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Keywords:

  • consensus;
  • SIGN;
  • treatment guideline;
  • urticaria;
  • wheal

Abstract

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound impact on the quality of life, and effective treatment is therefore required. The recommended first line treatment are nonsedating H1 antihistamines. They have proven to be effective in double-blind controlled studies, but dosages increased up to fourfold over the recommended doses may be necessary. However, for different urticaria subtypes and in view of individual variation in the course of the disease and response to treatment, additional or alternative therapies may be required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and formally approved by the European Union of Medical Specialists (UEMS).

Abbreviations:
AH

antihistamine

ns

nonsedating

RCT

randomized controlled trial

s

sedating

sg

second generation

This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. The authors as members of the panel had prepared their suggestions regarding the treatment of urticaria in advance, based on the existing consensus paper of the first symposium in 2000 (1). These suggestions were then discussed in detail among the panel and with the participants of the meeting, and consensus was reached using a simple voting system. With over 400 participants specialized in the field of urticaria from more than 20 countries, this consensus also includes any possible regional differences in therapeutic approach.

Although urticaria is elicited by a great diversity of factors and clinically presents in a highly variable way, its treatment follows the same principles. The therapy of urticaria is best subdivided into three basic lines of approach, which should be followed in each patient.

Avoidance elimination or treatment of the eliciting stimulus or cause

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

This approach is the most desirable since it is curative, but it is unfortunately not applicable in the majority of patients as the exact eliciting stimulus is frequently unknown. It can however be instituted for the rare patients with IgE-mediated urticaria and for all patients with physical urticaria. In the latter group, the impact of physical stimuli can be diminished and symptoms ameliorated by appropriate measures (e.g. cushioning in pressure urticaria). In chronic urticaria treatment of associated infectious and/or inflammatory processes, including Helicobacter pylori-associated gastritis, parasitic diseases and cancer, or of food and drug intolerance can be curative or at least helpful.

Therapy of target tissues of mast cell mediators

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

Currently, the most frequently used therapy aims at inhibiting the effect of mast cell mediators on the target tissue and thus at the suppression of symptoms.

The specific treatment options in these three categories have been evaluated in this guideline.

Methods

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

Studies were evaluated using the Methodology Checklist 2 for Randomized Controlled Trials of the Scottish Intercollegiate Guidelines Network (SIGN) resulting in the following 3-level code: ++, +, −. This code, together with the study type, decided the Level of Evidence (1++ to 1, 2++ to 2, 3, and 4) that led to the Grade of Recommendation (A–D). Literature search was done using PubMed/MEDLINE and EMBASE, in part also hand-searching. Studies that had no English abstract or investigated primarily first generation antihistamines, e.g. diphenhydramine, hydroxyzine, acrivastine, and also terfenadine and astemizole, which are no longer recommended due to adverse effects, were excluded.

Eliciting stimuli

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

With this therapeutic approach, an exact diagnosis is a basic prerequisite. If remission on elimination or avoidance of the suspected agent occurs, recurrence of symptoms on re-exposure provides more proof of its causative nature since spontaneous remission of urticaria might also occur incidentally on elimination of a suspected cause.

Drugs

When such agents are suspected in the course of diagnosis, they should be omitted entirely or substituted by another class of agents if indispensable. Drugs causing pseudoallergic reactions (the prototype being ASA) cannot only elicit, but also aggravate pre-existing chronic urticaria (2), so that elimination will only improve symptoms.

Physical stimuli

Avoidance of physical stimuli for the treatment of physical urticaria is desirable, but not always simple. Detailed information about the physical properties of the respective stimulus should make the patient sufficiently knowledgeable to recognize and control his exposure in normal daily life. Thus, it is important in demographic urticaria as well as in delayed pressure urticaria to point out that pressure is defined as force per area and that simple devices, such as broadening of the handle of heavy bags or reducing friction in case of demographic urticaria, may already be helpful in the prevention of symptoms. Similar considerations hold for cold urticaria. Here, the impact of the chill factor in cold winds needs to be remembered. For solar urticaria, the exact identification of the range of eliciting wavelengths may be important for the appropriate selection of sunscreens or for the selection of light bulbs with a UV-A filter. However, in many patients, the threshold for the individual eliciting stimulus is low and thus, total avoidance of symptoms is virtually impossible.

Eradication of infectious agents and treatment of inflammatory processes

In contrast to physical urticaria where coexisting, potentially disease-sustaining factors are only found in cold and demographic urticaria, chronic urticaria is often associated with a variety of inflammatory or infectious processes (3). This is regarded as significant in some instances. These infections include those of the gastrointestinal tract like H. pylori (4) or bacterial infections of the nasopharynx, which should be treated appropriately. Parasites, a rare cause of urticaria in industrial countries, should be eliminated (5). In the past, intestinal candidosis has been regarded as a highly important eliciting factor for chronic urticaria (6), but more recent findings fail to support a significant causative role (7). Nevertheless, it is recommended that massive candidosis should be treated.

Apart from infectious diseases, chronic inflammatory processes due to diverse other diseases have been identified as causative for urticaria in the recent past. This holds particularly for gastritis, reflux esophagitis or inflammation of the bile duct or bile gland (7, 8).

Removal of FcɛRI autoantibodies

There is currently little experience in the treatment of chronic urticaria by removal of autoantibodies. Plasmapheresis has been shown to be of temporary benefit in individual, severely affected patients (9, 10). Alternatively, immunological treatment with agents inhibiting antibody formation like cyclosporin as one of their actions (11–14) or high dose immunoglobulin infusions (15) have been proven to be helpful. Due to high costs, these therapies should be reserved for autoantibody-positive chronic urticaria patients unresponsive to other forms of treatment.

Dietary management

IgE-mediated food allergy is rare in urticaria (7, 16). If identified, the specific food allergens need to be omitted as best as possible. In a subgroup of chronic urticaria patients pseudoallergic reactions to naturally occurring food ingredients and in some cases to food additives are seen (7, 16–18). In these cases a diet containing only low levels of natural as well as artificial food pseudoallergens should be instituted and maintained for a prolonged period of at least 3–6 months. During this time spontaneous remission is achieved in approximately 50% of patients. It should be underlined that avoidance of type I – allergens clears urticaria symptoms within 24–48 h if relevant allergens are rapidly eliminated, whereas in pseudoallergy, a diet must often be maintained for 2–3 weeks before beneficial effects can be observed.

