AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

Urticaria was first described in the English literature in 1772, although the disease has been recognized throughout history. The disorder is marked by the onset of evanescent wheals (hives) associated with pruritus. Acute urticaria is a common disorder that often prompts patients to seek treatment in the emergency department (ED). In fact, it is the most common cutaneous disease treated in the ED. The eruption is symptomatic and can be visually apparent over many different parts of the skin. The natural course of the acute disease lasts from a one-time event of several hours' duration up to 6 weeks, depending on the etiology. If urticaria is present continuously over a 6-week period, it is categorized as chronic urticaria. Information on this entity is available in Urticaria, Chronic. Additionally, the Medscape Allergy Resource Center may be helpful. 

Individual lesions appear at different locations and fade without scarring, often in a matter of hours. In 50% of patients, a specific etiology can be identified. Brief episodes of urticaria can be associated with identifiable causes, and the method of exposure (ie, direct contact, oral or intravenous routes) is usually known. If the location of the wheals remains fixed for longer than 24 hours, the diagnosis may be urticarial vasculitis or bullous pemphigoid.

Pathophysiology

The release of histamine and other compounds by mast cells and basophils causes the appearance of urticaria. Immune Immune-mediated urticaria is from immunoglobulin E (IgE) binding specific antigen and the complex binding to FcER1 receptors to activate mast cells. Mast cell activation from crosslinking of FcER1 receptor causes degranulation of intracellular vesicles that contain histamine, leukotriene C4, prostaglandin D2, and other chemotactic mediators that recruit eosinophils and neutrophils into the dermis. Histamine and chemokine release lead to extravasation of fluid into the dermis (edema). Histamine effects account for many of the clinical and histologic findings of urticaria.

Histamine is the ligand for at least 2 types of membrane-bound receptors, H1 and H2 receptors, which are present on numerous cells. The activation of H1 histamine receptors on smooth muscle cells and endothelial cells leads to cellular contraction and increased vascular permeability. The activation of H2 histamine receptors causes vasodilation. Urticaria is a reaction pattern that reflects the activation of mast cells and basophils. The exact mechanism of action resulting in the release of the intracellular contents of mast cells and basophils is varied and can occur through immune-mediated or non–immune-mediated mechanisms.

Immune-mediated urticaria

Immune-mediated urticaria can be caused by 3 of 4 types of immune mechanisms.

• The type I allergic IgE response is initiated by antigen-mediated IgE immune complexes that bind and cross-link Fc receptors on the surface of mast cells and basophils. The types of antigens that bind to IgE are varied and include proteins, polysaccharides, and other immunogenic molecules.
• Type II responses are mediated by cytotoxic T cells. The disease process activates byproducts that cause urticarial vasculitis or bullous pemphigoid.
• Type III immune-complex disease is associated with systemic lupus erythematosus and other connective tissue disorders that activate urticaria.

Non–immune-mediated

Chemicals that can directly induce mast cell degranulation, presumably by altering the membrane properties, cause non–immune-mediated urticaria. Common agents associated with direct mast cell activation are opiates, antibiotics, curare, radiocontrast media, azo dyes, aspirin, and aspirin derivatives.

Frequency

United States

Urticaria affects 15-20% of the population at some point in their lives.

International

The international frequency is similar to the US frequency.

Mortality/Morbidity

Acute urticaria causes discomfort, but it does not cause mortality unless it is associated with angioedema involving the upper airways.^{1, 2, 3}

Race

No variation in race is reported.

Sex

Females have a slightly higher prevalence (61%) than males.

Age

Acute urticaria affects persons of all age groups. The mean age of persons who are affected is in the second to third decade of life.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

Acute urticaria is characterized by the onset of clinically apparent, edematous, evanescent, erythematous plaques. Individual lesions remain for less than 24 hours, exhibiting a transitory and migratory behavior. The etiology can be inferred in as many as 50% of new cases. In general, greater than 80% of new-onset urticaria resolves in 2 weeks and greater than 95% of new-onset cases resolve by 3 months. Atopy can often be identified in the patient or his or her family members. When urticaria persists for more than 6 weeks, it is considered chronic urticaria. Additional etiologies exist for chronic urticaria. A thorough medical evaluation is indicated to eliminate the possibility of treatable causes of urticaria, which include malignancies, connective tissue disorders, and chronic infections.

