Allergic Diseases and Chronic Adenotonsillar Diseases: A Mendelian Randomization Study.

OBJECTIVE: The existing epidemiological evidence regarding the intricate relationship between allergic diseases and chronic adenotonsillar diseases (CATD) remains inconclusive. Herein, the objective of our study is to explore the causal association using Mendelian randomization (MR). METHODS: Employing data from large genome-wide association studies, a comprehensive two-sample bidirectional MR study was conducted. The studied traits encompassed allergic rhinitis (cases n = 9707, controls n = 331173), allergic asthma (cases n = 8525, controls n = 193857), allergic conjunctivitis (cases n = 18321, controls n = 324178), atopic dermatitis (cases n = 11964, controls n = 306909), and CATD (cases n = 38983, controls n = 258553). All the patients were of European descent and participants in cohort studies. The primary analysis was executed using inverse-variance-weighted MR. Furthermore, six additional MR methods (MR-Egger, weighted median, simple mode, weighted mode, MR pleiotropy residual sum and outlier, MR robust adjusted profile score) were employed to ensure the reliability and detect potential horizontal pleiotropy within the results. The estimates obtained from the MR analysis were factored into the overall effect calculation. RESULTS: Genetically anticipated outcomes demonstrated a significant association between CATD risk and allergic rhinitis (OR = 1.141, p = 6.30E-06), allergic asthma (OR = 1.115, p = 8.31E-05), allergic conjunctivitis (OR = 1.197, p = 8.69E-07), and a suggestive association with atopic dermatitis (OR = 1.053, p = 0.040). However, no substantial correlation was observed in the reverse direction. CONCLUSIONS: Findings of our study provide evidence supporting a causal role of allergic diseases in the development of CATD, whereas the converse relationship does not appear to hold true. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2653-2658, 2024.

Deciphering the fate of slan+ -monocytes in human tonsils by gene expression profiling.

Monocytic cells perform crucial homeostatic and defensive functions. However, their fate and characterization at the transcriptomic level in human tissues are partially understood, often as a consequence of the lack of specific markers allowing their unequivocal identification. The 6-sulfo LacNAc (slan) antigen identifies a subset of non-classical (NC) monocytes in the bloodstream, namely the slan+ -monocytes. In recent studies, we and other groups have reported that, in tonsils, slan marks dendritic cell (DC)-like cells, as defined by morphological, phenotypical, and functional criteria. However, subsequent investigations in lymphomas have uncovered a significant heterogeneity of tumor-infiltrating slan+ -cells, including a macrophage-like state. Based on their emerging role in tissue inflammation and cancer, herein we investigated slan+ -cell fate in tonsils by using a molecular-based approach. Hence, RNA from tonsil slan+ -cells, conventional CD1c+ DCs (cDC2) and CD11b+ CD14+ -macrophages was subjected to gene expression analysis. For comparison, transcriptomes were also obtained from blood cDC2, classical (CL), intermediate (INT), NC, and slan+ -monocytes. Data demonstrate that the main trajectory of human slan+ -monocytes infiltrating the tonsil tissue is toward a macrophage-like population, displaying molecular features distinct from those of tonsil CD11b+ CD14+ -macrophages and cDC2. These findings provide a novel view on the terminal differentiation path of slan+ -monocytes, which is relevant for inflammatory diseases and lymphomas.

Differential chemokine expression patterns in tonsillar disease.

Expression profiles of CXC- and CC-chemokines in various forms of tonsillar disease were studied to evaluate whether certain chemokines play a predominant role in a specific subset of tonsillar disease. Total RNA was isolated from 89 biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory palatine tonsils and 27 chronic inflammatory palatine tonsils with histological prove of acute inflammation), reverse transcribed and subjected to PCR amplifying IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES. 2% agarose gel electrophoresis revealed a predominance of IL-8 in the chronic inflammatory palatine tonsil group compared to tonsillar hyperplasia. Furthermore, eotaxin-2 was strongly overexpressed in adenoid samples compared to chronic inflammatory specimens. Our data suggest that the majority of diseases related to adenoid formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory tonsillitis is associated with IL-8 upregulation. These data imply that adenoids are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based immune response.

The Psoriasis Risk Allele HLA-C*06:02 Shows Evidence of Association with Chronic or Recurrent Streptococcal Tonsillitis.

