Icatibant Outcome Survey in Patients with Hereditary Angioedema: Experience in Israel Compared with Other Countries.

BACKGROUND: Management of patients with hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is evolving worldwide. Evaluating the Israeli experience may provide valuable insights. OBJECTIVES: To compare demographics and icatibant treatment patterns and outcomes in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey (IOS) in Israel with those in other countries. METHODS: The IOS is an ongoing observational study that prospectively monitors real-world icatibant safety/tolerability and treatment outcomes. RESULTS: By July 2016, 58 patients from Israel and 594 patients from other countries were enrolled. Median age at diagnosis (16.7 vs. 21.3 years, P = 0.036) and median delay between symptom onset and diagnosis (0.8 vs. 6.6 years, P = 0.025) were lower in Israel compared with other countries, respectively. Differences in attack severity were not significant (P = 0.156); however, during follow-up, Israeli patients were less likely to miss > 7 days of work/school due to C1-INH-HAE-related complications (P = 0.007). A trend was also shown in Israel for earlier time to treatment (median 0.5 vs. 1.3 hours, P = 0.076), attack duration was shorter (median 5.0 vs. 9.0 hours, P = 0.026), and patients more often self-administered icatibant (97.2% vs. 87.5%, P = 0.003), respectively. However, Israeli patients were less likely to treat attacks (P = 0.036). Whereas patients in Israel reported exclusive use of danazol for long-term prophylaxis, those in other countries used various agents, including C1-INH. CONCLUSIONS: Recognition of C1-INH-HAE and timeliness of icatibant treatment appear more favorable, and attack duration shorter, in Israel compared with other countries.

Adaptation and Validation of the Israeli Version of the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL).

BACKGROUND: Chronic urticaria (CU) is a common disabling disorder. The CU-Q2oL (Chronic Urticaria Quality of Life Questionnaire) is a specific questionnaire for evaluating quality of life in CU patients. It consists of 23 items divided into six quality-of-life dimensions. It was initially developed in Italy and later validated in other countries. OBJECTIVES: To validate and adapt the CU-Q2oL to the Hebrew language in order to make it suitable for use in Israel. METHODS: The CU-Q2oL questionnaire was translated to Hebrew. A group of 119 CU patients were asked to complete this version, in addition to the Dermatology Life Quality Index (DLQI) and Urticaria Activity Score (UAS) questionnaires. A factorial analysis was performed to identify CU-Q2oL subscales, internal consistency and convergent validity assessment, as well as factors determining quality-of-life scores. RESULTS: The factor analysis identified six scales of the Israeli CU-Q2oL: (i) sleep and concentration, (ii) function and mental status, (iii) embarrassment and clothing limitations, (iv) itching, (v) eating behavior and medication side effects, and (vi) swelling, which accounted for 77% of the data variance. Five scales showed good internal consistency over 0.81. The mean ± SD score of CU-Q2oL in our patients with CIU was 41 ± 21.7. We found a strong positive correlation between the overall scores of CU-Q2oL and DLQI questionnaires (r = 0.8, P < 0.01). Additionally, we found a positive correlation between UAS and both CU-Q2oL and DLQI (r = 0.62, P < 0.01, and r = 0.53, P < 0.01, respectively). CONCLUSIONS: This study demonstrates that the Israeli CU-Q2oL questionnaire is suitable for both clinical use and research in Israel.

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.

Dose-response association between smoking and atopic eczema: results from a large cross-sectional study in adolescents.

BACKGROUND: Tobacco smoking and exposure to environmental tobacco smoke (ETS) are known risk factors for asthma, but their association with atopic eczema is unclear. OBJECTIVE: To investigate the association of smoking and exposure to ETS with prevalence of atopic eczema in a national sample of 13- to 14-year-olds in Israel. METHODS: Cross-sectional study within the framework of the International Study on Asthma and Allergies in Childhood. RESULTS: Complete data were available for 10,298 schoolchildren. Atopic eczema as well as asthma and allergic rhinitis were significantly more prevalent in smokers than nonsmokers. Multiple regression analysis revealed a dose-response association between smoking and atopic eczema compared to not smoking: occasional smokers, odds ratio (OR) = 1.6 (95% confidence interval (CI) = 1.2-2.3); daily smokers, OR = 2.2 (95% CI = 1.4-3.6). Exposure to ETS at home was significantly associated with asthma (OR = 1.25; 95% CI = 1.1-1.5) but not atopic eczema. CONCLUSIONS: The dose-response association between active smoking and atopic eczema in adolescents is a novel observation which deserves further consideration.

