Israel Medical Association Journal

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.

Background: Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monoclonal 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. 

The prevalence of food allergy is increasing in both the pediatric and adult populations. While symptom onset is mostly during childhood, there are a considerable number of patients whose symptoms first begin to appear after the age of 18 years. The majority of patients with adult‑onset food allergy have the pollen-plant allergy syndromes. Many of them manifest their allergy after exercise and consuming food to which they are allergic. Eosinophilic esophagitis, an eosinophilic inflammation of the esophagus affecting individuals of all ages, recently emerged as another allergic manifestation, with both immediate and late response to the ingested food. This review provides a condensed update of the current data in the literature on adult-onset allergy.

Background: Mite allergy is an indoor allergen responsible for most respiratory allergies in the western world. Environmental control can modify disease activity in these patients.

Objectives: To examine the benefit of the Plasma Cluster^® device (Sharp, Japan) for inactivating and removing mites from the environment of patients diagnosed with either mite‑sensitive perennial allergic rhinitis or mite‑sensitive allergic asthma.

Methods: Patients with AR[1] (n=30) or AA[2] (n=10) were enrolled into a prospective open observational 8 week study. The first 2 weeks involved initial evaluation, the following 4 weeks consisted of active usage of the device, and the last 2 weeks were designated for follow‑up. Symptom scores (recorded daily by patients and during visits by physicians) were recorded and analyzed.

Results: Patients with AR experienced a significant (P < 0.05) reduction in nasal discharge, post‑nasal drip, nasal congestion, nasal itching, watery eyes, itchy eyes, headache, itchy ears, night disturbances and an improvement in general well‑being during the last 2 days of the study compared to baseline. Patients with AA reported significant (P < 0.05) reduction in dyspnea, wheezing and the need to avoid dust mites. There was a significant (P < 0.05) improvement in mean peak expiratory flow rate at study closure compared to baseline.

Conclusions: Short-term usage of the Plasma Cluster^® device resulted in considerable clinical improvement and increased peak expiratory flow rate in patients with AR or AA. The findings of this pilot study warrant longer and controlled studies to determine the value of this device in the treatment of various allergic disorders.

Background: Dyspnea may be a presenting symptom of type I food hypersensitivity, and bronchial hyper-reactivity, without known asthma, can coexist in patients with food allergy.

Objective: To evaluate airway involvement in young adult patients with food allergy and no asthma and compare the findings to those of patients with food allergy and asthma, with food allergy and allergic rhinitis, with asthma and no food allergy, and of apparently healthy controls.

Methods: The evaluation involved prick skin test to food (65 allergens) and inhalants (24 allergens), spirometry, methacholine inhalation challenge, and induced sputum for cell analysis. The five groups consisted of 18 patients with food allergy alone, 11 with food allergy and asthma, 13 with food allergy and allergic rhinitis, 10 with asthma alone, and 10 controls.

Results: Patients with food allergy alone were mainly (86%) skin sensitive to pollens. Those with either asthma or allergic rhinitis were mainly (95%) sensitive to mites. BHR was detected in 40% of the patients with food allergy alone, 55% of the patients with allergic rhinitis, and 100% of the patients with asthma. Cell counts in the sputum of patients with asthma and in those with food allergy and asthma showed higher eosinophil counts compared to those with food allergy and allergic rhinitis. Patients with food allergy and no asthma, regardless of BHR status, had mainly neutrophils in the sputum.

Conclusions: Patients with food allergy are highly likely to have concomitant asymptomatic BHR. Mite sensitivity in patients with food allergy predicts respiratory allergy (either asthma or allergic rhinitis). High eosinophil levels in the sputum of food allergy patients predict respiratory involvement.

Background: The anti-inflammatory effect of montelukast, a leukotriene receptor antagonist, in patients with bronchial asthma is not entirely clear. Basophils can release a variety of mediators, including histamine and leukotriens, which most likely play an active part in the late allergic response.

Objectives: To study the effect of montelukast (10 mg/day) on histamine and cysteinyl leukotriene release from basophils taken from 12 mild atopic asthmatic patients who were given the drug for 4 weeks.

Methods: Basophils were withdrawn at baseline, and after 48 hours, 1 week, and 4 weeks of therapy. Histamine was measured by a radioenzymatic method and leukotrienes by immunologic assay. Histamine and cysLT release was measured spontaneously and following stimulation with interleukin-3 and anti-immunoglobulin E. Spirometry and symptom score were measured before and during treatment.

Results: During the treatment with montelukast there were no significant changes in spontaneous, IL-3 and anti-IgE‑induced histamine release. cysLT release decreased significantly only after 4 weeks of treatment (from 2899 ± 550 pg/ml at baseline to 2225 ± 430 pg/ml at 4 weeks, P = 0.02).

Conclusions: Montelukast does not seem to affect the release of histamine from basophils but mildly inhibits the cysLT release seen after 4 weeks of treatment.

Objective: To examine to what extent and for how long nedocromil sodium prevents exercise-induced asthma when given immediately before exertion compared to chronic administration.

Patients and Methods: Eighteen asthmatic patients were given 4 mg NS at 30 min or 3.5 hours before exertion. We compared the resultant effect with that of the same protocol measured after 2 and 4 weeks of continuous treatment with the drug.

Results: Nedocromil sodium decreased exercise-induced asthma similarly at both points when given acutely. Chronic treatment of up to 4 weeks did not improve this protective effect at either interval following the inhalation.

Conclusion: Nedocromil sodium most likely reaches its maximal effect on exercise-induced asthma upon the first administration, although treatment for longer than 4 weeks might be required to prove a chronic effect of the drug.