Altered serum antibody levels in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis.

Objectives: This study aimed to extend the literature by analyzing immunoglobulin (Ig) A, IgE, IgG, IgG2, IgG3, and IgM antibody levels in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) patients. Patients and methods: This study retrospectively analyzed the antibody test results of 20 pediatric patients (10 males, 10 females; mean age: 2.5±1.5 years; range, 0.5 to 5.4 years) with and without flare who were initially evaluated for a number of underlying diseases due to periodic fever/infectious symptoms but then diagnosed with PFAPA between January 2015 and December 2020. Antibody levels were determined by chemiluminescence microparticle immunoassay. The results were retrospectively compared with a group of healthy children after the PFAPA diagnosis was confirmed. Results: The chemiluminescence microparticle immunoassay revealed 35%, 65%, 20%, 86.6%, and 55% of PFAPA cases with low serum levels of IgA, IgG, IgG2, IgG3, and IgM respectively, while 56.2% had high IgE levels. Moreover, low serum levels of at least two antibody classes or subclasses were reported in 80% of the PFAPA children. While cases with low IgG serum levels were with the highest incidence rates among the low IgG3 PFAPA patient population, both high IgE and low IgM cases were common in the rest of the patients. Conclusion: Our results suggest an association between PFAPA and low serum antibody levels, particularly of IgG3. Future studies are needed to confirm our conclusion.

High fetal bisphenol A exposure enhances IL22 secretion: A proinflammatory cytokine.

BACKGROUND: Bisphenol A (BPA) is an industrial product, widely used in human consumed types of equipment that can be transmitted orally, by inhalation or through dermal absorption and is detectable in many body fluids including cord blood. A correlation between BPA concentration in maternal serum and cord blood has been demonstrated previously, suggesting a possible transfer of BPA via the transplacental path. OBJECTIVE: Our objective is to determine the impact of cord blood BPA level on cytokine responses. METHODS: In this cross-sectional study, healthy pregnant women who delivered healthy newborns followed by the Obstetrics and Gynecology Department between September 2016 to June 2017 were enrolled. Cord blood samples were obtained and BPA and IL4, IL5, IL10, IL17, IL22, IFN gama and TGF beta levels were studied by ELISA. RESULTS: Among 197 deliveries, 176 of them were included in the study. Due to lack of cut-off value, BPA levels were stratified as percentiles. No statistically significant difference was detected in comparison of cytokine levels based on BPA concentrations below and above the 25th and 50th percentiles. Significantly higher IL22 levels (p = 0.007) and increased ratio of IL22/TGFß (p = 0.04) were detected in those with BPA level above 75th percentile (>19.16 ng/ml) compared to the below group. CONCLUSIONS: This in vivo real-life study demonstrated that very high BPA levels in cord blood of expectant mothers enhances IL22 secretion in cord blood which is a proinflammatory cytokine. Studies evaluating long term immunological effects on those highly exposed newborns are necessitated.

Immune mechanisms induced by sublingual immunotherapy in allergic respiratory diseases.

Allergic respiratory diseases (ARDs) are still a major burden on global public health. Sublingual immunotherapy (SLIT) is a mode of allergen immunotherapy (AIT) which involves administration of the allergen under the tongue, and benefits from tolerogenic properties of the oral mucosa. Studies revealed reduced levels of eosinophilia and eosinophil-dominated inflammation in airways of both animals and humans after SLIT. SLIT was also suggested to lower basophil responsiveness and innate lymphoid cell-2 function in blood samples collected from patients with ARD. Moreover, apart from shifting pathogenic type 2 (TH2) to a type 1 (TH1) and protective regulatory (Treg) polarization of helper T-cell immune response, antibody isotype switch from IgE to IgG1, IgG2, IgG4 and IgA was also reported in patients with ARD receiving SLIT. Today, the literature on SLIT-mediated activities is still scarce and more studies are required to further enlighten the mechanisms utilized by SLIT for the induction of tolerance. The aim of this review is to summarize the current knowledge about the immune-regulatory mechanisms induced by SLIT against ARDs.