[Exercise induced vasculitis].

Exercise induced vasculitis (or purpura) is usually misdiagnosed and ignored in the literature, although it is not uncommon. We report two female patients who developed a rash on the lower legs after walking all day long. The rash was red, itchy with a burning sensation. The lesions resolved after a few days with and without steroid treatment. Allergic etiology was suspected, therefore they were sent to the allergy clinic for evaluation. Exercise-induced vasculitis tends to occur in healthy people, especially in hot weather. Extensive investigation with blood or allergy tests is not needed.

Association of food allergy with asthma severity and atopic diseases in Jewish and Arab adolescents.

AIM: To investigate the prevalence of reported food allergy and its association with atopic diseases and asthma severity among Jewish and Arab adolescents. SUBJECTS AND METHODS: The self-report questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) was administered to adolescents aged 13-14 years from randomly selected junior high schools in Israel. Questions regarding food allergy were added. RESULTS: A total of 11 171 questionnaires were available for analysis. Food allergy was reported by 3.6% of participants: 1.9% milk, 0.6% egg, 0.6% peanut and 0.4% sesame. On multivariate analysis, food allergy was strongly associated with current asthma (OR, 2.5; 95% CI, 1.8-3.3), atopic eczema (OR, 3.2; 95% CI, 2.4-4.3) and allergic rhinitis (OR, 2.4; 95% CI, 1.8-3.1). Arabs were significantly more allergic to peanut (OR, 2.5; 95% CI, 1.5-4.1), egg (OR, 3.5; 95% CI, 2.1-5.9) and sesame (OR, 2.3; 95% CI, 1.2-4.5) than Jews, and less allergic to milk (OR, 0.6; 95% CI, 0.4-0.9). Asthmatic subjects with food allergy had significantly more parameters of severe asthma than those without food allergy (p < 0.001). CONCLUSIONS: The prevalence of allergy to specific foods differs between Jews and Arabs. Asthmatic adolescents with food allergy report more severe asthma than those without food allergy.

Increased rate and greater severity of allergic reactions to insect sting among schoolchildren with atopic diseases.

The question of whether atopic diseases are a risk factor for allergic reactions to insect sting is still unresolved. The aim of this study was to evaluate the association between atopic diseases (asthma, allergic rhinitis, atopic eczema) and allergic reactions to insect stings among schoolchildren in Israel. A self-report questionnaire of the International Study of Asthma and Allergies in Childhood was administered to a national sample of 13-14-yr-old schoolchildren. Questions regarding reactions to insect stings were added. A total of 10,021 questionnaires were available for analysis. Among the children who reported insect stings (56.3%), the prevalence of current asthma was 6.0%, of allergic rhinitis, 10.5%, and of atopic eczema, 8.7%, with no significant differences from the whole study population. Among children with any of the atopic diseases, 36.9% reported an allergic reaction to insect sting compared to 24.8% of the non-atopic children (p < 0.0001). On multivariate analysis, asthma, allergic rhinitis, and atopic eczema were found to be significant risk factors for allergic reactions of any severity. Children in the atopic group had a significantly higher rate of severe allergic reactions than the non-atopic children, and relatively higher rates of milder ones (p < 0.0001). Asthmatic patients with severe allergic reactions had more parameters of severe asthma than asthmatic patients with mild or no reactions. In conclusions, allergic diseases are associated with a higher rate and greater severity of allergic reactions to insect sting in children. The severity of the allergic reaction is related to the severity of the asthma symptoms.

Association between asthma and migraine: A cross-sectional study of over 110 000 adolescents.

