A large single-center cohort of bare lymphocyte syndrome: Immunological and genetic features in Turkey.

Major histocompatibility complex class II (MHC-II) deficiency or bare lymphocyte syndrome (BLS) is a rare, early-onset, autosomal recessive, and life-threatening inborn error of immunity. We aimed to assess the demographic, clinical, laboratory, follow-up, and treatment characteristics of patients with MHC-II deficiency, together with their survival. We retrospectively investigated 21 patients with MHC-II deficiency. Female/male ratio was 1.63. The median age at diagnosis was 16.3 months (5 months-9.7 years). Nineteen patients (90.5%) had parental consanguinity. Pulmonary diseases (pneumonia, chronic lung disease) (81%), diarrhoea (47.6%), and candidiasis (28.6%) were common. Four (19%) had autoimmunity, two developed septic arthritis, and three (14%) developed bronchiectasis in the follow-up. Three patients (14%) had CMV viraemia, one with bilateral CMV retinitis. Eight (38.1%) had lymphocytopenia, and four (19%) had neutropenia. Serum IgM, IgA, and IgG levels were low in 18 (85.7%), 15 (71.4%), and 11 (52.4%) patients, respectively. CD4+ lymphocytopenia, a reversed CD4+/CD8+ ratio, and absent/low HLA-DR expressions were detected in 93.3%, 86.7%, and 100% of the patients, respectively. Haematopoietic stem cell transplantation (HSCT) was performed on nine patients, and four died of septicaemia and ARDS after HSCT. The present median age of patients survived is 14 years (1-31 years). Genetic analysis was performed in 10 patients. RFX5 homozygous gene defect was found in three patients (P1, P4 and P8), and RFXANK (P2 and P14) and RFXAP (P18 and P19) heterozygous gene defects were found in each two patients, respectively. This large cohort showed that BLS patients have severe combined immunodeficiency (SCID)-like clinical findings. Flow cytometric MHC-II expression study is crucial for the diagnosis, differential diagnosis with SCID, early haematopoietic stem cell transplantation (HSCT), and post-HSCT follow-up. Genetic studies are required first for matched family donor evaluation before HSCT and then for genetic counselling.

Phenotypes of persistent hen`s egg allergy in children and adolescents.

BACKGROUND: Optimum management of food allergy (FA) includes consideration of co-allergies and multimorbidities and tolerance assessment. Documentation of FA practices may pave the way for better practice. METHODS: Patients aged 3-18 years, with persistent IgE-mediated hen`s egg allergy were reviewed. RESULTS: A total of 102 children with a median age of 59 months (IQR= 40-84) (72.2% males) were included. All were diagnosed during infancy and the initial symptoms were atopic dermatitis (65.6%), urticaria (18.6%), and anaphylaxis (5.9%). Of the total population, 21 (20.6%) experienced anaphylaxis with hen`s eggs, and 79.4%, 89.2%, and 30.4% had multiple FAs (≥2 food categories), ever atopic dermatitis, and asthma, respectively. The most common co-allergies were tree nuts, cow`s milk, and seeds, respectively. From 52 heated egg yolk and 47 baked egg oral food challenges, 48 (92.3%) and 41 (87.2%) were found as tolerant, respectively. The baked egg nontolerant group had a greater egg white skin prick test diameter [9 mm (IQR: 6-11.5) vs. 6 mm (IQR: 4.5-9); (p=0.009)] and specific IgE [12.6 kU/L (IQR: 4.11-45.4) vs. 6.2 kU/L (IQR: 1.9-12.4) (p=0.009)], respectively. In the multivariate analysis, baked egg tolerance was more likely in those with egg yolk-tolerant subgroup (OR: 6.480, 95% CI: 2.524-16.638; p < 0.001) and heated egg tolerance in those with baked egg tolerance (OR: 6.943, 95% CI: 1.554-31.017; p=0.011). CONCLUSIONS: Persistent hen`s egg allergy is characterized by multiple food allergies and age-related multimorbidities. Baked egg and heated egg yolk tolerance were more likely to be considered in a subgroup with a high expectation for finding a way to eliminate their allergy.

Cupressus arizonica: an emerging aeroallergen for East Mediterranean children.

