Genotype-Phenotype Correlations in Chronic Granulomatous Disease: Insights From a Large National Cohort.

Neutrophils are the first line of defense against invading pathogens. Neutrophils execute and modulate immune responses by generating reactive oxygen species (ROS). Chronic Granulomatous Disease (CGD) is a primary immune deficiency disorder of phagocytes, caused by inherited mutations in the genes of the NADPH oxidase enzyme. These mutations lead to failure of ROS generation followed by recurrent bacterial and fungal infections, frequently associated with hyper-inflammatory manifestations. We report a multi-center cumulative experience in diagnosing and treating patients with CGD. From 1986 to 2021, 2,918 patients suffering from frequent infections were referred for neutrophil evaluation. Among them, 110 patients were diagnosed with CGD, 56 of Jewish ancestry, 48 of Arabic ancestry and 6 non-Jewish/non-Arabic. As opposed to other Western countries, the autosomal recessive (AR) CGD subtypes were predominant in Israel (71/110 patients). Thirty-nine patients had X-linked CGD, in most patients associated with severe infections (clinical severity score ≥3) and poor outcomes, presenting at a significantly earlier age than AR-CGD subtypes. The full spectrum of infections and hyper-inflammatory manifestations are described. Six patients had hypomorphic mutations with significantly milder phenotype, clinical severity score ≤2, and better outcomes. Hematopoietic stem cell transplantation was implemented in 39/110 patients (35.5%). Successful engraftment was achieved in 92%, with 82% long-term survival and 71% full clinical recovery. CGD is a complex disorder requiring a multi-professional team. Early identification of the genetic mutation is essential for prompt diagnosis, suitable management and prevention.

Chronic granulomatous disease: Clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients.

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life-threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live-births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR-CGD) and 32 (38%) with X-linked recessive inheritance (XLR-CGD). Consanguinity was detected in 64% of AR-CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR-CGD and 13 in AR-CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long-term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28-36, 2017. © 2016 Wiley Periodicals, Inc.

[RECOMMENDATION FOR EVALUATION AND TREATMENT OF CHRONIC URTICARIA - THE ISRAELI ASSOCIATION FOR ALLERGY AND CLINICAL IMMUNOLOGY].

INTRODUCTION: Chronic urticaria is a disease manifested by a pruritic rash lasting longer than 6 weeks that may severely affect quality of life and daily function. Chronic urticaria can be further divided into chronic spontaneous urticaria which appears without a trigger and chronic inducible urticaria which evolves following distinct physical triggers. These two clinical manifestations could coexist in the same patient. The pathogenesis of chronic urticaria is not fully elucidated, although it is considered an autoimmune disease in at least 50% patients that produce auto- IgG antibodies targeted against the high affinity Fc receptor and to a lesser extent against IgE itself. Auto-antibodies associated with different autoimmune diseases can be detected such as those directed at thyroid proteins. Urticaria tends to spontaneously resolve in 50% of patients within the first year while others will suffer from it for a much longer period of time. The treatment of chronic urticaria has dramatically progressed in the last decade, enabling reduction of systemic corticosteroid use which has been the cornerstone of treatment in the past. The recommended treatment for chronic urticaria is currently based on a stepwise approach that enables achieving disease control with a reasonably good quality of life. The first step of the treatment ladder consists of selective, new generation, anti-H1 histamine blockers, which do not cross the blood brain barrier, starting from the recommended dose (first line) and increasing up to four-fold (second line). The third line of treatment is the addition of immune modulators such as leukotriene receptor blockers (Singulair), anti-IgE biological therapy (Xolair), or cyclosporine. In this review we present the updates and considerations arising during evaluation and treatment of chronic urticaria. The need for specific tests, immunologist/allergologist evaluation, as well as treatment modalities taking into consideration the large body of evidence that has accumulated in the last few years, the new international guidelines as well as their application in Israel have been addressed.

Atopy and Asthma in Migrants: The Function of Parasites.