BACKGROUND: Epidemiological studies have reported an association between asthma and migraine, mainly in adults. OBJECTIVE: To examine the association between specialist-diagnosed asthma and migraine among adolescents. METHODS: The electronic database of a recruitment center was retrospectively searched for all 17-year-old draftees during the years 1987-2010. Diagnoses of asthma and migraine were made by certified specialists. The prevalence of migraine was compared among draftees with and without asthma. Covariate data on socio-demographics and associated medical conditions were recorded. RESULTS: A total of 113 671 adolescents were available for analysis. Asthma was diagnosed among 4.0% and migraine among 1.9%. Migraine was significantly more prevalent among adolescents with asthma [174 of the 4581 subjects (3.8%)] compared to those without asthma [1946 of the 109 090 (1.8%)] [OR = 2.17 (95% CI 1.86-2.55; P < 0.001)]. Rates of migraine among subjects with and without allergic rhinitis were 6.3% and 1.7%, respectively [OR = 4.04 (95% CI 3.58-4.56; P < 0.001)]. On multivariate analysis, there was a significant association between migraine and both asthma [OR = 1.42 (95% CI 1.19-1.68)] and allergic rhinitis [OR = 3.18 (95% CI 2.80-3.63)]. Other factors significantly associated with migraine were female gender, urban area of residence, recent immigration to Israel, having three or fewer siblings, and abnormal body mass index. CONCLUSION: Clinicians should be aware that asthma and allergic rhinitis are potential risk factors for migraine in adolescents. A combined finding of these conditions and recurrent headache is highly suggestive of migraine and warrants a different diagnosis and treatment approach from sinusitis.

Adolescent versus parent reports on asthma and asthma symptoms.

PURPOSE: Epidemiological studies of asthma in adolescence commonly rely on self-reports. This study aimed to compare adolescent and parent reports regarding the presence of asthma and asthma symptoms in two ethnic groups, Jews and Arabs, living in the same country. METHODS: Eighth-grade pupils attending five schools in Tel Aviv and four schools in two Arab cities in Israel were asked to complete the self-report International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire in the classroom. Their parents were interviewed by telephone using the parental ISAAC questionnaire. We assessed prevalence rates of asthma and asthma symptoms according to adolescent and parent responses. Agreement between adolescents and parents was assessed by Cohen's kappa coefficient. RESULTS: Adolescents reported more asthma and asthma symptoms than their parents in both the Jewish (327 adolescent-parent pairs) and the Arab (335 adolescent-parent pairs) groups. Both groups showed moderate adolescent-parent chance-corrected agreement for current asthma (kappa 0.59 in Jews, 0.52 in Arabs, P = 0.60) and lifetime asthma (kappa 0.53 Jews, 0.44 in Arabs, P = 0.33); and slight to fair chance-corrected agreement for asthma symptoms. There were no statistically significant differences between the Jewish and Arab populations in chance-corrected agreement for any of the parameters assessed. CONCLUSIONS: Jewish and Arab adolescents more often report asthma and asthma symptoms than do their parents. This seems to be a cross-cultural phenomenon. Therefore, particular attention should be paid to the source of information when comparing prevalence of asthma and asthma symptoms across studies. Pediatr Pulmonol. 2017;52:154-159. © 2016 Wiley Periodicals, Inc.

Value of a negative aeroallergen skin-prick test result in the diagnosis of asthma in young adults: correlative study with methacholine challenge testing.

BACKGROUND: None of the existing tests for the diagnosis of asthma are considered to be definitive. Certain circumstances require prompt diagnosis, and a test able to predict the absence of asthma would be very useful. OBJECTIVE: To evaluate the contribution of a skin-prick test (SPT) to the diagnostic workup of subjects with suspected asthma. PATIENTS AND METHODS: The study included three groups of subjects aged 18 to 24 years: group A, asthmatic patients (n = 175); group B, control subjects (n = 100); and group C, subjects with suspected asthma (n = 150) with normal spirometry findings and a negative exercise challenge test result. All underwent an SPT to a battery of common aeroallergens, and group C underwent a methacholine challenge test (MCT) in addition. The sensitivity, specificity, positive predictive value, and negative predictive values (NPV) of the SPT were calculated using provocative concentrations of methacholine causing a 20% fall in FEV(1) (PC(20)) of < 4 mg/mL and < 8 mg/mL as diagnostic cutoff values for asthma in the MCT. Bayes' formula was used to determine posttest probabilities of having asthma, both for positive and negative SPT results. RESULTS: A positive SPT result to at least one allergen was found in 95.5%, 54%, and 69% of patients in the three groups, respectively. The sensitivity, specificity, and NPV of the SPT were 90.7%, 52.0%, and 84.8%, respectively, with a cutoff value of PC(20) < 8 mg/mL. The lower cutoff, PC(20) < 4 mg/mL, increased the sensitivity and NPV to 98.2% and 97.8%, respectively. A negative SPT result decreased the probability of having asthma by 10-fold to 20-fold in subjects whose pretest probability was low to moderate. CONCLUSIONS: Incorporating an SPT into the workup of subjects with suspected asthma can reduce the cost of this process significantly. The SPT may be used as a simple, fast, safe, inexpensive, and reliable method to predict the absence of asthma in young adults.