Cutaneous Allergic reactions to pine processionary caterpillar (Thaumetopoea Pityocampa): a complicated cutaneous reaction in an infant and review of the literature.

BACKGROUND: Thaumetopoea Pityocampa (TP) are frequent in the Mediterranean region especially affecting forest workers in pinewood areas. The common symptoms include swelling, rash or burns like any form of dermatitis. The reactions can be triggered by mechanical, chemical or allergic factors and the `allergic` reaction is caused by sensitization to a hair protein named `thaumetopoein`. This protein triggers the IgE mediated reaction resulting in the mast cell degranulation causing urticaria. Different kinds of allergic reactions like urticaria or anaphylaxis have been reported previously commonly in adults, especially in forest workers while severe reactions without direct contact are rare in pediatric population. CASE: A 28 month old healthy boy was admitted to Near East University Pediatric Allergy and Immunology Outpatient Clinic in March with complaints of pain, hyperemia and swelling on the left hand. His complaints had started the day before his admission just after walking around in their garden which is surrounded by pine trees. On admission, his physical examination revealed serious edema and hyperemia on his left hand limiting his finger movements with a few bullae on the skin. His temperature was 38 C and the other vital parameters were normal. Based on hyperemia, swelling and high acute phase reactants he was hospitalized with the differential diagnosis of soft tissue inflammation and cellulitis. The case was treated with iv antihistamines, systemic steroids and antibiotics. CONCLUSIONS: Pine processionary (PP) is an important irritant and allergen especially in endemic areas like Cyprus which is a Mediterranean Country. It must be kept in mind in case of local or generalized urticaria, dermatitis, bullae and other allergic reactions even if there had been no direct contact with PP. Systemic involvement with fever and elevated acute phase reactants in infancy may necessitate hospitalization and intravenous treatment. Hereby, we reported an infant who presented with fever in addition to severe cutaneous lesions following the exposure to TP without direct contact. This is the first case reported from North Cyprus.

Maintained disease control and steroid-sparing effect of subcutaneous immunotherapy in allergic rhinitis and asthma.

BACKGROUND: Allergen immunotherapy is the only currently available treatment strategy that modifies the immune response to the causative allergen and induces clinical improvement and a steroid-sparing effect. OBJECTIVE: In this real-life study, we aimed to evaluate and compare the efficacy of subcutaneous immunotherapy (SCIT) with one allergen or multiple allergens in children and adults with asthma and/or allergic rhinitis in terms of disease control and a steroid-sparing effect. METHODS: Demographics, the initial inhaled corticosteroid (ICS) and/or intranasal corticosteroid (INS) dose, and other drugs of patients receiving SCIT for at least 12 months were recorded. Data on the final dose/use of ICS/INS and asthma and/or allergic rhinitis control were gathered. RESULTS: Of 104 patients included, 57.1% and 64.5% of patients with asthma and allergic rhinitis, respectively, were able to discontinue ICS and INS after SCIT. The median time to INS and ICS dose reduction was 6 months. SCIT with one allergen or multiple allergens effectively reduced the ICS and INS dose and led to control of asthma and allergic rhinitis, with no significant difference between the groups. When the efficacy of SCIT was compared in children and adults, there was no significant difference in terms of a steroid-sparing effect or the control of asthma and allergic rhinitis. SCIT was effective in both children and adult patients. CONCLUSIONS: In this real-life observational study, we have demonstrated a marked steroid-sparing effect while maintaining control of asthma and allergic rhinitis in children and adults treated with one allergen or multiple allergens.

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021.

Introduction: The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI. Results: In this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients' data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174). Conclusions: 1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.

Altered tonsillar toll-like receptor (TLR)-1 and TLR-2 expression levels between periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA), and group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis patients.

