AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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

INTRODUCTION

Section 2 of 11  

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

Background

Urticaria, commonly referred to as hives, is the most frequent dermatologic disorder seen in the ED. It appears as raised, well-circumscribed areas of erythema and edema involving the dermis and epidermis that are very pruritic. Urticaria may be acute (lasting less than 6 wk) or chronic (lasting more than 6 wk). A large variety of urticaria variants exist, including acute immunoglobulin E (IgE)–mediated urticaria, chemical-induced urticaria (non-IgE-mediated), urticarial vasculitis, autoimmune urticaria, cholinergic urticaria, cold urticaria, mastocytosis, Muckle-Wells syndrome, and many others.

Acute IgE-mediated urticaria is the most benign form of anaphylaxis. It usually occurs independently, but it may be accompanied by the more serious clinical manifestations of anaphylaxis, angioedema, and anaphylactic shock. The etiology of both acute and chronic urticaria are numerous (see Causes below). The etiologic agent is more likely to be identified in acute urticaria (40-60%) than in chronic urticaria (10-20%). The lesions of IgE-medicated urticaria usually last less than 24 hours and are often migratory, leaving no residual skin abnormalities. The lesions of urticarial vasculitis usually last longer than 24 hours, are both painful and pruritic, and often leave purpuric and hyperpigmented lesions.

For more information, see Medscape's Allergy Resource Center.

Pathophysiology

Urticaria results from the release of histamine, bradykinin, leukotriene C4, prostaglandin D2, and other vasoactive substances from mast cells and basophils in the dermis. These substances cause extravasation of fluid into the dermis, leading to the urticarial lesion. The intense pruritus of urticaria is a result of histamine released into the dermis. Histamine is the ligand for 2 membrane-bound receptors, the H1 and H2 receptors that are present on many cell types. The activation of the H1 histamine receptors on endothelial and smooth muscle cells leads to increased capillary permeability. The activation of the H2 histamine receptors leads to arteriolar and venule vasodilation.

This process is caused by several 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, thus causing degranulation with histamine release. The type II allergic response is mediated by cytotoxic T cells, causing deposits of immunoglobulins, complement, and fibrin around blood vessels. This leads to urticarial vasculitis. The type III immune-complex disease is associated with systemic lupus erythematosus and other autoimmune diseases that cause urticaria.

Complement-mediated urticarias include viral and bacterial infections, serum sickness, and transfusion reactions. Urticarial transfusion reactions occur when allergenic substances in the plasma of the donated blood product react with preexisting IgE antibodies in the recipient. Certain drugs (opioids, vecuronium, succinylcholine, vancomycin, and others) as well as radiocontrast agents cause urticaria due to mast cell degranulation through a non-IgE mediated mechanism. The physical urticarias in which some physical stimulus causes urticaria include immediate pressure urticaria, delayed pressure urticaria, cold urticaria, and cholinergic urticaria. Finally, there are urticarias, especially chronic urticarias, for which no cause can be found, despite exhaustive efforts—the so-called idiopathic urticarias.

Frequency

United States

Urticaria affects 15-20% of the general population at some time during their lifetime.

International

The frequency of urticaria internationally is similar to that in the United States.

Mortality/Morbidity

Pruritus (itching) and rash are the primary manifestations of urticaria, and hyperpigmentation or hypopigmentation are rare. Acute urticaria is usually self-limited and commonly resolves within 24 hours but may last up to 6 weeks. Chronic urticaria lasts more than 6 weeks. Neither acute nor chronic urticaria results in long-term consequences other than anxiety and depression. The depression can be severe enough to lead to suicide in rare cases. Also, many of the diseases associated with chronic urticaria may cause very significant morbidity and mortality.

Race

No variation in race is noted.

Sex

Incidence rates for acute urticaria are similar for men and women; chronic urticaria occurs more frequently in women (60%).

Age

Urticaria can occur in any age group, although chronic urticaria is more common in the fourth and fifth decades.

CLINICAL

Section 3 of 11  

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

History

Information regarding history of previous urticaria and duration of rash and itching is useful for categorizing urticaria as acute, recurrent, or chronic.

