Modification of allergen subcutaneous immunotherapy safety precautions and systemic allergic reaction rate reduction.

Background: Despite their life-threatening potential, medical team mistakes during subcutaneous immunotherapy are rarely discussed. Real data are missing, and a survey study estimated that dosing errors are responsible for 25% of systemic reactions during immunotherapy. To minimize errors, we modified our safety precautions and compared the rates of systemic allergic reactions before and after the change. Methods: Our retrospective comparative cohort study compared systemic allergic reaction rates during 2012-2015 and 2016-2019, after a second check of the injected allergen/s by another nurse/physician was added to the treatment protocol. Results: The rate of systemic allergic reaction per injection was reduced from 0.93 to 0.71%; p = 0.023. Conclusion: A second check prior to injection is beneficial and can reduce the allergic reaction rate during immunotherapy.

Many people suffer from allergies to dust or pollen, and they might suffer from a running nose when they come into contact with the allergens. This reaction is called hayfever or allergic rhinitis. Immunotherapy is a treatment which can help to treat patients with allergic rhinitis. During treatment, the patients receive injections of small amounts of dust or pollen, and with time become less allergic. The injections themselves might cause allergic reactions such as rash, hives, swelling or trouble breathing. Sometimes these allergic reactions are related to mistakes made by the medical team. In our study we changed safety instruction to add a second check of the materials and amounts before the injections were given to the patient. This was checked by two different nurses. We compared the number of allergic reactions to the shots before and after the change. We found that the number of allergic reactions was 9.3 for 1000 injections before and 7.1 for 1000 injections after the change. We think that a second check of the materials and amounts before giving the injections is helpful and can prevent some of the allergic reactions.

Immediate and delayed hypersensitivity reactions to corticosteroids - prevalence, diagnosis and treatment.

BACKGROUND: Corticosteroids, which are anti-inflammatory and immunosuppressive agents used for the treatment of various diseases including allergic disorders, can induce immediate and delayed hypersensitivity reactions. Although these reactions are not common, due to the wide usage of corticosteroid medications, corticosteroid hypersensitivity reactions are clinically important. OBJECTIVE: In this review, we summarise the prevalence, pathogenetic mechanism, clinical manifestations, risk factors, diagnostic and therapeutic approach for corticosteroid-induced hypersensitivity reactions. METHODS: An integrative review of the literature was conducted using PubMed searches (mainly large cohort-based studies) regarding the different aspects of corticosteroid hypersensitivity. RESULTS: Hypersensitivity reactions to corticosteroids can be immediate or delayed and can follow all modes of corticosteroid administration. Prick and intradermal skin tests are useful diagnostic tools for immediate hypersensitivity reactions, patch tests are useful for delayed hypersensitivity reactions. According to the diagnostic tests an alternative (safe) corticosteroid agent should be administered. CONCLUSION: Physicians of all medical disciplines should be aware that corticosteroids can cause (paradoxically) immediate or delayed allergic hypersensitivity reactions. The diagnosis of such allergic reactions is challenging since it is often difficult to distinguish between hypersensitivity reactions and deterioration of the basic inflammatory disease (e.g., worsening of asthma or dermatitis). Thus, a high index of suspicion is needed in order to identify the culprit corticosteroid.

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.

Venous thromboembolism prophylaxis in patients hospitalized in medical wards: A real life experience.