INTRODUCTION: Tonsillar microenvironment is thought to contribute to innate immune dysregulation responsible for the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) because of beneficial effects of tonsillectomy on treatment of the syndrome. Accordingly previous studies reported altered lymphocyte frequency, cytokine level and microbial composition in PFAPA tonsils. The aim of our study is to monitor expression levels of pro-inflammatory cell surface Toll-like receptors (TLRs) which have important role in induction of inflammation and maintaining tissue haemostasis. MATERIALS AND METHODS: Seven patients with PFAPA syndrome, and eight patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis were included in our study. Tonsillar expression levels of TLR-1, -2, -4, -5, and -6 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: IHC analysis demonstrated expression of all TLRs in tonsillar surface epithelium (SE) and lymphoid interior (LI) except for TLR-6 which was not present in the former. There has not been any statistically significant difference in TLR expression levels between PFAPA and GAßHS tonsils, except for TLR-1 and TLR-2 which were higher on LI and lower on SE of PFAPA tonsils, respectively, than that of the GAßHS samples. CONCLUSIONS: Altered TLR expression levels may be involved in PFAPA pathogenesis. Future studies with higher patient number, uninflamed tonsils and cellular markers are required to further enlighten the role of TLRs in the development of syndrome.

Planning and approach to allergen-specific immunotherapy in polyallergic patients.

Allergy immunotherapy (AIT) is currently the only disease-modifying treatment for allergic-respiratory diseases. Polysensitization may increase the severity of current disease resulting in subsequent asthma development in patients with allergic rhinitis. Due to the absence of general recommendations for the practical approach to polysensitized patients, clinical management is not standardized. The correlation between sensitizations and clinical symptoms, elimination of possible pollen cross-reactivities and principles of homologous allergen groups will guide the allergists to deduce the most relevant allergens for AIT. In the highlight of the previously proposed approach strategies to polyallergic patients, hereby we propose a revised practical stepwise approach based on the current European Medicine Agency (EMA) guidelines. However, more supporting data from well-designed, controlled, future studies are needed to improve clinical management recommendations for AIT in polyallergic patients.

Association of cord blood bisphenol A (BPA) with cord blood adiponectin, leptin, fetal growth; adiposity and neoantal complications in a newborn cohort.

Objective: To evaluate the relation between cord blood bisphenol A (BPA), leptin, adiponectin, birth weight, height, skin thickness, and postnatal results.Method: This study was performed in near East University Medical Faculty, Nicosia, Cyprus with 150 healthy newborns. Cord blood leptin, adiponectin, BPA levels were measured by ELISA and birth weight, heights and back, waist, and arm skin thickness were measured and postnatal problems noted.Results: One hundred eighty-seven newborns were included in the study. Mean ± SD of BPA, adiponectin, leptin levels were 48.3 ± 2.22 ng/mL, 65.60 ± 15.29 µg/mL and 3.08 ± 2.08 ng/mL. Mean birth weight, height, head circumferences were 3156.76 ± 493.45 g, 48.28 ± 2.04 cm, 34.14 ± 1.74 cm. The association anthropometric measurements, BPA, leptin, and adiponectin levels were not statistically significant (p>.05). The relation between cord blood leptin, adiponectin, and BPA levels and small for gestation, large for gestation and average for gestation groups were not significant (p>.05). Moreover, relation between back, waist and arm skin thickness and BPA, leptin, and adiponectin were not statistically significant (p>.05). However, newborns who were hospitalized and had newborn jaundice had higher BPA levels (p<.05).Conclusion: In previous studies, higher BPA levels were associated with small for gestational age (SGA) birth, however, this relation was not noted in our study. Furthermore, there is no relation between skin thickness, BPA, leptin, and adiponectin. This difference may be as a result of higher cord BPA levels compared with previous studies.

Headliner in Physiology and Management of Childhood Asthma: Hypothalamic-Pituitary-Adrenal Axis.

