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Chronic urticaria: Standard management and patient education
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2014. | This topic last updated: Sep 19, 2013.

INTRODUCTION — Chronic urticaria (CU) is defined by the presence of urticaria (hives) on most days of the week, for a duration of longer than six weeks. The prevalence of this disorder is up to one percent of the general population in the United States, and is believed similar around the world [1]. Associated angioedema occurs in about 40 percent of patients with CU and usually affects the lips, cheeks, periorbital areas of the face, extremities, and genitals [2].

The management of CU in most patients, as well as counseling of individuals with this disorder, will be discussed here. Treatment of CU that is refractory to standard management and the diagnosis, pathogenesis, and prognosis of CU are presented separately. (See "Chronic urticaria: Treatment of refractory symptoms" and "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history".)

Terminology — In this review, the term CU refers to patients with isolated chronic idiopathic urticaria (CIU), as well as those with both urticaria and angioedema. Disorders involving isolated angioedema, urticarial vasculitis, and specific physical forms of CU (such as delayed pressure urticaria, cholinergic urticaria, or cold urticaria) are discussed separately. (See "An overview of angioedema: Pathogenesis and causes" and "Urticarial vasculitis" and "Physical urticarias" and "Cold urticaria".)

Chronic autoimmune urticaria — In the discussion below, the terms CU and CIU are used synonymously. Some studies distinguish between patients with and without positive autologous serum skin tests (ASSTs) or other laboratory indicators of an autoimmune process. This distinction is mentioned in the text only if a study found a difference between these two patient groups. The interpretation of a positive ASST in patients with CU is reviewed elsewhere. (See "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history", section on 'Autoimmune theory'.)

PATIENT EDUCATION — Chronic urticaria (CU) causes marked distress to patients because it is physically uncomfortable, waxes and wanes unpredictably, interferes with work/school and sleep, and is often difficult to treat. The severity and duration of symptoms vary among individuals, and the underlying cause is not known in most cases. Furthermore, it can be misinterpreted by others to be infectious and patients may stay home to avoid embarrassment. All of these factors contribute to patient frustration and anxiety.

Reassurance — Patients with CU are often frustrated and fearful, and reassurance is an important component of successful management. There are three important concepts to relay to patients with CU:

  • Patients need to understand that CU is rarely permanent, and that almost 50 percent of patients undergo remission within one year [3].
  • While acute urticaria and angioedema may be manifestations of allergic reactions that can be life-threatening, chronic urticaria is a different disorder that rarely puts the patient at any acute risk.
  • The symptoms of CU can be successfully managed in the majority of patients.

Avoidance of exacerbating factors — No external cause can be identified in 80 to 90 percent of people affected by CU/angioedema. The evaluation and diagnosis of a patient with persistent urticaria are reviewed separately. (See "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history".)

Once the diagnosis of chronic idiopathic urticaria (CIU)/angioedema has been established, the clinician should begin educating the patient about management, including avoidance of things that can aggravate the condition, including:

  • Physical factors — A substantial subset of patients with CU have some flares that are triggered by physical stimuli. Educating patients about this can help them avoid these stimuli or simply make sense of their symptoms. As an example, heat (hot showers, extreme humidity) is a common trigger for many CU patients, and tight clothing or straps can also aggravate symptoms. In contrast, patients in whom physical factors are the main trigger for symptoms are more appropriately diagnosed as having a physical urticarial syndrome, such as cholinergic urticaria or delayed pressure urticaria. Physical urticarias are reviewed separately. (See "Physical urticarias" and "Cold urticaria".)
  • Antiinflammatory medications and alcohol — Nonsteroidal antiinflammatory drugs (NSAIDs) and alcohol worsen symptoms in many patients.

Dietary manipulations — It is particularly important to explain to patients that an undiscovered allergy to food or food additives is not likely to be responsible for their symptoms. IgE-mediated food reactions are not a cause of CU and testing for food allergy is not necessary [4]. (See "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history", section on 'Foods and food additives'.)

Although CU is not a manifestation of IgE-mediated food allergy, food can cause fluctuations in the symptoms of CU that are noticeable to patients. This is believed to be due to the presence of "pseudoallergens," which are substances in food that exacerbate CU. Pseudoallergens include artificial preservatives and dyes in processed foods, as well as naturally-occurring aromatic compounds in certain foods (many fruits and vegetables, seafood, others). Diets free of pseudoallergens are difficult to follow because the array of foods that must be avoided is so broad (table 1).

The utility of pseudoallergen-free diets in CU has been evaluated in uncontrolled studies. One study concluded that adherence to a diet low in pseudoallergens was helpful, since 73 percent of 64 CU patients had either cessation or a significant reduction of symptoms within two weeks of adopting a pseudoallergen-free diet [5]. However, only 19 percent of those who improved developed symptoms when subsequently challenged with individual pseudoallergens on provocation tests, suggesting that no one substance was responsible, and that benefit was dependent upon the strict avoidance of multiple foods. In contrast to the high rates of response in this study, a subsequent larger study of 140 patients placed on a pseudoallergen-free diet found that only 28 percent had a strong or partial response [6]. The foods and other substances that are prohibited in a pseudoallergen-free diet are listed in the table (table 1). Several weeks of adherence to this diet may be necessary for clinical improvement.