Mast cell directed therapy

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

At present, the most frequently used drugs inhibiting mast cell mediator release are corticosteroids. They should be avoided for long-term treatment of chronic urticaria, since dosages necessary to suppress symptoms are usually high with significant adverse effects. For acute urticaria, a short course of corticosteroids may however be helpful to reduce disease duration (19). Nevertheless, well-designed randomized controlled trials (RCT) are missing.

Cyclosporin A also has a moderate, direct effect on mast cell mediator release (20). Efficacy of cyclosporin A in combination with a nonsedating H1 antihistamine has been shown in a RCT (level of evidence 2++, grade of recommendation C, see Table 1), but this drug cannot be recommended as standard treatment due to a higher incidence of adverse effects.

Table 1.  Effective treatment in urticaria
Type of urticariaStandard treatmentMethodo- logical quality* Level of evidence†Grade of recommen- dation‡ReferenceTreatment for nonresponsive patientsMethodo- logical quality* Level of evidence†Grade of recommen- dation‡Reference
  1. *Rating of methodological quality of the study or review according to the Metholodogy Checklist 2: Randomized Controlled Trials of the Scottish Intercollegiate Guidelines Network (SIGN); ++, All or most of the criteria have been fulfilled. Where they have not been fulfilled, the conclusions of the study or review are thought very unlikely to alter; +, Some of the criteria have been fulfilled. Those criteria that have not been fulfilled or adequately described are thought unlikely to alter the conclusions; −, Few or no criteria have been fulfilled. The conclusions of the study are thought likely or very likely to alter; ‡The grade of recommendation according to SIGN criteria; 1++, High quality meta analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias; 1+, Well conducted meta analyses, systematic reviews of RCTs, or RCTs with a low risk of bias; 1, Meta analyses, systematic reviews of RCTs, or RCTs with a high risk of bias; 2++, High quality systematic reviews of case-control or cohort or studies. High quality case-control or cohort studies with a very low risk of confounding, bias, or chance and a high probability that the relationship is causal; 2+, Well conducted case control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal; 2, Case control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal; 3, Nonanalytic studies, e.g. case reports, case series; 4, Expert opinion; †The level of evidence provided by the study is derived from the code allocated for the methodological quality and the type of study, according to the Metholodogy Checklist 2: Randomized Controlled Trials of the Scottish Intercollegiate Guidelines Network (SIGN). A, At least one meta analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population; or a systematic review of RCTs or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results; B, A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 1++ or 1+; C, A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 2++; D, Evidence level 3 or 4; or extrapolated evidence from studies rated as 2+.

(a) Acute urticariaTreatment recommended by the majority of the panel and the audience
ns sg H1-AH 2D Prednisone, 2 × 20 mg/day for 4 days+2+D(45)
Loratadine2D(43)Prednisolone, 50 mg/day for 3 days2D(43)
Cetirizine2D(44)H2-blocker, single dose or 5 day+2D(46–48)
(b) Chronic urticariaTreatment recommended by the majority of the panel and the audience
ns sg H1-AH 1++A Combination therapy
Azelastine+1 (49, 50)ns sg H1-AH and cyclosporin A++2++C(84)
Cetirizine++1+ (51–61)ns sg H1-AH and montelukast+2D(85–87)
Desloratadine++1+ (62–64)ns sg H1 and H2-AH cimetidine+2D(88–91)
Ebastine+1 (65, 66)Monotherapy
Fexofenadine++1+ (67–71)Tricyclic antidepressants (doxepin)+2+D(92–94)
Levocetirizine++1+ (72, 73)Ketotifen++2++C(95)
Loratadine++1+ (74–76)Hydroxychloroquine2D(96, 97)
Mizolastine++1+ (77–83)DapsoneNo RCT3D 
Increase dosage 3C SulfasalazineNo RCT3D 
 if necessary    MethotrexateNo RCT3D 
 up to fourfold    CoticosteroidsNo RCT4D 
     Other treatment options
     Combination therapy
     ns sg H1-AH and stanazolol++2+D(98)
     ns sg H1-AH and zafirlukast2D(99)
     Monotherapy
     Oxatomide2D(100–102)
     Nifedipine 2D(103)
     Leukotriene antagonists:
      Montelukast2D(104, 105)
     Warfarin2D(106, 107)
     InterferonNo RCT3D 
     PlasmapheresisNo RCT3D 
     ImmunoglobulinsNo RCT3D 
     Azathioprine
     Climate therapy
     UV light treatment
(c) Physical urticariaAlways consider avoidance of stimuli     
Demographic urticariaTreatment recommended by the majority of the panel and the audience
ns sg H1-AH 2D Ketotifen (see also chronic urticaria)+2D(109)
Cetirizine+2+D(108)     
Delayed pressure urticariaTreatment recommended by the majority of the panel and the audience
ns sg H1-AH 2D Combination therapy
Cetirizine2D(110)Montelukast and ns H1-AH (loratadine)+2D(111)
High doseNo RCT3–4D Monotherapy
ns H1-AH    Prednisone 40–20 mg2D(112)
     DapsoneNo RCT3D 
     Other treatment options
     Combination therapy
     Ketotifen and nimesulide2D(112)
     Monotherapy
     Clobetasol prop. 0.5% ointment+2D(113)
     MethotrexateNo RCT3D 
     SulfasalazineNo RCT3D 
Cold urticariaTreatment recommended by the majority of the panel and the audience
ns sg H1-AH (overall)++2+B(114–117)Trial with penicillin i.m./p.o.No RCT3D 
Loratadine    Trial with doxycyline p.o.No RCT3D 
Cetirizine    Induction of physical tolerance    
Mizolastine         
Desloratadine    Other treatment options
     Cyproheptadine+2D(118)
     Ketotifen+2+D(119)
     MontelukastNo RCT3D 
Solar urticariaTreatment recommended by the majority of the panel and the audience
ns H1-AH  D Induction of physical tolerance cyclosporine A 3D 
Cetirizine2D(120)     
Fexofenadine 3D(121)Other treatment options
Loratadine 3D Plasmapheresis 3D 
     Plasmapheresis + PUVA 3D 
     Photopheresis 3D 
     Plasma exchange 3D 
     IVIGs 3D 
     Hydroxychloroquine 4D 
(d) Special types of urticaria
Cholinergic urticariaTreatment recommended by the majority of the panel and the audience
ns H1-AH  D ‘Exercise tolerance’    
Cetirizine+2D(122)     
Increase dosage++2+D(123)Other treatment options
 if necessary    Ketotifen+2D(109)
     Danazol+2D(124)

PUVA reduces the numbers of mast cells in the upper dermis. It has been successfully used in mastocytosis and is helpful in treatment-resistant patients with this condition (21, 22). For the treatment of chronic urticaria, UV-A and UV-B treatment for 1–3 months can be added to the antihistamine treatment (23, 24).