Background/aim: Cupressus sempervirens is a tree native to the Mediterranean region. We aimed to investigate the frequency of sensitization/allergy to Cupressus arizonica pollen, which is not native to Anatolia. Materials and methods: Patients aged 5-18 years who underwent respiratory allergy screening in Türkiye's largest referral center over a 1-year period were reviewed retrospectively for a diagnostic study of Cupressus allergy. Results: Of 246 patients, 207 (67.6% male) with a median age of 11.7 (IQR 9.2-15) years were found to be aeroallergen-sensitive and C. arizonica (32%) was the second most common sensitivity after grass pollen (83.6%). In the C. arizonica-sensitive subgroup, only 3% (2/67) were monosensitive, and grass (77.6%), cat (38.8%), and weeds (38.8%) were the most common co-sensitivities. Cup a 1 specific IgE (sIgE) was measured in 26 patients with C. arizonica sensitivity and all were found to be positive. A nasal allergen challenge (NAC) was performed for 44 of 67 patients with C. arizonica sensitivity, and 13 of 44 patients had a positive outcome (NAC+) at the highest two extract concentrations. The Cupressus wheal sizes and Cup a 1 sIgE levels of the NAC+ subgroup were higher than those of the NAC- subgroup but reached significance only for wheal size [6 (5-7.5) vs. 4.5 (4-6), p=0.004]. The NAC+ subgroup reported more frequent nasal discharge, congestion, and eye symptoms than the NAC- subgroup during the relevant pollen season. Conclusion: C. arizonica sensitivity has increased in the East Mediterranean region, similarly to North Mediterranean data, and this is associated with the presence of allergy both clinically and in laboratory findings. C. arizonica should be included in the aeroallergen screening panels of children from the East Mediterranean.

Comparison of miRNA expression in patients with seasonal and perennial allergic rhinitis and non-atopic asthma.

BACKGROUND: MicroRNAs (miRNA) are small non-coding molecules that play a significant regulatory role in several allergic diseases. However, their role in allergic rhinitis is still not clearly understood. The aim of this study was to identify the candidate miRNAs that can discriminate between different forms of allergic rhinitis and also differ in and out of the allergen season. METHODS: The study included 20 healthy children, 20 patients with seasonal allergic rhinitis (SAR), 20 non-atopic asthmatics (NA-A), and 12 patients with perennial allergic rhinitis (PAR). Patients with SAR were evaluated comparatively in and outside the allergen season. The changes in the expressions of selected miRNAs (miR- 125b, miR-126, miR-133b, miR-181a, and miR-206) that were found related to the allergic diseases according to the literature were determined using quantitative polymerase chain reaction. RESULTS: In the SAR group, expression levels of miR-125b (p=0.040) and miR181a (p=0.014) were lower than in the controls outside of the allergen season. Expression levels of miR-181a were different between patients with SAR and NA-A (p=0.003), also between the SAR and PAR (p=0.001) groups in multiple comparisons. In contrast, the expression of miR-206 was found to be decreased in patients with NA-A and PAR compared with the controls (p=0.005 and p=0.024, respectively). In correlation analysis, expression levels of miR-125b and peak expiratory flow (PEF) values were found to be negatively correlated in the SAR (p=0.013) and PAR (p=0.029) groups. The expression level of miR-206 was positively correlated with total IgE levels in PAR (p=0.007). Receiver operating characteristic analysis revealed that miR-125b and miR-181a predicted the risk of SAR (p=0.040 and p=0.014, respectively), and miR-206 for NA-A and PAR (p=0.005 and p=0.024, respectively). CONCLUSIONS: Our study showed that expression levels of miRNAs were different according to the type of allergic diseases and the presence of allergens. miR-181a and miR-125b can be candidate biomarkers for SAR, and miR-206 for NA-A and PAR.

Obesity is a risk factor for decrease in lung function after COVID-19 infection in children with asthma.

