arch Dermatol. 1998 Sep. 134(9):1165-6. [Medline].
Di Campli C, Gasbarrini A, Nucera E, Franceschi F, Ojetti V, Sanz Torre E, et al. Beneficial effects of Helicobacter pylori eradication on idiopathic chronic urticaria. Dig Dis Sci. 1998 Jun. 43(6):1226-9. [Medline].
Schnyder B, Helbling A, Pichler WJ. Chronic idiopathic urticaria: natural course and association with Helicobacter pylori infection. Int Arch Allergy Immunol. 1999 May. 119(1):60-3. [Medline].
Leznoff A, Josse RG, Denburg J, Dolovich J. Association of chronic urticaria and angioedema with thyroid autoimmunity. Arch Dermatol. 1983 Aug. 119(8):636-40. [Medline].
Rose RF, Bhushan M, King CM, Rhodes LE. Solar angioedema: an uncommonly recognized condition?. Photodermatol Photoimmunol Photomed. 2005 Oct. 21(5):226-8. [Medline].
Botto NC, Warshaw EM. Solar urticaria. J Am Acad Dermatol. 2008 Dec. 59(6):909-20; quiz 921-2. [Medline].
Kaplan AP. Urticaria angioedema. Adkinson NFY Jr, Busse WW, Bochner BS, Holgate ST, Simons FER, eds. Allergy: Principles and Practice. Philadelphia, Pa: Mosby; 2003. 1537-58.
Sackesen C, Sekerel BE, Orhan F, Kocabas CN, Tuncer A, Adalioglu G. The etiology of different forms of urticaria in childhood. Pediatr Dermatol. 2004 Mar-Apr. 21(2):102-8. [Medline].
Kaplan AP. Chronic urticaria and angioedema. N Engl J Med. 2002. Vol. 346:175-9.
Beltrani VS. Urticaria and angioedema. Dermatol Clin. 1996 Jan. 14(1):171-198. [Medline].
Soter NA. Acute and chronic urticaria and angioedema. J Am Acad Dermatol. 1991 Jul. 25(1 Pt 2):146-54. [Medline].
Varadarajulu S. Urticaria and angioedema. Controlling acute episodes, coping with chronic cases. Postgrad Med. 2005 May. 117(5):25-31. [Medline].
O'Donnell BF, Lawlor F, Simpson J, Morgan M, Greaves MW. The impact of chronic urticaria on the quality of life. Br J Dermatol. 1997 Feb. 136(2):197-201. [Medline].
Zuberbier T, Iffländer J, Semmler C, Henz BM. Acute urticaria: clinical aspects and therapeutic responsiveness. Acta Derm Venereol. 1996 Jul. 76(4):295-7. [Medline].
Davis MD, Brewer JD. Urticarial vasculitis and hypocomplementemic urticarial vasculitis syndrome. Immunol Allergy Clin North Am. 2004 May. 24(2):183-213, vi. [Medline].
Kaplan AP. Urticaria and angioedema. Middleton E, Reed CE, Ellis EF, et al, eds. Allergy: Principles and Practices. St. Louis, Mo: Mosby-Year Book; 1998. 1104-18.
Sheila MA, Stephen CD. Urticaria. Prim Care Clin Office Pract. 2008. Vol. 35:141-57.
Charlesworth EN. Urticaria and angioedema: a clinical spectrum. Ann Allergy Asthma Immunol Jun. 1996. 76(6):484-95.
Greaves M. Chronic urticaria. J Allergy Clin Immunol. 2000 Apr. 105(4):664-72. [Medline].
Hirschmann JV, Lawlor F, English JS, Louback JB, Winkelmann RK, Greaves MW. Cholinergic urticaria. A clinical and histologic study. Arch Dermatol. 1987 Apr. 123(4):462-7. [Medline].
Wong RC, Fairley JA, Ellis CN. Dermographism: a review. J Am Acad Dermatol. 1984 Oct. 11(4 Pt 1):643-52. [Medline].
Belani H, Gensler L, Bajpai U, Meinhardt E, Graf J, Pincus L, et al. Neutrophilic urticaria with systemic inflammation: a case series. JAMA Dermatol. 2013 Apr 1. 149(4):453-8. [Medline].
Schoepke N, Doumoulakis G, Maurer M. Diagnosis of urticaria. Indian J Dermatol. 2013 May. 58(3):211-8. [Medline]. [Full Text].
Dibbern DA Jr. Urticaria: selected highlights and recent advances. Med Clin North Am. 2006 Jan. 90(1):187-209. [Medline].
Dibbern DA Jr, Dreskin SC. Urticaria and angioedema: an overview. Immunol Allergy Clin North Am. 2004 May. 24(2):141-62, v. [Medline].
[Guideline] American Academy of Allergy, Asthma & Immunology. Consultation and referral guidelines citing the evidence: how the allergist-immunologist can help. J Allergy Clin Immunol. 2006 Feb. 117(2 Suppl Consultation):S495-523. [Medline].
Beltrani VS. Urticaria: reassessed. Allergy Asthma Proc. 2004 May-Jun. 25(3):143-9. [Medline].
Mortureux P, Léauté-Labrèze C, Legrain-Lifermann V, Lamireau T, Sarlangue J, Taïeb A. Acute urticaria in infancy and early childhood: a prospective study. Arch Dermatol. 1998 Mar. 134(3):319-23. [Medline].
Irinyi B, Széles G, Gyimesi E, Tumpek J, Herédi E, Dimitrios G, et al. Clinical and laboratory examinations in the subgroups of chronic urticaria. Int Arch Allergy Immunol. 2007. 144(3):217-25. [Medline].
[Guideline] Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau A, et al. EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy. 2009 Oct. 64(10):1417-26. [Medline]. [Full Text].
Brown NA, Carter JD. Urticarial vasculitis. Curr Rheumatol Rep. 2007 Aug. 9(4):312-9. [Medline].
Haas N, Toppe E, Henz BM. Microscopic morphology of different types of urticaria. Arch Dermatol. 1998 Jan. 134(1):41-6. [Medline].
[Guideline] Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau AM, et al. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy. 2009 Oct. 64(10):1427-43. [Medline]. [Full Text].