The limited clinical relevance of pseudoallergens in CU is also supported by the observation that patients in whom CU has remitted are able to eat anything without recurrence of urticaria [7].

In summary, we do not routinely advise CU patients to adopt pseudoallergen-free diets. However, if a patient is very motivated to try these diets, we do not object.

AGENTS AND EFFICACY — Most patients with chronic urticaria (CU) are initially treated with antihistamines, often in conjunction with limited courses of oral glucocorticoids for refractory symptoms. However, long-term systemic glucocorticoids are associated with significant adverse effects, and persistent symptoms should be treated instead with other immunosuppressive, immunomodulatory, or steroid-sparing agents.

The different medications used in the management of CU and studies of efficacy are discussed in this section. A stepwise approach to therapy, including recommended dosing and monitoring, is presented subsequently. (See 'Stepwise approach to treatment' below.)

H1 antihistamines — H1 antihistamines are the cornerstone of pharmacotherapy for CU and control symptoms to at least some degree in most patients [1,8-10]. Patients show variable responsiveness to antihistamines. The magnitude of effect is difficult to generalize, although in various reports, 50 to 95 percent of patients achieved satisfactory disease control with one or a combination of antihistamines, without other agents [9,11,12].

Several randomized, placebo controlled trials have demonstrated that both the first and second generation H1 antihistamines reduce the major symptoms of CU, (ie, pruritus, wheal (hive) formation, and disruption of sleep and daily activities) [2,13-16]. A systematic review concluded that nonsedating antihistamines improve quality of life for patients with CU [17].

The newer second generation agents (eg, cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine) are generally as effective and better tolerated (ie, less sedative and anticholinergic effects) than moderate doses of the older, first generation antihistamines (eg, hydroxyzine, diphenhydramine, chlorpheniramine, or mizolastine) [18,19].

A few trials have compared different second generation agents [20-23]. Cetirizine and levocetirizine were comparable in effectiveness and performed modestly better than other agents:

  • Cetirizine and levocetirizine were comparable in efficacy in a trial of 50 patients [23].
  • Levocetirizine (5 mg daily) produced a significantly greater reduction in pruritus severity and duration than desloratadine (5 mg daily) in a trial of 886 patients treated for four weeks [20].
  • Cetirizine compared to fexofenadine was significantly more likely to induce clearance of hives (52 versus 4 percent) with a similar rate of improvement of hives (37 versus 42 percent) in 117 patients [22].

A randomized trial comparing levocetirizine and rupatadine (not available in the US) found that rupatadine was more effective and better tolerated [24].

Dosing of second generation agents — As mentioned above, the second generation H1 antihistamines (eg, cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine) are generally as effective and better tolerated than the first generation agents.

Doses of second generation antihistamines as high as four times the recommended dose are advocated in international guidelines on CU, based largely upon expert opinion [9,10,25,26]. However, the limited number of published studies evaluating this approach has not demonstrated a clear increase in efficacy [12,13,27]:

  • A small observational study evaluated 21 CU patients with inadequate response after one to two weeks of cetirizine (10 mg daily) for improvement with cetirizine at a dose of 10 mg twice daily for an additional one to two weeks [28]. Subjects were then randomized to continue at a dose of either 20 mg daily or reduce to 10 mg daily for an additional two weeks. Both groups had improved urticarial scores on cetirizine 20 mg daily, but only the group that remained on the higher dose had continued improvement, with worsening symptoms in the group whose cetirizine dose was reduced.
  • A randomized trial of 80 patients referred to a tertiary center for refractory CU assigned subjects to either levocetirizine or desloratadine [12]. Initial doses were 5 mg of either drug, and doses were doubled at weekly intervals if patients had not responded (with response defined as >50 percent improvement), up to maximal doses of 20 mg by week three. If patients did not respond to 20 mg of one drug, they were then changed to 20 mg of the other during week four. Subjects did not demonstrate increased somnolence with either agent. Among those patients who responded (as defined previously), improvement was achieved in 52, 65, and 74 percent with 5, 10, and 20 mg of levocetirizine respectively, and 41, 56, and 63 percent with the same doses of desloratadine. Of note, there were 13 patients who became symptom free on standard 5 mg doses of either medication, raising the issue of whether these "refractory" subjects had been adherent with previous therapies. There were seven subjects who did not respond to 20 mg of desloratadine, but did respond to 20 mg of levocetirizine. There were no patients who responded to desloratadine after failing levocetirizine, suggesting that levocetirizine was the more effective agent. However, about 15 percent failed to respond to the highest doses of either drug, and overall, only about one-half of patients achieved complete control of symptoms by the conclusion of the trial. In addition, there was no placebo arm. Thus, this approach of doubling the dose stepwise in patients whose symptoms are not controlled appears to be safe for patients, and allows the clinician to individualize treatment to some extent. This study suggests that higher doses of either desloratadine or levocetirizine may be more effective than standard doses.

