Comparison of commercial allergen extract with various milk products of skin prick tests in diagnosing cow's milk protein allergy.

Introduction: In this study, we aimed to solve the incompatibilities between the skin prick test (SPT) result and the clinical picture encountered among patients. Thus, we used various milk products (raw, ultrahigh temperature [UHT], and pasteurized cow's milk) with commercial milk allergen extract in patients we think may have cow's milk protein allergy (CMPA) and made a comparison among the milk types. Methods: This study was conducted retrospectively between February 1, 2019, to June 1, 2019, at a pediatric allergy polyclinic of the university training/research hospital. A pair of 79 individuals, as control and patient groups, ages between 1 month and 21 years who were presented with a suspicion of CMPA and defined with SPT and/or allergen-specific immunoglobulin E (IgE) levels were included in the study. Allergen-specific IgE tests (specific IgE cow's milk, ß-lactoglobulin, α-lactalbumin, casein) were evaluated. SPT was performed with fresh/raw, UHT, and pasteurized (daily) cow's milk besides the standard used commercial extract. Results: In the group included in the study and defined as IgE-mediated CMPA, 52.9% of the 79 patients were boys (n = 46), 47.1% were girls (n = 33), and the median age was 6 months (5.0-8.0 months). In the group of specific IgE cow's milk reaction that was sought, frequency and wheal (induration) size of SPT reaction to fresh/raw milk was also found to be statistically significant between positive- and negative-reaction groups, not detected against other milk products. The area under the curve for the diagnostic value of fresh milk was 93.1%. For the cutoff value of 2.50 mm, 88.1% sensitivity and 90.8% specificity were determined. In the group of specific IgE ß-lactoglobulin reaction searched, there was a statistically significant difference in the frequency of SPT positivity and wheal size against UHT, fresh, and daily/pasteurized milk between positive and negative reaction groups. When the correlations of the mean induration axis in the tests were examined, it was found that, among raw milk, daily milk, cow's milk allergen extract, and UHT milk, a strong positive correlation was also statistically significant. Conclusion: The positivity that could not be detected with SPT when using allergen extract in a patient with positive specific IgE cow's milk result in the clinic can be detected with SPT made with fresh (raw) milk, which can be an alternative. In addition, specific IgE ß-lactoglobulin seems to be the most compatible with the SPT wheal size (induration) of other milk types rather than extract. Comparative studies of SPT allergen extracts and various milk types used in the diagnosis of CMPA are very scarce in the literature, and more studies are needed on this subject.

Adverse COVID-19 outcomes in immune deficiencies: Inequality exists between subclasses.

BACKGROUND: Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS-CoV-2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID-19 outcomes. METHODS: We studied 34 IEI patients (19M/15F, 12 [min: 0.6-max: 43] years) from six centers. We diagnosed COVID-19 infection by finding a positive SARS-CoV-2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. RESULTS: Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID-related death (OR: 2.630, 95% CI; 1.198-5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin-T, ferritin, and total-lung-score (p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p = .012, p = .022, p = .011; respectively). CONCLUSION: Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID-19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS-Cov-2 therapy trials.

Acquired Thrombotic Thrombocytopenic Purpura in a 5-Year-old Child With Wiskott-Aldrich Syndrome.

Thrombocytopenia is often seen as a laboratory finding during childhood. A supposed idiopathic thrombocytopenic purpura patient who was later diagnosed as Wiskott-Aldrich syndrome (WAS) and developed acquired thrombotic thrombocytopenic purpura (aTTP). Although autoimmune manifestations in WAS described, aTTP was reported just once. Five-year-old-boy was initially brought with cough, bloody stool (diarrhea), oral mucosal bleeding at 12th months of age. Following diagnosed with idiopathic thrombocytopenic purpura and receiving intravenous immunoglobulin, platelet count raised from 20,000 to 50,000/µL. One year after WAS diagnosis by mutation analysis, he presented with complaints of resistant fever, epistaxis, and melena. Hemoglobin decreased from 10 to 5.9 g/dL. Schistocytes in peripheral blood smear and high anti-ADAMTS-13 antibody level indicated development of aTTP.

Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood.

BACKGROUND: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. OBJECTIVE: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. METHODS: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. RESULTS: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). CONCLUSION: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.

Food-induced anaphylaxis in early childhood and factors associated with its severity.

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Serum levels of immunoglobulin isotypes and immunoglobulin g subtypes in healthy term turkish newborns.

AIMS: We aimed to determine the normal immunoglobulin values of Turkish new-borns by studying IgG, IgA, IgM, and IgG subgroups (IgG1, IgG2, IgG3, and IgG4) from term, healthy neonates born in the Sakarya province of Turkey. SUBJECTS AND METHODS: In our study, IgA, IgM, IgG, and IgG subgroup levels were measured nephelometrically in 54 new-borns (15-21-day-old). They were born between 39 and 41 weeks of gestation by problem-free delivery and with Apgar scores >8 at 1 and 5 minutes. The enrolled neonates were singletons and were free of congenital diseases/anomalies, history of perinatal infection, and with no known history of transfusion or chronic disease in the mother. The study findings were also evaluated in terms of differences based on delivery mode, feeding type, gender, and demographic characteristics. RESULTS: This study enrolled 54 new-borns, 42 (77.8%) of whom were born by cesarean section and 12 (22.2%) by spontaneous vaginal delivery. Of the new-borns, 41 (75.9%) were only breastfed, and 13 (24.1%) were fed with combined breast milk and baby formula. The 95% confidence intervals of serum immunoglobulins and IgG subgroups were as follows: IgG, 652-722 mg/dL; IgA, 6-8 mg/dL; IgM, 27-35 mg/dL; IgG1, 495.7-544.3 mg/dL; IgG2, 139.6-169.5 mg/dL; IgG3, 22.7-27.7 mg/dL; and IgG4, 21.5-33.7 mg/dL. There was no significant correlation between any demographic characteristic and any immunoglobulin type. A low-moderate but significant negative correlation (r: -0.34) was found between birth length and IgA and a low-moderate but significant positive correlation (r: 0.32) was found between head circumference and IgM level. CONCLUSION: Our study provided usable data on the normal values of serum IgG, IgA, IgM, and IgG subgroups among healthy Turkish new-borns. This study is thought to be one of the most standardized and reliable reference sources for our country.