• For chronic or recurrent urticaria, important considerations include previous causative factors and the effectiveness of various treatments.  
• • Ask about precipitants, such as heat, cold, pressure, exercise, sunlight, emotional stress, or chronic medical conditions (eg, hyperthyroidism, systemic lupus erythematosus [SLE], rheumatoid arthritis, polymyositis, amyloidosis, polycythemia vera, carcinoma, lymphoma).
  • Ask about other medical conditions that can cause pruritus (usually without rash), such as diabetes mellitus, chronic renal insufficiency, primary biliary cirrhosis, or other nonurticarial dermatologic disorders (eg, eczema, contact dermatitis).
  • Ask about family and personal medical history of angioedema, which is urticaria of the deeper tissues and can be life threatening if it involves the larynx and vocal cords. Causes specific to angioedema include hereditary angioedema (a deficiency in C1-inhibitors) and acquired angioedema (associated with angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers (ARBs). Characteristics of angioedema include the following: 
  • • Vasodilation and exudation of plasma into deeper tissues than is seen in simple urticaria
    • Swelling that is generally nonpitting and nonpruritic and usually occurs on the mucosal surfaces of the respiratory tract (lips, tongue, uvula, soft palate, and larynx) and GI tract (swelling of the intestine leading to severe abdominal pain)
    • Hoarseness, the earliest sign of laryngeal edema (Ask the patient if he or she has had a voice change.)
• For acute urticaria, ask about possible precipitants, such as the following: 
• • Recent illness (eg, fever, sore throat, cough, rhinorrhea, vomiting, diarrhea, headache)
  • Medication use including penicillins, cephalosporins, sulfas, diuretics, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), iodides, bromides, quinidine, chloroquine, vancomycin, isoniazid, antiepileptic agents, and other agents.
  • Intravenous radiocontrast media
  • Travel (amebiasis, ascariasis, strongyloidiasis, trichinosis, malaria)
  • Foods (eg, shellfish, fish, eggs, cheese, chocolate, nuts, berries, tomatoes)
  • New perfumes, hair dyes, detergents, lotions, creams, or clothes
  • Exposure to new pets (dander), dust, mold, chemicals, or plants
  • Pregnancy (usually occurs in last trimester and typically resolves spontaneously soon after delivery)
  • Contact with nickel (eg, jewelry, jeans stud buttons), rubber (eg, gloves, elastic bands), latex, industrial chemicals, and nail polish
  • Sun or cold exposure
  • Exercise

Physical

Urticaria is characterized by blanching, raised, palpable wheals, which can be linear, annular (circular), or arcuate (serpiginous). These lesions occur on any skin area and are usually transient and migratory.

• Dermographism may occur (urticarial lesions resulting from light scratching).
• The physical examination should focus on conditions that might precipitate urticaria or could be potentially life threatening.  
• • Pharyngitis or upper respiratory infections, particularly in children
  • Angioedema of the lips, tongue, or larynx 
  • Scleral icterus, hepatic enlargement, or tenderness that suggests hepatitis or cholestatic liver disease
  • Thyromegaly suggesting autoimmune thyroid disease 
  • Lymphadenopathy or splenomegaly that suggests lymphoma
  • Joint examination for any evidence of connective tissue disease, rheumatoid arthritis, or systemic lupus erythematosus (SLE)
  • Lungs for pneumonia or bronchospasm (asthma)
  • Extremities for evidence of bacterial or fungal infection

Causes

• The cause of acute generalized urticaria often is undetermined (some sources report that the cause is undetermined in more than 60% of cases). Known causes include the following:
• • Infections (eg, pharyngitis, GI infections, genitourinary infections, respiratory infections, fungal infections [eg, dermatophytosis], malaria, amebiasis, hepatitis, mononucleosis, coxsackievirus, mycoplasmal infections, infestations [eg, scabies], HIV, parasitic infections [eg, ascariasis, strongyloidiasis, schistosomiasis, trichinosis])
  • Foods (particularly shellfish, fish, eggs, cheese, chocolate, nuts, berries, tomatoes)
  • Drugs (eg, penicillins, sulfonamides, salicylates, NSAIDs, codeine, antihistamines)
  • Environmental factors (eg, pollens, chemicals, plants, danders, dust, mold)
  • Exposure to latex
  • Exposure to undue skin pressure, cold, or heat
  • Emotional stress
  • Exercise
  • Pregnancy (ie, pruritic urticarial papules and plaques of pregnancy [PUPPP])
• Chronic urticaria can be related to all of the above as well as to the following:
• • Autoimmune disorders (SLE, rheumatoid arthritis, polymyositis, thyroid autoimmunity, and other connective tissue diseases); probably up to 50% of chronic urticaria is autoimmune.
  • Cholinergic urticaria induced by emotional stress, heat, or exercise (Examine for other signs of cholinergic stimulation including lacrimation, salivation, and diarrhea.)
  • Chronic medical illness, such as hyperthyroidism, amyloidosis, polycythemia vera, malignant neoplasms, and lymphoma
  • Cold urticaria, cryoglobulinemia, cryofibrinogenemia, or syphilis
  • Mastocytosis
  • Muckle-Wells syndrome
  • Familial cold autoinflammatory syndrome
• The etiology of chronic urticaria is undetermined in at least 80-90% of patients.
• Urticaria pigmentosa is a familial dermatologic disorder characterized by hyperpigmented (yellow, tan, or brown) papules or plaques that may be associated with lymphoproliferative disorders. These lesions are composed of mast cells. When the skin overlying an individual lesion of urticaria pigmentosa is stroked, a linear wheal is formed; this characteristic and diagnostic sign is known as the Darier sign.
• Recurrent urticaria can be related to the following:
• • Sun exposure (solar urticaria, occurring only on skin exposed to the sun)
  • Exercise (cholinergic urticaria)
  • Emotional or physical stress
  • Water (aquagenic urticaria)

