Omalizumab withdrawal outcomes in chronic spontaneous urticaria are linked with baseline IgE and eosinophil levels.

Background: Chronic Spontaneous Urticaria (CSU) is an immune-mediated skin disease that may require prolonged treatments. Currently, there are no recommendations for treatment discontinuation once CSU symptoms are controlled, particularly among patients primarily diagnosed with severe CSU. Objective: In this real-life study we aimed to describe our experience of omalizumab (Oma) treatment withdrawal in CSU and define biomarkers related to these outcomes. Methods: CSU patients followed at our allergy clinic from January 2016 to December 2022 were included. Response to Oma therapy, and Oma-withdrawal outcomes among patients who reached complete remission for >6 months were analyzed. Results: During the study period 192/335(%) CSU patients were categorized as severe-CSU and entitled to receive Oma according to our country's regulations. Of them, 131/192(68%) were considered "Oma-responders", and 95/131(72.5%) patients underwent gradual treatment withdrawal. Successful Oma-withdrawal was documented in 47/95(49.5%) whereas 48/95(50.5%) patients experienced flare and were defined as unsuccessful OMA-withdrawal. The first was associated with shorter disease duration 7.1 ± 7.4 years vs. 10.7 ± 9.4 (P = 0.042), lower baseline-IgE 81.6 ± 84.1IU/ml vs. 324.7 ± 555.9 (P = 0.005), and lower baseline-eosinophils count 131.4 ± 110.5 vs. 195.6 ± 98.4 (P = 0.043) in comparison to failure of Oma-withdrawal group. Conclusion: OMA may be successfully withdrawn in up to 50% of severe CSU patients following complete remission of disease symptoms, utilizing a gradual withdrawal protocol. Oma-withdrawal failure was linked with longer duration of disease as well as high IgE and eosinophil counts prior to initiation of Oma therapy. These parameters may enable the design of a treatment withdrawal algorithm.

Peanut oral immunotherapy using an extensively heated and baked novel composition of peanuts.

BACKGROUND: Oral immunotherapy (OIT) is an increasingly acceptable therapeutic option for peanut-allergic (PA) children, despite significant side effects. Major peanut allergenic proteins are heat-resistant and are not rendered hypoallergenic after baking or cooking. Lyophilized peanut protein-MH (LPP-MH) is a novel composition from developing peanuts, enabling cooking-induced reduction in allergenicity. We aimed to explore the safety and efficacy of OIT, with extensively heated and baked (EHEB) LPP-MH in PA children. METHODS: In a single-arm, single-center, pilot study, PA children with a single highest tolerated dose of <100 mg peanut protein were placed on a 40-week OIT protocol with 300 mg daily of heat-treated LPP-MH. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-12 months of follow-up visit. RESULTS: Thirty-three children with PA were enrolled, with a mean cumulative tolerated dose (MCTD) of 71.2 mg PP (95% CI 45-100 mg). After 40 weeks, 32/33 patients were able to consume more than 300 mg of natural PP, with MCTD of 1709 mg (CI 365-3675 mg). There were no severe allergic reactions requiring epinephrine, during any of the observed LPP-MH challenges or any treatment related doses at home. After 6-12 months on daily maintenance, the MCTD was 8821 mg (95% CI 1930-13,500 mg). This enabled most children age-appropriate dietary inclusion of peanuts. CONCLUSION: An OIT protocol with heat-treated LPP-MH, a novel composition from developing peanuts, seems a potentially safe and efficacious OIT modality for PA children, enabling the introduction of dietary levels of peanut proteins in highly allergic PA children. Validation in randomized controlled studies is mandated.

The third dose of BNT162b2 COVID-19 vaccine is efficacious and safe for systemic lupus erythematosus patients receiving belimumab.

