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Urticaria: Treatment & Medication
Updated: Jun 5, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Food/symptom diaries
- For cases of acute urticaria (<6 wk) or to try to pinpoint a trigger, having the patient complete a food diary or symptom diary is sometimes helpful. For a preestablished duration (eg, 2 wk), the patient should record all foods that were eaten and all activities in which the patient was involved for 6-8 hours prior to the onset of an episode of urticaria.
- In a small number of cases, a pattern may emerge, pinpointing the offending agent.
- Excessive or prolonged use of a food or symptom diary is unlikely to be of benefit.
- Avoidance
- If a trigger can be identified, avoidance is the most effective form of management. This would include any food, medication, physical agent, or other factor that triggers the urticaria.
- Aspirin, NSAIDs,44,45 opiates, and alcohol have been reported to be nonspecific triggers of urticaria and might lower the threshold for urticaria in selected patients. Therefore, some specialists advise all patients with urticaria to avoid these agents. However, little experimental evidence is available to support this recommendation.
- Most cases of urticaria respond to pharmacotherapy (see Medication).
- Immunomodulatory and anti-inflammatory therapy
- Cyclosporin has been shown to be effective in two double-blind placebo-controlled studies. Intravenous gammaglobulin and plasmapheresis have been described as useful in a limited number of case studies.46,47,48,49 They can be a consideration in severe urticaria, particularly of the autoimmune type that is unresponsive to medications, but such treatment is usually only initiated by specialists with considerable expertise in urticaria.
- Colchicine and dapsone have also been reported to be useful for refractory urticaria and urticarial vasculitis,50,51 perhaps because of their ability to modulate PMN function. PMNs and a mixed infiltrate can be present in some urticarial lesions, particularly urticaria that is severe or refractory to antihistamine treatment.
- Some reports describe the effectiveness of the antileukotriene agents in urticaria,52,53 but extensive clinical trials have not been performed, so their usefulness is still questionable. Clinical trials might in the future support the theory that the antileukotriene agents can provide a synergistic response when used in conjunction with antihistamines.
- Early case reports and a clinical trial of omalizumab (monoclonal antibody to IgE) in chronic urticaria appear promising, but considerable further study is needed.54
- Because the use of the aforementioned agents is not widespread, details of dosage and administration are not provided, but references are listed in the bibliography. The use of corticosteroids is more common and is discussed in Medication.
- Complementary and alternative medicine: Alternative therapies for urticaria have not been properly evaluated and, therefore, are not recommended.
- Potential therapies in the future: Because physicians now know that a large number of cases of CIU appear to be autoimmune, focused targeting of the autoimmune process may be a potential form of therapy if the autoimmune cause is further verified in clinical studies.
Consultations
A primary care provider can manage most cases of acute urticaria, as well as uncomplicated cases of chronic urticaria.
If a trigger is easily identified and avoidance leads to resolution, then referral is not necessary. If an allergic trigger is suspected but not easily identified, then referral to an allergy specialist is warranted.55 Similarly, if avoidance of a trigger does not lead to resolution or if the patient does not respond well to antihistamines, then referral to an allergist or dermatologist is warranted.55
Diet
Dietary modification is only necessary if food allergy or food additive hypersensitivity has been established. Food additives or preservatives have been reported to cause chronic urticaria in 3-4% of cases, but the data are scarce and questionable (see Causes).
Medication
Most cases of acute and chronic urticaria respond to pharmacotherapy. Use of antihistamines is the mainstay of therapy. In acute cases, a short course of steroids can be very effective. Long-term treatment with steroids should be avoided, if possible, but may be necessary in severe cases. A number of other classes of medicines have been found to be effective, mostly on an experimental basis. If urticaria does not respond to antihistamine treatment (with the possible addition of a short course of steroids), then referral to a specialist is indicated.
H1 antagonists (antihistamines)
Primary agents used for urticaria.25 The older, first-generation H1 antagonists (eg, diphenhydramine, hydroxyzine) are effective in reducing the lesions and pruritus but can produce a number of adverse effects, such as drowsiness and anticholinergic effects.
They can be used as primary treatment of acute episodes, but the adverse effects may limit their usefulness for chronic urticaria. Some patients seem to develop a tolerance to the adverse effects with prolonged use, but they may still experience cognitive impairment, and their driving skills may still be affected.