COVID-19 and vaccination in hereditary angioedema: Single center experience.

Like many microbial agents, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccination may increase the frequency and/or severity of attacks. We aimed to observe/evaluate patients with hereditary angioedema (HAE) followed by Sakarya University Research/Training Hospital pediatric allergy unit, Sakarya, Türkiye, for the effects of SARS-CoV-2 infection and COVID-19 vaccination. Ten HAE patients-3 males and 7 females-were evaluated retrospectively. Their mean age was 31.80 ± 19.15 (min. 12 - max. 66) years. Four of 10 patients were diagnosed with type 1 HAE and 6 with type 2 HAE. Two out of 6 patients (mother and daughter) diagnosed with type 2 HAE had angioedema attacks during COVID-19 disease. Six out of 10 HAE patients received different COVID-19 vaccines available in Türkiye up to third and fourth doses. There was no increase in COVID-19 vaccine-related attacks during, after 72 hours, and up to the year after vaccination. As a result, we consider it safe to administer inactivated and/or mRNA vaccines in our patients with HAE. In addition, catching SARS-CoV-2 infection was not always associated with disease exacerbation or activation.

COVID-19 and cardiac complications: Myocarditis and multisystem inflammatory syndrome in children.

Coronavirus is an important pathogen causing disease in humans and animals. At the end of 2019, an investigation into an increase in pneumonia cases in Wuhan, Hubei Province, China, found that the cause was a new coronavirus. This disease, which spread rapidly across China and caused an outbreak worldwide, resulted in a pandemic. Although this virus has previously been referred to as 2019-nCoV, which causes coronavirus disease 2019 (COVID-19), later it was named severe acute respiratory syndrome coronavirus 2. Children were usually asymptomatic and rarely severely affected. In April 2020, reports from the United Kingdom indicated that children may have Kawasaki disease or a clinical condition similar to toxic shock syndrome. This clinical picture was later defined as multisystem inflammatory syndrome in children. Since then, similarly affected children as well as cases with other cardiac complications have been reported in other parts of the world. In this review, we aimed to evaluate COVID-19 in terms of cardiac involvement by reviewing the literature.

Mast cell activation syndrome: An up-to-date review of literature.

Mast cells are a subtype of white blood cells and are involved in the immune system. These cells contain many chemical substances called mediators, which are involved in the allergic response. The fact that mast cells play a role in many events that require urgent intervention, especially anaphylaxis, has led to a more detailed study of these cells. The diseases also caused by dysfunctions of mast cells have been examined in many circumstances. For instance, mast cell activation syndrome is known as an augmented number of cells due to decreased cell death, resulting in clinical symptoms affecting many systems. The main common symptoms include flushing, hypotension, urticaria, angioedema, headache, vomiting and diarrhea. Although the underlying mechanism is not yet clearly known, we aim to review the literature in a broad perspective and bring together the existing knowledge in the light of the literature due to the diversity of its involvement in the body and the fact that it is a little known syndrome.

Heavy Metal and Thiol/Disulfide in Children with Attention-Deficit and Hyperactivity Disorder.

Background: In the etiology of attention-deficit and hyperactivity disorder (ADHD), oxidative stress and heavy metal exposure are still controversial topics. In this study, our goal was to examine heavy metal levels and oxidative balance in newly diagnosed patients with ADHD and reveal whether heavy metal levels have an effect on the oxidation balance. Methods: The study included 35 patients with newly diagnosed ADHD and 31 healthy control groups of similar age and gender. Participants' parents or caregivers completed a semi-structured questionnaire regarding their children's breastfeeding and prenatal and postnatal smoking exposures. The levels of heavy metals lead (Pb), mercury (Hg), and cadmium were measured with inductively coupled plasma optical emission spectroscopy, and a unique automated spectrophotometric approach was used to quantify serum total thiol, native thiol, and disulfide quantities and ratios. Results: The rate of smoking during pregnancy was significantly higher in the ADHD group than in the control group (P = .030). Compared to the control group, the native and total thiol levels of children with ADHD were significantly higher (P < .001). Likewise, the ADHD group had significantly higher Hg levels compared to the control group (P = .002). Cadmium levels were substantially greater in the control group compared to the ADHD group (P < .001). However, there was no significant difference between Pb levels in the ADHD and the control group (P = .844). Conclusion: Exposure to Hg and prenatal smoking may contribute to the development of ADHD in childhood. In response to oxidative stress, the young brains of children with ADHD may enhance their antioxidant levels.

Omalizumab's efficacy and safety against chronic spontaneous urticaria.

I have read the article titled, "Efficacy and safety of omalizumab against chronic spontaneous urticaria: Real-world study from China", by Wang et al with great interest. Nevertheless, there are a couple of questions raised in my mind. And clarification of some aspects of the study will help the reader benefit and have a better understanding of the study.

Allergic Disease with Selective IgA Deficiency. Comment on Cinicola et al. The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study. J. Clin. Med. 2022, 11, 5705.

I read the article titled 'The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study' by Cinicola et al. with great interest [...].