Trends in the prevalence of asthma symptoms and allergic diseases in Israeli adolescents: results from a national survey 2003 and comparison with 1997.

PURPOSE: To investigate the temporal trends in the prevalence of asthma symptoms and allergies in Israeli adolescents. METHODS: A modified version of the International Study of Asthma and Allergies in Childhood questionnaire was administered to a national sample of Jewish and Arab schoolchildren in Israel. The results were compared to a similar survey conducted in 1997. RESULTS: Asthma prevalence was 7.0% in 1997 and 6.4% 2003 respectively (p = 0.1). Wheezing in the past 12 months decreased significantly from 17.9% in 1997 to 13.8% in 2003 (p < 0.001). Allergic rhinitis and atopic dermatitis increased from 9.4% to 10.5%, and from 5.9% to 8.7% respectively. The prevalence of allergic disease remained higher in Jewish compared with Arabs. CONCLUSIONS: The prevalence of asthma symptoms decreased in Israel from 1997 to 2003 while there was an increase in allergic rhinitis and atopic dermatitis.

Reproducibility of skin testing and serum venom specific IgE in Hymenoptera venom allergy.

BACKGROUND: The decision regarding an immunotherapy regimen for venom-allergic patients is based on the results of skin testing and serum venom specific IgE measurements. However, their reliability has been questioned, and their reproducibility has not been examined. OBJECTIVE: To evaluate the reproducibility and reliability of the results of skin testing and serum venom specific IgE measurement in venom-allergic patients. METHODS: Patients with a systemic reaction after an insect sting were evaluated twice, 2 to 6 weeks apart, by intradermal skin tests and by determination of serum venom specific IgE to Hymenoptera venoms. RESULTS: Thirty-five patients were evaluated 1 to 168 months (mean, 23 months) after the sting reaction. Reproducibility of skin test results for all venoms at the 2 sessions was found in 23 patients (66%). Reproducibility of venom specific IgE results for all venoms was found in 16 (59%) of 27 patients from whom 2 blood samples were available for evaluation. Concordance between skin test and venom specific IgE results for all venoms was found in 30 (51%) of 59 samples available for evaluation. CONCLUSIONS: The reproducibility of venom skin test and serum venom specific IgE results is relatively poor. It is common practice for therapeutic decisions regarding venom immunotherapy to be based on a single diagnostic evaluation. Consequently, many patients are either overtreated or undertreated. Better diagnostic methods are required in venom allergy.

Allergic reactions to insect stings: results from a national survey of 10,000 junior high school children in Israel.

BACKGROUND: Insect sting allergy is a medical condition the magnitude of which has not been fully estimated in children. OBJECTIVES: We sought to evaluate the prevalence of insect stings among schoolchildren in Israel, the rate of allergic reactions, and hospital attendance. METHODS: A self-report questionnaire of the International Study of Asthma and Allergies in Childhood was administered to a national sample of schoolchildren aged 13 to 14 years across Israel. Questions regarding insect stings, allergic reactions, and hospital attendance were added. RESULTS: Ten thousand twenty-one questionnaires were available for analysis. Most (56.3%) had been stung at least once in their lifetime. Of these, 20.5% had a large local reaction (LLR), 11.6% had a mild (cutaneous) systemic reaction (MSR), and 4.4% had a moderate-to-severe systemic reaction (SSR); 11.5%, 6.5%, and 2.5% of the study group, respectively. Arabs had significantly more allergic reactions of all 3 types than Jews (P < .0001). On multivariate analysis, LLR was associated with SSR (odds ratio, 6.25; 95% CI, 4.66-8.41) and MSR (odds ratio, 5.15; 95% CI, 4.24-6.25). More than 10% of the children with an LLR only attended a hospital compared with 7.5% of those with an MSR only and 14.5% with an SSR only. CONCLUSIONS: The frequency of reported allergic sting reactions in children might be higher than previously estimated. Arab children reported significantly more allergic reactions than Jews. Hospital attendance does not correlate with the severity of the allergic reaction, and only a minority of children with SSRs are treated in hospital. CLINICAL IMPLICATIONS: The improper care of severe reactions highlights the need for better public and physician education.

The child with asthma at school: results from a national asthma survey among schoolchildren in Israel.

