Henry K Wong, MD, PhD,
Associate Professor of Dermatology, Ohio
State University College of Medicine
EISAI Consulting
fee Speaking and
teaching; Amgen Consulting
fee Other; Abbott
Labs Grant/research
funds Other; Merck Honoraria Speaking
and
teaching; Centocor Honoraria Speaking
and teaching
Specialty Editor(s)
Daniel J Hogan, MD,
Clinical Professor of Internal Medicine
(Dermatology), NOVA Southeastern University; Investigator,
Hill Top Research, Florida Research Center
Nothing to disclose.
Jeffrey P Callen, MD,
Professor of Medicine (Dermatology), Chief,
Division of Dermatology, University of Louisville School of
Medicine
Joel M Gelfand, MD, MSCE,
Medical Director, Clinical Studies Unit,
Assistant Professor, Department of Dermatology, Associate
Scholar, Center for Clinical Epidemiology and Biostatistics,
University of Pennsylvania
Richard P Vinson, MD,
Assistant Clinical Professor, Department of
Dermatology, Texas Tech University School of Medicine;
Consulting Staff, Mountain View Dermatology,
PA
Nothing to disclose.
Chief Editor
Dirk M Elston, MD,
Director, Department of Dermatology,
Geisinger Medical Center
Nothing to disclose.
Background
Urticaria was first described in the English literature in 1772, although the disease has been recognized throughout history. Urticaria 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, acute urticaria is the most common cutaneous disease treated in the ED.[1] The eruption is symptomatic and can be visually apparent over many different parts of the skin. The natural course acute urticaria 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.
Individual lesions of acute urticaria can appear at different locations and fade without scarring, often in a matter of hours. In 50% of patients with acute urticaria, 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, and a skin biopsy is indicated for diagnosis.
The release of histamine and other compounds by mast cells and basophils causes the appearance of urticaria. Immune-mediated urticaria is from immunoglobulin E (IgE) binding specific antigen, and the IgE-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.[2, 3] 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, as follows:
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 urticaria
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.
Acute urticaria is characterized by the onset of clinically apparent, edematous, evanescent, erythematous plaques. Individual acute urticaria 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[7, 8] :
Recent infection from a viral syndrome or an upper respiratory tract illness (39%)
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.
Note the images below:
View Image
Urticaria from drug reaction.
View Image
Acute urticaria in a toddler affecting the face. Likely cause is postviral syndrome.
View Image
Acute urticaria associated with dermatographism.
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.
A definitive inciting agent can be identified in 40-50% of cases of acute urticaria. In one 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%.[9] Urticaria associated with the onset of autoimmune disorders or malignancy (eg, systemic lupus erythematosus, lymphoma) becomes chronic. Most cases of new-onset urticaria are idiopathic in nature.
No specific laboratory study is needed for acute urticaria unless the patient's history suggests a particular diagnostic test. A complete thorough medical and travel history is important to provide clues to a new presentation of infectious or medical problems. A thorough review of systems is essential.[10]
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.
The histologic findings of acute urticaria are not dramatic. No epidermal change is present. Acute urticaria demonstrates intravascular margination of neutrophils. Later lesions demonstrate diapedesis of neutrophils through the vessel wall in the absence of karyorrhexis. Late lesions demonstrate intravascular, perivascular and interstitial neutrophils with little to no karyorrhexis. A moderate number of eosinophils may be present.[11]
Identify the etiology of the acute urticaria if possible. If an inciting agent can be identified, instruct the patient to avoid it. The major goal is to control the severity of acute urticaria lesions until the process resolves over 4-6 weeks.
The cause is not known in greater than 50% of acute urticaria 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.[12]
Palliation of pruritus and discomfort associated with the acute urticaria 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).
Selected clinical guideline summaries are as follows:
British Association of Dermatologists - Guidelines for evaluation and management of urticaria in adults and children[13]
American Academy of Allergy, Asthma & Immunology -Consultation and referral guidelines citing the evidence: how the allergist-immunologist can help[14]
Joint Council of Allergy, Asthma and Immunology -The diagnosis and management of anaphylaxis: an updated practice parameter[15]
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.
With the development of numerous classes of drugs that affect the immune system, there are now many choices for the treatment of urticaria.[16] The drug of choice for control of urticaria initially 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. Additionally, leukotriene inhibitors can be added to antihistamines for recalcitrant cases of urticaria.[17] Finally, severe or refractory urticaria may benefit from a tapering course of prednisone in combination with an antihistamine.[18]
Newer nonsedating antihistamines may be tried initially to control urticaria. Agents include fexofenadine, loratadine, desloratadine, and cetirizine.[19, 20] 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.
Clinical Context:
For symptomatic relief of symptoms caused by release of histamine in allergic reactions. Ethanolamine antihistamine that is commonly prescribed. Can be purchased over-the-counter, but prescription doses are often necessary. Sedation is an associated effect.
Clinical Context:
Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS. Piperazine type of antihistamine that is effective and has fewer sedating effects compared with diphenhydramine. Usually well tolerated in most individuals.
Clinical Context:
Nonsedating antihistamine that has long-acting characteristics. Selectively inhibits peripheral histamine H1 receptors. Available as 10-mg tab, 10-mg RediTab, and syr at 5 mg/5 mL (tsp).
Clinical Context:
Second-generation antihistamine with markedly reduced sedative effects and reduced anticholinergic effects. Forms complex with histamine for H1 receptor sites in blood vessels, GI tract, and respiratory tract. Available as 5- and 10-mg tab, 5- and 10-mg chewable tab, and syr at 1 mg/mL or 5 mg/5 mL (tsp).
Clinical Context:
Long-acting tricyclic histamine antagonist selective for H1 receptor. Relieves nasal congestion and systemic effects of seasonal allergy. Is a major metabolite of loratadine, which, after ingestion, is metabolized extensively to active metabolite 3-hydroxydesloratadine. Available as 5-mg tab, syr at 0.5 mg/mL (2.5 mg/5 mL), and 2.5- and 5-mg RediTab (desloratadine orally disintegrating tab).
Clinical Context:
Competes with histamine for H1 receptors on GI tract, blood vessels, and respiratory tract, reducing hypersensitivity reactions. Does not sedate. Available as 30-, 60-, or 180-mg tab. Allegra ODT tab formulated for disintegration in mouth immediately following administration. Each orally disintegrating tab contains 30 mg fexofenadine hydrochloride. Oral susp contains 6 mg fexofenadine hydrochloride per mL or 30 mg/5 mL.
Clinical Context:
Useful in cases that have not responded to traditional antihistamine. For extensive symptomatic urticaria, a burst of prednisone over 4 d can lead to marked improvement and control of symptoms.
Clinical Context:
Inhibits histamine and acetylcholine activity. Has both H1 antagonist activity and H2 antagonist activity that is far more potent than traditional antihistamines. Has antidepressant properties attributed to blocking MAO.
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.
Clinical Context:
H2 antagonist that when combined with an H1 antagonist may be useful in treating itching and flushing in urticaria and contact dermatitis that do not respond to H1 antagonists alone. Use in addition to H1 antihistamines.
Clinical Context:
Inhibits effects by leukotriene receptor, whose activity has been associated with airway edema, smooth muscle contraction, and cellular activity associated with the symptoms.
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 emergency department until normal airway function is restored.
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.
){kind=link}
){kind=link}
){kind=link}