Tolerance induction may also be considered under the heading of mast cell directed therapy. This is sometimes used for cold urticaria, cholinergic urticaria and solar urticaria, where even a rush therapy with UVA has been proven to be effective within 3 days (25).

Therapy at the target organ

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

Nearly all symptoms of urticaria are primarily mediated by H1-receptors located on nerves and endothelials. Thus, H1-receptor antagonists are of eminent importance in the treatment of urticaria. With the availability of this group of substances since the 1950s, urticaria is one of the diseases that can be treated effectively with a very low adverse effect profile. The development of second generation, nonsedating or low-sedating antihistamines has allowed to improve the quality of life of urticaria patients. New generation antihistamines also exert anti-inflammatory effects such as cytokine release from basophils and mast cells (26, 27). This may be of additional benefit in controlling symptoms in urticaria if these effects occur at a clinically relevant dosage (28). There are some studies showing the benefit of a higher dosage of antihistamines in individual patients (29, 30), but further investigations in this field are necessary. The possibility of increased adverse cardiac effects, especially with terfenadine and astemizole (31), is a consideration in the choice of the specific antihistamine, especially when using higher dosages than recommended by the manufacturers. Further progress with regard to drug safety was achieved by the development of the new generation antihistamines fexofenadine and descarboxyloratadine, which are cytochrome P450 independent metabolites of earlier antihistamines. Levocetirizine is the active enantiomer of cetirizine, thus, where cetirizine is indicated as effective treatment, levocetirizine could also be considered. The highest reported accidental overdosage of antihistamine (50-fold of the prescribed dosage of cetirizine in a 18-month-old boy) induced no adverse effects (32). The main drug interactions have been described until recently for sedating antihistamines in association with drugs affecting the central nervous system, like analgetics, hypnotics, sedatives, and mood elevating drugs as well as alcohol. MAO inhibitors can prolong and intensify anticholinergic effects. With the exception of cetirizine, levocetirizine, and fexofenadine, other modern antihistamines are also metabolized by cytochrome P450 enzymes (33). This interaction leads to increased plasma levels when there is concomitant treatment with drugs employing this enzyme system for metabolism such as ketoconazole or erythromycin. In the case of fexofenadine, there is an interaction with the GP system in the intestine, resulting in an increased plasma concentration in case of concomitant administration of ketokonazole or erythromycin.

In summary, considering their good safety profile, second-generation antihistamines must be considered as first line symptomatic treatment for urticaria (level of evidence 1++, grade of recommendation A, see Table 1). Before considering alternative treatment, higher dosages up to a fourfold increase should be used (level of evidence 3, grade of recommendation C, see Table 1). Up to date, well-designed RCTs comparing efficacy and safety of different nonsedating H1-antihistamines in chronic urticaria are missing. The data available implicate that the differences are marginal, although different individual responses to nonsedating H1 antihistamines are accepted as expert opinion.

Further therapeutic possibilities

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

While antihistamines at higher dosages will control symptoms in the majority of patients with urticaria, alternative treatments are needed for the remaining unresponsive patients.

Since the severity of urticaria may fluctuate, and since spontaneous remission may occur at any time, it is recommended to re-evaluate the necessity for continued or alternative drug treatment every 3–6 months.

Many of the alternatives such as combinations of nonsedating H1 antihistamines with H2 antihistamines or with antileukotrienes are based on RCTs with low levels of evidence (Table 1). The same holds true for monotherapy with ketotifen, montelukast, warfarin, and hydroxychloroquine. In addition, evidence from older data investigating oxatomide, doxepin, and nifedipine is poor.

For dapsone, sulfasalazine, methotrexate, interferon, plasmapheresis, and immunoglobulins only uncontrolled trials or case series have been published (Table 1).

Recent RCTs addressed antileukotrienes (Tables 1 and 2). Studies are difficult to compare due to different populations (e.g. inclusion of only aspirin and food additive intolerant patients or exclusion of autologous serum skin test positive patients).

Table 2.  Studies with drugs showing no significant effect on urticaria
Type of urticariaIneffective treatmentMethodological quality*Level of evidence†Grade of recommendation‡Reference
  1. *Rating of methodological quality of the study or review according to the Metholodogy Checklist 2: Randomized Controlled Trials of the Scottish Intercollegiate Guidelines Network (SIGN).

  2. †The level of evidence provided by the study is derived from the code allocated for the methodological quality and the type of study, according to the Metholodogy Checklist 2: Randomized Controlled Trials of the Scottish Intercollegiate Guidelines Network (SIGN).

  3. ‡The grade of recommendation according to SIGN criteria.

  4. ++, All or most of the criteria have been fulfilled. Where they have not been fulfilled, the conclusions of the study or review are thought very unlikely to alter; +, Some of the criteria have been fulfilled. Those criteria that have not been fulfilled or adequately described are thought unlikely to alter the conclusions; −, Few or no criteria have been fulfilled. The conclusions of the study are thought likely or very likely to alter; 2+, Well conducted case control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal; 2, Case control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal; D, Evidence level 3 or 4; or extrapolated evidence from studies rated as 2+.

(a) Chronic urticariasH1-AH and H2-AH cimetidine2D(89)
sH1-AH and β-sympathomimetic terbutaline2D(125, 126)
Leukotriene antagonist montelukast++2+D(85)
Addition of montelukast to nsH1-AH (Desloratadine)++2+D(85)
Leukotriene antagonist zafirlukast++2+D(127)
Tranexamic acid (cyclokapron)2D(128)
Cromolyn2D(129)
(b) Physical urticaria
Delayed pressure urticariaColchicine+2D(130)
Indomethacin+2D(131)
Demographic urticariaAddition of H2-AH to sH1-AH or nsH1-AH+2D(132, 133)
Nifedipine+2D(134)

On the other hand, some treatment alternatives formerly proposed have been shown to be ineffective in double-blind, placebo controlled studies and should no longer be used (although grade of recommendation is low). These include tranexamic acid and sodium cromoglycate (DNCG) in chronic urticaria (34, 35), nifedipin in dermographic urticaria (36) and colchicine and indomethacin in delayed pressure urticaria (37, 38).