PURPOSE: To evaluate school absence and restriction in school activities of children with asthma, and to estimate the involvement of the school staff in asthma disabilities. METHODS: A modified version of the International Study of Asthma and Allergies in Childhood written questionnaire was administered to a national sample of 13-14-year-old schoolchildren across Israel. Questions regarding social and demographic factors, school absence owing to asthma symptoms, and school staff involvement were added. RESULTS: There were 10,057 complete questionnaires available for analysis; 710 children reported having asthma. Children with asthma were absent on the average 7.3 +/- 9.8 days in the past school year compared with 3.9 +/- 6.3 days in children without (p = .0001). Absenteeism owing to respiratory symptoms was significantly more common in children with asthma and associated with a more severe asthmatic condition. Four percent of the children with asthma were absent from school more than 30 days. Of the children reporting asthma, 25.9% were not allowed to participate in one or more school activities for medical reasons, compared with 4.2% of children without asthma. Of the children with asthma, 44.3% reported that the school nurse knew about their asthma, and only 13.8% reported that the nurse discussed their asthmatic condition with them; 38.2% of children with asthma reported that no one at school knew about their illness. CONCLUSIONS: Children with asthma are absent annually on average 3.4 days more than children without asthma. School absence is associated with the severity of asthma. A significant percentage of asthmatic children participate less in school activities. School staff awareness of the children illness is not satisfactory.

The efficacy of nasal surgery among patients with and without allergies.

Surgical intervention has been used widely for the correction of nasal obstruction. However, there are only a small number of studies confirming its advantages. This study summarizes our experience regarding patients' satisfaction with the operation results. We also examined whether the presence of allergic rhinitis can be used as a reliable predictive criterion for the operation outcome in an adult population. Fifty-three patients with perennial nasal obstruction who had been referred for nasal surgery underwent allergic evaluation. Patients with a positive skin-prick test to a perennial allergen were included in the allergic group, whereas those with a positive skin test to a seasonal allergen only or with negative skin tests were included in the nonallergic group. Patients filled out a symptom score before the operation and at 6 and 12 months after the operation and also were asked to grade their overall satisfaction with the outcome of the operation. One year after surgery, only 20 patients (38%) were definitely satisfied with its results. Twenty-eight patients (53%) were willing to undergo the same operation again had they known of its outcome in advance. There was no difference between the allergic and nonallergic groups regarding patient satisfaction or willingness to undergo the same operation again. We conclude that the allergic status of the patient is not an effective predictive criterion for the outcome of nasal surgery in patients with perennial nasal obstruction. The efficacy of this procedure is rather low and better preoperative criteria are required to improve its efficacy.

Prevalence and risk factors for allergic rhinitis and atopic eczema among schoolchildren in Israel: results from a national study.

BACKGROUND: There is growing evidence that the prevalence rates of asthma and allergic diseases are increasing, especially among children. Several risk factors are under investigation. OBJECTIVE: To evaluate the prevalence and risk factors for allergic diseases, including allergic rhinitis (AR) and atopic eczema (AE), among 13- to 14-year-old schoolchildren in Israel. METHODS: A modified version of the International Study of Asthma and Allergies in Childhood written questionnaire was administered to a national sample of schoolchildren 13 to 14 years old in Israel. The questionnaire was completed by the schoolchildren themselves. RESULTS: There were 10,057 complete questionnaires available for analysis. The prevalence of AR symptoms ever and current AR were 41.6% and 9.4%, respectively. Allergic rhinoconjunctivitis symptoms ever were reported by 15.8% of the children. The prevalence rates of 6 months of itchy rash ever and AE were 5.9% and 7.8%, respectively. After adjustment for demographic and environmental factors, current asthma, parental history of asthma, and population group were the most significant risk factors for current AR (odds ratio [OR], 4.47; 95% confidence interval [CI], 3.70-5.40; OR, 1.30; 95% CI, 1.02-1.66; and OR, 1.75; 95% CI 1.45-2.13; respectively) and AE (OR, 2.30; 95% CI, 1.80-2.90; OR, 1.80; 95% CI, 1.40-2.30; and OR, 1.70; 95% CI, 1.40-2.00; respectively). CONCLUSIONS: Israeli children have a low prevalence rate of current AR and a midrange rate of AE. Arabs have lower prevalence rates of allergic diseases than Jews, and the prominent risk factors for those diseases are current asthma and parental history of asthma.