IL-17 serum level in patients with chronic mucocutaneous candidiasis disease.

BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is defined by recurrent or persistent superficial infections involving nails, skin, and/or oral and genital mucosae. IL-17 promotes the recruitment, chemotaxis, and expansion of neutrophils and acts directly on keratinocytes and epithelial cells, driving the production of antimicrobial peptides, essential for the immune response against Candida. AIM: To evaluate the serum level of IL-17 in a family affected by CMC restricted to the nails of the hands and feet. METHODS: Serum IL-17 was assayed on 16 patients (aged 21 ± 3.1 years) suffering from persistent onychomycosis caused by Candida and 18 healthy controls (aged 19 ± 2.7 years). Comparisons between groups were performed by Student's unpaired t-test. The level of significance was set at 0.05. RESULTS: The mean serum IL-17 level in patients was 74 ± 1.42 pg/ml, whereas the control group showed a significantly lower level of 25.6 ± 6.7 pg/ml (p < 0.05). CONCLUSIONS: We showed a potential defect in the IL-17 signaling pathway in a family affected by CMC restricted to the nails of the hands and feet. Further research is needed to clarify the immunological mechanisms and the genetic etiology at the basis of the unusual clinical presentation in this family.

Recurrent respiratory infections between immunity and atopy.

Recurrent respiratory infections (RRIs) are frequent in children and are characterized by more than 6 airway infections in 1 year or more than 1 upper airway infection per month in the period between September and April or more than 3 lower airway infections in 1 year. Often pediatric RRIs are related to predisposing factors, such as reduced airway size, poor tussive reflex, and immaturity of the immune system. RRIs due to immature immune system are a transient condition, with spontaneous resolution in the school age. However, some RRIs are expression of more complex diseases. Red flags are the onset of symptoms in the first year of life, the involvement of other systems, unusual pathogens, slowing of growth, severe infections of the lower airways, and recurrence of the infection site. To help the pediatrician in the RRI differential diagnosis, we have created a roadmap based on scientific literature data and clinical practice that identifies 6 macro areas: immunodeficiencies, simple minimal genetic immunodeficiency, atopy, obesity, nutritional deficiencies, autoinflammatory diseases, and complex diseases.

Antihistamines: ABC for the pediatricians.

Antihistamines are currently one of the most commonly administered drugs in children. They are used to treat symptoms that depend on histamine release, namely allergic diseases, such as rhinitis, asthma, urticaria, and anaphylaxis. It is possible to distinguish first- and second-generation antihistamines. Pharmacological effects and therapeutic indications are similar, but second-generation antihistamines have fewer adverse effects because they are more selective for peripheral H1 receptors. Although they have been on the market for several years, there are still many adverse effects linked to the antihistamine safety profile, especially in the first years of life. Thus, many antihistamines are prescribed off-label, especially in children younger than 2 years of age, which is the age-group where most of the data on drug safety are lacking and many antihistamines are not recommended. This article aims to provide a practical update on the use of antihistamines in children.

Cetirizine use in childhood: an update of a friendly 30-year drug.

Cetirizine is a second-generation antihistamine, derived from the metabolism of hydroxyzine, highly specific for the H1 receptors, and with marked antiallergic properties. Although its history began more than 30 years ago, it remains one of the most used drugs in children with a leading role in the medical care of children with allergic diseases. Cetirizine use is licensed for paediatric patients for the treatment of allergic rhinitis, and chronic spontaneous urticaria, in Europe in children older than 2 years old and in the USA in children older than 6 months old. This review provides a practical update on the use of cetirizine in children and adolescents.

Antihistamines: Recommended Dosage - Divergence between Clinical Practice and Guideline Recommendations.

The updosing of second-generation antihistamines for chronic urticaria is based on inconsistent findings. Herein, we report data on the treatment of children with chronic spontaneous urticaria (CSU) unresponsive to single doses of second-generation H(1)-antihistamines in whom an increase in antihistamine was performed without improvement and with a high prevalence of adverse events. Thus, it appears that well-controlled, well-designed clinical trials are needed to clarify which nonsedating antihistamines should be used, in what dose, and for how long in patients not responding to the standard treatment, despite the improvement in health care that guidelines help to incorporate. Furthermore, a critical use of such guidelines should be done to improve the knowledge in CSU, especially in the pediatric population.

