Food-induced anaphylaxis during infancy is associated with later sleeping and eating disorders.

BACKGROUND: Accumulating evidence suggests that food-induced anaphylaxis (FIA) may induce different psychological disorders (PDs). In this study, we aimed to further evaluate the effect of FIA, specifically when occurring in early life, on subsequent PDs development. METHODS: We conducted a population-based, retrospective, matched-cohort study of pediatric patients (age ≤ 18 years) treated at the "Clalit" healthcare organization during the period 2001-2021. Children diagnosed with FIA were propensity score-matched with patients without any allergies (controls) of similar demographic parameters. Associations between FIA and different PDs were examined by multivariable regression models. RESULTS: The cohorts comprised 545 FIA patients and 4514 controls. Most patients were <3 years old [87.6% of controls (N = 3955) and 87.3% of the FIA cohort (N = 476)]. In this age group, the major food allergens were cow's milk (N = 258; 54.2%), eggs (N = 60; 12.6%), and peanuts (N = 20; 4.2%). The multivariable regression model identified an association between FIA and any PDs (p < .001), sleeping disorders (p < .001), and eating disorders (p = .050). Kaplan-Meier curves revealed that patients who experienced FIA before 3 years of age had an increased cumulative risk over the follow-up time of developing any PDs, sleeping disorders, and eating disorders. CONCLUSION: FIA during the first 3 years of life increases the risk of later developing eating and sleeping disorders, which can last into adulthood. Further attention should be focused on accurately diagnosing these children.

Early childhood allergy linked with development of attention deficit hyperactivity disorder and autism spectrum disorder.

BACKGROUND: Previous studies reported controversial results regarding the association between allergic disorders and attention deficit hyperactivity disorder (ADHD)/autism spectrum disorder (ASD). The aim of this article was to investigate whether allergic disorders are associated with ADHD/ASD in a large cohort of pediatric patients. METHODS: A retrospective study using the pediatric (0-18 year) database (ICD-9-CM codes) of Clalit Health Services during the years (2000-2018). Diagnosis of all disorders was made by specialist physicians. RESULTS: A total of 117 022 consecutive non-selective allergic children diagnosed with one or more allergic disorder (asthma, rhinitis, conjunctivitis, skin, food, or drug allergy) and 116 968 non-allergic children were enrolled to our study. The mean follow-up period was 11 ± 6 years. The presence of allergic disorders in early childhood (mean age of allergic diagnosis 4.5 ± 4.3 years) in boys as well as in girls significantly increased the risk to develop ADHD (O.R 2.45, CI 2.39-2.51; p < .0001), ASD (O.R 1.17, CI 1.08-1.27; p < .0001), or both ADHD + ASD (O.R 1.5, CI 1.35-1.79; p < .0001). Children with more than one allergic comorbidity revealed a much higher risk. In a multivariable analysis (adjusted for age at study entry, number of yearly visits, and gender), the risk of allergic children to develop ADHD and ADHD + ASD, but not ASD alone, remained significantly higher. CONCLUSION: Allergic disorder in early childhood significantly increased the risk to develop ADHD, and to a less extend ASD, in later life.

Characteristics of patients with spontaneous resolution of sesame allergy.

BACKGROUND: The prevalence of sesame allergy is increasing; strict avoidance is the mainstay of therapy. Lately, sesame oral immunotherapy was presented as an alternative treatment, with a high rate of success. Therefore, data on the natural history and the clinical characteristics of patients with persistent sesame allergy are important for the management of patients with sesame allergy. OBJECTIVE: To describe the natural history of patients with sesame allergy and the clinical characteristics of patients with spontaneous resolution of sesame allergy compared with patients with persistent sesame allergy. METHODS: In our retrospective study, electronic health records of patients with sesame allergy diagnosis were reviewed for demographic and clinical data. Statistical analysis of clinical characteristics of patients with spontaneous resolution compared with persistent sesame allergy was performed. RESULTS: A total of 190 patients with sesame allergy were followed for 3.86 ±4.43 years. Of these patients, 61 (32.1%) had spontaneous resolution of sesame allergy. Patients with mild, early (before the age of 10 months) first sesame allergic reaction, with smaller than 7-mm skin prick test and without concomitant tree nut allergy had better resolution rate (56.1%). CONCLUSION: Sesame allergy spontaneously resolved in approximately one-third of our patients and in more than half of the patients with mild first reaction (grade 1) at a young age (<10 months), with small skin prick test (<7 mm) and no concomitant tree nut allergy. Larger prospective studies with longer follow-up period are needed to better characterize the sesame allergic patients with persistent allergy who may need oral immunotherapy.