Migration studies have shown that environmental factors in more developed and industrialized countries facilitate atopy and asthma in a time-dependent manner and are affected by age at immigration. Levels of immunoglobulin E are higher in immigrants than in the local population and gradually decrease to the levels of the general population. Parasitic infestation may function in the prevention and pathogenesis of atopic conditions in immigrants from developing countries. Helminths are associated with a reduced prevalence of clinically important atopic disorders, likely because of induction of a regulatory cell population mechanism. Improved understanding of the immunologic background of helminths and their protective function in humans has led to a growing interest in the possibility of reversal of allergies using parasites and the development of new therapies, such as immunomodulation for allergy using ova from parasites orally or intranasally. Strategies for primary prevention in high-risk atopic individuals and secondary prevention guidelines should be developed for populations in developing countries and for immigrants from developing countries to atopy-prevalent developed countries. Improved understanding of the function of parasitic infection in modulation of the immune response may lead to new therapeutic options for allergic conditions.

[SEAFOOD ALLERGY IN ISRAEL].

Allergy to seafood such as shrimps, crab, lobster and fish eggs is relatively infrequent in Israel compared to fish allergies and allergies to other foods. This is mainly due to the fact that most of the population and restaurants preserve and maintain Kosher food. Changes in the population eating habits, partly due to immigration, were followed by increased frequency of such sensitivities in recent years. We describe three typical cases that illustrate the characteristics of allergy to sea foods. Allergy to seafood can present as a single sensitivity or be part of an allergic tendency, atopy, with other allergic manifestations. Diagnosis by allergy skin test or laboratory evaluation by specific IgE is available for most sea foods but not for fish eggs. The current therapeutic approach is strict avoidance and all patients should be provided with and carry with them an epinephrine auto-injector.

Subcutaneous immunotherapy in Northern Israel: efficacy and safety.

BACKGROUND: The efficacy of subcutaneous immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity has been demonstrated in several studies. OBJECTIVES: To investigate the effectiveness and side effects of immunotherapy in Israel and the relationship between local and systemic side effects. METHODS: This retrospective study was based on patient records and a computerized database for drug dispensing over a 5 year period. Success was rated as partial or complete. Side effects were classified as local or systemic. Systemic side effects were further classified according to severity, as mild (cutaneous), moderate (respiratory symptoms), or severe (cardiovascular). RESULTS: Of the 135 patients on aero-allergen immunotherapy who reached maintenance, 120 (88.9%) exhibited complete or partial improvement and 15 (11.1%) did not improve. All of the 44 patients on hymenoptera immunotherapy reached effective maintenance doses. The mean percent side effects calculated per treatment (injection) were 2.49 for local and 1.58 for a systemic reaction during the build-up phase, and 1.13 and 1.12 during the maintenance phase, respectively. Rates of systemic reactions were 1.3% for cutaneous, 1.14% for respiratory and 0.97% for cardiovascular reactions during the build-up phase, and 1.11%, 0.53%, and 0.51% during the maintenance phase, respectively. The odds of systemic reactions were significantly higher in patients with local reactions both in the build-up phase (P = 0.03) and in the maintenance phase (P = 0.0003). The number of annual medications dispensed per patient decreased from 31.5 to 26.0 during the first year after reaching maintenance, and to 22.5 in the second year. Pharmaceutical costs were 67% lower 1 year after the start of the maintenance phase, compared to the year before the start of immunotherapy, and 63% lower in the second year (P = NS). CONCLUSIONS: Immunotherapy was effective and safe. Recognizing the benefits and safety of immunotherapy by physicians and health authorities is necessary to provide better care for allergic patients.

Omalizumab therapy for chronic spontaneous urticaria: the Israeli experience.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monclonal antibody, was recently shown to be effective in treating resistant CSU. OBJECTIVES: To investigated the treatment of CSU with omalizumab in Israel. METHODS: We conducted a multicenter retrospective analysis of patients with refractory CSU treated with omalizuamb in Israel during 2012-2013. Complete improvement was defined as resolution of symptoms with no need for other medications, or satisfactory when patients' condition improved but required regular or intermittent doses of antihistamines. RESULTS: Forty-three patients received omalizumab off-label for refractory CSU. Their mean age was 45 +/- 12 years and CSU duration was 4.3 +/- 4 years. In this cohort, 98% were unsuccessfully treated with high dose H(1)-antihistamines, 88% with systemic glucocorticoids and 30% with cyclosporine and/ or other immune-modulators. Fourteen patients received only one injection of omalizumab, while the other 29 received on average of 4.3 +/- 3.2 injections; 30 patients received 150 mg/ month and 13 received 300 mg/month. Following omalizumab therapy, disease remitted within weeks in 86% of patients, of whom half achieved complete remission. The latter was associated with usage of high dose omalizumab, 300 mg/month vs. 150 mg/month (P = 0.02) and repeated therapy (i.e., multiple injections vs. a single injection) (P = 0.0005). CONCLUSIONS: Omalizumab is an effective and safe treatment for refractory CSU with rapid onset of action for inducing and maintaining remission. Treating CSU patients mandates an individual approach, because while low dose omalizumab will suffice for some patients others might need higher doses and prolonged therapy.