High mobility group box 1 and markers of oxidative stress in human cord blood.

BACKGROUND: Parturition induces considerable oxidative stress and many inflammatory mediators, such as high mobility group box 1 (HMGB1), are involved from the beginning of the pregnancy to birth. The aim of the present study was to evaluate serum cord blood concentration of diacron-reactive oxygen metabolites (d-ROM), biological antioxidant potential (BAP), and HMGB1 to investigate the perinatal oxidative status of neonates and correlation with mode of delivery, as well as the influence of labor. METHODS: The subjects consisted of 214 neonates delivered at University Hospital "G. Martino", Messina, in a 6 months period. Venous blood samples were collected from the umbilical cord after cord separation. RESULTS: Umbilical cord venous blood HMGB1 was significantly higher in the spontaneous vaginal delivery (SVD) group than in the elective or emergency cesarean section (CS) group (P = 0.018). Regarding labor, there was no significant difference in HMGB1 concentration in umbilical vein blood between the spontaneous and induced labor groups (P = 0.250). Furthermore, d-ROM was significantly different between the SVD group and the elective or emergency CS group (P = 0.044). BAP concentration, however, was not significantly different, not even with regard to mode of labor. CONCLUSION: Oxidation is higher in newborns delivered by SVD than in those delivered by CS, and HMGB1 may be involved in the mechanisms of birth, and responsible for decidual modifications that lead to birth.

Induction of high-mobility group Box-1 in vitro and in vivo by respiratory syncytial virus.

BackgroundDespite decades that have passed since its discovery, accurate biomarkers of respiratory syncytial virus (RSV) disease activity and effective therapeutic strategies are still lacking. The high-mobility group box type 1 (HMGB1) protein has been proposed as a possible link between RSV and immune system, but only limited information is currently available to support this hypothesis.MethodsExpression of HMGB1 gene and protein was analyzed by quantitative PCR, enzyme-linked immunosorbent assay (ELISA), western blot, immunocytochemistry, and confocal microscopy in immortalized and primary human bronchial epithelial cells, as well as in rat pup lungs. The role of HMGB1 in RSV infection was explored using glycyrrhizin, a selective HMGB1 inhibitor.ResultsRSV infection strongly induced HMGB1 expression both in vitro and in vivo. Glycyrrhizin dose-dependently inhibited HMGB1 upregulation in both RSV-infected immortalized and primary human bronchial epithelial cells, and this effect was associated with significant reduction of viral replication.ConclusionOur data suggest that HMGB1 expression increases during RSV replication. This seems to have a critical pathogenic role as its selective inhibition virtually modified the infection. These observations provide further insight into the pathophysiology of RSV infection and uncover a potential biomarker and therapeutic target for the most common respiratory infection of infancy.

Association between Allergies and Hypercholesterolemia: A Systematic Review.

BACKGROUND: There is controversy in the literature regarding the potential relationship between atopic predisposition (AP) and serum cholesterol levels. To this purpose, we reviewed human studies that investigated this possible link. METHODS: Following PRISMA guidelines, a literature search of PubMed and Science Direct for peer-reviewed journal articles in English from January 2003, with updates through to August 2016, was conducted. Relevant publications were reviewed that included pediatric and adult populations. Information on the study design, sample, intervention, comparators, outcome, time frame, and risk of bias were abstracted for each article. RESULTS: Of 601 reviewed reports, 18 were included in this systematic review. Fifteen studies assessed the relationship between AP and serum cholesterol levels. Due to the lack both of observational and cross-sectional studies from the literature search at this time (only 8 studies also analyzed confounding factors) there is a high possibility of confounding variables (familial and genetic predisposition, age, gender, BMI, comorbidity, and medication status) that could not be ruled out. CONCLUSION: Existing studies are heterogeneous, making it difficult to draw broad conclusions. Future studies and more detailed analyses, considering confounding variables and including a larger and homogeneous population, are needed to strengthen the argument for a link between lipid metabolism and atopy.

Soluble hemojuvelin in transfused and untransfused thalassaemic subjects.