The impact of allergies and smoking status on nasal mucosa of hypertrophied turbinates - an immunohistologic analysis.

Background: Allergies and smoking are common reasons for nasal mucosa inflammations, which in turn, cause nasal obstructions. Nevertheless, the impact of coexisting allergies and smoking on nasal mucosa inflammation has not been studied.Objectives: To study the impact of smoking with relation to allergies on nasal mucosa histology and to characterize an immunologic profile using immunohistochemical (IHC) staining.Methods: A cross-sectional study. Nasal biopsies of inferior turbinates from smokers with different allergic statuses were compared. Demographics, comorbidities, histologic, and immunohistochemical (IHC) staining of CD3, CD68, CD 20, and CD138 receptors were compared and analyzed.Results: A total of 53 patients were included, of which 20 (37.7%) were smokers, and 20 (37.7%) had allergic backgrounds. Smokers, both allergic and non-allergic, demonstrated reduced edema compared to the control group (p Value = 0.034) and significantly lower eosinophil density in the stroma compared to the allergic nonsmokers' group (p Value = 0.04). Smokers had a significant negative correlation between the number of cigarettes per day and the expression of CD20 in the stroma (-0.452, p Value = 0.045) and the epithelium (-0.432, p Value = 0.057) in IHC staining. Allergic smokers had a negative correlation (-0.705, p Value = 0.023) between the number of cigarettes per day and the CD68 marked cell expression in the epithelium.Conclusion: The coexistence of an allergic background and smoking alters known immunologic responses within the nasal mucosa. Smoking may have an immunosuppressive role in the nasal mucosa in both innate and humoral immune systems.

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.

Indoleamine-2,3-dioxygenase in murine and human systemic lupus erythematosus: Down-regulation by the tolerogeneic peptide hCDR1.

וֹndoleamine-2,3-dioxygenase (IDO) plays a role in immune regulation. Increased IDO activity was reported in systemic lupus erythematosus (SLE). We investigated the effects of the tolerogenic peptide hCDR1, shown to ameliorate lupus manifestations, on IDO gene expression. mRNA was prepared from splenocytes of hCDR1- treated SLE-afflicted (NZBxNZW)F1 mice, from blood samples of lupus patients, collected before and after their in vivo treatment with hCDR1 and from peripheral blood mononuclear cells (PBMC) of patients incubated with hCDR1. IDO gene expression was determined by real-time RT-PCR. hCDR1 significantly down-regulated IDO expression in SLE-affected mice and in lupus patients (treated in vivo and in vitro). No effects were observed in healthy donors or following treatment with a control peptide. Diminished IDO gene expression was associated with hCDR1 beneficial effects. Our results suggest that the hCDR1-induced FOXP3 expressing regulatory T cells in lupus are not driven by IDO but rather by other hCDR1 regulated pathways.

The tolerogenic peptide hCDR1 immunomodulates cytokine and regulatory molecule gene expression in blood mononuclear cells of primary Sjogren's syndrome patients.

Primary Sjogren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands. We investigated whether the tolerogenic peptide, hCDR1, that ameliorates lupus manifestations would have beneficial effects on pSS as well. The in vitro effects of hCDR1 on gene expression of pro-inflammatory cytokines and regulatory molecules were tested in peripheral blood mononuclear cells (PBMC) of 16 pSS patients. hCDR1, but not a control peptide, significantly reduced gene expression of IL-1ß, TNF-α, MX-1 and BlyS and up-regulated immunosuppressive (TGF-ß, FOXP3) molecules in PBMC of pSS patients. hCDR1 did not affect gene expression in patients with rheumatoid arthritis and anti-phospholipid syndrome. Further, hCDR1 up-regulated the expression of Indoleamine 2,3-dioxygenase (IDO) via elevation of TGF-ß. IDO inhibition led to a significant decrease in the expression of FOXP3 which is crucial for the induction of T regulatory cells. Thus, hCDR1 is potential candidate for the specific treatment of pSS patients.

Upper Extremity Deep Vein Thrombosis: Symptoms, Diagnosis, and Treatment.

BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) is defined as thrombosis of the deep venous system (subclavian, axillary, brachial, ulnar, and radial veins), which drains the upper extremities. It can be caused by thoracic outlet anatomic obstruction, such as Paget-Schroetter syndrome, (primary) or by central intravenous catheters (secondary). UEDVT may be asymptomatic or present with acute severe pain and arm swelling. Clinical suspicion should be confirmed by diagnostic imaging procedures such as duplex ultrasound, computed tomography scan, or magnetic resonance imaging. UEDVT is managed by anticoagulant treatment. In addition to that, early thrombolysis aimed at preventing post-deep vein thrombosis syndrome and thoracic outlet decompression surgery should be given to patients with primary UEDVT. Anticoagulation without thrombolysis is the treatment of choice for patients with catheter-related thrombosis. Mandatory functioning catheters can remain in place with anticoagulant treatment. All other catheters should be immediately removed. The management of patients with UEDVT requires an experience multidisciplinary team comprised of internists, radiologists, hematologists, and vascular surgeons. Understanding the risk factors for the development of UEDVT, the diagnostic procedures, and the treatment modalities will improve the outcome of those patients.

Anti-BLyS Treatment of 36 Israeli Systemic Lupus Erythematosus Patients.

BACKGROUND: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment. OBJECTIVES: To evaluate the "real-life" safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers. METHODS: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3-4 months. Adverse events were obtained from patients' medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response. RESULTS: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1-7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%). CONCLUSIONS: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.

HIV-associated neurocognitive disorders (HAND).

Neurocognitive impairment still occurs in the era of HAART, though its onset appears to be delayed and its severity reduced, while HIV-infected individuals live longer with the infection. HAND defines three categories of disorders according to standardized measures of dysfunction: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). The pathogenic mechanisms underlying HAND involve host and virus characterizations and interactions and seem to depend heavily on the overall condition of the immune system. Since there are insufficient data at this point to determine the best therapeutic approach, and since HAART apparently is not sufficient to prevent or reverse HAND, therapy with a combination of drugs with high CPE should be considered while adjunctive and alternative therapies are being explored.

Granulomatous Lobular Mastitis.

BACKGROUND: Granulomatous lobular mastitis (GLM) is a rare disorder that can clinically mimic breast carcinoma. The recommendation for diagnosis and treatment of GLM has not yet been established. OBJECTIVES: To assess a series of GLM patients, including their clinical presentation, diagnosis, treatment and outcome. METHODS: We retrospectively analyzed the clinical data and treatment of 17 female patients with biopsy-proven GLM. Breast tissue was obtained by a core needle biopsy (15 patients) or open biopsy (2 patients). Images were reviewed by an experienced radiologist. RESULTS: The mean age of the patients at diagnosis was 44.6 ± 12.6 years. Five patients (29%) presented with bilateral disease, and seven (41%) presented with a mass, suggesting the initial diagnosis of breast carcinoma. Treatment comprised observation alone (23%), antibiotics (58.8%) and/or corticosteroids (with or without methotrexate) (35%). At the end of the study 70.6% of the patients demonstrated complete remission. None of the patients developed any systemic (granulomatous) disease or breast carcinoma during the follow-up period (4.7 ± 3.8 years). CONCLUSIONS: Core needle biopsy is mandatory for the diagnosis of GLM and the exclusion of breast carcinoma. The recommended treatment modalities are observation alone or corticosteroids; surgery should be avoided. GLM is a benign disease with a high rate of resolution and complete remission.

Type I interferon signature in systemic lupus erythematosus.

Type I interferons (IFN) are primarily regarded as an inhibitor of viral replication. However, type I IFN, mainly IFNalpha, plays a major role in activation of both the innate and adaptive immune systems. Systemic lupus erythematosus (SLE) is a chronic, multi-systemic, inflammatory autoimmune disease with undefined etiology. SLE is characterized by dysregulation of both the innate and the adaptive immune systems. An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE. We review here the role of IFNalpha in the pathogenesis and course of SLE and the possible role of IFNalpha inhibition as a novel treatment for lupus patients.