Asthma is the most common chronic inflammatory disease of children. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy which are the most effective, commonly used treatment of persistent asthma. Mostly, studies on the relationship between asthma and cortisol have focused on side effects of treatment. Recently, asthmatic patients not treated with ICS have been reported to have an attenuated activity and/or responsiveness of their Hypothalamic-Pituitary- Adrenal (HPA) axis. Moreover, it has been proposed that asthma worsening with stress may be due to a dysfunctional HPA axis, or cortisol insensitivity due to chronic psychological stress through impaired glucocorticoid receptor expression or function. Although long-term ICS treatment might produce adrenal suppression or iatrogenic Cushing syndrome, improvement of adrenal function has also been detected in some of asthmatic cases. Thus, the response scheme of HPA axis still contains undiscovered features in asthma. The management of asthma can be improved by increasing knowledge on the role of HPA axis in asthma pathophysiology. The risk for side effects of ICS can be minimized through increased awareness, early recognition of at-risk patients and regular patient follow-up. This review was written to draw attention to the role of HPA axis in both asthma and its treatment and to illustrate a follow up algorithm of HPA axis in the management of asthma.

Evaluation of Dose Dependent Maternal Exposure to Bisphenol A on Thyroid Functions in Newborns.

Bisphenol A (BPA) is an endocrine-disrupting chemical compound that is mainly used in industrial products as packaging and plastics. It usually transmits to humans via oral route from food-contact material. BPA has demonstrated to be found in body fluids with a higher amount of fetal tissues due to bio-accumulation. Although it has been reported to affect the endocrine system, results on thyroid functions of newborns are conflicting. The aim of the present study is to demonstrate the effect of different levels of BPA in cord blood on the thyroid functions of newborns, according to gender. METHODS: The study population included 88 newborns. The BPA levels, Thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels of cord blood were measured. In addition, SPINA-GT (thyroid' incretory capasity), TSH Index (TSHI), standardized TSHI (sTSHI) were calculated and demographic characteristics of participants were noted. RESULTS: The mean of cord blood BPA was 4.934 ± 2.33 ng/mL. When evaluated according to quantiles of BPA, no association was found between BPA and thyroid hormone levels, as well as, SPINA-GT, TSHI, sTSHI in both genders. CONCLUSION: Although BPA has been shown to contaminate cord blood, no significant effect was detected on thyroid hormones, SPINA-GT, TSHI and sTSHI. Further investigations with larger study populations are warranted.

Tonsillar antimicrobial peptide (AMP) expression profiles of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) patients.

INTRODUCTION: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) is the most frequent non-infectious cause of high fever observed among the European child population. While its cause is still not yet fully identified, PFAPA patients were previously shown to have altered tonsillar microbiome composition. Our study hypothesized that this is associated with a change in antimicrobial peptide (AMP) expression levels, as in the case of Crohn's disease which is another autoinflammatory disorder. METHODS AND MATERIALS: The tonsil specimens were isolated from seven patients with PFAPA syndrome, and six patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis. Tonsillar expression levels of human beta-defensin 1-2, cathelicidin, ribonuclease-7, and liver expressed antimicrobial peptide-1 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: Our results showed no significant difference in AMP expression levels between PFAPA and GAßHS patients. Immunolocalization of human beta-defensin 1 was different between the two groups; expressed at higher levels on tonsil surface epithelium (SE) than lymphoid interior (LI) in PFAPA patient group, while this was not evident in GAßHS patients group. CONCLUSIONS: Our results suggest that, PFAPA patients may be associated with altered AMP expression as in other autoinflammatory diseases. Future studies with subjects without any inflammatory condition are required for more precise conclusions.

Is celiac disease misdiagnosed in children with functional constipation?