INTRODUCTION: It is not clear whether asthma, the most frequent chronic disease in childhood, is a risk for severe SARS-CoV-2 infection in the pediatric population and how SARS-CoV-2 infection affects the lung functions in these patients. PURPOSE: We aimed to investigate the course and the consequences of SARS-CoV-2 infection among children with asthma and determine the risk factors for the decline in lung function tests (LFTs). METHODS: In this retrospective study, asthmatic children with coronavirus disease 2019 (COVID-19) were compared with a random control group of asthmatic patients without COVID-19. In addition, the clinical course and the effect on LFTs of COVID-19 among children with asthma were also evaluated. RESULTS: One hundred eighty-nine patients who had COVID-19, and 792 who did not were included in the study. Fever, fatigue, and cough were the most frequent symptoms during COVID-19. Regarding the severity of COVID-19, 163 patients (87.6%) had a mild clinical condition, 13 (7%) had moderate disease, 1 (0.5%) had severe disease, and 2 had (1.1%) critically ill disease. Two patients were diagnosed with multisystem inflammatory syndrome in children (MIS-C), one patient suffered from pneumothorax. LFTs of the patients before and after COVID-19 infection were analyzed; no significant differences were found in FEV1 % (91.7% vs. 90.9%, p = 0.513), FVC% (89.8% vs. 90.8%, p = 0.502) and FEV1 /FVC (103.1% vs. 100.6%, p = 0.056), while FEF25%-75% values (107.6% vs. 98.4%, p < 0.001) were significantly lower after the COVID-19 infection. Obesity (odds ratio [OR]: 3.785, 95% confidence interval [CI]: 1.152-12.429, p = 0.028] and having a family history of atopy (OR: 3.359, 95% CI: 1.168-9.657, p = 0.025] were found to be the independent risk factors for ≥25% decrease in FEF25-75 after COVID-19 infection. CONCLUSION: COVID-19 infection leads to dysfunction of the small airways in asthmatic children and obesity is an independent risk factor for a ≥25% decrease in FEF25-75. The long-term effects of COVID-19 infection especially on small airways require close monitoring in children with asthma.

IgE mediated legume allergy in east Mediterranean children: A reflection of multiple food allergies.

BACKGROUND: Legumes are nutritionally valuable as an inexpensive protein source, but may cause severe allergic reactions. This study aimed to identify the characteristics of legume allergies (LAs) in Turkish children. METHODS: A total of 87 children (4.9 (3.1-7.0) years) with LAs confirmed by either oral food challenge (OFC) or consistent history were reviewed. RESULTS: The median age of onset was 19 (12-38) months. The most frequent LA was lentil (n = 57, 66%), followed by peanut (n = 53, 61%), chickpea (n = 24, 28%), pea (n = 21, 24%), bean (n = 7, 8%), and soybean (n = 1, 1%). From these, it was observed that 60% had multilegume (≥2) allergies and the age of onset occurred earlier compared with the single LA subgroup (18 (11-30) vs. 28 (17-42) months, p = .042). Single LA was present in peanut (51%) and lentil (16%) allergies, but not chickpea, pea, and bean. Fifteen patients had tolerated lentils before their first allergic reaction. The majority of children with LA (91.9%) were allergic to multiple foods including tree nuts (71%), hen's egg (66%), and cow's milk (49%). Seventy-eight patients (89.7%) also presented with atopic comorbidities concerning atopic dermatitis (70%), asthma (40%), and allergic rhinitis (30%). Patients with anaphylactic type of reaction (20%) had higher frequency of aeroallergen sensitization (p = .001). Lip dose challenge with legume paste predicted the result of OFC with a diagnostic accuracy of 81.82% and a positive likelihood ratio of 10.8. CONCLUSION: In Turkey, LA is a reflection of multiple food allergies and the presence of allergy to a least frequently encountered legume is a sign of multiple LA.

Clinical Validation of the Spirohome Clinic Ultrasonic Spirometer in Child and Adolescent Patients.

BACKGROUND: Spirometers are critical devices that reveal the respiratory dynamics caused by respiratory problems and their severity and facilitate their diagnosis and follow-up. Hand-held spirometers have emerged relatively recently and offer several advantages over conventional desktop systems. There remains, however, a need for reassurance of high-quality spirometry testing with next-generation portable spirometers that connect over Bluetooth® to smart device applications. In this study, we examine the accuracy and repeatability of lung function measurements of a novel hand-held ultrasonic spirometer, the Spirohome Clinic and compare its clinical performance to a reference device, the EasyOne Air. METHODS: Benchtop validation of the spirometers was conducted using a lung simulator device according to ATS/ERS guidelines and the ISO 26782 standard waveforms. Subsequently, 48 volunteers (pediatric patients between 6 and 11 years of age and adolescent patients between 12 and 18 years of age) performed spirometry with both the Spirohome Clinic and the EasyOne Air spirometer during their clinic visits. Spirometric data including repeated FEV1, FVC, FEV6, FEF25-75, and PEF measurements were collected. RESULTS: Both the Spirohome Clinic and the EasyOne Air successfully passed requirements for accuracy stated in relevant guidelines and standards for spirometry. The only statistically significant (p<0.05) difference was for FVC measurement accuracy. Clinical comparisons revealed strong correlation between spirometers in the measurement of key pulmonary function parameters including FEV1 and FVC with a Pearson's correlation coefficient of 0.99. Bland-Altman plots showed good agreement between mean differences of FEV1 and FVC with the majority measurements remaining between the limits of 95% agreement for both the entire patient cohort and also in age and gender subsets. CONCLUSION: The present study demonstrated that the Spirohome Clinic spirometer conforms to ATS/ERS performance requirements and validates the clinical comparability of its measurement accuracy and repeatability to the EasyOne Air. These findings support the indicated use of the Spirohome Clinic for high-quality lung function testing in clinical settings.

