The role of molecular diagnosis in anaphylactic patients with dual or triple-sensitization to Hymenoptera venoms.

BACKGROUND: The poly-sensitization to Hymenoptera venom makes it difficult to select genuine allergens for immunotherapy and increases patients' costs. The objective of this study was to determine the culprit allergen in dual or triple-sensitized patients to three Hymenoptera venoms through molecular diagnosis and evaluating the results of incorporating the molecular diagnosis with skin tests. METHODS: Thirty-two patients with anaphylactic reactions and dual or triple-sensitization to Hymenoptera venoms in skin tests entered this study. IgE-sensitization to whole extracts and molecules of Apis mellifera (Api m), Vespula vulgaris (Ves v), and Polistes dominulus (Pol d) was evaluated utilizing ALEX or ImmunoCAP. RESULTS: Twenty-nine patients (90.6%) were male. IgE-sensitization to at least one of the allergenic molecules related to Apis mellifera, Vespula vulgaris, and Polistes dominulus was seen in 59.4, 53.1, and 21.9%, respectively. Among 32 patients, 14 (43.8) and 8 (25%), were mono-sensitized to Api m and Ves v components in ALEX, respectively. Double sensitization to Hymenoptera was identified in 18.8% of patients in ALEX. Api m 1+/Api m 2-/Api m 10- and Ves v 1+/Ves v 5+ demonstrated the most prevalent sensitizations patterns in our patients. CONCLUSIONS: The molecular diagnosis of IgE-sensitization to Hymenoptera venoms can be valuable, especially in patients who show dual or triple-sensitization in skin tests, as the ALEX results revealed mono and double-sensitization to Hymenoptera venoms in 22 and 6 patients, respectively. Regarding the high cost and adverse reactions of venom immunotherapy, especially for two or three venoms, incorporating the molecular diagnosis alongside skin tests for accurate diagnosis of the culprit venom could help decrease costs for patients.

Diagnosis and selection of alternative antibiotics in beta-lactams hypersensitivity reactions: Current recommendations and challenges.

Beta-lactam (BLM) antibiotics, including amino-penicillin and cephalosporins, are typically the first-choice treatment for bacterial infections. However, adverse reactions to these antibiotics are frequently reported, causing non-allergist physicians to select alternative broad-spectrum antibiotics that can have harmful consequences. Patients with unclear histories of hypersensitivity reactions to BLMs should undergo an allergy workup to establish a firm diagnosis, particularly when different drugs are prescribed simultaneously. However, finding the safest, most precise, and cost-effective methods for confirming BLMs hypersensitivity and selecting the most appropriate alternative BLM is uncertain, particularly in severe delayed reactions. This review aims to provide data and recommendations on the availability and validity of skin tests (STs), drug provocation test (DPT) protocols, based on the latest published literature and guideline. To make the process more practical, we focused on cross-reactivity between BLMs and diagnostic tests. There are two main novel aspects of this document: 1) For T-cell-mediated reactions, patient stratification into high, moderate, and low-risk groups based on the mortality and morbidity of adverse drug reactions. 2) For IgE-mediated reactions, stratification of individuals with isolated limited urticarial without anaphylaxis in a low-risk group and removal of the extensive limitation.

Dietary intake of micronutrients are predictor of premenstrual syndrome, a machine learning method.

BACKGROUND & AIMS: Premenstrual syndrome (PMS) is a common disorder affecting 30-40% of women of reproductive age. Many modifiable risk factors associated with PMS involve nutrition and poor eating habits. This study aims to explore the correlation between micronutrients and PMS in a group of Iranian women and to build a predictor model showing the PMS using nutritional and anthropometric variables. METHODS: This is a cross-sectional study which was conducted on 223 females in Iran. Anthropometric indices were measured, including Body Mass Index (BMI) and skinfold thickness. Machine learning methods were used to assess participants' dietary intakes, Food Frequency Questionnaire (FFQ) and analyze the data. RESULTS: After applying different variable selection techniques, we have created machine learning models such as KNN. KNN achieved 80.3% accuracy rate and 76.3% F1 score indicating that our model is a curate and valid proof to show a strong relationship between input variables (sodium intake, Skin fold thickness of suprailiac, irregular menstruation, total calorie intake, total fiber intake, trans fatty acids, painful menstruation (dysmenorrhea), total sugar intake, total fat intake, and biotin) and the output variable (PMS). We sorted these effective variables based on their 'Shapley values' and figured out that Na intake, suprailiac skinfold thickness, biotin intake, total fat intake and total sugar intake have a major impact on having PMS. CONCLUSIONS: Dietary intake and anthropometric measurements are highly associated with the occurrence of PMS, and in our model, these variables can predict PMS in women with a high accuracy rate.