Table 1 summarizes the consensus of the current standard drug treatment and alternatives in several subtypes of urticaria, whereas Table 2 summarizes ineffective drugs in controlled trials.

Taken together, grade A recommendations exist only for symptomatic therapy with nonsedating antihistamines. However, it should be considered that these drugs are insufficient in several patients with urticaria and that RCTs often included patients with mild to moderate disease only. In contrast, most alternatives have been tested in patients previously not responding to antihistamines.

Thus, we clearly need more and well-designed RCTs to recommend or refuse potential alternatives.

Quality of life

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

Health Related Quality of Life (HRQoL) parameter is presently recognized as a primary outcome in clinical trials, population studies and public health. Both physicians and researchers are aware that it is nowadays a need, rather than a simple option. The assessment of this parameter allows to complete the traditional assessment based on biomedical and socio-economic data in order to obtain a global evaluation of both disease and treatment.

While HRQoL has been extensively assessed in numerous dermatological conditions, a literature search shows that only few studies evaluate this topic in patients with chronic urticaria. The available data indicate that chronic urticaria has a detrimental effect on both objective functioning and subjective well being. For example, O'Donnell et al. showed that health status scores in patients with chronic urticaria are comparable to those reported from patients with coronary artery disease (39). Furthermore, both health status and subjective satisfaction in patients with chronic urticaria is lower than in healthy subjects and in patients with respiratory allergy (40). A study of Poon et al. focuses on the extent and nature of disability in different types of chronic urticaria, showing a large variation in HRQoL scores within different urticarial subsets (41).

In these mentioned studies, the assessment of HRQoL was performed by using generic questionnaires (applicable to all health conditions) and by specialty specific questionnaire (developed for skin diseases). There is only one disease specific questionnaire applied in patients with chronic urticaria, but it has not been validated (39).

Recently a questionnaire specifically developed for chronic urticaria has been validated, including physical, emotional, social and practical aspects that characterize this condition (42). The aim was to offer the research community a sensible and simple tool to evaluate specifically HRQoL in urticaria patients. This new tool named Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) was generated and tested following well-established procedures and applied to other similar instruments. The CU-Q2oL met the standards for validity with good construct validity, internal consistency, reliability, and responsiveness. These psychometric characteristics make the new questionnaire adapted for the assessment of the specific burden of both chronic urticaria and its treatment on HRQoL.

Conclusion

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

The quality of life in urticaria is severely affected and management of the disease should therefore be prompt and in close cooperation between patient and physician. Due to high variability of disease severity, an individual approach is necessary for each patient. As a first line, triggering factors should be avoided as far as possible and any associated diseases should be treated. In the majority of patients, symptomatic pharmacological treatment is possible with new generation antihistamines, with a very low adverse effect profile and good patient compliance. In nonresponding patients, higher dosages (up to fourfold) and alternative medication should be tried. Most of these, such as corticosteroids or cyclosporin, should be reserved for severely affected patients because of their unfavorable adverse effect profile.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References

This guideline was generated in cooperation with the German Urticaria Patient Association ‘Patientenkreis Urtikaria’ (Head: Frau Heidrun Martin, Idstein, Germany). The Global Allergy and Asthma European Network (GA2LEN) and the EAACI Dermatology section have provided institutional and logistic support and like to thank the European Center for Allergy Research Foundation (ECARF) for organizing and financing the symposium and the publication of this guideline. ECARF is a nonprofit foundation administered by the Stifterverband für die Deutsche Wissenschaft (Donors’ Association for the Promotion of the German Sciences and Humanities) with its office at the Department of Dermatology and Allergy at the Charité– Universitätsmedizin Berlin (see http://www.ecarf.org). ECARF is funded mainly by private donations; for parts of the funding of the symposium, ECARF has received an educational grant by UCB Farchim. The authors like to thank Ilaria Baiardini for her contribution on the issue of quality of life in urticaria patients. Formal approval of the guideline by the UEMS was obtained through the Section of Dermatology in May 2005.