INTRODUCTION: Over 95% of healthy subjects develop anti-COVID IgG antibodies after receiving two doses of BNT162b2 COVID-19 vaccine. In comparison, 20%-30% of SLE patients do not seroconvert following 1-2 doses of COVID vaccines, potentially due to immunosuppression. The aim of this study was to assess immunogenicity and safety of BNT vaccine in SLE patients treated with Belimumab and especially the yield of a booster third dose in this population. METHODS: SLE patients treated with Belimumab in the Sheba Medical Center, Israel, were included in this study. All were recommended to receive the BNT vaccine according to national guidelines; and were advised to perform serologic tests after receiving second and third doses. Clinical data included demographics, SLE treatments, adverse effects to vaccines and SLEDAI scores performed 2 weeks before vaccinations and 6-12 weeks after receiving the second or third dose of the vaccine. RESULTS: Our cohort included 17 patients, 14 (82.35%) females, median age 50 ± 14.2 years, and disease duration 12 ± 10.57 years. Belimumab therapy was given for a mean of 6 ± 2.5 years. Of them, 15/17 patients received 3-doses of BNT vaccine. Serologic assessment was performed for 10 patients, 7/10(70%) became seropositive following the second dose, while 2/3 patients seroconverted only after the third dose. Vaccinations were well tolerated with minimal adverse events and no disease flares. SLEDAI scores before and after vaccinations were 4 ± 3.8 and 4 ± 2.7 (p = 0.69), respectively. CONCLUSIONS: Immunization with the BNT vaccine is efficacious and safe for SLE patients treated with Belimumab. Following the third dose of vaccine, immunogenicity among SLE patients mounted to 90%, thereby approximating the general healthy population. No SLE disease flares and/or significant adverse events were noted in our cohort. Assessment of seroconversion and consideration of subsequent boosters of COVID-vaccine should be considered in this group of patients.

Late Hypersensitivity Reactions to the BNT162b2 SARS-CoV-2 Vaccine Are Linked to Delayed Skin Sensitization and Prior Exposure to Hyaluronic Acid.

Background: Late hypersensitivity reactions (HSRs) to the BNT162b2-vaccine have raised concerns regarding its safety, particularly as further immunizations are required. The yield of skin testing with the BNT162b2v is unclear, as well as the risk factors and outcomes of re-immunization after late HSRs. Objective: We studied a series of patients with late HSRs to BNT162b2v. Methods: Patients referred to the Sheba medical center from December 2020 to May 2021 with late HSRs to the first dose of BNT162b2 were included. HSRs were defined as late if they appeared or lasted >24 h after inoculation. We compared late HSRs to immediate HSRs that appeared within minutes−2 h after vaccination. Intradermal testing with PEG-containing medication and BNT162b2v was performed. Results: A total of 17 patients that presented with late HSRs (study group) were compared to 34 patients with immediate HSRs (control group). Delayed sensitivity to intradermal testing of the BNT162b2v was observed in 9/17 (53%) of the study group compared to 4/34 (12%) in the control group (p = 0.01). Former exposure to a dermal filler with hyaluronic acid was documented among 7/17 (41%) vs. 2/34 (6%) in the study and control groups, respectively, (p = 0.0038). All patients who presented with late HSRs were advised to receive subsequent doses of the BNT162b2v vaccine with or without concomitant medication, and all were re-immunized successfully. Conclusions: Late HSRs to BNT162b2v were linked with positive responses to intradermal testing with the vaccine and prior exposure to derma fillers with hyaluronic acid. This may elude to an immune mechanism triggered by former exposures. Although further studies are needed, late HSRs to the BNT162b2-vaccine did not prevent patients from receiving subsequent doses of the vaccines.

A clinical pathway for the diagnosis of sesame allergy in children.