• Acute urticaria is commonly caused by a variety of infections, medications, food allergies, physical stimulants, chemicals, chronic inflammatory diseases, and insect bites, as follows:
• • Recent infection from a viral syndrome or an upper respiratory illness (39%)
  • Medications (eg, ACE inhibitors, aspirin, nonsteroidal anti-inflammatory drugs, sulfa-based drugs, penicillins, diuretics, opioids, polymyxin B)
  • Food and food additives (eg, nuts, fish, shellfish, eggs, chocolate, strawberries, salicylate, benzoates)
  • Parasitic infections (eg, Ascaris, Ancylostoma, Strongyloides, Echinococcus, Trichinella, Filaria)
  • Physical stimulants (eg, cold, pressure, aquagenic)
  • Chemicals (eg, latex, ammonium persulfate in hair chemicals)
  • Intravenous radiocontrast media
  • Arthropod bites
• New-onset fever and constitutional symptoms suggest chronic autoimmune disease.

Physical

Lesions of urticaria can be polymorphic and vary from several millimeters to large, continuous plaques.

• Plaques have smooth surfaces with polycyclic curved borders. Lesions do not have scales.
• Lesions show an intense erythema in the newest areas, with a trailing clearing region in older areas.
• Central clearing can cause a target configuration in expanding plaques. The advancing border shows a discrete edge followed by a faint, trailing, diffuse border.
• Lesions last less than 24 hours, and scars do not develop.
• Erythema multiforme can resemble urticaria.
• • Both processes can be a reaction to medication.
  • Early lesions of erythema multiforme may appear edematous, round, targetoid, and polycyclic as the lesion expands. However, in erythema multiforme, each lesion can be differentiated by the stationary nature and the progression to a dusky color with bulla formation.

Causes

A definitive inciting agent can be identified in 40-50% of cases of acute urticaria.

• In one recent study, causes were identified as an upper respiratory tract infection in 39.5% of the total cases, analgesics in 9%, and food intolerance in 0.9%.
• Urticaria associated with the onset of autoimmune disorders or malignancy (eg, systemic lupus erythematosus, lymphoma) will become chronic.
• Most cases of new-onset urticaria are idiopathic in nature.

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• No specific laboratory study is needed unless the patient's history suggests a particular diagnostic test. Carefully obtain a complete medical and travel history to exclude a new presentation of infectious or medical problems. A thorough review of systems is essential.

Imaging Studies

• Obtain imaging studies if indicated by the patient's history.

Other Tests

• Obtain other tests if indicated by the patient's history.

Procedures

• No procedures are necessary for the diagnosis of acute urticaria. If the lesion remains for longer than 24 hours or if it blisters, a skin biopsy is suggested to investigate for other possibilities in the differential diagnosis.

Histologic Findings

The histologic findings of acute urticaria are not dramatic. No epidermal change is present. The dermis may show increased spacing between collagen fibers, suggestive of dermal edema. Dilated lymphatics and dilated capillaries can be seen in the involved skin. A sparse, perivascular, lymphocytic infiltrate and a few eosinophils may be present. Mast cells are increased in number in the involved skin.⁴

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

To prevent recurrence, identify the inciting agent and instruct the patient to avoid it.

• The cause is not known in greater than 50% of the cases. The most commonly identified cause is a recent infection or viral syndrome, and, under these circumstances, the patient should be informed of the self-limiting duration of the disorder.
• Palliation of pruritus and discomfort associated with the lesions is the primary goal of treatment in the initial visit. Therapy aims to block histamine action. Classes of drugs to consider are H1 antihistamines, H2 antihistamines, glucocorticoids, and tricyclic antidepressants that have combined H1 and H2 antagonists (eg, doxepin).

Surgical Care

None

Consultations

Consult appropriate specialists as indicated by the patient's history and a thorough review of systems.