References

  1. Top of page
  2. Abstract
  3. Avoidance elimination or treatment of the eliciting stimulus or cause
  4. Inhibition of mast cell mediator release
  5. Therapy of target tissues of mast cell mediators
  6. Methods
  7. Eliciting stimuli
  8. Mast cell directed therapy
  9. Therapy at the target organ
  10. Further therapeutic possibilities
  11. Quality of life
  12. Conclusion
  13. Acknowledgments
  14. References
  • 1
    Zuberbier T, Greaves MW, Juhlin L, Merk H, Stingl G, Henz BM. Management of urticaria – a consensus report. J Invest Dermatol Symp Proc 2001;6: 128131.
  • 2
    Wüthrich B. Adverse reactions to food additives. Ann Allergy 1993;71: 379384.
  • 3
    Wedi B, Raap U, Kapp A. Chronic urticaria and infections. Curr Opin Allergy Clin Immunol 2004;4: 387396.
  • 4
    Wedi B, Kapp A. Helicobacter pylori infection in skin diseases: a critical appraisal. Am J Clin Dermatol 2002;3: 273282.
  • 5
    Henz BM, Zuberbier T. Causes of urticaria. In: HenzBM, ZuberbierT, GrabbeJ, MonroeE, editors. Urticaria. Clinical, diagnostic and therapeutic aspects. Berlin: Springer, 1998: 1938.
  • 6
    Champion RH, Roberts SOB, Carpenter RG, Roger JH. Urticaria and angio-oedema. A review of 554 patients. Br J Dermatol 1969;81: 588597.
  • 7
    Zuberbier T, Chantraine-Hess S, Hartmann K, Czarnetzki BM. Pseudoallergen-free diet in the treatment of chronic urticaria. Acta Derm Venereol (Stockh) 1995;75: 484487.
  • 8
    Bruno G, Andreozzi P, Graf U. Exercise-induced urticaria – angioedema syndrome: a role in gastroesophageal reflux. In: VenaGA, PudduP, editors. Proceedings of the International Symposium on Urticaria. Bari: Publ Scientif., 1998: 8589.
  • 9
    Grattan CEH, Francis DM, Slater NGP, Barlow RJ, Greaves MW. Plasmapheresis for severe unremitting chronic urticaria. Lancet 1992;339: 10781080.
  • 10
    Greaves M. Chronic urticaria. J Allergy Clin Immunol 2000;105: 664672.
  • 11
    Grattan CEH, O'donnell BFO, Francis DM, Niimi N, Barlow RJ, Seed PT et al. Randomized double-blind study of cyclosporin in chronic ‘idiopathic’ urticaria. Br J Dermatol 2000;143: 365372.
  • 12
    Barlow RJ, Black AK, Greaves MW. Treatment of severe chronic urticaria with cyclosporin A. Eur J Dermatol 1993;3: 273275.
  • 13
    Fradin MS, Ellis CN, Goldfarb MT, Voorhees JJ. Oral cyclosporin for severe chronic idiopathic urticaria and angioedema. J Am Acad Dermatol 1991;25: 10651067.
  • 14
    Toubi E, Blant A, Kessel A, Golan TD. Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria. Allergy 1997;52: 312316.
  • 15
    O'donnell BF, Barr RM, Black AK, Francis DM, Kermani F, Niimi N et al. Intravenous immunoglobulin in autoimmune chronic urticaria. Br J Dermatol 1998;138: 101106.
  • 16
    Juhlin L. Recurrent urticaria: clinical investigation of 330 patients. Br J Dermatol 1981;104: 369381.
  • 17
    Pfrommer C, Bastl R, Vieths S, Ehlers I, Henz BM, Zuberbier T. Characterization of naturally occurring pseudoallergens causing chronic urticaria. J Allergy Clin Immunol 1996;97: 367.
  • 18
    Pigatto PD, Valsecchi RH. Chronic urticaria: a mystery. Allergy 2000;55: 306308.
  • 19
    Zuberbier T, Iffländer J, Semmler C, Czarnetzki BM. Acute urticaria – clinical aspects and therapeutical responsiveness. Acta Derm Venereol (Stockh) 1996;76: 295297.
  • 20
    Stellato C, De Paulis A, Ciccarelli A, Cirillo R, Patella V, Casolaro V et al. Anti-inflammatory effect of cyclosporin A on human skin mast cells. J Invest Dermatol 1992;98: 800804.
  • 21
    Godt O, Proksch E, Streit V, Christophers E. Short- and long-term effectiveness of oral and bath PUVA therapy in urticaria pigmentosa and systemic mastocytosis. Dermatology 1997;195: 3539.
  • 22
    Horio T. Indications and action mechanisms of phototherapy. J Dermatol Sci 2000;23(Suppl. 1):S17S21.
  • 23
    Hannuksela M, Kokkonen EL. Ultraviolet light therapy in chronic urticaria. Acta Derm Venereol 1985;65: 449450.
  • 24
    Olafsson JH, Larko O, Roupe G, Granerus G, Bengtsson U. Treatment of chronic urticaria with PUVA or UVA plus placebo: a double-blind study. Acta Dermatol Res 1986;278: 228231.
  • 25
    Beissert S, Stander H, Schwarz T. UVA rush hardening for the treatment of solar urticaria. J Am Acad Dermatol 2000;42: 10301032.
  • 26
    Lippert U, Krüger-Krasagakes S, Möller A, Kiessling U, Czarnetzki BM. Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist descarboethoxy-loratadine and dexamethasone from human mast and basophilic cell lines. Exp Dermatol 1995;4: 272276.
  • 27
    Lippert U, Möller A, Welker P, Artuc M, Grützkau A, Henz BM. Inhibition of cytokine secretion from human mast cells and basophils by H1- and H2-receptor antagonists. Exp Dermatol 2000;9: 118124.
  • 28
    Merk H, Sauer RR, Steigleder GK. Histamine release in cold urticaria – effect of ketotifen and oxatomide. In: ChampionRH, GreavesMW, Kobza-BlackA, PyeRJ, editors. The urticarias. London: Churchill Livingston, 1985: 222223.
  • 29
    Zuberbier T, Münzberger CH, Haustein U, Trippas E, Mariz SD, Czarnetzki BM. Double-blind crossover study of high dose cetirizine in cholinergic urticaria. Dermatology 1996;193: 324327.
  • 30
    Kontou-Fili K, Maniakatou G, Demaka P, Paleologos G. Therapeutic effect of cetirizine 2HCl in delayed pressure urticaria. Health Sci Rev 1989;3: 2325.
  • 31
    Lindquist M, Edwards R. Risks of non-sedating antihistamines. Lancet 1997;349: 1322.
  • 32
    Ridout SM, Tariq SM. Cetirizine overdose in a young child. J Allergy Clin Immunol 1997;99: 860861.
  • 33
    Renwick AG. The metabolism of antihistamines and drug interactions: the role of cytochrome P450 enzymes. Clin Exp Allergy 1999;29(Suppl. 3):116124.
  • 34
    Thormann J, Laurberg G, Zachariae H. Oral sodium cromoglycate in chronic urticaria. Allergy 1980;35: 139141.
  • 35