Background: Sesame allergy (SA) is a common cause of life-threatening, persistent food allergy, not only in the Middle East and Asia, but increasingly worldwide. Commercially available tests such as extracts for skin testing or specific IgE for sesame or its components in serum, have very limited predictive values. Therefore the diagnosis is dependent on the performance of oral food challenges (OFC), frequently avoided in children, due to time and resource constraints, as well as the risk of anaphylaxis. In the current study we aimed to develop a simple, readily available, clinical tool, able to predict sesame OFC outcomes in children. Methods: Children with a history of SA were evaluated in the outpatient allergy clinic. All children underwent natural sesame OFC, with an additional baked-sesame challenge offered to children with SA. Clinical data were compared between the sesame tolerant (ST) and SA groups. Machine-learning tools were applied, to create a simple, clinically driven, decision tree analysis (DTA), predicting the outcome of sesame OFCs and the diagnosis of SA. Results: One hundred four children, mean age 47.2 months, 58% boys were included, with a high prevalence of additional food allergies, atopic dermatitis, asthma, and rhinitis. Following OFC, 56 (54%) were diagnosed as ST and 48 (46%) SA. Among SA children, 85% were able to consume baked-sesame in equal or higher protein amounts compared to natural sesame paste. Compared to ST, SA children had a tendency towards a higher incidence of allergic rhinitis (5% Vs 17%, p = 0.062), multiple food allergies (3.6% vs 12.5%, p = 0.09) and requiring medical treatment after the initial SA reaction (27% vs 41%, p = 0.022). As a group, skin tests with both commercial and natural tahini paste differed significantly between ST and SA (mean wheal in mm, for extract 4.2 vs 13.4, p < 0.001 and for natural sesame paste 6.7 vs 24.4, p < 0.001), However, the PPV of any individual test was only between 60%-85%. Our exploratory, clinical DTA, predicted OFC outcomes and the presence or absence of Sesame Allergy, with ≥96% positive (PPV) and negative (NPV) predictive values. Conclusion: OFCs remain the gold standard for the diagnosis of Sesame Allergy and are indicated to define ST/SA status even in highly atopic patients with previous immediate allergic reactions to sesame. A decision-tree analysis based on clinical parameters easily available in every allergy clinic, can predict the outcome of sesame OFC in the vast majority of children, increasing the safety and availability of such diagnostic procedures.

Assessment of Immediate Allergic Reactions After Immunization With the Pfizer BNT162b2 Vaccine Using Intradermal Skin Testing With the COVID-19 Vaccines.

BACKGROUND: Allergic reactions to the coronavirus disease 2019 (COVID-19) vaccines have raised concerns, particularly as repeated doses are required. Skin tests with the vaccines excipient were found to be of low value, whereas the utility of skin tests with the whole vaccine is yet to be determined. OBJECTIVE: To evaluate a panel of skin tests and the outcomes of subsequent doses of immunization among subjects who suffered an immediate allergic reaction to the BioNTech (BNT162b2) COVID-19 vaccine. METHODS: Between March and December 2021, patients who experienced symptoms consistent with immediate allergic reactions to the BNT162b2 vaccine and were referred to the Sheba Medical Center underwent skin testing with polyethylene glyol (PEG)-containing medicines, Pfizer-BNT162b2, and Oxford-AstraZeneca vaccine (AZD1222). Further immunization was performed accordingly and under medical observation. RESULTS: A total of 51 patients underwent skin testing for suspected allergy to the COVID vaccines, of which 38 of 51 (74.5%) were nonreactive, 7 of 51(13.7%) had no skin sensitization but suffered a clinical reaction during skin testing (mainly cough), and 6 of 51 (11.7%) exhibited immediate skin sensitization. Both skin sensitization and cough during testing were related to a higher use of adrenaline following immunization (P = .08 and P = .024, respectively). Further immunization with the BNT162b2 vaccine was recommended unless sensitization or severe reaction to previous immunization was evident. The latter were referred to be tested/receive the alternative AZD1222 vaccine. Ten patients underwent skin testing with AZD1222: 2 of 10 (20%) demonstrated skin sensitization to both vaccines; thus, 8 of 10 were immunized with the AZD1222, of which 2 of 8 (25%) had allergic reactions. CONCLUSIONS: Immediate allergic reactions to COVID-19 vaccines are rare but can be severe and reoccur. Intradermal testing with the whole vaccine may discriminate sensitized subjects, detect cross-sensitization between vaccines, and enable estimation of patients at higher risk.

Oral immunotherapy for children with a high-threshold peanut allergy.