Diet

• Educate patients to avoid food and food additives if identified as the cause of urticaria.
• Review medications to screen for the use of aspirin, salicylates, and nonsteroidal anti-inflammatory drugs. If identified, these nonimmunologic histamine releasers should be discontinued.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The drug of choice for control of urticaria is an H1 antihistamine. Numerous choices are available from this group, each with a different adverse effect profile. The choice is based on the patient's needs and tolerability to a particular antihistamine. With the number of nonsedating antihistamines available today, these agents should be tried first to facilitate disappearance of the lesions and symptoms of pruritus. To achieve optimal control of urticaria, try different agents or increase the dose to maximum tolerable levels for that agent. In difficult cases, a combination of H1 and H2 antihistamines may be more effective. Doxepin has both H1 antihistaminic properties and H2 antihistaminic properties and can be used when a single H1 agent fails to control disease activity. Severe or refractory urticaria may benefit from a tapering course of prednisone in combination with an antihistamine agent.

Drug Category: Antihistamines

Newer nonsedating antihistamines may be tried initially to control urticaria. Agents include fexofenadine, loratadine, desloratadine, and cetirizine. If additional antihistamines are needed, traditional agents can be considered. The 6 traditional classes of antihistamines are alkylamine, ethylenediamine, ethanolamine, propylamine, phenothiazine, and piperazine. Each has different adverse effects that may vary among individuals. Nonsedating H1 antihistamines with similar effectiveness in the treatment of urticaria are available. The choices for treatment are broad, and therapeutic options are tailored to the patient. The examples of drugs below do not represent the preferred agents or the specific recommendation of the author. Other antihistamines should also be considered and reviewed before treatment.

Drug Category: Corticosteroids

Prednisone taper can be effective when combined with an antihistamine.

Drug Category: Tricyclic antidepressants

Doxepin has been used in urticaria and pruritus.

Drug Category: Histamine H2 antagonists

Used for treatment of duodenal ulcer disease; however, can be used in combination with H1 antihistamines when H1 antihistamines alone do not provide adequate relief.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

• Acute urticaria restricted to the skin does not require hospitalization and can be managed with outpatient care.
• Shortness of breath suggests respiratory involvement and a diagnosis of angioedema. In this situation, the patient should be monitored in the ED until normal airway function is restored.

Further Outpatient Care

• Patients with acute urticaria can be treated in an outpatient setting to assess the efficacy of the treatment plan.
• A dermatologist should examine patients in 4-6 weeks to determine if urticaria may be chronic in nature.

Deterrence/Prevention

• Patients should avoid known precipitating agents.

Prognosis

• Acute urticaria is self-limited and usually resolves in less than 3 weeks.

Patient Education

• Reassure the patient that the disorder is often limited in duration. If an inciting agent can be identified, teach avoidance.
• For excellent patient education resources, visit eMedicine's Allergy Center and Skin, Hair, and Nails Center. Also, see eMedicine's patient education article Hives and Angioedema.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to educate the patient on the adverse effects and the drug interactions of the medications is a pitfall. Carefully inform patients about the adverse effects of antihistamines (eg, sedation) and potential drug interactions.

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Urticaria from drug reaction.
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Media file 2:  Acute urticaria in a toddler affecting the face. Likely cause is postviral syndrome.
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Media file 3:  Acute urticaria associated with dermatographism.
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REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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3. Varadarajulu S. Urticaria and angioedema. Controlling acute episodes, coping with chronic cases. Postgrad Med. May 2005;117(5):25-31. [Medline].
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10. 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. Mar 1998;134(3):319-23. [Medline].
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12. Sackesen C, Sekerel BE, Orhan F, Kocabas CN, Tuncer A, Adalioglu G. The etiology of different forms of urticaria in childhood. Pediatr Dermatol. Mar-Apr 2004;21(2):102-8. [Medline].
13. Simonart T, Askenasi R, Lheureux P. Particularities of urticaria seen in the emergency department. Eur J Emerg Med. Jun 1994;1(2):80-2. [Medline].
14. Slater JW, Zechnich AD, Haxby DG. Second-generation antihistamines: a comparative review. Drugs. Jan 1999;57(1):31-47. [Medline].
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Article Last Updated: Jul 15, 2008