The first-generation agents can sometimes be useful if administered at bedtime because the sedative effects can help with sleep, but the sedation and cognitive effects may continue until the next day. The newer second-generation antihistamines are nonsedating in most patients, with very few side effects reported (cetirizine can cause drowsiness in up to 10% of patients).56 Therefore, many specialists prefer the use of second-generation agents for chronic urticaria, with first-generation agents reserved for acute or refractory cases. The experimental evidence comparing the various possible regimens and rates of adverse effects in the long term is still minimal.
Any patient who is taking a medication that has potential sedative effects should be cautioned about driving and operating heavy machinery. Commonly used first-generation agents include diphenhydramine, hydroxyzine, doxepin, chlorpheniramine, and cyproheptadine. The second-generation agents that are currently available in the United States are cetirizine, levocetirizine, desloratadine, loratadine, and fexofenadine. All five are active in chronic urticaria. They have not been extensively compared with each other for this indication.
Loratadine (Claritin)
Tolerated very well, with a rate of sedation that is not significantly different from placebo. The once-daily dosing makes it convenient.
Adult
10 mg PO qd
Pediatric
<6 years: Not established
>6 years: Administer as in adults
Ketoconazole, erythromycin, procarbazine, and alcohol may increase loratadine levels
Documented hypersensitivity
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 impairment; caution in pregnancy and lactation
Desloratadine (Clarinex)
Long-acting tricyclic histamine antagonist selective for H1 receptor. Is a major metabolite of loratadine, which, after ingestion, is metabolized extensively to active metabolite 3-hydroxydesloratadine.
Adult
5 mg PO qd
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Limited data exist; erythromycin and ketoconazole increase desloratadine and 3-hydroxydesloratadine plasma concentrations, but no increase in clinically relevant adverse effects, including QTc, was observed
Documented hypersensitivity
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
Decrease dose in hepatic impairment; rarely causes pharyngitis or dry mouth
Fexofenadine (Allegra)
A second-generation agent that is effective in urticaria.57 Tolerated very well, with a rate of sedation that is not significantly different from placebo.
Adult
60 mg IR PO bid (maximum FDA-approved dose) or 180 mg SR PO qd
Pediatric
<6 years: Not established
6-12 years: 30 mg PO bid
>12 years: Administer as in adults
Levels may increase with coadministration of erythromycin and ketoconazole
Documented hypersensitivity
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
Adjust dose in renal impairment; caution in pregnancy and lactation
Levocetirizine (Xyzal)
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 uncomplicated skin manifestations of chronic idiopathic urticaria
Adult
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
<6 years: Not established
6-12 years: 2.5 mg (half tab) PO qd in evening
>12 years: Administer as in adults
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%
Documented hypersensitivity; CrCl <10 mL/min or hemodialysis; children aged 6-11 y with renal impairment
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
Cetirizine (Zyrtec)
Second-generation agent that is frequently used in urticaria. Once-daily dosing makes it convenient. Sedation occurs in approximately 10% of patients. Dosing qhs may be useful if sedation is a problem. Although the standard dose is 5-10 mg qd, some specialists increase this to 10 mg bid for chronic urticaria that is not responding to the usual FDA-approved maximum dose.
Adult
5-10 mg PO qd
Pediatric
<6 years: Not established
>6 years: 5-10 mg PO qd
Increases CNS toxicity of depressants; theophylline decreases clearance of cetirizine
Documented hypersensitivity
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; 10 mg/d may cause drowsiness in approximately 10% of patients
Diphenhydramine (Benadryl, Benylin)
A common first-generation agent that is available without a prescription in the United States.
Adult
25-50 mg PO/IV/IM q4-6h
Pediatric
5 mg/kg/d PO/IV/IM divided tid/qid; not to exceed 300 mg/d
Potentiates effect of CNS depressants; due to alcohol content, do not administer syrup dosage form to patient taking medications that can cause disulfiramlike reactions
Documented hypersensitivity; MAOIs
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 glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur
Cyproheptadine (Periactin)
First-generation agent. Historically has been a drug of choice for prophylaxis of primary acquired cold-induced urticaria.