Allergic reactions against Covid-19 vaccines

Coronavirus Disease 2019 (COVID-19) affected the whole world in a short time. One of the most influential public health initiatives modern medicine has to offer, the vaccine has become even more important as the COVID-19 pandemic continues to worsen worldwide. Many vaccine trials were launched during the COVID-19 pandemic, and these vaccines were widely used around the world, offering realistic hope for ending the pandemic. Allergic reactions to vaccines were reported shortly after their approval. These reactions, in general, are rare, but, in some circumstances, they can be serious. Allergy to vaccines can occur because of either the active vaccine component or vaccine ingredients. The spectrum of the reactions may be just a local hypersensitiviy reaction or may be as severe as an anaphylaxis, which is an acute severe, life-threatening systemic hypersensitive reaction, and it requires quick intervention. If an allergy is suspected, a correct examination followed by algorithms is important for true diagnosis, treatment, and decision regarding revaccination. Patients who experience an allergic reaction with the first dose of covid 19 vaccine should be directed to the allergy-immunologist, and the evaluation of at-risk patients should be individualized. Finally, we should point out that the benefits of current COVID-19 vaccines go far beyond the side effects, and that the vaccine is the most important way to recover from the pandemic.

Oral food challenge in IgE mediated food allergy in eastern Mediterranean children.

BACKGROUND: The oral food challenge (OFC) in IgE mediated food allergy causes anxiety both in parents and in patients due to its inherent risks. OBJECTIVE: Documentation of the rate, spectrum, and predictors of positive reactions is instructive. METHODS: Children, who underwent OFC between January 1, 2017 and December 31, 2019 were analyzed. RESULTS: A total of 1361 OFCs in 613 cases were reviewed. Most of them were performed in preschool children (≤2 years 50%) and 55% of them had more than one OFC. Mainly considered food groups were cow's milk (31.8%), hen's egg (28.5%), tree nuts (20%), legumes (7%), seeds (4.9%), and wheat (2.7%). The overall OFC positivity was 9.6%, whereas 6.7% with cow's milk, 4.9% with hen's egg, 16.1% with tree nuts, 21.6% with wheat, and 32.8% with seeds. The severity scoring revealed grade I (24.4%), II (45.8%), and III (29.7%) reactions. Fifty (38%) cases required epinephrine and four cases required hospitalization. OFCs with sesame seeds (odds ratio [OR]: 7.747, [confidence interval (CI) 95%: 4.03-14.90]), wheat (OR: 3.80, [CI: 1.64-8.84]), and tree nuts (OR: 2.78, [CI: 1.83-4.23]) predicted a positive OFC while a concomitant asthma (OR: 3.61 [CI: 1.27-10.28]) was more likely to elicit anaphylaxis. CONCLUSION: In OFC practice, priority is given to basic nutritional sources and the most frequent food allergens, where preschool children with multiple sensitizations are the primary subjects. Increased risks of positive reactions with sesame, tree nut, and wheat and increased risk of anaphylaxis with concomitant asthma should be considered while performing OFC.

Oral food challenge in IgE mediated food allergy in eastern Mediterranean children

Background: The oral food challenge (OFC) in IgE mediated food allergy causes anxiety both in parents and in patients due to its inherent risks. Objective: Documentation of the rate, spectrum, and predictors of positive reactions is instructive. Methods: Children, who underwent OFC between January 1, 2017 and December 31, 2019 were analyzed. Results A total of 1361 OFCs in 613 cases were reviewed. Most of them were performed in preschool children (≤2 years 50%) and 55% of them had more than one OFC. Mainly considered food groups were cow’s milk (31.8%), hen’s egg (28.5%), tree nuts (20%), legumes (7%), seeds (4.9%), and wheat (2.7%). The overall OFC positivity was 9.6%, whereas 6.7% with cow’s milk, 4.9% with hen’s egg, 16.1% with tree nuts, 21.6% with wheat, and 32.8% with seeds. The severity scoring revealed grade I (24.4%), II (45.8%), and III (29.7%) reactions. Fifty (38%) cases required epinephrine and four cases required hospitalization. OFCs with sesame seeds (odds ratio [OR]: 7.747, [confidence interval (CI) 95%: 4.03–14.90]), wheat (OR: 3.80, [CI: 1.64–8.84]), and tree nuts (OR: 2.78, [CI: 1.83–4.23]) predicted a positive OFC while a concomitant asthma (OR: 3.61 [CI: 1.27–10.28]) was more likely to elicit anaphylaxis. Conclusion In OFC practice, priority is given to basic nutritional sources and the most frequent food allergens, where preschool children with multiple sensitizations are the primary subjects. Increased risks of positive reactions with sesame, tree nut, and wheat and increased risk of anaphylaxis with concomitant asthma should be considered while performing OFC (AU)

Relationship between urinalysis findings and responsible pathogens in children with urinary tract infections.