Evolutionary immune response to conserved domains in parasites and aeroallergens.

The immune response based on immunoglobulin E (IgE) evolved as a defense against specific parasitic infections. In the absence of active helminthic infections, the immune system has redirected its IgE epitopes toward innocuous environmental antigens. Helminths and aeroallergens have a similar stereotypical IgE response to unique antigens that can not be explained by chance alone. This study was designed to evaluate potential homology between conserved protein domains embedded in parasitic organisms and aeroallergens. Search and retrieval systems for nucleotide and protein sequences (Entrez, BLAST, and National Center for Biotechnology Information) were searched to identify conserved domains between allergens and certain parasites. A total score was developed that correlated positively with homology between compared sequences. Over 2000 domains were examined. We found matches with a high total score (>100) that signified a strong positive correlation between sequences in allergens (n = 30) and parasites (n = 13). Multiple shared conserved domains were identified between parasites and allergens. Parasite-allergen combinations with the most significant homology (greatest total score) were Plasmodium falciparum enolase and Hev b9 (total score, 612), Schistosoma mansoni albumin and Fel d 2 (total score, 991), Ascaris lumbricoides tropomyosin and Ani s3 (total score, 531), and Wuchereria bancrofti trypsin and Blo t3 (138). Homologous conserved domains exist in specific parasites and allergens, consistent with the theory that the human IgE-eosinophil immune response to common allergens is a direct consequence of stimulation by parasitic organisms.

Omalizumab reduces corticosteroid use in patients with severe allergic asthma: real-life experience in Israel.

OBJECTIVE: Approved by the FDA in 2003, omalizumab is the first recombinant humanized monoclonal anti-immunoglobulin E antibody developed for the treatment of allergic asthma. Due to the heterogeneity of asthma symptoms, investigation of the efficacy of omalizumab in patients outside controlled trials is particularly important. The purpose of the current study was to evaluate the efficacy of omalizumab as an add-on treatment for allergic asthma in a real-life setting in Israel. METHODS: This was a retrospective study based on patient records and computerized database for drug dispensing, emergency room visits, and hospital admissions. RESULTS: The sample comprised 33 individuals (18 men, 15 women; mean age 50.0 ± 12.2, range 25-79) who were treated with omalizumab for severe allergic asthma for a duration of at least 16 weeks. After the initiation of omalizumab therapy, the number of patients who used oral or injected corticosteroids decreased (p < .003, .03, respectively), as did the median dosage of oral corticosteroids (p < .02). Visits to the emergency room decreased from an incidence of 0.526 visits per person-year to an incidence of 0.246 per person-year (p < .05). No adverse reactions to omalizumab were observed. CONCLUSION: Omalizumab as an add-on therapy reduced the use of corticosteroids and improved the control of asthma, as evidenced by reduced asthma-related emergency room visits. This study supports both controlled and uncontrolled studies that have demonstrated the efficacy and safety of omalizumab, and particularly those that demonstrated effectiveness among severe asthma patients. "Real-life" studies are important to identify patients who will most benefit from omalizumab therapy.

[Chronic rhinitis--clinical guidelines 2010].

Chronic rhinitis (CR) affects large populations worldwide, diagnosed in 40% of the population and is often associated with co-morbidities, such as asthma, sinusitis, rhinoconjunctivitis cognitive dysfunction, and leads to loss of work and school days. Recently, global clinical guidelines were proposed for allergic rhinitis (AR). Similarly, an Israeli expert panel, consisting of ENT and Allergy/Immunology specialists, was delegated to discuss the current approaches to CR (including allergic and non-allergic rhinitis) and to submit a consensus paper. The guidelines, briefly presented herein, describe the epidemiology, mechanisms, diagnostic procedures, treatment modalities and clinical-management algorithms. It is adapted to the Israeli health system and will be distributed to all physicians by the Israel Medical Association. The new clinical guidelines are expected to update current knowledge, improve communication between medical disciplines, provide medico-legal support and improve the management of CR.

[Allergic rhinitis and its impact on asthma].