Adult
2-4 mg PO tid
Pediatric
0.25 mg/kg/d PO divided bid/tid
Potentiates effects of CNS depressants; MAOIs may prolong and intensify anticholinergic and sedative effects of antihistamines
Documented hypersensitivity; glaucoma; symptomatic prostatic hypertrophy; bladder neck obstruction; pyloroduodenal obstruction; severe lower respiratory tract symptoms
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with a predisposition to urinary retention, poorly controlled asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension; may thicken bronchial secretions caused by anticholinergic properties and may inhibit expectoration and sinus drainage
Chlorpheniramine (Chlor-Trimeton)
First-generation agent. One of the safest antihistamines to use during pregnancy.
Adult
4 mg PO q4-6h
10-20 mg per dose IV/IM/SC; not to exceed 40 mg/d
Pediatric
<2 years: Not established
2-6 years: 1 mg PO q4-6h; not to exceed 4 mg/d
6-12 years: 2 mg PO q4-6h; not to exceed 12 mg/d
>12 years: Administer as in adults
CNS toxicity increases with coadministration of other CNS depressants, tricyclic antidepressants, MAOIs, and phenothiazines
Documented hypersensitivity; asthma attacks; narrow-angle glaucoma; symptomatic prostate hypertrophy; bladder neck obstruction; pyloroduodenal obstruction
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause significant confusional symptoms; not for administration to premature or full-term neonates
Hydroxyzine (Atarax, Vistaril, Vistazine)
Effective first-generation agent, but frequently produces sedation, particularly with higher doses. Historically has been considered a drug of choice for cholinergic urticaria. SC and IV are not recommended administration routes.
Adult
10-100 mg PO/IM q6-8h
Pediatric
0.6 mg/kg/dose PO q6h
0.5-1 mg/kg/dose IM q4-6h
CNS depression may increase with alcohol or other CNS depressants
Documented hypersensitivity
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
Associated with clinical exacerbations of porphyria (may not be safe for porphyric patients); ECG abnormalities (alterations in T waves) may occur; may cause drowsiness
Doxepin (Sinequan)
A tricyclic antidepressant that has potent H1-blocking activity as well as H2 blocking activity, making it quite useful for urticaria.58 However, it has very potent sedative and anticholinergic effects. Can be quite effective if used at bedtime, because the sedative effects can help an itching patient sleep. Can be helpful for cold-induced urticaria.
Adult
10-150 mg/d PO hs or divided bid/tid
Pediatric
<12 years: Not recommended
>12 years: 25-50 mg/d PO hs or bid/tid and increase gradually to 100 mg/d
Decreases antihypertensive effects of clonidine but increases effects of sympathomimetics and benzodiazepines; antagonized by phenytoin, carbamazepine, and barbiturates
Documented hypersensitivity; urinary retention; acute recovery phase following myocardial infarction; glaucoma
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
Caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, and patients receiving thyroid replacement therapy
H2 antagonists (antihistamines)
These drugs are usually used to decrease gastric acid secretion. When used as a single agent for urticaria, they are not effective. However, the combination of an H1 antagonist with an H2 antagonist has been shown to be more effective than an H1 antagonist alone.59 Any of the H2 blockers can be used. Two of the most commonly used agents are ranitidine and cimetidine.
Cimetidine (Tagamet)
If no response to H1 antagonist alone occurs, coadministration with this H2 antagonist can be useful to treat urticaria.
Adult
300 mg PO qid or 400 mg PO bid
Pediatric
Infants: 10-20 mg/kg/d PO q6h
Children: 20-40 mg/kg/d PO in divided doses separated at least 6 h
Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Elderly patients may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur
Ranitidine (Zantac)
H2 antagonist that, when combined with an H1 type, may be useful in treating urticaria when urticaria is not responsive to H1 antagonists alone.
Adult
150 mg PO bid
Pediatric
1.5-2 mg/kg per dose PO bid
May alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal function or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
Corticosteroids
In some instances of acute or chronic urticaria, antihistamines may fail, even at high doses, or side effects may be problematic. Mediators other than histamine may be involved. In such situations, urticaria should respond to corticosteroids. If not, then consider the possibility of another disease process (eg, malignancy, mastocytosis, vasculitis). Corticosteroids may also be used in urticarial vasculitis, which usually does not respond to antihistamines.