[Guideline] Zuberbier T. A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria. World Allergy Organ J. 2012 Jan. 5 Suppl 1:S1-5. [Medline].
Slater JW, Zechnich AD, Haxby DG. Second-generation antihistamines: a comparative review. Drugs. 1999 Jan. 57(1):31-47. [Medline].
Breneman DL. Cetirizine versus hydroxyzine and placebo in chronic idiopathic urticaria. Ann Pharmacother. 1996 Oct. 30(10):1075-9. [Medline].
Bleehen SS, Thomas SE, Greaves MW, Newton J, Kennedy CT, Hindley F, et al. Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: a multi-centre randomized double-blind study. Br J Dermatol. 1987 Jul. 117(1):81-8. [Medline].
Lin RY, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, et al. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists. Ann Emerg Med. 2000 Nov. 36(5):462-8. [Medline].
Pollack CV Jr, Romano TJ. Outpatient management of acute urticaria: the role of prednisone. Ann Emerg Med. 1995 Nov. 26(5):547-51. [Medline].
Bluestein HM, Hoover TA, Banerji AS, Camargo CA Jr, Reshef A, Herscu P. Angiotensin-converting enzyme inhibitor-induced angioedema in a community hospital emergency department. Ann Allergy Asthma Immunol. 2009 Dec. 103(6):502-7. [Medline].
Grattan CE, O'Donnell BF, Francis DM, Niimi N, Barlow RJ, Seed PT, et al. Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria. Br J Dermatol. 2000 Aug. 143(2):365-72. [Medline].
Vena GA, Cassano N, Colombo D, Peruzzi E, Pigatto P. Cyclosporine in chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. J Am Acad Dermatol. 2006 Oct. 55(4):705-9. [Medline].
O'Donnell BF, Barr RM, Black AK, Francis DM, Kermani F, Niimi N, et al. Intravenous immunoglobulin in autoimmune chronic urticaria. Br J Dermatol. 1998 Jan. 138(1):101-6. [Medline].
Grattan CE, Francis DM, Slater NG, Barlow RJ, Greaves MW. Plasmapheresis for severe, unremitting, chronic urticaria. Lancet. 1992 May 2. 339(8801):1078-80. [Medline].
Werni R, Schwarz T, Gschnait F. Colchicine treatment of urticarial vasculitis. Dermatologica. 1986. 172(1):36-40. [Medline].
Ruzicka T, Goerz G. Systemic lupus erythematosus and vasculitic urticaria. Effect of dapsone and complement levels. Dermatologica. 1981. 162(3):203-5. [Medline].
Nettis E, Dambra P, D'Oronzio L, Loria MP, Ferrannini A, Tursi A. Comparison of montelukast and fexofenadine for chronic idiopathic urticaria. Arch Dermatol. 2001 Jan. 137(1):99-100. [Medline].
Asero R, Tedeschi A, Lorini M. Leukotriene receptor antagonists in chronic urticaria. Allergy. 2001 May. 56(5):456-7. [Medline].
Gober LM, Sterba PM, Eckman JA, Saini SS. Effect of anti-IgE (omalizumab) in chronic idiopathic urticaria (CIU) patients. J Allergy Clin Immunol. 2008. 121(2 supp 1):S147. [Full Text].
Wong JT, Nagy CS, Krinzman SJ, Maclean JA, Bloch KJ. Rapid oral challenge-desensitization for patients with aspirin-related urticaria-angioedema. J Allergy Clin Immunol. 2000 May. 105(5):997-1001. [Medline].
Grattan CE. Aspirin sensitivity and urticaria. Clin Exp Dermatol. 2003 Mar. 28(2):123-7. [Medline].
Díaz Jara M, Pérez Montero A, Gracia Bara MT, Cabrerizo S, Zapatero L, Martínez Molero MI. Allergic reactions due to ibuprofen in children. Pediatr Dermatol. 2001 Jan-Feb. 18(1):66-7. [Medline].
Lancey RA, Schaefer OP, McCormick MJ. Coronary artery bypass grafting and aortic valve replacement with cold cardioplegia in a patient with cold-induced urticaria. Ann Allergy Asthma Immunol. 2004 Feb. 92(2):273-5. [Medline].
Simonart T, Askenasi R, Lheureux P. Particularities of urticaria seen in the emergency department. Eur J Emerg Med. 1994 Jun. 1(2):80-2. [Medline].
Simons FE. Anaphylaxis. J Allergy Clin Immunol. 2010 Feb. 125(2 Suppl 2):S161-81. [Medline].
Najib U, Sheikh J. An update on acute and chronic urticaria for the primary care provider. Postgrad Med. 2009 Jan. 121(1):141-51. [Medline].
Poonawalla T, Kelly B. Urticaria : a review. Am J Clin Dermatol. 2009. 10(1):9-21. [Medline].
Simons FE. H1-Antihistamines: more relevant than ever in the treatment of allergic disorders. J Allergy Clin Immunol. 2003 Oct. 112(4 Suppl):S42-52. [Medline].
Bains SN, Hsieh FH. Current approaches to the diagnosis and treatment of systemic mastocytosis. Ann Allergy Asthma Immunol. 2010 Jan. 104(1):1-10; quiz 10-2, 41. [Medline].
Baek YS, Jeon J, Kim JH, Oh CH. Severity of acute and chronic urticaria correlates with D-dimer level, but not C-reactive protein or total IgE. Clin Exp Dermatol. 2014 Oct. 39 (7):795-800. [Medline].
Zuberbier T, et al. European Academy of Allergy and Clinical Immunology, Global Allergy and Asthma European Network, European Dermatology Forum, World Allergy Organization. The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014 Jul. 69 (7):868-87. [Medline].
Cooke A, Bulkhi A, Casale TB. Role of biologics in intractable urticaria. Biologics. 2015. 9:25-33. [Medline].