OBJECTIVE: The hemojuvelin-bone morphogenetic protein axis is the principal iron-dependent mechanism of hepcidin regulation. The determination of soluble hemojuvelin (sHJV) levels could allow for a better understanding of the pathophysiological mechanisms of hepcidin regulation in thalassaemia. METHOD: We have assessed sHJV in 45 transfused and 15 untransfused thalassaemic patients in comparison with 15 healthy subjects, evaluating its relationships with some parameters of iron overload, anaemia and erythropoiesis. RESULTS: Untransfused thalassaemic patients had more severe anaemia and erythropoietic activity, while in transfused patients, the transfused RBCs reduced % reticulocytes and sTfR, increased serum indices of iron overload and iron stores in the liver (low MRI T2* values). sHJV levels were higher in patients than in controls and in untransfused in comparison with transfused patients. In the transfused group, we also found that sHJV values are significantly related to serum ferritin, cardiac MRI T2* and growth differentiation factor 15 and are sensitive to hepatitis C virus infection. CONCLUSION: These results suggest that sHJV synthesis seems to be affected by an erythropoietic/hypoxic signal in untransfused patients that have severe anaemia, while in regularly transfused subjects, it is influenced by iron stores.

A systematic review of food protein-induced enterocolitis syndrome from the last 40 years.

OBJECTIVE: To provide a complete, exhaustive summary of current literature relevant to food protein-induced enterocolitis syndrome (FPIES). DATA SOURCES: Data have been extracted from PubMed and Science Direct databases. STUDY SELECTIONS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, a literature search for peer-reviewed journal articles in English through January 1975 with updates through October 2016 was conducted. Relevant publications were reviewed that included pediatric and adult populations. Information on the study design, sample, intervention, comparators, outcome, timeframe, and risk of bias were abstracted for each article. RESULTS: Of 135 reviewed reports, 52 were included in this systematic review. In accordance with the age at onset, clinical features, and offending foods, it is possible to distiguish different types of FPIES. An immune systemic involvement can occur in patients with FPIES. In addition to the most common causative foods (cow's milk, soy, and rice), any food can potentially cause FPIES. Although specific diagnostic tests are not available, open food challenge remains the gold standard for FPIES diagnosis. Moreover, because of the lack of randomized clinical trials and of use of different adopted methods, confounding factors might mask critical findings, leading to poor knowledge of this pleiotropic clinical entity. CONCLUSION: Multicenter studies are needed to better develop an evidence-based approach to pathophysiology, prevalence, diagnosis, and natural history of the disease.

Filaggrin mutations and Molluscum contagiosum skin infection in patients with atopic dermatitis.

BACKGROUND: Although mutations in the filaggrin (FLG) gene have been reported to predispose patients with atopic dermatitis (AD) skin infection susceptibility, to date, the data reported in the literature are still controversial. OBJECTIVE: To evaluate the role of FLG polymorphisms expression and risk of developing a concomitant Molluscum contagiosum sustained skin infection in the pediatric population with AD. METHODS: A total of 100 children with AD and 97 healthy children were enrolled. AD was diagnosed and assessed according to the validated European Task Force on Atopic Dermatitis. DNA samples of patients were analyzed for allelic variants in the promoter and coding exon of FLG. Genotyping was performed with polymerase chain reaction amplification and direct sequencing. RESULTS: Sixteen FLG variants have been detected in 29% of patients with AD: 2 synonymous (rs79808464 and rs116222149), 12 missense (rs11584340, rs113136594, rs145828067, rs374910442, rs747005144, rs145627745, rs144209313, rs74129443, rs192455877, rs150957860, rs138055273, rs147472105), 1 stop gained (rs183942200), and 1 frameshift (rs 558269137). In contrast, only 13% of the control group reported FLG mutations (22 heterozygous variants). In addition, the age at disease onset correlated significantly with FLG variants (P < .001). In addition, the AD with FLG gene variants (rs145627745, rs79808464, rs150957860, rs145828067, rs747005144, rs374910442, rs138055273, rs183942200, rs11584340, and rs113136594) reported moderate to severe Scoring Atopic Dermatitis scores. Finally, the AD group and the AD plus M contagiosum skin infection group had a significant association with FLG mutations when compared with the control group (P < .01). CONCLUSION: FLG mutations are associated with early onset of AD, more severe clinical course of disease, and a significantly increased risk of M contagiosum sustained skin infection.

High mobility group box 1: Biomarker of inhaled corticosteroid treatment response in children with moderate-severe asthma.