    Laurberg G. Tranexamic acid (Cyklokapron) in chronic urticaria: a double-blind study. Acta Derm Venereol 1977;57: 369370.
  • 36
    Lawlor F, Ormerod AD, Greaves MW. Calcium antagonist in the treatment of symptomatic dermographism. Low-dose and high-dose studies with nifedipine. Dermatologica 1988;177: 287291.
  • 37
    Lawlor F, Black AK, Ward AM, Morris R, Greaves MW. Delayed pressure urticaria, objective evaluation of variable disease using a dermographometer and assessment of treatment using colchicine. Br J Dermatol 1989;120: 403408.
  • 38
    Dover JS, Kobza-Black A, Ward AM, Greaves MW. Delayed pressure urticaria. Clinical features, laboratory investigations, and response to therapy of 44 patients. J Am Acad Dermatol 1988;18: 12891298.
  • 39
    O'Donnell BF, Lawlor F, Simpson J, Morgan M, Greaves MW. The impact of chronic urticaria on the quality of life. Br J Dermatol 1997;136: 197201.
  • 40
    Baiardini I, Giardini A, Pasquali M, Dignetti P, Guerra L, Specchia C et al. Quality of life and patients’ satisfaction in chronic urticaria and respiratory allergy. Allergy 2003;58: 621623.
  • 41
    Poon E, Seed PT, Greaves MW, Kobza-Black A. The extent and nature of disability on different urticarial conditions. Br J Dermatol 1999;140: 667671.
  • 42
    Baiardini I, Pasquali M, Braido F, Fumagalli F, Guerru L, Compalati E et al. A new tool to evaluate the impact of chronic urticaria on quality of life: chronic urticaria quality of life questionnaire (CU-QoL). Allergy 2005;60: 10731078.
  • 43
    Zuberbier T, Ifflander J, Semmler C, Henz BM. Acute urticaria: clinical aspects and therapeutic responsiveness. Acta Derm Venereol 1996;76: 295297.
  • 44
    Simons FER. Prevention of acute urticaria in young children with atopic dermatitis. J Allergy Clin Immunol 2001;107: 703706.
  • 45
    Pollack CV, Romano TJ. Outpatient management of acute urticaria: the role of prednisone. Ann Emerg Med 1995;26: 547551.
  • 46
    Watson NT, Weiss EL, Harter PM. Famotidine in the treatment of acute urticaria. Clin Exp Dermatol 2000;25: 186189.
  • 47
    Pontasch MJ, White LJ, Bradford JC. Oral agents in the management of urticaria: patient perception of effectiveness and level of satisfaction with treatment. Ann Pharmacother 1993;27: 730731.
  • 48
    Moscati RM, Moore GP. Comparison of cimetidine and diphenhydramine in the treatment of acute urticaria. Ann Emerg Med 1990;19: 1215.
  • 49
    Camarasa JM, Aliaga A, Fernandez-Vozmediano JM, Fonseca E, Iglesias L, Tagarro I. Azelastine tablets in the treatment of chronic idiopathic urticaria. Phase III, randomised, double-blind, placebo and active controlled multicentric clinical trial. Skin Pharmacol Appl Skin Physiol 2001;14: 7786.
  • 50
    Henz BM, Metzenauer P, O'keefe E, Zuberbier T. Differential effects of new-generation H1-receptor antagonists in pruritic dermatoses. Allergy 1998;53: 180183.
  • 51
    La Rosa M, Leonardi S, Marchese G, Corrias A, Barberio G, Oggiano N et al. Double-blind multicenter study on the efficacy and tolerability of cetirizine compared with oxatomide in chronic idiopathic urticaria in preschool children. Ann Allergy Asthma Immunol 2001;87: 4853.
  • 52
    Handa S, Dogra S, Kumar B. Comparative efficacy of cetirizine and fexofenadine in the treatment of chronic idiopathic urticaria. J Dermatolog Treat 2004;15: 5557.
  • 53
    Lambert D, Hantzperg M, Danglas P, Bloom M. Double-blind comparative study of terfenadine and cetirizine in chronic idiopathic urticaria. Allergy Immunol (Paris) 1993;25: 235240.
  • 54
    Breneman DL. Cetirizine versus hydroxyzine and placebo in chronic idiopathic urticaria. Ann Pharmacother 1996;30: 10751079.
  • 55
    Breneman D, Bronsky EA, Bruce S, Kalivas JT, Klein GL, Roth HL et al. Cetirizine and astemizole therapy for chronic idiopathic urticaria: a double-blind, placebo-controlled, comparative trial. J Am Acad Dermatol 1995;33: 192198.
  • 56
    Andri L, Senna GE, Betteli C, Givanni S, Andri G, Lombardi C et al. A comparison of the efficacy of cetirizine and terfenadine. A double-blind, controlled study of chronic idiopathic urticaria. Allergy 1993;48: 358365.
  • 57
    Goh CL, Wong WK, Lim J. Cetirizine vs placebo in chronic idiopathic urticaria—a double blind randomised cross-over study. Ann Acad Med Singapore 1991;20: 328330.
  • 58
    Juhlin L. Cetirizine in the treatment of chronic urticaria. Clin Ther 1991;13: 8186.
  • 59
    Alomar A, De La C, Fernandez J. Cetirizine vs astemizole in the treatment of chronic idiopathic urticaria. J Int Med Res 1990;18: 358365.
  • 60
    Kalivas J, Breneman D, Tharp M, Bruce S, Bigby M. Urticaria: clinical efficacy of cetirizine in comparison with hydroxyzine and placebo. J Allergy Clin Immunol 1990;86: 10141018.
  • 61
    Juhlin L, Arendt C. Treatment of chronic urticaria with cetirizine dihydrochloride a non-sedating antihistamine. Br J Dermatol 1988;119: 6771.
  • 62
    Monroe E, Finn A, Patel P, Guerrero R, Ratner P, Bernstein D. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. J Am Acad Dermatol 2003;48: 535541.
  • 63
    Monroe EW. Desloratidine for the treatment of chronic urticaria. Skin Therapy Lett 2002;7: 12, 5.
  • 64
    Ring J, Hein R, Gauger A, Bronsky E, Miller B. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study. Int J Dermatol 2001;40: 7276.
  • 65
    Kalis B. Double-blind multicentre comparative study of ebastine, terfenadine and placebo in the treatment of chronic idiopathic urticaria in adults. Drugs 1996;52(Suppl. 1):3034.
  • 66
    Peyri J, Vidal J, Marrón J, Fonseca E, Suãrez E, Ledo A et al. Ebastine in chronic urticaria: a double-blind placebo-controlled study. J Dermatolog Treat 1991;2: 5153.
  • 67
    Degonda M, Pichler WJ, Bircher A, Helbling A. Chronic idiopathic urticaria: effectiveness of fexofenadine. A double-blind, placebo controlled study with 21 patients. Schweiz Rundsch Med Prax 2002;91: 637643.