Allergic rhinitis causes major illness and disability worldwide, but it is still underdiagnosed and undertreated. Allergic rhinitis is a risk factor for both the development and for exacerbations of asthma. Up to 30% of patients with rhinitis suffer from asthma, and the majority of patients with asthma suffer from rhinitis. Measurements of allergic status can help to identify risk factors that cause asthma. Hence, the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative recommends that the presence of asthma must be considered in all patients with rhinitis, and that in planning treatment, both should be considered together in terms of efficacy and safety. Treatment of rhinitis may improve asthma symptoms. Due to new studies and diagnostic techniques the ARIA guidelines, initially formed in 1999, were recently updated. They are intended for specialists, general physicians and health care providers in order to increase the knowledge on allergic rhinitis and its impact on asthma and to provide evidence-based revision on the diagnostic methods, treatments and a stepwise approach to management. There is a need for a collaborative effort of all specialists and primary physicians involved in the treatment of rhinitis and asthma for the proper implementation of the guidelines.

International expert consensus on the management of allergic rhinitis (AR) aggravated by air pollutants: Impact of air pollution on patients with AR: Current knowledge and future strategies.

Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking.

Chronic granulomatous disease in Israel: clinical, functional and molecular studies of 38 patients.

Chronic granulomatous disease (CGD) is an innate immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. In the course of 21 years, 38 Israeli CGD patients were diagnosed with 17 gene mutations, seven of which were new. Clinical, functional, and molecular studies were accomplished. Although X-linked recessive (XLR)-CGD is worldwide the most common genotype of the disease (~70%), in our study only 11 patients (29%) suffered from XLR-CGD. In Israel, the higher incidence of the autosomal recessive (AR) form of CGD (63%) may be related to consanguineous marriages. In three patients (8%), all four proteins of the NADPH oxidase were present. Severe clinical expression was found both in the XLR and AR forms, but in general a milder disease was evident in AR-CGD, particularly in patients with p47(phox) deficiency. Despite early and aggressive therapy, a mortality rate of 26% was noted. Given that bone-marrow transplantation was successful in five of seven patients, it is recommended to perform it as early as possible before tissue damage is irreversible.

The predictive value of specific immunoglobulin E on the outcome of milk allergy.

BACKGROUND: Cow's milk allergy is the most prevalent food hypersensitivity, affecting 2-3% of infants, but it tends to resolve with age. Cow's milk-specific immunoglobulin E in the serum is an important measure in the diagnosis and follow-up of infants and children with cow's milk allergy. OBJECTIVES: To examine the relation between CmsIgE and the probability of resolution of milk allergy. METHODS: CMsIgE was determined in the serum of 1800 infants and children referred for the evaluation of possible milk allergy. All children with CmslgE of 1 kU/L or above were followed at the allergy clinic and, according to their condition, underwent milk challenge. The diagnosis of cow's milk allergy was made on the basis of a significant and specific history or a positive oral food challenge. Subsequently, oral tolerance was defined as an uneventful oral challenge. RESULTS: A total of 135 infants and children had milk-specific IgE greater than 1 kU/L. Forty-one percent of children still had clinical milk allergy after the age of 3 years. Sixty-eight percent of children older than 3 years with persistence of cow's milk allergy had milk-specific IgE > 3 IU/ml before the age of 1 year. Furthermore, 70% of children who at 3 years old had resolved their cow's milk allergy had milk-specific IgE that was lower than 3 IU/ml before the age of 1 year. The positive predictive value of CmsIgE > 3 IU/ml to persistent cow's milk allergy at age 3 years was 82.6% (P = 0.001), with a sensitivity of 67.9% and specificity of 70.4%. CONCLUSIONS: Milk-specific IgE concentration in the first year of life can serve as a predictor of the persistence of milk allergy.

Mast cells, which interact with Escherichia coli, up-regulate genes associated with innate immunity and become less responsive to Fc(epsilon)RI-mediated activation.