BACKGROUND: High mobility group box 1 (HMGB1) is abnormally expressed in serum and sputum of patients with allergic asthma. OBJECTIVE: The aim of this study was to investigate the role of HMGB1 as guidance for treatment management of children with asthma. METHODS: Thirty children with asthma and 44 healthy children were enrolled. The patients were classified according to Global Initiative for Asthma Guideline disease severity criteria. Sputum HMGB1 levels and lung function index (percentage forced expiratory volume in 1 second [FEV1%]) were recorded in the cohort study at baseline (T0) and after 3 (T3) and 6 (T6) months of inhaled corticosteroids (ICS) treatment. RESULTS: Sputum HMGB1 levels were significantly higher in all the patients with asthma (p < 0.001). An inverse correlation between sputum HMGB1 levels and pulmonary function parameters was observed only in the children with moderate asthma (T0: FEV1%, r = -0.9891, p < 0.001; T3: FEV1%, r = -0.6763, p < 0.001; T6: FEV1%, r = -0.5419, p < 0.05) and in the children with severe asthma (T0: FEV1%, r = -0.8696, p < 0.001; T3: FEV1%, r = -0.6477, p < 0.05; T6: FEV1%, r = -0.8627, p < 0.001). After ICS treatment, a significant decrease of sputum HMGB1 levels was noted in moderate (T0 [93.44 ± 20.65 ng/mL] versus T3 [77.96 ± 1.81 ng/mL] versus T6 [67.75 ± 3.01 ng/mL]; p < 0.0001) and in the children with severe asthma (T0 [130.3 ± 7.48 ng/mL] versus T3 [156.9 ± 1.09 ng/mL] versus T6 [116.08 ± 4.77 ng/mL]; p < 0.0001) data are mean ± standard deviation, respectively. The area under the receiver operating characteristic curve, performed to define the diagnostic profile of sputum HMGB1 levels in identifying the children with asthma, was 0.713. CONCLUSION: In addition to the findings that HMGB1 is a sensitive biomarker of allergic asthma in children, our data demonstrated a significant correlation between the decrease of HMGB1 levels and a successful treatment response.

Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis.

Subjects affected by thalassemia major (TM) often have reduced bone mass and increased fracture risk. Strontium ranelate (SrR) is an effective treatment for postmenopausal and male osteoporosis. To date, no data exist on the use of SrR in the treatment of TM-related osteoporosis. Our aim was to evaluate the effects of SrR on bone mineral density (BMD), bone turnover markers and inhibitors of Wnt signaling (sclerostin and DKK-1). Twenty-four TM osteoporotic women were randomized to receive daily SrR 2 g or placebo in addition to calcium carbonate (1,000 mg) and vitamin D (800 IU). BMD at the lumbar spine and femoral neck, bone turnover markers (C-terminal telopeptide of procollagen type I [CTX], bone-specific alkaline phosphatase [BSAP]) and insulin-like growth factor-1 (IGF-1), sclerostin and DKK-1 were assessed at baseline and after 24 months. Back pain was measured by visual analog scale (VAS) every 6 months. After 24 months, TM women treated with SrR had increased their spine BMD values in comparison to baseline (p < 0.05). Moreover, they also exhibited a reduction of CTX and sclerostin levels (but not DKK-1) and exhibited an increase of BSAP and IGF-1 (p < 0.05); however, no significant changes were observed in the placebo group. In the SrR group, a reduction of back pain was observed after 18 months in comparison to baseline (p < 0.05) and after 24 months in comparison to placebo (p < 0.05). Our study reports for the first time the effects of SrR in the treatment of TM-related osteoporosis. SrR treatment improved BMD and normalized bone turnover markers, as well as lowering sclerostin serum levels.

Role of prebiotics and probiotics in pediatric diseases.

The increasing knowledge about the composition and activities of the microflora has shown the close link between the bacteria and the health of the human organism. For this reason it has focused attention on the possibility of modulating the gut flora. The use of probiotics and prebiotics has increased enormously in recent years, more for real beneficial effects demonstrated in patients than for their safety profiles. However, it is recorded an indiscriminate use also in conditions in which there are no scientific evidence to support. Their use in case of immunocompromised patients or with severe and debilitating chronic diseases should be very prudent, because of the risk of complications including sepsis. The use of a probiotic cannot ignore the knowledge of the genus and species of the strain and in pediatric patients has been demonstrated their role for treating acute viral gastroenteritis and preventing antibiotic-associated diarrhea in healthy children. Moreover probiotics are considered as an option for recurrent and relapsing antibiotic sensitive pouchitis and in select patients with mild ulcerative colitis. Further studies are needed to evaluate clinical conditions that may require their use and to define the optimal doses and intake durations.