Studies of other second generation antihistamines have not shown improved efficacy at higher doses [13,27]:

  • A multicenter randomized trial of 418 patients treated with fexofenadine at doses of 20 mg, 60 mg, 120 mg, or 240 mg twice daily found that the three higher doses provided better disease control than the lowest dose (which was below the lowest recommended adult dose), but there were no significant differences in effectiveness among the higher doses [13]. Another study of very similar design, also using fexofenadine, 20 mg, 60 mg, 120 mg, or 240 mg twice daily, found no difference in efficacy among the three highest doses [29].
  • A small observational study of 22 patients found that increasing the cetirizine dose from 10 mg once daily to 10 mg three times daily improved disease control in only one patient [27].

Thus, the evidence for higher doses of second generation antihistamines is mixed and varies for different antihistamines. To summarize [30]:

  • Desloratadine and levocetirizine may be more effective at higher doses and do not cause clinically significant sedation.
  • Fexofenadine is not more effective at higher doses.
  • The evidence for the efficacy of higher doses of cetirizine in CU is conflicting and based on very low quality evidence. Information about sedation at higher doses is lacking.

Dosing of first generation agents — Higher doses of first generation antihistamines have been recommended by several authors, particularly when second generation antihistamines do not produce an adequate response [10]. The primary concern with higher dose therapy is sedation and performance impairment, and clinicians should inform patients specifically about this side effect.

In children younger than two years of age, first generation, sedating antihistamines should be avoided, as these drugs can cause paradoxical agitation and over-the-counter cold remedies containing them have been linked to a small number of deaths in this age group. (See "The common cold in children: Treatment and prevention", section on 'Treatment'.)

Studies of first generation antihistamines in adults, at usual doses, have shown tolerance to performance impairment after three to five days of therapy [31-33]. Studies in patients with CU given higher doses are lacking, although many patients with CU seem to tolerate high doses without difficulty. Based upon this information, some authors suggest a gradual titration of first generation antihistamines. As an example, hydroxyzine can be started at 10 to 25 mg daily and increased in 10 to 25 mg increments every five to seven days to a maximum of 25 to 50 mg four times daily [7,34].

Another approach is to administer first generation antihistamines as a single dose in the evening, in combination with a second generation antihistamine given in the morning [1,34]. First generation antihistamines typically have long half-lives and a single nighttime dose may reduce daytime sedation compared to frequent daytime dosing; however these proposed regimens have not been compared in terms of either efficacy or adverse effects in patients with CU.

H2 antihistamines — Patients whose symptoms are not adequately controlled on H1 antihistamines alone may experience modest improvement with the addition of H2 antihistamines [35,36]. Some studies of H1 and H2 antihistamine combinations have used agents that are metabolized by the same liver enzymes, raising the possibility that the benefit was largely due to increased serum concentrations of one or both drugs, rather than a true synergistic effect [37]. Thus, a trial of H2 antihistamines can be considered as additive therapy in patients whose symptoms do not respond adequately to H1 antihistamines alone.

Topical agents — While there are isolated, anecdotal reports that suggest benefit of some topical agents for CU, routine use is discouraged as they rarely result in sustained improvement and are rarely used as intended outside of clinical trials. Some of the agents that have been used include emollients that contain menthol, phenol or pramoxine, substances that are benign but minimally effective. Others contain high-potency topical corticosteroids, which can cause dermal atrophy, or topical antihistamines (eg, doxepin-containing preparations), which can cause contact sensitization [38].

Systemic glucocorticoids — Systemic (usually oral) glucocorticoids are effective in controlling symptoms in most patients with CU. However, administration beyond several weeks is not justified for a disorder that, in itself, has an excellent long-term prognosis, since glucocorticoids have predictable and significant adverse effects. In addition, a retrospective study found that the addition of glucocorticoids to antihistamines during the initial weeks of treatment did not hasten the time required to achieve control of symptoms, compared with treatment with antihistamines alone [39]. Thus, there is no evidence that glucocorticoids have a disease modifying effect. We view glucocorticoids as rescue therapy that should be used to attain temporary control of severe symptoms. (See "Major side effects of systemic glucocorticoids".)

Most guidelines suggest that oral glucocorticoids be considered as an initial additive therapy for patients with symptoms refractory to one or more antihistamines at full dose [8-10]. Optimal dosing has not been formally studied, although our approach is described below. In many cases, symptoms recur as glucocorticoids are tapered or discontinued, and these agents are not believed to alter the long-term course of the disease. (See 'Systemic glucocorticoids for rescue therapy' below.)

Leukotriene modifiers — Leukotrienes are believed involved in the pathogenesis of urticaria. Activated mast cells generate and release leukotrienes in addition to histamine, and intradermally injected leukotriene D4 causes a strong wheal and flare response [40-42]. Antileukotriene medications include the leukotriene receptor antagonists, montelukast and zafirlukast, as well as the 5-lipoxygenase inhibitor zileuton.

Available evidence suggests that these agents may be useful either as monotherapy or add-on therapy in some patients with CU. One subgroup that may respond more predictably to these agents is patients with CU that is exacerbated by ingestion of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs), since abnormal leukotriene regulation is believed to be important in the pathogenesis of this type of urticaria [43,44]. (See "NSAIDs (including aspirin): Allergic and pseudoallergic reactions".)