Venous thromboembolism (VTE) is a preventable cause of morbidity and mortality in acutely ill patients hospitalized in medical departments. Thromboprophylaxis with anticoagulants was shown to be safe and effective in medical patients with high risk to develop VTE. Despite guidelines recommendations, the rate of thromboprophylaxis in those patients is low. The objective of the study was to evaluate the rate of VTE risk assessment in routine medical department practice, the rate of eligible patients for thromboprophylaxis, the rate of patients who received thromboprophylaxis, and their outcome.Medical records of consecutive patients (3000 at 2013, 1000 at 2018) hospitalized in medical department were reviewed, retrospectively, for demographic, clinical characteristics, thromboprophylaxis treatment with enoxaparin and outcome (up to 90 days following discharge). Padua score was used for VTE risk assessment. VTE diagnosis was based on clinical suspicion.The mean patient's age (52.6% females) was 67.95 ±â€Š21.56 years. 21% were eligible for thromboprophylaxis. Routine VTE risk assessment rate increased significantly following its incorporation into quality parameters, but the rate of treated patients was low (22% at 2013; 46% at 2018). The patients who received thromophylaxis were sicker compared to eligible patients without thromboprophylaxis. The rate of symptomatic VTE was low (0.24%; 0.12% and 0.55% for low and high VTE risk, respectively). Thromboprophylaxis did not have significant effect on the low number of VTE events. No major bleeding was observed.Major efforts are still needed to increase the rate of thromboprophylaxis in all eligible medical patients according to the guidelines recommendations.

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.

Hospitalizations of HIV patients in a major Israeli HIV/AIDS center during the years 2000 to 2012.

To evaluate hospitalization rates and causes among human immunodeficiency virus (HIV) patients in the late highly active antiretroviral therapy (HAART) era. Data during the years 2000 to 2012 were obtained from hospital/clinical charts. Hospitalizations were defined as a ≥24 hours hospital admission. Obstetric admissions were excluded. Causes of hospitalizations were defined as acquired immune deficiency syndrome (AIDS)-defining illnesses, AIDS-related diseases (HAART adverse events, metabolic complications and non-AIDS-defining tumors/infections), and non-HIV-related diseases. Hospitalization rates are presented as admissions per 100 patient years. The number of HIV patients (58% males) in our center increased from 521 in 2000 to 1169 in 2012. 1676 hospital admissions (in 557 patients) were observed during the years of the study. The mean number of admissions per hospitalized patient was 3 ±â€Š3.39. Hospitalization rates of HIV patients declined significantly (18.4/100 in 2000, 9/100 patient years in 2012; P = .0001), but it was higher than the rates reported in the Israeli general population (X8.76 in 2000, X6.04 in 2012). Furthermore, hospitalizations for AIDS-defining illness declined (from 46.9% to 16.1%) whereas non-HIV-related hospitalizations increased (from 31.3% to 60.1%). Lower cluster of differentiation 4 (CD4) cell counts and older age, at the time of HIV diagnosis, were associated with higher rates of admissions (especially for AIDS-defining illnesses) and mortality. Hospitalization rates of HIV patients, especially for AIDS-defining illness, continue to decline in the late HAART era despite the increasing age of the patients, though it is still higher than that of the general population. Low CD4 cell counts and older age, at the time of HIV diagnosis, are associated with readmissions and mortality.

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.

Two case reports of severe myocarditis associated with the initiation of dolutegravir treatment in HIV patients.

RATIONALE: The integrase inhibitor dolutegravir is now recommended as first-line treatment for HIV. A single case of myocarditis after treatment with dolutegravir was reported in the FLAMINGO trial. We present here 2 cases of severe myocarditis that occurred shortly after the initiation of dolutegravir treatment. PATIENTS CONCERNS: The first case is a 45-year-old female who developed severe congestive heart failure and died, weeks after the initiation of dolutegravir treatment (for simplification of her antiretroviral regimen). The second case was a 51-year-old male who presented with effort dyspnea 3 weeks after the initiation of dolutegravir treatment and was later diagnosed as severe congestive heart failure. The treatment was changed and the patient survived, but he still suffers from severe heart failure with functional impairment. DIAGNOSIS AND OUTCOME: Patient 1 died, patient 2 suffers from severe heart failure. LESSONS: We discuss here the possible relationship between the initiation of dolutegravir treatment and the development of lymphocytic myocarditis in our patients, and we suggest a possible mechanism.

Increased soluble CD72 in systemic lupus erythematosus is in association with disease activity and lupus nephritis.