Prevalence of Deafness-Associated Connexin-26 (GJB2) and Connexin-30 (GJB6) Pathogenic Alleles in a Large Patient Cohort from Eastern Sicily.

Mutations in the gene encoding the gap junction protein connexin 26 (GJB2) and connexin 30 (GJB6) have been shown to be a major contributor to prelingual, sensorineural, nonsyndromic deafness. The aim of this study was to characterize and establish the prevalence of GJB2 and GJB6 gene alterations in 196 patients affected by sensorineural, nonsyndromic hearing loss, from Eastern Sicily. We performed sequence analysis of GJB2 and identified sequence variants in 68 out of 196 patients (34.7%); (28 homozygous for c.35delG, 22 compound heterozygous and 11 with only one variant allele). We found 12 different allelic variants, the most prevalent being c.35delG, which was found on 89 chromosomes (65.5%), followed by other alleles with different frequencies (p.E47X, c.-23+1G>A, p.L90P, p.R184W, p.M34T, c.167delT, p.R127H, p.M163V, p.V153I, p.W24X, and p.T8M). Importantly, for the first time we present the frequency and spectrum of GJB2 mutations in NSHL patients from Eastern Sicily. No alterations were found in the GJB6 gene, confirming that alterations in this gene are uncommon in our geographic area. Note that 65.3% and 23.5% of our patients, respectively were found to be negative or carriers by GJB2 molecular screening. This emphasizes the need to broaden the genetic analysis to other genes involved in hearing loss.

Thalassaemia major and infectious risk: High Mobility Group Box-1 represents a novel diagnostic and prognostic biomarker.

High mobility group box -1 (HMGB1) represents a common causal agent for various types of diseases, including infective pathologies. This study aimed to investigate the role of HMGB1 in ß-thalassemia major (TM) by evaluating its diagnostic and prognostic role. Fifty-one TM patients and 30 healthy subjects (HS) were enrolled. Receiver operating characteristics (ROC) analysis was employed to calculate the area under the curve (AUC) for HMGB1 to determine the best cut-off values capable of identifying infectious episodes. Adjusted risk estimates for infective events were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Serum HMGB1 levels were higher in TM patients than in HS (14·6 ± 8·7 vs. 2·08 ± 0·9 ng/ml, P < 0·0001). Patients who underwent splenectomy were characterized by lower levels of HMGB1, when compared with patients with an intact spleen (10·2 ± 8 vs. 19·1 ± 7 ng/ml, P = 0·004). ROC analyses revealed an AUC for serum HMGB1 of 0·801, with a sensitivity and specificity of 92·3% and 68·2% to detect an infectious episode. Low HMGB1 levels predicted high risk of infective events (HR: 0·81; P = 0·006). HMGB1 represents a prognostic marker for TM patients and a predictive factor for infectious events.

Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2* MRI assessment.

INTRODUCTION: Endocrinopathies and metabolic disorders-characterized ß thalassemic (ßT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in ßT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. PATIENTS AND METHODS: Seventy-two ßT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan-Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. RESULTS: High ferritin levels were observed in patients with hypothyroidism [1500 (872.5-2336.5) µg/L], hypogonadism [878 (334-2010) µg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367-1857) µg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = -0.64; P:0.0006) and liver (r = -0.40; P:0.03) values was observed. Patients with ferritin values above 1800 µg/L experienced a significantly faster evolution to hypothyroidism [log-rank (χ(2) ):7.7; P = 0.005], hypogonadism [log-rank (χ(2) ):10.7; P = 0.001], and multiple endocrinopathies [log-rank (χ(2) ):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P < 0.0001). The intensification of chelation therapy led to an amelioration of hypothyroidism. CONCLUSIONS: Ferritin represents a prognostic marker for ßT patients and a predictive factor for progression to endocrine dysfunctions. Intensive chelation therapy allows the reversibility of hypothyroidism.

Sputum high mobility group box-1 in asthmatic children: a noninvasive sensitive biomarker reflecting disease status.