  • 68
    Kawashima M, Harada S, Tango T. Review of fexofenadine in the treatment of chronic idiopathic urticaria. Int J Dermatol 2002;41: 701706.
  • 69
    Kawashima M, Harada S. Efficacy and safety of fexofenadine HCl in Japanese patients with chronic idiopathic urticaria. Int Arch Allergy Immunol 2001;124: 343345.
  • 70
    Nelson HS, Reynolds R, Mason J. Fexofenadine HCl is safe and effective for treatment of chronic idiopathic urticaria. Ann Allergy Asthma Immunol 2000;84: 517522.
  • 71
    Thompson AK, Finn AF, Schoenwetter WF. Effect of 60 mg twice-daily fexofenadine HCl on quality of life, work and classroom productivity, and regular activity in patients with chronic idiopathic urticaria. J Am Acad Dermatol 2000;43: 2430.
  • 72
    Kapp A, Pichler WJ. Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind placebo-controlled, parallel, multicenter study. Int J Dermatol 2005; DOI: 10.1111/j.1365-4632.2005.02609.
  • 73
    Kapp A, Wedi B. Chronic urticaria: clinical aspects, and focus on a new antihistamine, levocetirizine. J Drugs Dermatol 2004;3: 632639.
  • 74
    Monroe EW. Relative efficacy and safety of loratadine, hydroxyzine, and placebo in chronic idiopathic urticaria and atopic dermatitis. Clin Ther 1992;14: 1721.
  • 75
    Belaich S, Bruttmann G, Degreef H, Lachapelle JM, Paul E, Pedrali P et al. Comparative effects of loratadine and terfenadine in the treatment of chronic idiopathic urticaria. Ann Allergy 1990;64: 191194.
  • 76
    Monroe EW, Fox RW, Green AW, Izuno GT, Bernstein DI, Pleskow WW et al. Efficacy and safety of loratadine (10 mg once daily) in the management of idiopathic chronic urticaria. J Am Acad Dermatol 1988;19: 138139.
  • 77
    Kapp A, Guinnepain MT, Lachapelle JM, Murrieta-Aguttes M. Mizolastine in the treatment of chronic urticaria: a European clinical experience with 2452 patients managed in daily practice (PANEOS CU Study). In: MaroneG, editor. Clinical immunology and allergy in medicine. Naples: JGC Editions, 2003.
  • 78
    Leynadier F, Duarte-Risselin C, Murrieta M. Comparative therapeutic effect and safety of mizolastine and loratadine in chronic idiopathic urticaria. URTILOR study group. Eur J Dermatol 2000;10: 205211.
  • 79
    Lorette G, Giannetti A, Pereira RS, Leynadier F, Murrieta-Aguttes M. One-year treatment of chronic urticaria with mizolastine: efficacy and safety. URTOL study group. J Eur Acad Dermatol Venereol 2000;14: 8390.
  • 80
    Dubertret L, Murrieta AM, Tonet J. Efficacy and safety of mizolastine 10 mg in a placebo-controlled comparison with loratadine in chronic idiopathic urticaria: results of the MILOR Study. J Eur Acad Dermatol Venereol 1999;12: 1624.
  • 81
    Ring J, Brockow K, Ollert M, Engst R. Antihistamines in urticaria. Clin Exp Allergy 1999;29(Suppl. 1):3137.
  • 82
    Lachapelle JM, Tennstedt D, Murrieta M. Comparative efficacy and safety of mizolastine 10 mg o.d. versus placebo in chronic idiopathic urticaria. Allergy 1998;53: 57.
  • 83
    Brostoff J, Fitzharris P, Dunmore C, Theron M, Blondin P. Efficacy of mizolastine, a new antihistamine, compared with placebo in the treatment of chronic idiopathic urticaria. Allergy 1996;51: 320325.
  • 84
    Grattan CE, O'Donnell BF, Francis DM, Niimi N, Barlow RJ, Seed PT et al. Randomized double-blind study of cyclosporin in chronic ‘idiopathic’ urticaria. Br J Dermatol 2000;143: 365372.
  • 85
    Di Lorenzo G, Pacor ML, Mansueto P, Pellitteri ME, Lo Bianco C, Ditta V 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: 619625.
  • 86
    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: 14011407.
  • 87
    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: 484488.
  • 88
    Bleehen SS, Thomas SE, Greaves MW, Newton J, Kennedy CT, Hindley F et al. Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: a multi-centre randomized double-blind study. Br J Dermatol 1987;117: 8188.
  • 89
    Diller G, Orfanos CE. Management of idiopathic urticaria with H1 + H2 antagonists. A crossover double blind long-term study. Z Hautkr 1983;58: 785793.
  • 90
    Harvey RP, Wegs J, Schocket AL. A controlled trial of therapy in chronic urticaria. J Allergy Clin Immunol 1981;68: 262266.
  • 91
    Monroe EW, Cohen SH, Kalbfleisch J, Schulz CI. Combined H1 and H2 antihistamine therapy in chronic urticaria. Arch Dermatol 1981;117: 404407.
  • 92
    Goldsobel AB, Rohr AS, Siegel SC, Spector SL, Katz RM, Rachelefsky GS et al. Efficacy of doxepin in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol 1986;78: 867873.
  • 93
    Greene SL, Reed CE, Schroeter AL. Double-blind crossover study comparing doxepin with diphenhydramine for the treatment of chronic urticaria. J Am Acad Dermatol 1985;12: 669675.
  • 94
    Harto A, Sendagorta E, Ledo A. Doxepin in the treatment of chronic urticaria. Dermatologica 1985;170: 9093.
  • 95
    Kamide R, Niimura M, Ueda H, Imamura S, Yamamoto S, Yoshida H et al. Clinical evaluation of ketotifen for chronic urticaria: multicenter double-blind comparative study with clemastine. Ann Allergy 1989;62: 322325.
  • 96
    Reeves GEM, Boyle MJ, Bonfield J, Dobson P. Impact of hydroxychloroquine therapy on chronic urticaria: chronic autoimmune urticaria study and evaluation. Int Med J 2004;34: 182186.
  • 97
    Baumgart KW, Mullins R. Use of hydroxychloroquine in refractory urticaria. J Allergy Clin Immunol 2000;105: 795796.
  • 98
    Parsad D, Pandhi R, Juneja A. Stanozolol in chronic urticaria: a double blind, placebo controlled trial. J Dermatol 2001;28: 299302.
  • 99
    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: 134140.
  • 100
    Beck HI, Cramers M, Herlin T, Sondergaard I, Zachariae H. Comparison of oxatomide and clemastine in the treatment of chronic urticaria. A double blind study. Dermatologica 1985;171: 4951.