DIFFERENTIALS

Section 4 of 11  

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

Other Problems to be Considered

Contact dermatitis
Neurodermatitis
Eczema

WORKUP

Section 5 of 11  

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

Lab Studies

• For acute urticaria, laboratory studies generally are not indicated. The patient's history and physical examination should direct any diagnostic studies.¹
• For chronic or recurrent urticaria, basic laboratory studies should include a CBC, erythrocyte sedimentation rate, TSH and an ANA looking for possible causes of the urticaria.²

Imaging Studies

• Imaging studies generally are not indicated unless a specific finding on clinical examination or history suggests an underlying etiology that may warrant further diagnostic studies.^{1, 2}

Procedures

If urticarial vasculitis is suspected (urticaria lasting longer than 24 h; significant pain as well as pruritus), a punch biopsy of the lesion should be performed and sent to the pathology lab to look for leukocytoclastic vasculitis.³

TREATMENT

Section 6 of 11  

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

Prehospital Care

• Timely transport to the ED for any patient with signs or symptoms of an allergic reaction, including urticaria, angioedema, or anaphylactic shock is essential. Acute urticaria may progress to life-threatening angioedema and/or anaphylactic shock in a very short period of time, although it usually presents as rapid-onset shock with no urticaria or angioedema.¹
• If associated angioedema is present, prehospital administration of 0.3-0.5 mg of intramuscular epinephrine may be warranted.
• If associated bronchospasm is present, prehospital nebulized albuterol may be warranted.
• Other measures may be appropriate, such as continuous ECG, blood pressure and pulse oximetry monitoring; administering intravenous crystalloids if the patient is hypotensive; and administering oxygen.
• Diphenhydramine (25 mg IV or 50 mg IM or PO) or hydroxyzine (50 mg IM or PO) should be administered.⁴

Emergency Department Care

The management of urticaria is straightforward and typically is not altered by underlying etiology. The mainstay is avoidance of further exposure to the antigen.

• Antihistamines, primarily those that block the H1 receptors, are the first line of therapy for urticaria.⁴  
• • Diphenhydramine and hydroxyzine are the most commonly used H1-blocking antihistamine. They act more rapidly than the minimally sedating H1-blocking antihistamines. These medications are potentially sedating, and the patient should not be allowed to drive within 6 hours of their administration.
  • H1-blocking antihistamines are effective in relieving the pruritus and rash of acute urticaria in most cases.
• Newer H1-blocking minimally sedating antihistamines are now available and include fexofenadine, loratadine, desloratadine, cetirizine, and levocetirizine.⁵ These are used primarily in the management of chronic urticaria rather than acute urticaria.⁶ However, if acute urticaria persists for more than 24-48 hours, the minimally sedating antihistamines should be prescribed, with supplementation with the sedating antihistamines if the pruritus and urticaria are refractory to the longer-acting, minimally sedating antihistamines.⁴
• H2 antihistamines, such as cimetidine, famotidine, and ranitidine, may have a role when used in combination with H1 antihistamines in selected instances of urticaria. H1 and H2 antihistamines are thought to have a synergistic effect and often result in a more rapid and complete resolution of urticaria than H1 antihistamines alone, especially if given simultaneously intravenously.⁷ Oral H2 antihistamines may occasionally be effective in patients with both acute and chronic urticaria refractory to H1 blockers alone.^{1, 8}
• Doxepin is an antidepressant and an antihistamine that blocks both H1 and H2 receptors and may be effective in refractory cases of urticaria in doses of 25-50 mg at bedtime or 10-25 mg 3-4 times a day.⁹
• Glucocorticoids stabilize mast cell membranes and inhibit further histamine release. They also reduce the inflammatory effect of histamine and other mediators.  
• • The efficacy of glucocorticoids in acute urticaria remains controversial. In one study, acute urticaria improved more quickly in the group treated with prednisone than in the group treated with placebo.¹⁰
  • In adults, 40-60 mg daily of prednisone for 5 days is a reasonable therapeutic regimen. In children, the treatment is 1 mg/kg/d for 5 days. Tapering of the corticosteroid dose is not necessary in most cases of acute urticaria.
• The efficacy of epinephrine in acute urticaria is controversial.⁴ If angioedema is present with urticaria, 0.3-0.5 mg of epinephrine should be administered intramuscularly. Remember that ACE-inhibitor–induced angioedema usually does not respond to epinephrine or most other common therapies, since it is not an IgE-mediated process.¹⁰
• The use of methotrexate, colchicine, dapsone, indomethacin, and hydroxychloroquine may be effective in the management of vasculitic urticaria.³
• Patients with chronic or recurrent urticaria should be referred to a dermatologist for further evaluation and management.