  • Case reports described the use of montelukast to block acute urticaria secondary to NSAIDs [45,46], and another described a patient with NSAID-exacerbated CU, who responded to both zafirlukast and zileuton [43].
  • Two small randomized trials found montelukast to be superior to cetirizine and placebo in patients with NSAID-exacerbated CU [47,48].

Patients with the rare disorder of antihistamine-induced urticaria [49] might also benefit from antileukotriene agents. A case report described four such patients, three of whom responded to montelukast [50].

In unselected populations of patients with CU, the data in support of leukotriene modifiers are less robust:

  • Montelukast (10 mg once daily), either alone or in combination with antihistamines, has demonstrated efficacy in randomized controlled trials [36,47,48,51,52]. However, not all trials were positive [53,54], and one found montelukast to be less effective than desloratadine for 160 patients with relatively mild CU [55].
  • Studies of zafirlukast are mixed as well. The combination of zafirlukast and cetirizine was shown to be superior to cetirizine alone in a randomized trial of patients with a positive autologous serum skin test (ASST), but not in patients with a negative ASST [56]. This distinction was not confirmed in a separate open trial [57]. A second randomized trial was negative, showing no statistical difference between zafirlukast and placebo in 52 CU patients [58].
  • Zileuton has not been formally studied in the treatment of CU. The only published experience with pranlukast described two patients who experienced an exacerbation during therapy [59]. No head-to-head studies have compared different leukotriene modifiers in the treatment of CU.

Choice of agent and time to response — The preferred agents are montelukast and zafirlukast, because these drugs are widely available and require no monitoring of laboratory studies. In contrast, zileuton use requires that liver function tests be followed. Time to benefit can be fairly rapid in some patients, while others appear to require several weeks of treatment [60]. One study suggested persistent drug-free remission [48], although most studies did not observe this outcome.


Patients with concomitant borderline or elevated blood pressure — Dihydropyridine calcium channel blockers may reduce the proliferation of stimulated T-lymphocytes and inhibit mast cell mediator release [61,62]. A small, randomized, controlled, crossover trial of 10 patients with chronic idiopathic urticaria (CIU) treated with nifedipine (up to 20 mg three times daily) demonstrated benefit in seven patients, with mild adverse effects [63]. Other evidence consists of case reports.

Advantages of this agent include a relatively rapid therapeutic response, familiarity of clinicians with this class of drug, and wide availability. Thus, a trial of calcium channel blockers may be reasonable for patients who can tolerate the hemodynamic effects, or for those with concomitant hypertension.

In addition, there is preliminary evidence that the presence of systemic hypertension is associated with longer chronic urticaria (CU) duration, as discussed elsewhere. (See "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history", section on 'Natural history and prognosis'.)

Patients with thyroid autoantibodies — Thyroid autoimmunity, as determined by the presence of elevated levels of thyroid peroxidase antibodies or antithyroglobulin antibodies, is found in patients with CU at a greater than expected frequency [64-66]. However, the patient's thyroid status does not necessarily correlate with the presence of urticaria. Patients with CU/angioedema and evidence of thyroid autoimmunity may be euthyroid, hypothyroid, or hyperthyroid [64,67]. (See "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history".)

Patients with thyroid autoantibodies and laboratory evidence of clinical hypothyroidism may benefit from thyroid hormone replacement. In contrast, the treatment of euthyroid patients with CU is controversial. There are several reports of apparently successful treatment of euthyroid patients with thyroid hormone at doses that suppress the level of thyroid stimulating hormone (TSH) [64,65,67-70]. A proposed mechanism of action is reduction in complement activation by the complement controller domain of thyroperoxidase [71]. We have seen some euthyroid patients with thyroid autoantibodies respond to thyroxine therapy without adverse effects, but the results are mixed and unpredictable. If this therapy is used, the uncertain benefits must be balanced with potential risks of iatrogenic hyperthyroidism and osteoporosis [72].

Pregnant or lactating women — Pregnant women with urticaria with/without angioedema should be treated with the least amount of medication possible. Most patients can be treated with H1 antihistamines alone, with occasional short courses of oral glucocorticoids for severe flares. The safety of different antihistamines, leukotriene modifying drugs, and other agents in pregnancy and lactation is discussed separately. (See "Recognition and management of allergic disease during pregnancy", section on 'Urticaria and angioedema'.)

STEPWISE APPROACH TO TREATMENT — This section describes an approach to the treatment of chronic urticaria (CU) using the different medications discussed previously. This approach represents that of the author and editors of UpToDate. Practice Parameters for the management of CU have been published by expert panels of allergists/immunologists and/or dermatologists in the United States, United Kingdom, and Europe [8-10]. The approach described herein is relatively consistent with these practice parameters, although there are differences among these parameters and the best approach is not known. All doses listed are for adults, unless otherwise noted.