BACKGROUND: Between 25% and 30% of children with peanut allergy (PA) have a relatively high-threshold peanut allergy (HTPA), with a single maximal tolerated dose (SMTD) higher than 100 mg of peanut protein (PP). However, this threshold may decrease with time, age, exercise, illness, sleep deprivation, and other covariates. OBJECTIVE: To explore the feasibility of a simplified oral immunotherapy (OIT) protocol in a group of children with HTPA. METHODS: Children with PA with an SMTD higher than 100 mg were placed on a 40-week OIT protocol of either 300 mg/d of PP or 100 mg/d for 20 weeks followed by 300 mg/d for 20 weeks. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-month follow-up visit. After the 40-week challenge, all children received a maintenance dosage of 2 gPP 3 times a week. RESULTS: A total of 28 children with HTPA were enrolled, with 56% boys, 89% younger than 6 years old, and a mean SMTD of 304 mg (95% confidence interval 229-378). All were placed on the described OIT protocol. Overall, 2 children were not compliant and 3 had allergic reactions at home on the dose previously tolerated in clinic, 23 completed the 40-week protocol, and all were able to consume 2 g of PP. The mean tolerated dosage at the 6-month follow-up was 8 g. This enabled most children age-appropriate dietary inclusion of peanut-containing products. CONCLUSION: In children with HTPA, a simple, fixed-dose OIT can be both safe and efficacious.

Diagnosis of Peanut Allergy in Preschool Children: The Impact of Skin Testing With a Novel Composition of Peanuts.

Peanut allergy is an increasing concern in younger children. Available bedside diagnostic tools, i.e., prick tests with commercial extracts or peanut-containing foods have only limited predictive values. In a cohort of preschoolers with both a history of allergic reactions and sensitization to peanut proteins, we aimed to characterize the impact of skin tests with a novel composition of peanuts LPP-MH. Almost one quarter (27/110) of preschool children, with a history of allergic reactions to peanuts and positive standard IgE-mediated tests for peanut allergy, can tolerate the reintroduction of peanut proteins into their diet after resolving their allergy and, thus, can avoid adverse health outcomes associated with the false diagnosis. In the younger age group, a quarter of peanut allergic children, display a relatively high threshold, potentially enabling an easier and safer oral immunotherapy protocol in this window of opportunity in childhood. The use of the novel diagnostic skin test, LPP-MH, significantly improves the predictive value of outpatient evaluation for the outcomes of peanut challenge as well as the expected threshold at which the PA child will react, thus, making for a better informed decision of how, when, and where to challenge.

Prevalence of Allergic Reactions After Pfizer-BioNTech COVID-19 Vaccination Among Adults With High Allergy Risk.

Importance: Allergic reactions among some individuals who received the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine discourage patients with allergic conditions from receiving this vaccine and physicians from recommending the vaccine. Objective: To describe the assessment and immunization of highly allergic individuals with the BNT162b2 vaccine. Design, Setting, and Participants: In a prospective cohort study from December 27, 2020, to February 22, 2021, 8102 patients with allergies who applied to the COVID 19 vaccine referral center at the Sheba Medical Center underwent risk assessment using an algorithm that included a detailed questionnaire. High-risk patients (n = 429) were considered "highly allergic" and were immunized under medical supervision. Exposures: Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Main Outcomes and Measures: Allergic and anaphylactic reactions after the first and second doses of BNT162b2 vaccine among highly allergic patients. Results: Of the 429 individuals who applied to the COVID-19 referral center and were defined as highly allergic, 304 (70.9%) were women and the mean (SD) age was 52 (16) years. This highly allergic group was referred to receive immunization under medical supervision. After the first dose of the BNT162b2 vaccine, 420 patients (97.9%) had no immediate allergic event, 6 (1.4%) developed minor allergic responses, and 3 (0.7%) had anaphylactic reactions. During the study period, 218 highly allergic patients (50.8%) received the second BNT162b2 vaccine dose, of which 214 (98.2%) had no allergic reactions and 4 patients (1.8%) had minor allergic reactions. Other immediate and late reactions were comparable with those seen in the general population, except for delayed itch and skin eruption, which were more common among allergic patients. Conclusions and Relevance: The rate of allergic reactions to BNT162b2 vaccine, is higher among patients with allergies, particularly among a subgroup with a history of high-risk allergies. This study suggests that most patients with a history of allergic diseases and, particularly, highly allergic patients can be safely immunized by using an algorithm that can be implemented in different medical facilities and includes a referral center, a risk assessment questionnaire, and a setting for immunization under medical supervision of highly allergic patients. Further studies are required to define more specific risk factors for allergic reactions to the BNT162b2 vaccine.