Consultations

Consultation with or referral to a dermatologist, allergist, immunologist, or rheumatologist may be appropriate in selected cases, particularly in cases of complicated, recurrent, refractory, severe, or chronic urticaria. Dermatology referral is mandatory if vasculitic urticaria is suspected.

MEDICATION

Section 7 of 11  

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

Most cases of simple acute urticaria can be treated with H1 antihistamine agents. In cases of severe or persistent urticaria, H2 antihistamines may be added and are probably additive to the effect of H1 antihistamines if given simultaneously intravenously. This combination may also be effective orally in a small percentage of patients with chronic urticaria.

Refractory cases of chronic urticaria may improve with glucocorticosteroids. Chronic urticaria may benefit from doxepin, a tricyclic antidepressant with potent antihistamine properties. Because of its significant sedative properties, it should be given at bedtime. Topical therapy with 5% doxepin cream (Zonalon) or capsaicin may also be used in refractory cases. Cyproheptadine may be useful to suppress recurrent cold urticaria. Cyclosporin has recently been shown to be effective in cases of refractory chronic urticaria.

Drug Category: H1-receptor antagonist antihistamines

These agents block the histamine response in sensory nerve endings and blood vessels. They act by competitive inhibition of histamine at the H1 receptor, which mediates wheal and flare reactions, bronchial constriction, mucus secretion, smooth muscle contraction, and edema. They may cause hypotension, CNS depression, urinary retention, and cardiac arrhythmias.

Drug Name	Diphenhydramine (Benadryl, Benylin, Diphen)
Description	Sedating peripheral H1 receptor antagonist. Used for symptomatic relief of allergic symptoms caused by histamine released in response to allergens.
Adult Dose	25-50 mg PO q6-8h prn; 10-50 mg IV/IM q6-8h prn; not to exceed 400 mg/d
Pediatric Dose	12.5-25 mg PO q6-8h prn, or 5 mg/kg/d PO divided q6-8h prn, or 150 mg/m2/d PO divided q6-8h prn; not to exceed 300 mg/d
Contraindications	Documented hypersensitivity
Interactions	Potentiates effect of CNS depressants; because of alcohol content, do not give syrup dosage form to patients taking medications that can cause disulfiramlike reactions; pramlintide and sodium oxybate may potentiate CNS depressant effects of diphenhydramine
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction (anticholinergic side effects)

Drug Name	Cyproheptadine (Periactin)
Description	Sedating H1 antihistamine for symptomatic relief of allergic symptoms caused by histamine released in response to allergens and skin manifestations.
Adult Dose	4 mg PO q8h initial dose, increase by 2 mg q8h to effect; 32 mg/d maximum
Pediatric Dose	Calculate total daily dosage as 0.25 mg/kg (0.11 mg/lb) or 8 mg/m2 <2 years: Not established 2-6 years: 2 mg q8-12h prn 7-14 years: 4 mg q8-12h prn; not to exceed 16 mg/d >14 years: Administer as in adults
Contraindications	Documented hypersensitivity; narrow-angle glaucoma; stenosing peptic ulcer; symptomatic prostatic hypertrophy; bladder neck obstruction; pyloroduodenal obstruction; lower respiratory tract symptoms
Interactions	Potentiates effect of CNS depressants; MAOIs may prolong and intensify anticholinergic and sedative effects
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in patients with predisposition to urinary retention, history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension; may thicken bronchial secretions caused by anticholinergic properties and may inhibit expectoration and sinus drainage