Systemic glucocorticoids for rescue therapy — Systemic glucocorticoids may be required periodically to gain temporary control of symptoms during severe exacerbations of urticaria that significantly impair quality of life. These rescue courses of glucocorticoids may be required at any point in therapy and are generally added on to the medications that the patient is already taking. However, long-term (eg, months to years) of systemic glucocorticoid therapy should be avoided, as discussed previously. (See 'Systemic glucocorticoids' above.)

The optimal dose and duration of glucocorticoids used for CU exacerbations has not been systematically studied, and recommendations vary among urticaria specialists. In addition, patients differ in their responsiveness to glucocorticoids in both the dose and duration of treatment required to control symptoms.

We prefer to use relatively brief (ie, 3 to 10 day) courses of prednisone, and typically begin with a dose of 20 mg twice daily for two to three days. Occasional patients require higher initial doses.

Once symptoms are controlled, the dose should be tapered down to 10 mg daily or less, which can typically be done in increments of 10 mg. Rebound worsening of urticaria may occur with tapering or discontinuation of systemic glucocorticoids and if this occurs, we return to the last effective dose and then try to taper again more gradually. Some authors suggest that once the dose has been reduced to 20 mg daily, the frequency of administration may be changed to every other day, and then the dose tapered further.

Step 1: Second generation H1 antihistamine — We administer a second generation antihistamine at standard therapeutic dose as initial therapy. We prefer cetirizine 10 mg once daily, but the following other agents are appropriate alternatives (see 'H1 antihistamines' above):

Step 2: Increase dose — We instruct patients to increase the dose of the second generation antihistamine to twice daily if once daily does not control symptoms adequately within several days. Another option is to add a different second generation antihistamine (eg, fexofenadine 180 mg in the morning, and cetirizine 10 mg at night). This can be particularly helpful when patients develop increased sedation from higher doses of certain agents, such as cetirizine. Dosing up to four times standard doses may be considered with some agents, such as desloratadine and levocetirizine, although it is not useful with fexofenadine. (See 'Dosing of second generation agents' above.)

Step 3: Add or substitute other types of antihistamines — If increased doses of a second-generation H1 antihistamine do not control symptoms, we then either add or substitute a first generation H1 antihistamine at bedtime, or add an H2 antihistamine.

We prefer to add one of the following potent H1 receptor antagonists:

  • Hydroxyzine: This agent may be dosed once at bedtime, or alternatively in divided doses throughout the day. Adults may be given 10 or 25 mg initially at bedtime, and increased in weekly increments as tolerated, typically up to a maximum of 100 mg as a single dose before bedtime. Alternatively, total daily doses of up to 100 to 200 mg may be given, divided into three or four doses in a 24-hour period. Sedating antihistamines may be used cautiously in children. Children ≥6 years of age may be given up to 50 to 100 mg per day in divided doses.
  • Doxepin: Doxepin (in adults), may be initiated at 10 or 25 mg and increasing in weekly increments to 100 to 150 mg, given once at bedtime or alternatively in divided doses throughout the day. Doxepin is generally avoided in children <12 years of age due to limited clinical experience.(See 'H1 antihistamines' above.)
  • Some clinicians add an H2 antagonist, such as ranitidine, 150 mg twice daily, to the patient's H1 antagonist. (See 'H2 antihistamines' above.)

Step 4: Leukotriene modifier — If symptoms are refractory to high-doses or combinations of H1 antihistamines and/or H2 antihistamines, or if patients experience excessive sedation or anticholinergic side effects, we then consider non-antihistamine therapies.

Our preferred initial add-on therapy is a leukotriene modifier. We usually prescribe montelukast 10 mg daily, while maintaining the patient on the highest tolerated dose of H1 antihistamines. We allow at least four weeks to gauge the effect of the leukotriene modifier. If there is no improvement, we discontinue the medication. (See 'Leukotriene modifiers' above.)

Step 5: Consider immunomodulatory and immunosuppressive agents — For patients whose symptoms are refractory to the measures discussed so far in this review, additional therapies should be considered and are presented separately. (See "Chronic urticaria: Treatment of refractory symptoms".)

Maintenance therapy — Many patients with CU require multiple medications to control symptoms fully. Once symptoms have come under control, the patient should be maintained on those agent(s) for a period of time before withdrawal of medications is considered.

The optimal duration of maintenance therapy in a variable disease like CU has not been studied. Patients whose symptoms were easily and completely controlled with one or two agents may begin to taper therapy after a month or two of well-controlled symptoms. For the majority of patients, we generally recommend three months of good control prior to tapering therapies, and we extend this longer for patients with one or more of the following characteristics:

  • Symptoms that were present for years, were very severe, or were difficult to control
  • Concomitant physical urticarias, which tend to be longer-lasting than simple CU
  • Symptoms that are mostly controlled, but still present at a low level

We typically discontinue agents that have been deemed ineffective, including antihistamines in patients who are completely antihistamine resistant. In patients responsive to antihistamine therapy, we gradually reduce antihistamine doses every two to four weeks, beginning with first generation agents. Other agents can be tapered in a similar fashion. In patients dependent on systemic glucocorticoids, we reduce the dose as quickly as possible once their urticaria has been stabilized.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)