BACKGROUND/AIMS: Functional constipation is one of the common problems in childhood, and it comprises approximately 5% of the pediatric outpatient clinical applications. On the other hand, celiac disease (CD) is an immune enteropathy with the prevalence between 1/150 and 1/200. In addition to the classical symptoms of the disease such as diarrhea and weight loss, the incidence of atypical symptoms is increasing. This study aims to determine the prevalence of CD in patients with chronic constipation. MATERIALS AND METHODS: The study was conducted between 2010 and 2012 and included 1046 children (range, 2-18 y; median, 11.4 y) diagnosed with chronic constipation according to the Rome III criteria. Serum immunoglobulin A, tissue transglutaminase, and/or anti-endomysial antibodies were examined. The patients with serological positive results were subjected to upper gastrointestinal system endoscopy and duodenal biopsy to confirm the diagnosis of CD. RESULTS: Blood tests were positive in 36 patients (3.25%). One of the patients had Hashimoto's thyroiditis, and 4 patients had short stature. Endoscopic findings included nodularity in bulbus and duodenal mucosa (n=16), scalloping fold (n=13), and normal mucosa (n=5). Histopathologic findings revealed that 10 patients had total villous atrophy, 24 patients had subtotal and partial villous atrophy, and 34 patients had intraepithelial lymphocyte infiltration. All patients followed a gluten-free diet, resulting in a resolution of symptoms. CONCLUSION: In the present study, a CD ratio of 1:28 was diagnosed in chronically constipated children. The use of screening tests for CD should be considered in children with conventional treatment-resistant constipation.

A propósito de un caso: enfermedad de Kawasaki incompleta en un niño con hipogammaglobulinemia / A case report: incomplete Kawasaki disease in a hypogammaglobulinemic child

La enfermedad de Kawasaki (EK) es una vasculitis autoinmunitaria sistémica que afecta a los vasos pequeños y medianos. La complicación principal de la enfermedad de Kawasaki es el aneurisma de las arterias coronarias, cuyo riesgo es más alto si se retrasa el diagnóstico y el tratamiento. Si bien hasta la fecha se han presentado casos de EK completa e incompleta en diferentes tipos de enfermedades por inmunodeficiencia, no se ha informado acerca de la evolución clínica de la EK en pacientes con hipogammaglobulinemia (HG). En este artículo, se presenta un caso de diagnóstico de EK incompleta en un niño con HG transitoria de la infancia. También se resumen casos previamente informados de EK e inmunodeficiencia. En el caso de una inmunodeficiencia, las infecciones recurrentes pueden ocultar la EK, lo que retrasa el diagnóstico y aumenta el riesgo de complicaciones. En pacientes inmunodeficientes, debe tenerse en cuenta la posibilidad de EK cuando la fiebre es prolongada.

Kawasaki Disease (KD) is a systemic autoimmune vasculitis that affects small and medium sized vessels. Main complication of Kawasaki Disease is coronary artery aneurism, which has higher risk in case of delayed diagnosis and treatment. Although, complete and incomplete KD cases in different types of immune deficiency diseases have been presented up to date, clinical course of KD in patients with hypogammaglobulinemia (HG) has not been reported. Herein, a case diagnosed as incomplete KD in a child with transient HG of infancy has been reported. Previously reported cases with KD and immunedeficiency have also been summarized. Recurrent infections in case of immunedeficiency may mask KD disease resulting in delay in diagnosis and increased risk of complication. KD should be kept in mind in immunedeficient patients in case of prolonged fever.

A case report: incomplete Kawasaki disease in a hypogammaglobulinémie child. / A propósito de un caso: enfermedad de Kawasaki incompleta en un niño con hipogammaglobulinemia.

Kawasaki Disease (KD) is a systemic autoimmune vasculitis that affects small and medium sized vessels. Main complication of Kawasaki Disease is coronary artery aneurism, which has higher risk in case of delayed diagnosis and treatment. Although, complete and incomplete KD cases in different types of immune deficiency diseases have been presented up to date, clinical course of KD in patients with hypogammaglobulinemia (HG) has not been reported. Herein, a case diagnosed as incomplete KD in a child with transient HG of infancy has been reported. Previously reported cases with KD and immunedeficiency have also been summarized. Recurrent infections in case of immunedeficiency may mask KD disease resulting in delay in diagnosis and increased risk of complication. KD should be kept in mind in immunedeficient patients in case of prolonged fever.