A Patient with CTLA-4 Haploinsufficiency with Multiple Autoimmune Presentations: A Case Report.

Increased susceptibility to autoimmunity, malignancy, and allergy in addition to recurrent infections are the main characteristics suggesting for the primary immunodeficiency diseases (PID). CTLA-4 is predominantly expressed on activated and regulatory T-cells, which can bind to CD80/CD86 molecules on antigen-presenting cells as a negative regulator. Here, we describe a 24-year-old male born from consanguineous parents with heterozygous CTLA-4 mutation who presented with multiple autoimmune diseases. His past clinical history revealed alopecia areata at four years old and subsequently, he developed Evans syndrome, type 1 diabetes mellitus, hypothyroidism, and chronic diarrhea while chronic rhinosinusitis and cytomegalovirus (CMV) colitis were the only infectious manifestations. Immunologic investigations revealed: low B cell count, abnormal Lymphocyte transformation test (LTT) to phytohemagglutinin (PHA), and hypogammaglobulinemia. Although all available treatments such as Intravenous Immunoglobulin (IVIG) therapy, immunosuppressive drugs, and antibiotic therapy were applied, diarrhea was not controlled due to colitis, which remained challenging. Whole exome sequencing was performed and the result showed heterozygous variant CHR2.204,735,635 G>A in the CTLA-4 gene, which was confirmed by the Sanger method. CTLA4 haploinsufficiency leads to autoimmune disorders, recurrent respiratory infections, hypogammaglobulinemia, lymphoproliferation with organ infiltration, and lymphocytic interstitial lung disease.

Chronic Eosinophilic Pneumonia: a Case Report.

Chronic eosinophilic pneumonia (CEP) is a rare idiopathic interstitial lung disease, predominantly observed in females. Eosinophilia is present in most cases, and alveolar eosinophilia is a diagnostic criterion in more than 40% of bronchoalveolar lavage (BAL) samples. The current study reported a 27-year-old male patient, non-smoker, with a history of uncontrolled asthma, presented to the emergency room with a complaint of cough, fever, and moderate dyspnea. A 30% eosinophilia was reported in his peripheral blood sample. A chest-X ray examination showed an upper and middle lobe consolidation, especially in the left lung. Broad-spectrum antibiotics were then started with a presumptive diagnosis of pneumonia, but no improvements were evident. The chest computed tomography scan showed air space opacities with septal thickening and predominant involvement of upper and middle lobes. Flexible bronchoscopy was performed, and the BAL sample analysis showed eosinophil infiltration, while negative culture. No parasites were identified. Transbronchial biopsies demonstrated eosinophil accumulation in alveoli and interstitium. CONCLUSION: Early recognition, diagnosis, and prompt treatment with corticosteroids are the main therapeutic approaches to CEP.

A newly found homozygous mutation in recombination activating gene 1 in a patient with leaky severe combined immunodeficiency disorder.

The recombination activating genes, including RAG1 and RAG2, are essential for V(D)J somatic recombination in lymphocytes. Leaky severe combined immunodeficiency disorder (SCID) is characterized by normal or intermediate T cells and normal to absent B cells associated with partial T cell and B cell dysfunction. We present a newly found RAG1 deficiency in a 21-year-old boy with leaky SCID. Immunoglobulin levels, flow cytometry, and whole exome sequencing (WES) were evaluated. Flow cytometric analysis revealed a decreased number of CD3+, CD4+, and CD8+ T cells, and B cells whereas NK cell counts were normal. Immunoglobulin levels were also decreased. The WES revealed a newly found homozygous mutation of RAG1 gene (NM_000448: exon 2: c.C2275T). Atypical features, including leukopenia, candidiasis, and low lymphocyte counts in patients with late-onset combined immunodeficiency disorders (CID) such as leaky SCID due to RAG1 deficiency may result in misdiagnosis and inadequate therapy instead of adopting the curative hematopoietic stem cell transplantation in these patients.