  • Patients with chronic urticaria (CU) are often frustrated and anxious. Education and reassurance are critical components of successful management and should begin as soon as the diagnosis is made. (See 'Patient education' above.)
  • Systemic glucocorticoids should be reserved for short-term control of refractory symptoms. (See 'Systemic glucocorticoids for rescue therapy' above.)
  • For all patients with CU, we recommend H1 antihistamines as initial therapy (Grade 1A). We recommend nonsedating second generation agents, rather than first generation agents (Grade 1B). We typically administer cetirizine, 10 mg once daily. (See 'H1 antihistamines' above and 'Step 1: Second generation H1 antihistamine' above.)
  • For patients whose symptoms persist, we suggest either increasing the dose of the nonsedating H1 antihistamine (eg, cetirizine 10 mg twice daily) or adding a different second generation antihistamine (eg, fexofenadine 180 mg in the morning, and cetirizine 10 mg at night) (Grade 2C). (See 'Step 2: Increase dose' above.)
  • For patients whose symptoms persist, we suggest adding or substituting a first generation H1 antihistamine (Grade 2C). It can be administered initially at bedtime, to avoid excessive daytime sedation. Alternatively, it can be given in divided doses throughout the day, starting at low doses and gradually increasing. The patient should be informed about sedation and anticholinergic side effects. Another option is the addition of an H2 antihistamine. (See 'Step 3: Add or substitute other types of antihistamines' above.)
  • For patients whose symptoms persist, we suggest maintaining the highest effective and tolerated dose of H1 antihistamines, and adding montelukast (10 mg daily) (Grade 2C). A trial of two to four weeks should be sufficient to assess response. (See 'Step 4: Leukotriene modifier' above.)
  • Once symptoms are controlled, we continue the drug(s) required for control for a minimum of one to three months before attempting to taper doses or discontinue medications. We extend this maintenance period even longer in patients whose disease was particularly difficult to suppress. (See 'Maintenance therapy' above.)
  • For patients whose symptoms are not controlled by the above stepwise approach, other immunomodulatory or immunosuppressant therapies may be needed. (See "Chronic urticaria: Treatment of refractory symptoms".)