La enfermedad de Kawasaki (EK) es una vasculitis autoinmunitaria sistémica que afecta a los vasos pequeños y medianos. La complicación principal de la enfermedad de Kawasaki es el aneurisma de las arterias coronarias, cuyo riesgo es más alto si se retrasa el diagnóstico y el tratamiento. Si bien hasta la fecha se han presentado casos de EK completa e incompleta en diferentes tipos de enfermedades por inmunodeficiencia, no se ha informado acerca de la evolución clínica de la EK en pacientes con hipogammaglobulinemia (HG). En este artículo, se presenta un caso de diagnóstico de EK incompleta en un niño con HG transitoria de la infancia. También se resumen casos previamente informados de EK e inmunodeficiencia. En el caso de una inmunodeficiencia, las infecciones recurrentes pueden ocultar la EK, lo que retrasa el diagnóstico y aumenta el riesgo de complicaciones. En pacientes inmunodeficientes, debe tenerse en cuenta la posibilidad de EK cuando la fiebre es prolongada.

A predictive score for retinopathy of prematurity by using clinical risk factors and serum insulin-like growth factor-1 levels.

AIM: To detect the impact of insulin-like growth factor-1 (IGF-1) and other risk factors for the early prediction of retinopathy of prematurity (ROP) and to establish a scoring system for ROP prediction by using clinical criteria and serum IGF-1 levels. METHODS: The study was conducted with 127 preterm infants. IGF-1 levels in the 1st day of life, 1st, 2nd, 3rd and 4th week of life was analyzed. The score was established after logistic regression analysis, considering the impact of each variable on the occurrences of any stage ROP. A validation cohort containing 107 preterm infants was included in the study and the predictive ability of ROP score was calculated. RESULTS: Birth weights (BW), gestational weeks (GW) and the prevalence of breast milk consumption were lower, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and necrotizing enterocolitis (NEC) were more frequent, the duration of mechanical ventilation and oxygen supplementation was longer in patients with ROP (P<0.05). Initial serum IGF-1 levels tended to be lower in newborns who developed ROP. Logistic regression analysis revealed that low BW (<1250 g), presence of intraventricular hemorrhage (IVH) and formula feeding increased the risk of ROP. Afterwards, the scoring system was validated on 107 infants. The negative predictive values of a score less than 4 were 84.3%, 74.7% and 79.8% while positive predictive values were 76.3%, 65.5% and 71.6% respectively. CONCLUSION: In addition to BW <1250 g and IVH, formula consumption was detected as a risk factor for the development of ROP. Breastfeeding is important for prevention of ROP in preterm infants.

Steroid sparing effect of sublingual immunotherapy: real life study in mono/polisensitized children with asthma.

AIM: Steroid-sparing effect of sublingual immunotherapy (SLIT) in mono/polisensitized asthmatic children were evaluated. MATERIALS AND METHODS: Children undergoing allergen-specific SLIT between 2010 and 2014 were included. Asthma control and usage/dose of inhaled corticosteroid (ICS) in the previous year was determined. Asthma control without ICS need ≥6 months was defined as 'ICS avoidance'. RESULTS: 90 children (mean ± SD age 8.92 ± 4.17 years) were enrolled, 56.7% (n = 60) being polysensitized. Mono, 2-simultaneous and multiple-pollen-mix allergen SLIT were prescribed in 84.4, 17.8 and 7.8%, respectively. ICS was avoided in 70%, with no significant difference in mono- versus poly-sensitized patients. ICS-avoidance rates in mono-allergen, pollen-mixture and 2-simultaneous-allergen SLIT were 93.6, 83.3 and 73.7%, respectively. Longer-duration SLIT resulted in significantly more ICS-avoidance (p:0.0001). CONCLUSION: SLIT with mono/multiple-mixed/simultaneous allergens in childhood asthma resulted in retained-avoidance of ICS. Steroid-sparing effect of SLIT in polysensitized children warrants further investigation.

A Novel TBX19 Gene Mutation in a Case of Congenital Isolated Adrenocorticotropic Hormone Deficiency Presenting with Recurrent Respiratory Tract Infections.