How face masks influence the sinonasal quality of life during the COVID-19 pandemic.

PURPOSE: To study different mask types' impact on a sinonasal quality of life. METHODS: For this observational cross-sectional study, a web-based survey was distributed via social media forums. We used the validated Hebrew version of the Sinonasal Outcome Test-22 followed by a questionnaire developed specifically for the present study, focusing on the time of the COVID-19 pandemic (Mask Sinonasal Outcome Test), and questions regarding general health issues. The participants' mask-wearing routine was also studied. RESULTS: Seventy percent of 351 participants had experienced a change in their breathing during the time of the pandemic. The median total Sinonasal Outcome Test-22 score was 13, and 10% of the participants reported a significantly impaired quality of life. According to multivariate analyses, the only subject-related variables significantly associated with the reduced sinonasal quality of life were female gender, younger age, a background of chronic rhinitis and sinusitis, and the mask-wearing average daily duration. The mask sinonasal outcome test convergent validity was confirmed. CONCLUSION: The majority of our survey's responders, predominantly female and younger participants, reported reduced sinonasal quality of life in the COVID-19 pandemic period. It can be attributed to mask-wearing, especially for a prolonged time, irrespective of the existing mask type. These findings should encourage medical companies to produce more "airway-minded" personal protection equipment.

Efficacy of omalizumab treatment for pediatric chronic spontaneous urticaria: A multi-center retrospective case series.

BACKGROUND: Chronic urticaria is defined by the presence of itchy wheals, sometimes accompanied by angioedema, lasting for at least 6 weeks. In children, most cases occur without an eliciting factor and are defined as chronic spontaneous urticaria (CSU). CSU affects up to 0.75% of children with a negative impact on quality of life and school performance. CSU is treated in adults with second-generation antihistamines, increased up to four times normal doses for second-line treatment. Omalizumab (a monoclonal antibody to IgE) may be recommended as third-line therapy. A similar protocol is used in children, yet little is known of its efficacy and safety. OBJECTIVES: To summarize our multi-center experience in treating children with recalcitrant CSU with omalizumab. METHODS: A retrospective multi-center case series conducted in 5 tertiary care centers in Israel. Patients included were children <18 years old diagnosed with recalcitrant CSU who were treated with omalizumab. Patients were followed up throughout the duration of omalizumab therapy/symptom remission. Patients' electronic medical records were used to gather data. RESULTS: Nineteen participants (11 F; 8 M) presented with CSU between ages 6 and 16.9 years. Sixteen (84%) responded to omalizumab, including children <12 years old, although two became non-responsive after 6-12 months of therapy. Another three patients (16%) were resistant to treatment, achieving remission through fourth-line (Cyclosporine A) or other therapies. CONCLUSION: Children with recalcitrant CSU, even those <12 years old, respond well to standard-dose, third-line omalizumab therapy at rates similar to adults. Yet, some cases may become non-responsive with ongoing treatment.

Combination therapy with omalizumab and an immune-suppressive agent for resistant chronic spontaneous rrticaria - A real-life experience.