Drug Name	Cetirizine (Zyrtec)
Description	Selectively inhibits peripheral histamine H1-receptors. Minimally sedating.
Adult Dose	5-10 mg PO qd (chronic urticaria)
Pediatric Dose	<6 months: Not established 6-12 months: 2.5 mg PO qd 12-24 months: 2.5 mg PO qd/bid 2-5 years: 2.5-5 mg PO qd >5 years: 5-10 mg PO qd
Contraindications	Documented hypersensitivity
Interactions	Increases CNS toxicity of depressants
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in hepatic or renal dysfunction; doses higher than 10 mg/d may cause drowsiness

Drug Name	Levocetirizine (Xyzal)
Description	Histamine1-receptor antagonist. Active enantiomer of cetirizine. Peak plasma levels reached within 1 h and half-life is about 8 h. Available as a 5-mg breakable (scored) tab. Indicated for seasonal and perennial allergic rhinitis.
Adult Dose	5 mg PO qd in evening CrCl 50-80 mL/min: 2.5 mg (half tab) PO qd in evening CrCl 30-49 mL/min: 2.5 mg PO qod CrCl 10-29 mL/min: 2.5 mg PO 2 times/wk
Pediatric Dose	<6 years: Not established 6-12 years: 2.5 mg (half tab) PO qd in evening >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; CrCl <10 mL/min or hemodialysis; children aged 6-11 y with renal impairment
Interactions	Coadministration with CNS depressants (eg, alcohol, sedative-hypnotics) may increase somnolence; ritonavir increased plasma AUC of measurable cetirizine by 42% and half-life by 53%
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Common adverse effects include somnolence, nasopharyngitis, fatigue, xerostomia, and pharyngitis in adults and children >12 y; pyrexia, somnolence, cough, and epistaxis commonly observed in children 6-12 y; caution with activities requiring mental alertness

Drug Name	Fexofenadine (Allegra)
Description	Selectively inhibits peripheral histamine H1-receptors. Minimally sedating.
Adult Dose	180 mg PO qd (chronic urticaria)
Pediatric Dose	Not indicated for chronic urticaria
Contraindications	Documented hypersensitivity
Interactions	Toxicity increases with coadministration of erythromycin and ketoconazole
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Animal studies using very large doses in first trimester of pregnancy resulted in increased birth defects (not studied in humans); should probably avoid in first trimester of pregnancy; no data available on use while breastfeeding

Drug Name	Loratadine (Claritin, Alavert)
Description	Selectively inhibits peripheral histamine H1-receptors. Minimally sedating.
Adult Dose	10 mg PO qd on empty stomach
Pediatric Dose	<2 years: Not established 2-6 years: 5 mg/d qd >6 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Ketoconazole, erythromycin, procarbazine, and alcohol may increase loratadine levels,
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Initiate therapy at lower dose in liver or renal impairment

Drug Name	Desloratadine (Clarinex)
Description	Long-acting tricyclic histamine antagonist selective for H1-receptor. Major metabolite of loratadine, which after ingestion is extensively metabolized to active metabolite 3-hydroxydesloratadine.
Adult Dose	5 mg PO qd
Pediatric Dose	<6 months: Not established 6-11 months: 1 mg PO qd 12 months to 5 years: 1.25 mg PO qd 6-11 years: 2.5 mg PO qd >12 years: Administer as in adults
Contraindications	Documented hypersensitivity to desloratadine or loratadine
Interactions	Limited data exist; erythromycin and ketoconazole increase desloratadine and 3-hydroxydesloratadine plasma concentrations, but no increase was observed in clinically relevant adverse effects, including QTc
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Animal studies using very large doses in first trimester of pregnancy resulted in increased birth defects (not studied in humans); should probably avoid in first trimester of pregnancy; decrease dose in hepatic or renal impairment; caution in phenylketonuria

Drug Category: Tricyclic antidepressants (TCAs)

These agents are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin. Some TCAs (eg, doxepin) have antihistamine effects, blocking both the H1 and H2 receptors and have been used in the treatment of allergic reactions, especially urticaria.

Drug Category: Glucocorticoids

These agents decrease the inflammation associated with urticaria resistant to H1- and H2-receptor antihistamine therapy. They do not inhibit mast cell degranulation and are of limited efficacy in acute urticaria. They are often effective in chronic urticaria but should be tapered to the lowest effective dose to prevent long-term complications.