INTRODUCTION: Congenital isolated adrenocorticotropic hormone deficiency (CIAD) is a rare disease characterized by low adrenocorticotropic hormone (ACTH) and cortisol levels. To date, recurrent pulmonary infections in infancy have not been reported as an accompanying symptom of CIAD. CASE PRESENTATION: A 7-year-old boy was hospitalized nine times for recurrent lower respiratory tract infections. The results of all tests for the possible causes of wheezing were within the normal limits. His ACTH and cortisol levels were persistently low. All other pituitary hormone levels, and adrenal ultrasound and pituitary magnetic resonance imaging results, were normal. Molecular analyses confirmed the diagnosis of CIAD by identifying compound heterozygosity for two mutations in the TBX19 gene. The first was a novel frameshift c.665delG variant in exon 4 of the TBX19 gene, leading to premature termination that was predicted to result in a non-functional truncated protein. The second was a nonsense C-to-T transition in exon 6 of the TBX19 gene, resulting in an arg286-to-ter mutation (dbSNP: rs74315376). Both parents were heterozygous for one of the mutations. CONCLUSION: Here, we presented a new mutation in the TBX19 gene in a patient with CIAD who presented with recurrent respiratory tract infections. This expands the mutation spectrum in this disorder. To conclude, adrenal insufficiency should be considered in patients with unexplained recurrent infections to prevent a delay in diagnosis.

Prevalence of Mediterranean FeVer Gene Mutations in Turkish Cypriot Population.

OBJECTIVES: This study aims to determine the carrier frequency and the most common mutations of the Mediterranean FeVer (MEFV) gene in healthy Cypriot population of Turkish origin. PATIENTS AND METHODS: A total of 296 healthy participants (102 males, 194 females; median age 30 years; range 1 to 81 years) were evaluated. The exon 2, 3, 5 and 10 of MEFV genes were amplified by polymerase chain reaction. RESULTS: The participants demonstrated an extremely high carrier rate (12.5%). Most commonly detected mutations were E148Q and A74S, with rates of 7.3% and 2.8%, respectively. CONCLUSION: Mediterranean FeVer gene mutation types and carrier rates in Turkish Cypriot population are different than other Mediterranean populations in the region. MEFV mutation carriage is frequent in North Cyprus and familial Mediterranean fever might be one of the causes for end stage renal disease in Turkish Cypriots.

Predictive risk factors for relapse after cessation of inhaled corticosteroids in well-controlled childhood asthma.

BACKGROUND: There is limited data for predicting the risk of exacerbations following the cessation of inhaled corticosteroids (ICS) in well controlled childhood asthma. In current study, clinical, functional and inflammatory parameters at the time of ICS withdrawal were investigated in that respect. METHODS: Forty children asymptomatic for at least 3 months on low dose ICS's were enrolled and ICS were discontinued in summer. At enrolment symptom/medication diary, pulmonary function parameters, methacholine provocation testing, peripheral blood eosinophilia, serum total and allergen-specific IgE levels and skin prick testing were performed. In a subgroup of patients, phytohemaglutinin induced secretion of IL-5, IL-13, IFN-γ and IL-10 from blood mononuclear cells were measured. Patients were assessed with symptom/medication diary and pulmonary function test every 2 months for 6 months. RESULTS: Eighteen of 37 patients experienced recurrence of acute asthma symptoms. In patients with acute attack (group I), changes in rhinitis symptom scores at 2nd month vs. baseline were statistically higher. In addition, group I had significantly higher rhinitis symptom scores compared to group II at fourth-month visit. Patients with acute exacerbation revealed a significant decrease in FEV1% at 2nd month compared to baseline. Moreover, group I showed significantly lower FEF 25-75% compared to group II at 2nd month. Baseline bronchial hyper-responsiveness with methacholine was found to be an independent risk factor for asthma exacerbation. CONCLUSIONS: The findings of this study identified baseline bronchial hyperreactivity, higher rhinitis symptom scores and gradual decrease in pulmonary function parameters during follow-up as risk factors for subsequent exacerbation of asthma.