Mast cells, which are associated with T helper cell type 2-dependent inflammation, have now been implicated in the innate immune response. To further characterize how mast cells are programmed to respond to infectious organisms, we used expression profiling using DNA microarray analysis of gene expression by human mast cells (huMC) during ingestion of Escherichia coli and examined immunoglobulin E (IgE)-mediated degranulation. Analysis of data revealed that specific groups of genes were modulated, including genes encoding transcription factors, cell signaling molecules, cell cycle regulators, enzymes, cytokines, novel chemokines of the CC family, adhesion molecules, and costimulatory molecules. Enzyme-linked immunosorbent assay analysis confirmed the production of tumor necrosis factor and the chemokines CC chemokine ligand (CCL)-1/I-309, CCL-19/macrophage-inflammatory protein-3beta (MIP-3beta), and CCL-18/MIP-4; flow cytometry confirmed the up-regulation of carcinoembryonic antigen-related cell adhesion molecule 1, the integrin CD49d, and CD80. Coincubation with E. coli down-regulated Fc receptor for IgE I (FcepsilonRI) expression and FcepsilonRI-mediated huMC degranulation. These data are consistent with the concept that bacterial exposure directs mast cell responses toward innate immunity and away from IgE-mediated effects.

International Consensus (ICON): allergic reactions to vaccines.

BACKGROUND: Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines. METHODS: Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists. RESULTS: Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines. CONCLUSIONS: This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines.

Mast cells and autoimmunity.

Mast cells (MCs) are major effector cells in allergic diseases. Recently, it has become evident that the contribution of MCs extends far beyond their accepted role in allergic disease, and that they play a more extensive role in a variety of non-allergic immune processes such as the innate immunity response. These cells have a key role in both the induction and elicitation of several autoimmune conditions. Targeting MC development, maturation or activation may be of value in future prevention and treatment of autoimmune conditions.

Hospital admission trends for pediatric asthma: results of a 10 year survey in Israel.

BACKGROUND: In the last decade there has been an increase in asthma morbidity. Hospital admission rates for childhood asthma are influenced by the prevalence of asthma and the quality of asthma care. OBJECTIVES: To assess trends in hospital admission and readmission rates for childhood asthma in the Jezreel Valley in Israel in the last decade, and to evaluate the possible effect of changes in asthma treatment on hospitalization for acute asthma during this period. METHODS: All records of pediatric patients from the central hospital in the Jezreel Valley in northeastern Israel over a 10 year period from 1990 through 1999 who were diagnosed as having asthma were thoroughly reviewed and analyzed for admissions, re-admissions, and treatment before and during admissions RESULTS: There were 1584 admissions, 1208 were first-time admissions and 376 were re-admissions. The number of first-time admissions increased significantly over time (P < 0.0001), with a significant decrease in re-admissions (P < 0.005); this finding was more significant in children under the age of 8 years (P < 0.005). The length of hospital stay decreased significantly from 3.3 days to 2.7 days (P < 0.002). Significant changes in the use of medications included an increase in inhalant glucocorticoids and a decrease in the use of sodium cromoglycate and theophylline. Controller medication use was concomitant with a significant decrease in the re-admission rates. CONCLUSIONS: The increase in the admission rate and the decrease in the rate of re-admissions and the length of hospital stay probably reflect the increase in the prevalence of asthma and changes in its treatment, respectively. It is essential that asthma be recognized as a significant cause of morbidity and that controller medications be administered to decrease its severity, morbidity, and resultant hospital admissions.

[Desloratadine for chronic idiopathic urticaria].

BACKGROUND: Chronic idiopathic urticaria (CIU) is a common and frustrating disorder defined as a regular recurrence of hives for a period of more than 6 weeks, and has a major impact on patients' daily quality of life--H1 receptor antagonists are considered to be particularly effective in reducing pruritus, and are recommended as first-line treatment in patients with CIU. However, the efficacy of the treatment is insufficient. OBJECTIVE: To evaluate the efficacy of desloratadine in CIU in Israeli patients. METHODS: An open label multicenter study in 10 centers in Israel. Upon completion of 3-14 days screening for eligibility, eligible patients were given desloratadine 5 mg for 4 weeks. The DLQI questionnaire and the severity of CIU were assessed at baseline and each week for 28 days. RESULTS: One hundred and four patients aged 19 to 85 years (mean +/- SD 45.6 +/- 15.6) who suffered from moderate CIU, despite previous treatment with anti-histamine agents, were selected and treated with desloratadine 5 mg daily for 28 days. There was significant improvement for dermatologic quality of life in each of 10 parameters and in work productivity, and significant decrease in CIU symptoms and signs including the number and size of hives. In the overall evaluation of treatment 51% of patients reported complete or marked relief and 20% had no relief. Adverse events were reported as mild in 10 patients and moderate to severe in 2 patients who discontinued the study due to headache. CONCLUSION: Desloratadine can be successfully used in the treatment of CIU.