BLyS levels in sera of patients with systemic lupus erythematosus: clinical and serological correlation.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of the innate and adaptive immune systems with the production of autoantibodies by stimulated B lymphocytes. The BLyS protein (B lymphocyte stimulator) is secreted mainly by monocytes and activated T cells and is responsible for the proliferation, maturation and survival of B cells. OBJECTIVES: To study sera BLyS level and its clinical significance in Israeli lupus patients overtime. METHODS: The study population included 41 lupus patients (8 males, 33 females; mean age 35.56 +/- 15.35 years) and 50 healthy controls. The patients were followed for 5.02 +/- 1.95 years. We tested 221 lupus sera (mean 5.4 samples/patient) and 50 normal sera for BLyS levels by a capture ELISA. Disease activity was determined by the SLEDAI score. RESULTS: Sera BLyS levels were significantly higher in SLE patients than in controls (3.37 +/- 3.73 vs. 0.32 +/- 0.96 ng/ml, P < 0.05). BLyS levels were high in at least one sera sample in 80.5% of the patients but were normal in all sera in the control group. There was no correlation between sera BLyS and anti-ds-DNA autoantibody levels. BLyS levels fluctuated over time in sera of lupus patients with no significant correlation to disease activity. CONCLUSIONS: Most of our lupus patients had high sera BLyS levels, suggesting a role for BLyS in the pathogenesis and course of SLE. Our results support the current novel approach of targeting BLyS (neutralization by antibodies or soluble receptors) in the treatment of active lupus patients.

[Situations in which the primary care physician should suspect the presence of HIV-1 infection].

We are living in an era in which AIDS is no longer a terminal disease. It has become a chronic treatable disease. HIV-1 patients are mostly treated in specialized clinics by specialists in cLinical immunology or infectious diseases. In Israel, there are seven authorized centers for the diagnosis and treatment of HIV/AIDS. The primary caregiver for patients (family physician or internist) has to know the risk factors, risk groups and cLinical situations which are highly related to HIV-1 infection. These situations obligate a high clinical suspicion for early detection and diagnosis of HIV-1 infection. Early diagnosis has high clinical, prognostic and even epidemiological value. In this review, we highlight the main clinical situations in which the primary care physician should conduct an HIV-1 test as part of the clinical and Laboratory workup performed on the patient.

[The immunological mechanisms contributing to the clinical efficacy of allergen specific immunotherapy (SIT) in allergic diseases].

The prevalence of allergic diseases has increased dramatically in the western world. In the last 2 decades, the frequency of asthma and allergic rhinitis has doubled. Allergen specific immunotherapy [SIT] has been used successfully for more than 100 years for the treatment of allergic disorders. Allergen SIT provides not only symptomatic relief, but it is potentially curative. The immunologic mechanisms of allergen SIT include all parts of the immune system. Regulatory T cells (TR1, Treg), have a major pivotal role in the success of immunotherapy. Along with the regulatory T cells, elevated suppressor cytokines (IL-10), suppression of TH2 cells, increasing titer of specific IgG4 and gradual decline in the number and function of basophils and mast cells also contribute to the success of the treatment (SIT). The above immune mechanisms are connected and related to each other acting at different times with the treatment with SIT. In this review we focused on the current knowledge and understanding of the different immune mechanisms which are involved in the success of SIT.

[SOCS--suppressor of cytokine signaling proteins and their role in the pathogenesis of allergic and autoimmune disorders].

Cytokines play a major role in the innate and the adaptive immune responses. Since cytokines are very powerful messengers, several regulatory systems (in all levels: production, secretion, effect on target) control their action in order to prevent overstimulation of cytokines. Recently, a negative feedback of cytokine activity in the target cell, namely suppressor of cytokine signaling (SOCS) was defined. This regulatory system consist of 8 proteins (CIS.SOCS 1-7) n which each one of them specifically regulates one or more cytokines. Malfunction of the SOCS proteins may lead to unregulated activity of cytokines which may lead to the development of allergic and autoimmune disorders.

[Allergy to drugs and contrast media--recommendations of the Israeli Allergy and Clinical Immunology Association].

Drug hypersensitivity is an adverse reaction that was brought about by a specific immunologic response, not related to the pharmacological components of the drug. Additionally, drug related pseudoallergic and anaphylactoid reactions have been encompassed under the umbrella of hypersensitivity. Some of these reactions are linked with significant morbidity and mortality. Nowadays, the hypersensitivity reactions of most drugs can be well defined and recurrence risk following exposure to the culprit drug and/or related drugs can be assessed. Medical history skin, blood and challenge tests, conducted in an allergy clinic, enable prediction and prevention of repeated events as well as unnecessary avoidance of certain compounds. For instance, most patients who report a prior reaction to penicillin are not allergic to beta-lactams upon allergic evaluation, while avoidance of penicillin based on self-reporting alone often leads to the use of an alternate antibiotic with greater cost or side effect profile. On the other hand, for patients who previously exhibited hypersensitivity to a compound which is currently required, premedication or a desensitization protocol can be recommended to allow the use of this compound. Drug hypersensitivity is most commonly attributed to beta-lactams antibiotics, contrast media reagents and non-steroidal anti-inflammatory drugs (NSAID). Hence, in the current review the recommendations of the Israeli Association for Allergy and Clinical Immunology for the evaluation and treatment of patients suspected to have hypersensitivity to beta-lactams and contrast media reagents are detailed. Recommendations regarding the evaluation of NSAID hypersensitivity will be published on the IMA website, together with those explicated herein.