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  1. Kaplan AP. Clinical practice. Chronic urticaria and angioedema. N Engl J Med 2002; 346:175.
  2. Goldsobel AB, Rohr AS, Siegel SC, et al. Efficacy of doxepin in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol 1986; 78:867.
  3. Kozel MM, Mekkes JR, Bossuyt PM, Bos JD. Natural course of physical and chronic urticaria and angioedema in 220 patients. J Am Acad Dermatol 2001; 45:387.
  4. Bernstein IL, Li JT, Bernstein DI, et AL. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol 2008; 100:S1 (Abstract).
  5. Zuberbier T, Chantraine-Hess S, Hartmann K, Czarnetzki BM. Pseudoallergen-free diet in the treatment of chronic urticaria. A prospective study. Acta Derm Venereol 1995; 75:484.
  6. Magerl M, Pisarevskaja D, Scheufele R, et al. Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial. Allergy 2010; 65:78.
  7. Kaplan AP. What the first 10,000 patients with chronic urticaria have taught me: a personal journey. J Allergy Clin Immunol 2009; 123:713.
  8. Zuberbier T, Bindslev-Jensen C, Canonica W, et al. EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of urticaria. Allergy 2006; 61:316.
  9. Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy 2009; 64:1427.
  10. Powell RJ, Du Toit GL, Siddique N, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy 2007; 37:631.
  11. Humphreys F, Hunter JA. The characteristics of urticaria in 390 patients. Br J Dermatol 1998; 138:635.
  12. Staevska M, Popov TA, Kralimarkova T, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol 2010; 125:676.
  13. Nelson HS, Reynolds R, Mason J. Fexofenadine HCl is safe and effective for treatment of chronic idiopathic urticaria. Ann Allergy Asthma Immunol 2000; 84:517.
  14. Ring J, Hein R, Gauger A, et al. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study. Int J Dermatol 2001; 40:72.
  15. Ortonne JP, Grob JJ, Auquier P, Dreyfus I. Efficacy and safety of desloratadine in adults with chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Clin Dermatol 2007; 8:37.
  16. Kamide R, Niimura M, Ueda H, et al. Clinical evaluation of ketotifen for chronic urticaria: multicenter double-blind comparative study with clemastine. Ann Allergy 1989; 62:322.
  17. Grob JJ, Lachapelle JM. Non-sedating antihistamines in the treatment of chronic idiopathic urticaria using patient-reported outcomes. Curr Med Res Opin 2008; 24:2423.
  18. Kalivas J, Breneman D, Tharp M, et al. Urticaria: clinical efficacy of cetirizine in comparison with hydroxyzine and placebo. J Allergy Clin Immunol 1990; 86:1014.
  19. Belaich S, Bruttmann G, DeGreef H, et al. Comparative effects of loratadine and terfenadine in the treatment of chronic idiopathic urticaria. Ann Allergy 1990; 64:191.
  20. Potter PC, Kapp A, Maurer M, et al. Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients. Allergy 2009; 64:596.
  21. Purohit A, Melac M, Pauli G, Frossard N. Comparative activity of cetirizine and desloratadine on histamine-induced wheal-and-flare responses during 24 hours. Ann Allergy Asthma Immunol 2004; 92:635.
  22. Handa S, Dogra S, Kumar B. Comparative efficacy of cetirizine and fexofenadine in the treatment of chronic idiopathic urticaria. J Dermatolog Treat 2004; 15:55.
  23. Garg G, Thami GP. Comparative efficacy of cetirizine and levocetirizine in chronic idiopathic urticaria. J Dermatolog Treat 2007; 18:23.
  24. Maiti R, Jaida J, Raghavendra BN, et al. Rupatadine and levocetirizine in chronic idiopathic urticaria: a comparative study of efficacy and safety. J Drugs Dermatol 2011; 10:1444.
  25. Ortonne JP. Chronic urticaria: a comparison of management guidelines. Expert Opin Pharmacother 2011; 12:2683.
  26. Church DS, Baiardini I, Staevska M, et al. The effectiveness of antihistamines in up to four-times conventional doses on urticarial discomfort and quality of life in difficult to treat urticaria. Abstract 1501, Warsaw XXVIII EAACI Congress, 2009.
  27. Asero R. Chronic unremitting urticaria: is the use of antihistamines above the licensed dose effective? A preliminary study of cetirizine at licensed and above-licensed doses. Clin Exp Dermatol 2007; 32:34.
  28. Kameyoshi Y, Tanaka T, Mihara S, et al. Increasing the dose of cetirizine may lead to better control of chronic idiopathic urticaria: an open study of 21 patients. Br J Dermatol 2007; 157:803.
  29. Finn AF Jr, Kaplan AP, Fretwell R, et al. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol 1999; 104:1071.
  30. Kavosh ER, Khan DA. Second-generation H1-antihistamines in chronic urticaria: an evidence-based review. Am J Clin Dermatol 2011; 12:361.
  31. Schweitzer PK, Muehlbach MJ, Walsh JK. Sleepiness and performance during three-day administration of cetirizine or diphenhydramine. J Allergy Clin Immunol 1994; 94:716.
  32. Hindmarch I, Johnson S, Meadows R, et al. The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare. Curr Med Res Opin 2001; 17:241.
  33. Verster JC, Volkerts ER, van Oosterwijck AW, et al. Acute and subchronic effects of levocetirizine and diphenhydramine on memory functioning, psychomotor performance, and mood. J Allergy Clin Immunol 2003; 111:623.
  34. Khan DA. Chronic urticaria: diagnosis and management. Allergy Asthma Proc 2008; 29:439.
  35. Monroe EW, Cohen SH, Kalbfleisch J, Schulz CI. Combined H1 and H2 antihistamine therapy in chronic urticaria. Arch Dermatol 1981; 117:404.
  36. Wan KS. Efficacy of leukotriene receptor antagonist with an anti-H1 receptor antagonist for treatment of chronic idiopathic urticaria. J Dermatolog Treat 2009; 20:194.
  37. Jáuregui I, Ferrer M, Montoro J, et al. Antihistamines in the treatment of chronic urticaria. J Investig Allergol Clin Immunol 2007; 17 Suppl 2:41.
  38. Ellingsen AR, Thestrup-Pedersen K. Treatment of chronic idiopathic urticaria with topical steroids. An open trial. Acta Derm Venereol 1996; 76:43.