Drug Category: H2-receptor antagonists

These are reversible, competitive blockers of histamine at H2 receptors, particularly those in gastric parietal cells. The H2 antagonists are highly selective, do not affect H1 receptors, and are not anticholinergic agents. They block the vasodilation mediated by the H2 receptors in blood vessels, possibly leading to less edema formation in urticaria.

The combination of H1 and H2 antagonists may be useful in acute urticaria as well as chronic idiopathic urticaria not responding to H1 antagonists alone. This combination in IV form also may be useful for itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis.

Drug Name	Ranitidine (Zantac)
Description	H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Adult Dose	150 mg PO bid; not to exceed 600 mg/d 50 mg/dose IV/IM q6-8h; not to exceed 400 mg/d; 50 mg IV with 25 mg diphenhydramine IV for acute urticaria
Pediatric Dose	<12 years: Not established >12 years: 1.25-2.5 mg/kg/dose PO q12h; not to exceed 300 mg/d; 0.75-1.5 mg/kg/dose IV/IM q6-8h; not to exceed 400 mg/d
Contraindications	Documented hypersensitivity
Interactions	Inhibits CYP450 3A4 and 2D6, so may increase the levels of many drugs; may decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in patients with renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Name	Cimetidine (Tagamet)
Description	H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Adult Dose	300-800 mg PO q6-8h; 300 mg IV/IM q6-8h; 300 mg IV with diphenhydramine 25 mg IV for acute urticaria
Pediatric Dose	20-40 mg/kg/d PO/IV/IM qd divided q6h
Contraindications	Documented hypersensitivity
Interactions	Inhibits multiple P450 liver enzymes responsible for the metabolism of many drugs: CYP1A2, 2c19, 2D6, and 3A4; can increase blood levels of amiodarone, some beta-blockers, theophylline, warfarin, tricyclic antidepressants, carbamazepine, phenytoin, cyclosporine, clozapine, fluconazole, metformin, sulfanylureas, quinidine, procainamide, lidocaine, and many other drugs
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	May cause neutropenia, thrombocytopenia, agranulocytosis, aplastic anemia; elderly patients may experience confusional states; in young males, may cause impotence and gynecomastia due to weak antiandrogen properties; may increase levels of many drugs; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

FOLLOW-UP

Section 8 of 11  

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

Further Inpatient Care

• In general, patients with urticaria can be cared for on an outpatient basis unless they progress to laryngeal angioedema and/or anaphylactic shock, or have comorbidities that require inpatient therapy.

Further Outpatient Care

• Most patients with urticaria can be treated at home on H1 antihistamines (ie, diphenhydramine 50 mg q6h or hydroxyzine 50 mg q6h for 24-48 hours) or, in refractory cases, use a combination of H1 and H2 antihistamines plus oral glucocorticoids.
• If the patient has angioedema that is treated successfully in the ED, the patient should be sent home with an EpiPen prescription and told to keep it with him or her at all times.
• Consultation with or referral to a dermatologist, allergist, immunologist, or rheumatologist may be appropriate in cases of suspected urticarial vasculitis and in cases of chronic or recurrent urticaria.

Deterrence/Prevention

• Patients with urticaria should avoid any medication, food, or other allergen that has precipitated urticaria or other serious allergic reaction previously.

Prognosis

• The prognosis in acute urticaria is excellent, with most cases resolving within 1-4 days.
• The prognosis in chronic urticaria is more guarded and depends upon the comorbid disease causing the urticaria as well as the response to therapy.

Patient Education

• Education regarding avoidance of the suspected offending allergen is essential.
• 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 11  

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

Medical/Legal Pitfalls

• Missing the diagnosis of life-threatening laryngeal angioedema in a patient presenting with the primary complaint of urticaria is a pitfall. The physician can avoid this pitfall by always asking the patient if he or she has had a change in his or her voice or hoarseness.
• Missing the diagnosis of anaphylactic shock in a patient presenting with acute urticaria
• Missing the diagnosis of severe asthma in a patient presenting with acute urticaria
• Prescribe medications for urticaria that may have significant drug-drug interactions (especially true with ranitidine and cimetidine, which are both inhibitors of the P450 enzyme system in the liver)

Special Concerns

• Do not miss laryngeal angioedema in a patient presenting with urticaria

ACKNOWLEDGMENTS

Section 10 of 11  

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

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Mary Beth Crawford, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

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

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Article Last Updated: Apr 9, 2008