[Demographic and clinical characterizations of newly diagnosed patients with HIV/AIDS above fifty years of age].

BACKGROUND: Major changes happened in the last decade in the HIV/AIDS pandemic. The disease is no longer limited to young age. Due to the effectiveness of HAART (Highly Active Anti-Retroviral Therapy) as well as new diagnosis in older age groups, many patients in AIDS centers are above 50 years of age. AIM: To determine the prevalence, demographics and clinical characteristics of newly diagnosed HIV/AIDS patients older than 50 years compared to younger newly diagnosed patients. METHODS: Retrospective single center analysis of the demographics and clinical characterizations of 62 newly diagnosed HIV/AIDS patients over 50 years of age. RESULTS: The average age at diagnosis of the whole cohort was 39+/-16 years. There was a gradual increase in the age at diagnosis over the years, as well as the percent of patients above the age of 50 diagnosed with the disease. In comparison to younger patients, in the older group there were more males compared to females and less patients who acquired the HIV/AIDS in unprotected homosexual sex. Furthermore, CD4 cells counts were lower and viral load leveLs were higher at diagnosis in the older group. Despite good adherence, patients above the age of 50 don't achieve adequate immunological response and many are left with significant immunodeficiency (CD4<200). CONCLUSION: The prevaLence of patients above the age of 50 Living with HIV/AIDS in Israel is rising. Programs aimed at prevention, education and screening for this unique group are mandatory. An AIDS center should adopt new programs and routines to cope with the increasing number of patients over the age of 50 Living with HIV/AIDS.

[HIV post exposure prophylaxis therapy - the experience of two major AIDS centers].

BACKGROUND: During recent years, the use of antiretroviral therapy expanded beyond the treatment of HIV-infected patients. Since the outset of the HIV epidemic, antiretroviral drugs were also used for post-exposure prevention of HIV infection in health workers and implemented after possible exposure during sex. In this study, we summarize the cases from the AIDS center in the Kaplan Medical Center and the Sheba Medical Center after possible exposure to HIV (occupational or sexual). AIM: The study aims to validate the different types of potential exposures to HIV encountered, the treatment and outcomes. METHODS: All the data regarding attendance at the AIDS Center in the Kaplan Medical Center during the years 2008-2010 for any possible HIV exposure (occupational or sexual) and for sexual exposure in the Sheba Medical Center AIDS Clinic during the years 2003-2008 was collected retrospectively. RESULTS: During the years of the study, 448 patients attended the Kaplan Medical Center for consultation after a potential exposure to HIV; 314 of the cases were because of occupational exposure, however, only in 11 (3.5%) of the cases, post exposure prophylaxis (PEP) treatment was advised. In the other 134 patients who attended for non-occupational potential exposure to HIV (18 cases of needle stick or sharp object injury and 116 of sexual exposure), for 46 (40%) of these cases, PEP was recommended. No evidence of HIV infection was found for any of the 448 patients who attended the clinic for possible exposure to HIV, regardless of the consultation that they received. In the Sheba Medical Center, during the years 2003-2008, 175 patients attended for consuLtation after potential sexual exposure to HIV. The medical staff of the clinic decided, after risk assessment, to recommend PEP to 140 (80%) of the cases. Similarly, in this case, no evidence of HIV infection was found (regardless of whether PEP was given or not). DISCUSSION: In potential occupational exposure to HIV it is possible, in most cases, to assess the risk for infection sufficiently so that only a few cases will need PEP. In potential sexual exposure to HIV, there are many cases where data regarding the potential source of infection is partial or missing, making the risk assessment more difficult. This may be the reason for the high percentage of patients in this situation who received PEP. From the data in this study, our cohort support PEP as being effective and safe.