  39. Kim S, Baek S, Shin B, et al. Influence of initial treatment modality on long-term control of chronic idiopathic urticaria. PLoS One 2013; 8:e69345.
  40. Maxwell DL, Atkinson BA, Spur BW, et al. Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects. J Allergy Clin Immunol 1990; 86:759.
  41. Bisgaard H. Vascular effects of leukotriene D4 in human skin. J Invest Dermatol 1987; 88:109.
  42. Wedi B, Novacovic V, Koerner M, Kapp A. Chronic urticaria serum induces histamine release, leukotriene production, and basophil CD63 surface expression--inhibitory effects ofanti-inflammatory drugs. J Allergy Clin Immunol 2000; 105:552.
  43. Ellis MH. Successful treatment of chronic urticaria with leukotriene antagonists. J Allergy Clin Immunol 1998; 102:876.
  44. Asero R. Leukotriene receptor antagonists may prevent NSAID-induced exacerbations in patients with chronic urticaria. Ann Allergy Asthma Immunol 2000; 85:156.
  45. Pérez C, Sánchez-Borges M, Capriles E. Pretreatment with montelukast blocks NSAID-induced urticaria and angioedema. J Allergy Clin Immunol 2001; 108:1060.
  46. Serrano C, Valero A, Picado C. Usefulness of montelukast to prevent adverse reactions to COX-2 selective inhibitors: a case report. J Investig Allergol Clin Immunol 2005; 15:156.
  47. Pacor ML, Di Lorenzo G, Corrocher R. Efficacy of leukotriene receptor antagonist in chronic urticaria. A double-blind, placebo-controlled comparison of treatment with montelukast and cetirizine in patients with chronic urticaria with intolerance to food additive and/or acetylsalicylic acid. Clin Exp Allergy 2001; 31:1607.
  48. Erbagci Z. The leukotriene receptor antagonist montelukast in the treatment of chronic idiopathic urticaria: a single-blind, placebo-controlled, crossover clinical study. J Allergy Clin Immunol 2002; 110:484.
  49. Rodríguez del Río P, González-Gutiérrez ML, Sánchez-López J, et al. Urticaria caused by antihistamines: report of 5 cases. J Investig Allergol Clin Immunol 2009; 19:317.
  50. Catelain A, Freymond N, Queuille E, Nicolas JF. [Urticaria paradoxically aggraved by H1 antihistamines]. Ann Dermatol Venereol 2004; 131:451.
  51. Nettis E, Dambra P, D'Oronzio L, et al. Comparison of montelukast and fexofenadine for chronic idiopathic urticaria. Arch Dermatol 2001; 137:99.
  52. Nettis E, Colanardi MC, Paradiso MT, Ferrannini A. Desloratadine in combination with montelukast in the treatment of chronic urticaria: a randomized, double-blind, placebo-controlled study. Clin Exp Allergy 2004; 34:1401.
  53. Godse KV. Oral montelukast monotherapy is ineffective in chronic idiopathic urticaria: a comparison with oral cetirizine. Indian J Dermatol Venereol Leprol 2006; 72:312.
  54. Kosnik M, Subic T. Add-on montelukast in antihistamine-resistant chronic idiopathic urticaria. Respir Med 2011; 105 Suppl 1:S84.
  55. Di Lorenzo G, Pacor ML, Mansueto P, et al. Randomized placebo-controlled trial comparing desloratadine and montelukast in monotherapy and desloratadine plus montelukast in combined therapy for chronic idiopathic urticaria. J Allergy Clin Immunol 2004; 114:619.
  56. Bagenstose SE, Levin L, Bernstein JA. The addition of zafirlukast to cetirizine improves the treatment of chronic urticaria in patients with positive autologous serum skin test results. J Allergy Clin Immunol 2004; 113:134.
  57. Sanada S, Tanaka T, Kameyoshi Y, Hide M. The effectiveness of montelukast for the treatment of anti-histamine-resistant chronic urticaria. Arch Dermatol Res 2005; 297:134.
  58. Reimers A, Pichler C, Helbling A, et al. Zafirlukast has no beneficial effects in the treatment of chronic urticaria. Clin Exp Allergy 2002; 32:1763.
  59. Ohnishi-Inoue Y, Mitsuya K, Horio T. Aspirin-sensitive urticaria: provocation with a leukotriene receptor antagonist. Br J Dermatol 1998; 138:483.
  60. Mora PM, González Pérez Mdel C, Jiménez Villarruel M, et al. [Therapeutic options in idiopathic chronic urticaria]. Rev Alerg Mex 2005; 52:77.
  61. Kotturi MF, Carlow DA, Lee JC, et al. Identification and functional characterization of voltage-dependent calcium channels in T lymphocytes. J Biol Chem 2003; 278:46949.
  62. Kim YY, Holgate ST, Church MK. Inhibition of histamine release from dispersed human lung and tonsillar mast cells by nicardipine and nifedipine. Br J Clin Pharmacol 1985; 19:631.
  63. Bressler RB, Sowell K, Huston DP. Therapy of chronic idiopathic urticaria with nifedipine: demonstration of beneficial effect in a double-blinded, placebo-controlled, crossover trial. J Allergy Clin Immunol 1989; 83:756.
  64. Leznoff A, Josse RG, Denburg J, Dolovich J. Association of chronic urticaria and angioedema with thyroid autoimmunity. Arch Dermatol 1983; 119:636.
  65. Doutre MS. Chronic urticaria and thyroid auto-immunity. Clin Rev Allergy Immunol 2006; 30:31.
  66. Confino-Cohen R, Chodick G, Shalev V, et al. Chronic urticaria and autoimmunity: associations found in a large population study. J Allergy Clin Immunol 2012; 129:1307.
  67. Rumbyrt JS, Katz JL, Schocket AL. Resolution of chronic urticaria in patients with thyroid autoimmunity. J Allergy Clin Immunol 1995; 96:901.
  68. Dreyfus DH, Schocket AL, Milgrom H. Steroid-resistant chronic urticaria associated with anti-thyroid microsomal antibodies in a nine-year-old boy. J Pediatr 1996; 128:576.
  69. Gaig P, García-Ortega P, Enrique E, Richart C. Successful treatment of chronic idiopathic urticaria associated with thyroid autoimmunity. J Investig Allergol Clin Immunol 2000; 10:342.
  70. Monge C, Demarco P, Burman KD, Wartofsky L. Autoimmune thyroid disease and chronic urticaria. Clin Endocrinol (Oxf) 2007; 67:473.
  71. Kirkpatrick CH. A mechanism for urticaria/angioedema in patients with thyroid disease. J Allergy Clin Immunol 2012; 130:988.
  72. Kisakol G, Kaya A, Gonen S, Tunc R. Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism. Endocr J 2003; 50:657.
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