Media Gallery

Urticaria associated with a drug reaction.
Urticaria developed after bites from an imported fire ant.
Local urticaria on a patient with latex allergy who was touched with a latex glove.
Urticaria from drug reaction.
Photograph of dermographism.
Pressure urticaria (dermatographia) developed after strokes.
Acute urticaria associated with dermatographism.
Urticaria associated with acute group A beta-hemolytic streptococci infection.
Acute urticaria in a toddler affecting the face. Likely cause is postviral syndrome.

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Author

Henry K Wong, MD, PhD Professor and Chairman, Department of Dermatology, University of Arkansas for Medical Sciences College of Medicine

Henry K Wong, MD, PhD is a member of the following medical societies: American Academy of Dermatology, International Society for Cutaneous Lymphomas, Medical Dermatology Society, Society for Investigative Dermatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Seattle Genetics, Actillion, Celgene, Kyowa-Kirin<br/>Serve(d) as a speaker or a member of a speakers bureau for: Amgen<br/>Received income in an amount equal to or greater than $250 from: Celgene<br/>Received honoraria from Amgen for speaking and teaching; Received grant/ Received grant/research funds from Celgene for none; Received grant/research funds from Abbott Labs for independent contractor; Received grant/research funds from Amgen for none; Received honoraria from Seattle Genetics for consulting. for: Actelion-Advisory board, grants;Seattle Genetics - Advisory board.

Coauthor(s)

Umer Najib, MD Clinical Research Fellow, Department of Medicine, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Javed Sheikh, MD Assistant Professor of Medicine, Harvard Medical School; Clinical Director, Division of Allergy and Inflammation, Clinical Director, Center for Eosinophilic Disorders, Beth Israel Deaconess Medical Center

Javed Sheikh, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Received grant/research funds from Genentech for other.

Acknowledgements

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Consulting fee Consulting; Celgene Honoraria Safety Monitoring Committee; GSK - Glaxo Smith Kline Consulting fee Consulting; TenXBioPharma Consulting fee Safety Monitoring Committee

Kevin P Connelly, DO Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University School of Medicine; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center

Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association