BACKGROUND: Chronic Spontaneous Urticaria (CSU) is a relatively common immune mediated disease that can be effectively treated nowadays. Nevertheless, for some patients remission cannot be achieved following current treatment recommendations, defined as resistant CSU (r-CSU). Treating r-CSU is challenging, and, currently, there are no recommended interventions. In this real-life study we describe successful therapy of 18 r-CSU patients using an "intensified protocol" of anti-IgE-antibody (omalizumab) concomitantly with an immunosuppressant. We defined the r-CSU phenotype and compared it to omalizumab-responsive CSU (Or-CSU) phenotype. METHODS: Clinical and serological data of 72 CSU patients (ie, 18 r-CSU and 54 age and sex matched Or-CSU) were retrospectively collected and analyzed. All patients were diagnosed with CSU for ≥6 months and treated at the Sheba Medical Center during 2013-2018. RESULTS: Of 289 CSU patients, 18 (6%) were diagnosed with r-CSU and treated with the "intensified protocol" including omalizumab and cyclosporine-A (16p), methotrexate (1p), and azathioprine (1p). Of which, 14/18 (78%) achieved complete remission, 2/18 (11%) partial remission, and 2/18 (11%) no remission. During follow-up no serious adverse events were documented. r-CSU patients received higher doses of antihistamine (p < 0.0001) and omalizumab (425 ± 58 mg/month vs. 283 ± 86 mg/month; p < 0.0001) compared to Or-CSU. The r-CSU phenotype was linked with concomitant autoimmunity (p = 0.0005) and a lower level of IgE prior to initiation of therapy (p = 0.027). CONCLUSION: r-CSU may be a distinct CSU phenotype characterized by severe disease, concomitant autoimmunity, and lower baseline-IgE levels (low "autoallergy"). An "intensified protocol" with omalizumab and an immunosuppressive agent was found to be efficacious and safe for r-CSU. Further larger studies are required to verify these results.

Minor Clinical Impact of COVID-19 Pandemic on Patients With Primary Immunodeficiency in Israel.

In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system. While human immunity against COVID-19 is not fully understood, it is, so far, well documented, that both adaptive and innate cells have a critical role in protection against SARS-CoV-2. Here, we aimed to summarize the clinical and laboratory data on primary immunodeficiency (PID) patients in Israel, who were tested positive for SARS-CoV-2, in order to estimate the impact of COVID-19 on such patients. Data was collected from mid-February to end-September. During this time Israel experienced two "waves" of COVID-19 diseases; the first, from mid-February to mid-May and the second from mid-June and still ongoing at the end of data collection. A total of 20 PID patients, aged 4 months to 60 years, were tested positive for SARS-CoV-2, all but one, were detected during the second wave. Fourteen of the patients were on routine monthly IVIG replacement therapy at the time of virus detection. None of the patients displayed severe illness and none required hospitalization; moreover, 7/20 patients were completely asymptomatic. Possible explanations for the minimal clinical impact of COVID-19 pandemic observed in our PID patients include high level of awareness, extra-precautions, and even self-isolation. It is also possible that only specific immune pathways (e.g. type I interferon signaling), may increase the risk for a more severe course of disease and these are not affected in many of the PID patients. In some cases, lack of an immune response actually may be a protective measure against the development of COVID-19 sequelae.

The innate immune perspective of autoimmune and autoinflammatory conditions.

Innate immunity is one of two immune defence system arms. It is present at birth and does not require 'learning' through exposure to foreign organisms. It activates various mechanisms collectively to eliminate pathogens and hold an infection until the adaptive response are mounted. The innate immune system consists of four elements: the epithelial barrier, cells (e.g. macrophages, NK cells), plasma proteins (e.g. complement) and cytokines. These components act in concert to induce complex processes, as well as recruitment, activation and differentiation of adaptive responses. The innate response is more than just the 'first line of defence', as it essentially withholds the vast majority of any intruder, has a complex interplay with the adaptive arm and is crucial for survival of the host. Finally, yet importantly, a myriad of diseases has been linked with innate immune dysregulation. In this mini-review we will shed some light on these conditions, particularly regarding autoinflammatory ones.

A structured graduated protocol with heat denatured eggs in the treatment of egg allergy.