BACKGROUND: The monitoring of asthma is based mainly on clinical history, physical examination, and lung function test evaluation. To improve knowledge of the disease, new biomarkers of airway inflammation, including high mobility group box-1 (HMGB1), are being developed. OBJECTIVE: To evaluate sputum HMGB1 levels in children with stable, off-therapy, allergic asthma and to evaluate the relation between HMGB1 levels and lung function parameters. METHODS: Fifty children with asthma (28 boys and 22 girls, median age 11.56 ± 1.41 years) and 44 healthy children (22 boys and 22 girls, median age 11.07 ± 2.12 years) were enrolled. Sputum HMGB1 was assessed in the cohort study. Lung function (predicted percentage of forced expiratory volume in 1 second [FEV1%] and forced expiratory flow between 25% and 75% [FEF25%-75%]), serum total IgE levels, and asthma severity by validated Global Initiative for Asthma criteria were recorded. RESULTS: Sputum HMGB1 levels were higher in children with asthma than in healthy controls (100.68 ± 10.03 vs 9.60 ± 3.76 ng/mL, P < .0001). Sputum HMGB1 levels also were positively related to total IgE levels in children with asthma (r = 0.6567, P < .0001). An inverse and strict correlation between sputum HMGB1 levels and pulmonary function indices also were observed in children with mild (FEV1%, r = -0.86544, P < .0001; FEF25%-75%, r = -0.53948, P < .05), moderate (FEV1%, r = -0.99548, P < .0001; FEF25%-75%, r = -0.48668, P < .05), and severe (FEV1%, r = -0.90191, P < .0001; FEF25%-75%, r = -0.66777, P < .05) asthma. CONCLUSION: The present study provides evidence that sputum HMGB1 is a sensitive biomarker of allergic asthma in children because it was increased and correlated directly with asthma severity and inversely with lung function indices.

Mode of delivery and risk for development of atopic diseases in children.

Atopic diseases are a major public health problem worldwide, and several factors are thought to contribute to this rapid increase. The observed association between mode of delivery and risk of atopy in childhood has had a great deal of interest during the past few decades. In fact, even during delivery, exposure to antigens can index immune system in newborn, which induces the release of biologically active molecules, which are polarizing immune responses toward the T-helper 2 atopic profile. However, to date, studies on the relationship between mode of delivery and atopy have produced conflicting findings. The aim of this review was to summarize what is known about the relationship between mode of delivery and risk of atopic diseases in children. A literature search of electronic databases was undertaken for the major studies published from 1994 to today. The databases searched were PubMed, EMBASE, Medline, and Cochrane Library. The following key words were used: mode of delivery, cesarean section, vaginal delivery, atopy, and atopic diseases.

Serum interleukin 17, interleukin 23, and interleukin 10 values in children with atopic eczema/dermatitis syndrome (AEDS): association with clinical severity and phenotype.

To date cytokines profile in AEDS is poorly described in children. We evaluated the interleukin (IL)-17, IL-23, and IL-10 levels in atopic eczema/dermatitis syndrome (AEDS) children and healthy controls, in atopic AEDS (aAEDS) and nonatopic (naAEDS) subtypes and their relationship with disease severity. A total of 181 children with aAEDS and 93 healthy children were evaluated. According to the skin-prick test (SPT) for allergens and serum total IgE, all patients were subdivided in two groups: 104 aAEDS and 77 naAEDS. In all patients, serum IL-17, IL-23, and IL-10 levels were detected. Serum IL-17 and IL-23 levels were significantly higher, and serum IL-10 levels were significantly lower in AEDS children than healthy group (p < 0.001). Moreover, serum IL-17 and IL-23 levels were significantly higher in aAEDS than in naAEDS subtypes (p < 0.001). Differently, serum IL-10 levels resulted similar in both subtypes. There was a correlation between Score Atopic Dermatitis (SCORAD) index and both IL-17 and IL-23 and an inverse correlation between SCORAD index and IL-10 in aAEDS and naAEDS types. Serum IL-17 and IL-23 values were positively related to total IgE levels (p < 0.0001) in aAEDS. Further increase of IL-17 and IL-23 levels was detected in aAEDS subjects with atopic diseases such as asthma and rhinitis than children with only allergic sensitization. Our study confirms the role of IL-17, IL-23, and IL-10 and their relationship with the severity of AEDS. We firstly found a correlation between high IL-17/IL-23 axis levels and different phenotypes of AEDS in children, suggesting its role as marker of "atopic march" and disease severity.