BACKGROUND: Pyuria, presence of bacteria, leukocyte esterase, and nitrite positivity in urinalysis should be considered together, and simultaneous urine culture test should be performed in the diagnostic evaluation of urinary tract infection (UTI). The absence of pyuria in urinalysis cannot exclude UTI in patients with suggestive clinical findings. OBJECTIVE: It was aimed to assess relationship between urinalysis tests and uropathogen and to evaluate antibiotic resistance in children. METHODS: The study included patients (aged 0-18 years) with significant uropathogen growth in urine culture tests. The patients' data regarding age, gender, results of urine microscopy, urine culture, and antibiogram were recorded retrospectively. RESULTS: Overall, 705 patients (562 girls, 143 boys) with significant growth in urine culture test were included. Median age was 72 months among girls and 12 months among boys. Most common uropathogens were Escherichia coli (79.6%) and Klebsiella pneumoniae (8.2%). E. coli was more commonly among girls (87%) and Klebsiella spp. among boys (53.3%). Pyuria was positive in urinalysis in 75% of patients. Pyuria presence was more common in patients with E.coli or Proteus spp. (80.6% and 71.4%, respectively) than those with Enterococcus spp. and Klebsiella spp. (52.0% and 53.3%, respectively). In culture antibiogram tests, ampicillin resistance was 100% in Klebsiella oxytoca and Enterobacter spp. and 72% in E. coli strains. No ceftriaxone resistance was observed in K. oxytoca, Citrobacter spp., Pseudomonas aeruginosa, and Enterobacter spp. DISCUSSION: Most UTIs were seen in older girls. Pyuria might be lacking in UTIs associated to Klebsiella spp. and Enterococcus spp., and absence of pyuria may not exclude UTI in patients with compatible clinical findings. Ceftriaxone is still an option in empirical treatment; unnecessary use of third-generation cephalosporins should be avoided, particularly in infections other than UTI. CONLUSIONS: It was found that E. coli more commonly caused leukocyturia, leukocyte esterase positivity, and pyuria; that pyuria might be lacking in UTIs associated to Klebsiella spp. and Enterococcus spp. and that pyuria was more prevalent among girls. It is though that urine culture tests should be performed in children with suspected UTI even in the absence of pyuria because lack of pyuria may lead delay in diagnosis and treatment as well as renal scar formation.

Secondary hemophagocytic lymphohistiocytosis in pediatric patients: a single center experience and factors that influenced patient prognosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of excessive immune activation. Secondary HLH syndrome develops as a complication of infection, drugs, rheumatologic conditions, or malignancy. The main objectives of this work were to identify the etiology of secondary HLH and prognostic factors associated with mortality. Patients diagnosed with secondary HLH, between January 2011 and December 2016, were retrospectively included in this study. We analyzed clinical and laboratory findings as well as prognostic factors from 24 pediatric patients diagnosed with secondary HLH. The mean age of patients at the time of diagnosis was 79.9 ± 68.7 months (range: 2-202) and 54.2% of the patients were male. The most frequent HLH-2004 criterion was fever (100%). Underlying triggers of HLH were as follows: 13 (54.1%) infections, juvenile idiopathic arthritis in 5 patients (20.8%), drugs in 3 patients (12.5%), malignancies in 2 (0.8%), Kawasaki disease in 1 (0.4%) patient, and 1 (0.4%) with unknown triggers. The median time of diagnosis was 3 days (1-67 days). Overall, the mortality rate was 20.8%. In our logistic regression model, factors associated with mortality were decreased albumin levels (OR1 = 2.3[1.48-3.43]) and etoposide usage (OR2 = 1.22 [1.14-1.89]). The patient's 30-day survival was inferior among patients whose albumin level was 2 g/dL or less compared to those over 2 g/dL. Increased awareness of the underlying condition is critical in HLH patients. Our study emphasizes the prognostic significance of albumin level.