  • 101
    Demaubeuge J, Tennstedt D, Broux R. Does mast cell protection plus mediator antagonism surpass the effect of a classic antihistaminic in the treatment of chronic urticaria? A double-blind comparison of oxatomide and mequitazine. Dermatologica 1982;164: 386394.
  • 102
    Peremans W, Mertens RL, Morias J, Campaert H. Oxatomide in the treatment of chronic urticaria. A double-blind placebo-controlled trial. Dermatologica 1981;162: 4250.
  • 103
    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: 756763.
  • 104
    Nettis E, Dambra P, D'oronzio L, Loria MP, Ferrannini A, Tursi A. Comparison of montelukast and fexofenadine for chronic idiopathic urticaria. Arch Dermatol 2001;137: 99100.
  • 105
    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: 16071614.
  • 106
    Parslew R, Pryce D, Ashworth J, Friedmann PS. Warfarin treatment of chronic idiopathic urticaria and angio-oedema. Clin Exp Allergy 2000;30: 11611165.
  • 107
    Barlow RJ, Greaves MW. Warfarin in the treatment of chronic urticaria/angio-edema. Br J Dermatol 1992;126: 415416.
  • 108
    Sharpe GR, Shuster S. The effect of cetirizine on symptoms and wealing in dermographic urticaria. Br J Dermatol 1993;129: 580583.
  • 109
    Cap JP, Schwanitz HJ, Czarnetzki BM. Effect of ketotifen in urticaria factitia and urticaria cholinergica in a crossover double-blind trial. Hautarzt 1985;36: 509511.
  • 110
    Kontou-Fili K, Maniatakou G, Demaka P, Gonianakis M, Palaiogolos G, Aroni K. Therapeutic effects of cetirizine 2HCl in delayed pressure urticaria: clinicopathologic findings. J Am Acad Dermatol 1991;24: 10901093.
  • 111
    Nettis E, Pannofino A, Cavallo E, Ferrannini A, Tursi A. Efficacy of montelukast, in combination with loratadine, in the treatment of delayed pressure urticaria. J Allergy Clin Immunol 2003;112: 212213.
  • 112
    Vena GA, D'argento V, Cassano N, Mastrolonardo M. Sequential therapy with nimesulide and ketotifen in delayed pressure urticaria. Acta Derm Venereol (Stockh) 1998;78: 304305.
  • 113
    Barlow RJ, Macdonald DM, Black AK, Greaves MW. The effects of topical corticosteroids on delayed pressure urticaria. Arch Dermatol Res 1995;287: 285288.
  • 114
    Juhlin L. Inhibition of cold urticaria by desloratadine. J Dermatolog Treat 2004;15: 5159.
  • 115
    Bonadonna P, Lombardi C, Senna G, Canonica GW, Passalacqua G. Treatment of acquired cold urticaria with cetirizine and zafirlukast in combination. J Am Acad Dermatol 2003;49: 714716.
  • 116
    Dubertret L, Pecquet C, Murrieta-Aguttes M, Leynadier F. Mizolastine in primary acquired cold urticaria. J Am Acad Dermatol 2003;48: 578583.
  • 117
    Villas MF, Contreras FJ, Lopez Cazana JM, Lopez Serrano MC, Martinez AF. A comparison of new nonsedating and classical antihistamines in the treatment of primary acquired cold urticaria (ACU). J Investig Allergol Clin Immunol 1992;2: 258262.
  • 118
    Wanderer AA, St Pierre PJ, Ellis EF. Primary acquired cold urticaria. Double-blind comparative study of treatment with cyproheptadine, chlorpheniramine, and placebo. Arch Dermatol 1977;113: 12751277.
  • 119
    St Pierre JP, Kobric M, Rackham A. Effect of ketotifen treatment on cold-induced urticaria. Ann Allergy 1985;55: 840843.
  • 120
    Roelandts R. Diagnosis and treatment of solar urticaria. Dermatol Ther 2003;16: 5256.
  • 121
    Bilsland D, Ferguson J. A comparison of cetirizine and terfenadine in the management of solar urticaria. Photodermatol Photoimmunol Photomed 1991;8: 6264.
  • 122
    Zuberbier T, Aberer W, Burtin B, Rihoux JP, Czarnetzki BM. Efficacy of cetirizine in cholinergic urticaria. Acta Derm Venereol 1995;75: 147149.
  • 123
    Zuberbier T, Munzberger C, Haustein U, Trippas E, Burtin B, Mariz SD et al. Double-blind crossover study of high-dose cetirizine in cholinergic urticaria. Dermatology 1996;193: 324327.
  • 124
    Wong E, Eftekhari N, Greaves MW, Ward AM. Beneficial effects of danazol on symptoms and laboratory changes in cholinergic urticaria. Br J Dermatol 1987;116: 553556.
  • 125
    Harvey RP, Wegs J, Schocket AL. A controlled trial of therapy in chronic urticaria. J Allergy Clin Immunol 1981;68: 262266.
  • 126
    Spangler DL, Vanderpool GE, Carroll MS, Tinkelman DG. Terbutaline in the treatment of chronic urticaria. Ann Allergy 1980;45: 246247.
  • 127
    Reimers A, Pichler C, Helbling A, Pichler WJ, Yawalkar N. Zafirlukast has no beneficial effects in the treatment of chronic urticaria. Clin Exp Allergy 2002;32: 17631768.
  • 128
    Laurberg G. Tranexamic acid (Cyklokapron) in chronic urticaria: a double-blind study. Acta Derm Venereol 1977;57: 369370.
  • 129
    Thormann J, Laurberg G, Zachariae H. Oral sodium cromoglycate in chronic urticaria. Allergy 1980;35: 139141.
  • 130
    Lawlor F, Black AK, Ward AM, Morris R, Greaves MW. Delayed pressure urticaria, objective evaluation of a variable disease using a dermographometer and assessment of treatment using colchicine. Br J Dermatol 1989;120: 403408.
  • 131
    Dover JS, Black AK, Ward AM, Greaves MW. Delayed pressure urticaria. Clinical features, laboratory investigations, and response to therapy of 44 patients. J Am Acad Dermatol 1988;18: 12891298.
  • 132
    Sharpe GR, Shuster S. In dermographic urticaria H2 receptor antagonists have a small but therapeutically irrelevant additional effect compared with H1 antagonists alone. Br J Dermatol 1993;129: 575579.
  • 133
    Matthews CN, Boss JM, Warin RP, Storari F. The effect of H1 and H2 histamine antagonists on symptomatic dermographism. Br J Dermatol 1979;101: 5761.
  • 134
    Lawlor F, Ormerod AD, Greaves MW. Calcium antagonist in the treatment of symptomatic dermographism. Low-dose and high- dose studies with nifedipine. Dermatologica 1988;177: 287291.