INTRODUCTION: B cell receptor (BCR) -mediated signals are enhanced when CD72 expression is deficient on B cells in autoimmune diseases. The significance of soluble CD72 (sCD72) has not been elucidated. METHODS: Soluble CD72 was analyzed in the serum of 159 SLE patients, 40 rheumatoid arthritis (RA) patients, and 100 healthy individuals. Correlations between sCD72 and SLE disease activity (SLEDAI) were assessed. RESULTS: Soluble CD72 was found increased in SLE patients, when compared to both RA patients and healthy individuals (20.2 ± 1.2 ng/ml; 10.6 ± 4.6 ng/ml and 7.2 ± 3.3 ng/ml; p < 0.001). Soluble CD72 level was significantly higher in SLE patients with renal involvement than in patients without (31.8 ± 2.3 ng/ml vs 13.9 ± 0.9 ng/ml; p < 0.001) and also with the presence of auto-antibodies. CONCLUSION: Soluble CD72 is significantly increased in SLE patients mainly in those with renal involvement. Increased sCD72 may become a potential biomarker for renal involvement in SLE.

Characteristics and Outcome of Patients Diagnosed With HIV at Older Age.

To characterize the clinical, virological, and immunological status at presentation as well as the outcome of patients diagnosed with HIV above the age of 50. A retrospective study of 418 patients newly diagnosed with HIV in 1 Israeli center, between the years 2004 and 2013. Patients with new HIV diagnosis ≥ 50 years of age defined as "older' and < 50 defined as "younger.' Patients were evaluated every 1 to 3 months (mean follow-up 53 ± 33 months). Patients with < 2 CD4/viral-load measurements or with < 1 year of follow-up were excluded. Time of HIV infection was estimated by HIV sequence ambiguity assay. Ambiguity index ≤ 0.43 indicated recent (≤ 1 year) HIV infection. Eighty nine (21%) patients were diagnosed with HIV at an older age. Those older patients presented with significant lower CD4 cell counts and higher viral-load compared with the younger patients. At the end of the study, the older patients had higher mortality rate (21% vs 3.5%; P < 0.001) and lower CD4 cell counts (381 ± 228 vs 483 ± 26 cells/µL; P < 0.001) compared with the younger patients. This difference was also observed between older and younger patients with similar CD4 cell counts and viral load at the time of HIV diagnosis and among patients with a recent (≤ 1 year) HIV infection. One-fifth of HIV patients are diagnosed at older age (≥ 50 years). Those older patients have less favorable outcome compared with the younger patients. This point to the need of educational and screening programs within older populations and for a closer follow-up of older HIV patients.

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.

A Population-Structured HIV Epidemic in Israel: Roles of Risk and Ethnicity.

BACKGROUND: HIV in Israel started with a subtype-B epidemic among men who have sex with men, followed in the 1980s and 1990s by introductions of subtype C from Ethiopia (predominantly acquired by heterosexual transmission) and subtype A from the former Soviet Union (FSU, most often acquired by intravenous drug use). The epidemic matured over the last 15 years without additional large influx of exogenous infections. Between 2005 and 2013 the number of infected men who have sex with men (MSM) increased 2.9-fold, compared to 1.6-fold and 1.3-fold for intravenous drug users (IVDU) and Ethiopian-origin residents. Understanding contemporary spread is essential for effective public health planning. METHODS: We analyzed demographic and virologic data from 1,427 HIV-infected individuals diagnosed with HIV-I during 1998-2012. HIV phylogenies were reconstructed with maximum-likelihood and Bayesian methods. RESULTS: Subtype-B viruses, but not A or C, demonstrated a striking number of large clusters with common ancestors having posterior probability ≥0.95, including some suggesting presence of transmission networks. Transmitted drug resistance was highest in subtype B (13%). MSM represented a frequent risk factor in cross-ethnic transmission, demonstrated by the presence of Israeli-born with non-B virus infections and FSU immigrants with non-A subtypes. CONCLUSIONS: Reconstructed phylogenetic trees demonstrated substantial grouping in subtype B, but not in non-MSM subtype-A or in subtype-C, reflecting differences in transmission dynamics linked to HIV transmission categories. Cross-ethnic spread occurred through multiple independent introductions, with MSM playing a prevalent role in the transmission of the virus. Such data provide a baseline to track epidemic trends and will be useful in informing and quantifying efforts to reduce HIV transmission.