A short course of an oral corticosteroid (administered daily for 5-7 d, with or without a taper) or a single dose of a long-acting injectable steroid is not usually associated with long-term sequelae and can be helpful when used for an acute episode of urticaria nonresponsive to antihistamines.2
Because of adverse effects of chronic or recurrent use of systemic corticosteroids, the long-term use of these agents should be avoided in chronic urticaria, when possible. If urticaria is severe and cannot be safely controlled with other medications, low-dose therapy and/or alternate day therapy can be considered.
A large number of preparations are available. Representative examples are prednisone, prednisolone, methylprednisolone, and triamcinolone.
Prednisolone (Pediapred, Prelone, Delta-Cortef)
Available in both tablet and liquid forms. Reduces capillary permeability.
Adult
40-60 mg/d PO qd or divided bid
Pediatric
0.5-2 mg/kg/d PO divided bid/qid
Decreases effects of toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects of corticosteroids
Documented hypersensitivity; viral, fungal, or tubercular skin diseases
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, and infections may occur with glucocorticoid use
Methylprednisolone (Medrol, Depo-Medrol, Solu-Medrol)
For treatment of severe urticaria reactions. Reverses increased capillary permeability.
Adult
4-48 mg/d PO
Acetate/Depo-Medrol: 40-120 mg IM single dose; should not be repeated because knowing whether urticaria has resolved due to the prolonged effect of this medication is difficult
Sodium succinate/Solu-Medrol: 10-60 mg/dose IV/IM; this drug is most often used for acute urticaria associated with an allergic emergency and is not used for chronic urticaria
Pediatric
0.16-0.8 mg/kg/d PO divided bid/qid
Sodium succinate/Solu-Medrol: 0.5-2 mg/kg per dose IV/IM repeated at intervals depending on clinical response; this drug is most often used for acute urticaria associated with an allergic emergency and is not used for chronic urticaria
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Documented hypersensitivity; viral, fungal or tubercular infections
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
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use
Prednisone (Deltasone, Orasone, Meticorten)
A commonly used oral agent. Must be metabolized to the active metabolite prednisolone for effect. Conversion may be impaired in liver disease.
Adult
40-60 mg/d PO divided 1-2 doses/d
Pediatric
0.5-2 mg/kg/d PO divided 1-4 doses/d
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; active peptic gastrointestinal bleeding
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
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Adrenergic agents
For use if urticaria is accompanied by a potentially life-threatening condition, such as anaphylactic shock, respiratory tract angioedema (which may manifest as stridor), or significant wheezing.
Epinephrine (Adrenalin, Sus-Phrine, Epi-Pen, Ana-Guard, Twinject)
Not indicated in uncomplicated urticaria. Any patient who has had a potentially life-threatening allergic reaction should have injectable epinephrine available for use at all times (eg, portable Epi-Pen). Any use of epinephrine necessitates an immediate evaluation in the nearest emergency department. Intramuscular administration of epinephrine is preferred over subcutaneous.
Adult
0.2-0.5 mg IM/SC single dose; can be repeated in 15- to 20-min intervals prn
Most single-dose autoinjectors administer a dose of 0.3 mg
IM administration has been associated with a faster time of onset than SC when studied in pediatric and adult populations
Pediatric
0.01 mg/kg, up to 0.5 mg, IM/SC single dose; can be repeated in 15- to 20-min intervals prn
IM administration has been associated with a faster time of onset than SC when studied in pediatric and adult populations
Increases toxicity of beta- and alpha-blocking agents and that of halogenated inhalational anesthetics
Documented hypersensitivity; coronary insufficiency; cardiac arrhythmias; glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; use with caution during labor (may delay second stage of labor)
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
Caution in elderly patients and patients with diabetes mellitus, cardiovascular diseases, hyperthyroidism, cerebral arteriosclerosis, Parkinson disease, and pregnancy
More on Urticaria |
| Overview: Urticaria |
| Differential Diagnoses & Workup: Urticaria |
 Treatment & Medication: Urticaria |
| Follow-up: Urticaria |
| Multimedia: Urticaria |
| References |
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Further Reading
Keywords
urticaria, hives, acute urticaria, chronic urticaria, chronic idiopathic urticaria, CIU, angioedema, welts, pruritus, dermographism, erythema, itching, delayed pressure urticaria, urticarial vasculitis, anaphylaxis