BACKGROUND: Most children with egg allergy (EA) can tolerate extensively heated and baked egg (EHBE). Consumption of EHBE may promote faster resolution of EA; however, no consensus exists as to the required amounts and treatment protocols. OBJECTIVE: To evaluate the efficacy and safety of a structured graduated exposure protocol (SGEP) with EHBE in promoting tolerance to eggs in EA children under 2 years of age. METHODS: In a case-control study, EA children aged < 2 years who were treated with SGEP including EHBE were compared to children treated with strict avoidance. Data were collected from records and telephone questionnaires. Analysis was performed using non-parametric Kaplan-Meier and Cox proportional hazard regression models. RESULTS: Thirty-nine egg-allergic children with a median age at intervention of 16 months (interquartile range: 13-19) were treated with SGEP and followed to a median age of 39 months (26.8-50.0). The median age at resolution of EA was compared to a matched group of 80 children treated with strict avoidance at least until 2 years of age or earlier natural resolution and followed to a median age of 69 months (46-104). The median estimated age at EA resolution in the SGEP group was 24 months (95% CI, 19.5-28.5 months), compared to 78 months (95% CI, 53-102) in the control group, P < .001. At last follow-up, 82% of treated children were tolerant to lightly cooked eggs vs 54% of controls, P = .001. CONCLUSION: A structured protocol with EHBE appears to promote faster resolution of EA.

A Structured Gradual Exposure Protocol to Baked and Heated Milk in the Treatment of Milk Allergy.

OBJECTIVE: To evaluate the efficacy and safety of a structured gradual exposure protocol (SGEP) with extensively heated and baked milk in promoting allergy resolution in children with cow milk allergy (CMA). STUDY DESIGN: In a case control study, children with CMA aged 1-4 years who were treated with SGEP including extensively heated and baked milk, were compared with children treated with strict avoidance. Data were collected from medical records and from validated telephone questionnaires. Data analysis was performed using a nonparametric Kaplan-Meier and proportional hazard Cox regression model, after evaluation of the adequacy of the case control matching. RESULTS: There were 43 children with milk allergy-26 (62%) males with a mean age at intervention of 21 months (range, 12-47 months)-who were treated with SGEP and followed to a mean age of 40 months (range, 20-82 months). The median age at resolution of CMA was compared with a matched group of 67 children treated with strict avoidance at least until 4 years of age or followed until earlier resolution, with a mean age at follow-up of 71 months (range, 11-176 months). The median estimated age at CMA resolution in the SGEP group was 36 months (95% CI, 34.5-49.7) compared with 98 months (95% CI, 82.4-114.1) in controls (P < .001). At last follow-up, 86% of treated children were tolerant to unheated milk proteins vs 52% of controls (P = .003). CONCLUSION: A structured protocol with extensively heated and baked milk seems to promote faster resolution of CMA.

[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.

[The sick building syndrome as a part of 'ASIA' (autoimmune/auto-inflammatory syndrome induced by adjuvants)].

The entity 'sick building syndrome' is poorly defined and comprises of a set of symptoms resulting from environmental exposure to a work or a living environment. The symptoms are mainly "allergic"-like and include nasal, eye, and mucous membrane irritation, dry skin as well as respiratory symptoms and general symptoms such as fatigue, lethargy, headaches and fever. The Autoimmune [Auto-inflammatory] Syndrome Induced by Adjuvants (ASIA) is a wider term which describes the role of various environmental factors in the pathogenesis of immune mediated diseases. Factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were found in association with defined and non-defined immune mediated diseases. The sick building syndrome and ASIA share a similar complex of signs and symptoms and probably the same immunological mechanisms which further support a common denominator.

[Post mortem dissections -the legal status in Israel].

Forensic medicine is the application of science to the medical disciplines to answer questions related to criminal law. Most forensic practitioners are physicians with expertise in pathology. In the field of post mortem surgeries, the extensive area of the encounter between the law and medicine is compLicated. The doctor who is responsible for the procedure needs to take decisions on the cause of death, as well as considerations of Legal and religious issues. Furthermore, the doctor needs to take into consideration the requests of the family of the deceased. This article aims to reveal the legal, medical and moral complexity of post mortem surgeries, especially in the last few years during which new imaging techniques developed may pose as reasonable alternatives for such surgeries.