Pharyngeal tonsillitis is one of the most common upper respiratory tract infections, and group A streptococcus is the most important bacterial pathogen causing it. While most patients experience tonsillitis only rarely, a subset of patients suffers from recurrent or chronic tonsillitis or pharyngitis. The predisposing factors for recurring or chronic forms of this disease are not yet fully understood, but genetic predisposition has been suggested. A genetic association study using Illumina's Immunochip single-nucleotide polymorphism (SNP) array was performed to search for new genetic biomarkers in pharyngeal tonsillitis. More than 100,000 SNPs relevant to immune-mediated diseases were analyzed in a cohort of 95 patients subjected to tonsillectomy due to recurrent/chronic tonsillitis and 504 controls. Genetic association between the cases and controls showed strongest association with two peaks in the HLA locus (odds ratio [OR], 3.7 to 4.7; P = 4.9 × 10-6 to 5.7 × 10-6). Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele HLA-C*06:02 as a risk factor for tonsillitis (P = 4.8 × 10-4; OR, 2.3). In addition, the imputed HLA haplotype HLA-C*06:02/HLA-B*57:01, a reported risk haplotype in psoriasis, had the strongest risk for tonsillitis (P = 3.2 × 10-4; OR, 6.5). These findings further support the previously reported link between streptococcal throat infections and psoriasis.

[Clinical and genetic analysis of 11 cases with periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome].

Objective: To investigate the clinical, inflammatory and genetic characteristics of cases with periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Methods: Clinical and inflammatory manifestations and gene sequencing of 11 cases with PFAPA were retrospectively analyzed. Inflammatory markers including white blood cell (WBC) , C reactive protein (CRP) , and serum amyloid A (SAA) were compared between febrile period and intermittent period. Fifteen normal children were taken as healthy controls. The levels of plasma inflammatory cytokines including interleukin(IL)1ß, IL-6, IL-17, tumor necrosis factor(TNF)-α, interferon (IFN)-γ, and granulocyte-colony stimulating factor(G-CSF) were compared between febrile period and intermittent period with paired-sample t test, and compared between febrile cases and healthy controls with independent t test. Results: A total of 11 cases (7 females and 4 males) were included. The median onset age was 24 (3-60) months, and the median age of diagnosis was 69 (11-151) months. The median febrile duration was 4 (1-8) days, and the intermittent period lasted 1 to 8 weeks. All the cases had periodic fever and pharyngitis/tonsillitis, 7 of whom had combined lymphadenitis, and 5 of whom suffered from oral ulcers. Compared to intermittent-period-status,WBC ((14.7±4.1) ×10(9)/L vs. (8.4±1.9) ×10(9)/L, P<0.05), CRP((24.2±21.1) vs. (3.3±2.1)mg/L, P<0.05), SAA ((136.4±47.7) vs. (7.1±1.1)mg/L, P<0.05) were significantly elevated in febrile period. Compared to intermittent-period-status and healthy controls, plasma levels of IL-6 ((38±10) vs. (8±4) and (8±5)ng/L, t=6.514 and 6.830 respectively, P<0.05), IFN-γ ((132±43) vs.(49±21) and (53±21)ng/L, t=4.069 and 4.276 respectively, P<0.05), G-CSF ((403±12) vs. (175±90) and (121±49)ng/L, t=4.219 and 9.047 respectively, P<0.05) were significantly higher in febrile period, while no differences were found in levels of IL-1ß, IL-17 and TNF-α. Gene sequencing found MEFV gene heterozygous variation in 8 cases. Conclusions: PFAPA often manifests as periodic fever, pharyngitis, tonsillitis, aphthous stomatitis and adenitis. Gene sequencing analysis, detection of inflammation markers and cytokines could help with the diagnose of this disease.

Detection of GSK-3ß activation index in pediatric chronic tonsillitis is an indicator for chronic recurrent inflammation.

PURPOSE: Chronic tonsillitis (TC) is among the most common bacterial diseases in pediatric otolaryngology. We aimed to evaluate the expression of glycogen synthase kinase 3ß (GSK-3ß) in a cohort of children with chronic tonsillitis (TC), and the correlation between GSK-3ß activity index and inflammatory profiles of TC. MATERIALS AND METHODS: The expression of GSK-3ß was comparably evaluated between children with TC (n = 26) and tonsillar hypertrophy (TH, n = 26). GSK-3ß expression was detected by immunohistochemistry, RT-qPCR, and Western blot. The inflammatory profiles between the TC and TH groups were also evaluated. RESULTS: We found that while GSK-3ß was highly expressed in both TC and TH groups, no significant difference were detected at mRNA and protein levels between groups. The protein level of p-GSK-3ß was significantly lower in the TC group as compared to the TH group. Additionally, the inflammatory markers, including NF-κB, T-bet, and IFN-γ were higher in the TC group compared to TH group. The GSK-3ß activation index was positively correlated with the levels of NF-κB, T-bet, and IFN-γ in the TC group. CONCLUSIONS: Our findings suggested that GSK-3ß activation index was demonstrated to be a clinically applicable indicator for chronic recurrent inflammation in pediatric TC.

STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles.

A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57- PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57- PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-function STAT3 mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1hi cells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.

Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections.

Infectious diseases have a profound impact on our health and many studies suggest that host genetics play a major role in the pathogenesis of most of them. We perform 23 genome-wide association studies for common infections and infection-associated procedures, including chickenpox, shingles, cold sores, mononucleosis, mumps, hepatitis B, plantar warts, positive tuberculosis test results, strep throat, scarlet fever, pneumonia, bacterial meningitis, yeast infections, urinary tract infections, tonsillectomy, childhood ear infections, myringotomy, measles, hepatitis A, rheumatic fever, common colds, rubella and chronic sinus infection, in over 200,000 individuals of European ancestry. We detect 59 genome-wide significant (P < 5 × 10-8) associations in genes with key roles in immunity and embryonic development. We apply fine-mapping analysis to dissect associations in the human leukocyte antigen region, which suggests important roles of specific amino acid polymorphisms in the antigen-binding clefts. Our findings provide an important step toward dissecting the host genetic architecture of response to common infections.Susceptibility to infectious diseases is, among others, influenced by the genetic landscape of the host. Here, Tian and colleagues perform genome-wide association studies for 23 common infections and find 59 risk loci for 17 of these, both within the HLA region and non-HLA loci.

The carriage of interleukin-1B-31*C allele plus Staphylococcus aureus and Haemophilus influenzae increases the risk of recurrent tonsillitis in a Mexican population.

The aim of the present study was to estimate the relative contribution of immunogenetic and microbiological factors in the development of recurrent tonsillitis in a Mexican population. Patients (n = 138) with recurrent tonsillitis and an indication of tonsillectomy (mean age: 6.05 years ± 3.00; median age: 5 years, female: 58; age range: 1-15 years) and 195 non-related controls older than 18 years and a medical history free of recurrent tonsillitis were included. To evaluate the microbial contribution, tonsil swab samples from both groups and extracted tonsil samples from cases were cultured. Biofilm production of isolated bacteria was measured. To assess the immunogenetic component, DNA from peripheral blood was genotyped for the TNFA-308G/A single-nucleotide polymorphism (SNP) and for the IL1B -31C/T SNP. Normal microbiota, but no pathogens or potential pathogens, were identified from all control sample cultures. The most frequent pathogenic species detected in tonsils from cases were Staphylococcus aureus (48.6%, 67/138) and Haemophilus influenzae (31.9%, 44/138), which were found more frequently in patient samples than in samples from healthy volunteers (P < 0.0001). Importantly, 41/54 (75.9%) S. aureus isolates were biofilm producers (18 weak and 23 strong), whereas 17/25 (68%) H. influenzae isolates were biofilm producers (10 weak, and 7 strong biofilm producers). Patients with at least one copy of the IL1B-31*C allele had a higher risk of recurrent tonsillitis (OR = 4.03; 95% CI = 1.27-14.27; P = 0.013). TNFA-308 G/A alleles were not preferentially distributed among the groups. When considering the presence of IL1B-31*C plus S. aureus, IL1B-31*C plus S. aureus biofilm producer, IL1B-31*C plus H. influenzae or IL1B-31*C plus H. influenzae biofilm producer, the OR tended to infinite. Thus, the presence of IL1B-31*C allele plus the presence of S. aureus and/or H. influenzae could be related to the development of tonsillitis in this particular Mexican population.

Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerular disease, in which the mucosal immune response elicited particularly in the tonsils or intestine has been estimated to be involved in the development of the disease. To explore the relationship between IgAN and bacterial flora in the tonsils, we conducted a comprehensive microbiome analysis. METHODS: We enrolled 48 IgAN patients, 21 recurrent tonsillitis (RT) patients without urine abnormalities and 30 children with tonsillar hyperplasia (TH) who had undergone tonsillectomy previously. Genomic DNA from tonsillar crypts of each patient was extracted, and V4 regions of the 16S ribosomal RNA gene were amplified and analysed using a high-throughput multiplexed sequencing approach. Differences in genus composition among the three study groups were statistically analysed by permutational multivariate analysis of variance and visualized by principal component analysis (PCA). RESULTS: Substantial diversity in bacterial composition was detected in each sample. Prevotella spp., Fusobacterium spp., Sphingomonas spp. and Treponema spp. were predominant in IgAN patients. The percentage of abundance of Prevotella spp., Haemophilus spp., Porphyromonas spp. and Treponema spp. in IgAN patients was significantly different from that in TH patients. However, there was no significant difference in the percentage of abundance of any bacterial genus between IgAN and RT patients. PCA did not distinguish IgAN from RT, although it discriminated TH. No significant differences in microbiome composition among the groups of IgAN patients according to clinicopathological parameters were observed. CONCLUSIONS: Similar patterns of bacteria are present in tonsillar crypts of both IgAN and RT patients, suggesting that the host response to these bacteria might be important in the development of IgAN.

HLA-Cw6 homozygosity in plaque psoriasis is associated with streptococcal throat infections and pronounced improvement after tonsillectomy: A prospective case series.

BACKGROUND: Carriage of the HLA-Cw*0602 allele is associated with a particular set of clinical features and treatment responses in psoriasis. Tonsillectomy can improve psoriasis. OBJECTIVES: We sought to evaluate whether HLA-Cw*0602 predicts a favorable outcome after tonsillectomy of patients with psoriasis. METHODS: This prospective case series followed up 28 tonsillectomized patients with plaque psoriasis for 24 months. The Psoriasis Area and Severity Index, Psoriasis Disability Index, and Psoriasis Life Stress Inventory were used for assessment. Tonsils were swabbed for bacteria and patients genotyped for HLA-Cw*0602. RESULTS: After tonsillectomy, HLA-Cw*0602 homozygotes showed significantly more improvement, compared with heterozygous and HLA-Cw*0602-negative patients. Thus, Psoriasis Area and Severity Index score was reduced by 82% in the homozygous patients compared with 42% and 31%, respectively (P < .001), Psoriasis Disability Index score improved by 87% compared with 38% and 41%, respectively (P < .001), and Psoriasis Life Stress Inventory score was 82% reduced compared with 60% and 54%, respectively (P < .001). The homozygotes more often had psoriasis onset associated with a throat infection (P = .007) and an increased frequency of streptococcal throat infections per lifetime (P = .038). LIMITATIONS: Few patients were included and some data were retrospective. CONCLUSIONS: Homozygous HLA-Cw*0602 carriage in plaque psoriasis may predict a favorable outcome after tonsillectomy.

Lactoferrin gene polymorphisms in Italian patients with recurrent tonsillitis.

INTRODUCTION: Recurrent tonsillitis is an oral pathology characterized by inflammation of tonsils. The disease susceptibility depends upon environmental and host factors, specifically the innate immune response, the first line of host defence could play an important role. Among innate immunity members, lactoferrin, known for its antimicrobial properties, was previously correlated with the risk of oral pathology as periodontitis and dental caries. METHODS: 89 Italian children presenting recurrent tonsillitis and 95 healthy children were genotyped for two LTF non-synonymous polymorphisms, called Thr29Ala and Arg47Lys, in order to investigate their potential role in recurrent tonsillitis susceptibility. RESULTS: no different allele, genotype and haplotype frequency distributions were detected comparing patients and controls. CONCLUSION: data from the current study indicate that LTF polymorphisms might not be involved in recurrent tonsillitis development in our Italian population. However, since the importance of lactoferrin in oral immunity has been previously assessed, further studies should be necessary to unravel the potential role of LTF genetic variants in oral cavity.

FCN2 c.772G>T polymorphism is associated with chronic adenoiditis and/or tonsillitis, but not -4 A>G and -602 G>A.

OBJECTIVE: Ficolins are complement activating peptides that play a role in the initial host defense against infectious pathogens. In the present study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in the ficolin 2 gene (FCN2) and chronic adenotonsillitis in pediatric cases. STUDY DESIGN: Case-control study. METHODS: A total of 101 pediatric patients diagnosed with chronic adenotonsillitis and 100 healthy children were enrolled in the study. Genotypes of FCN2 promoter SNPs - 602 G>A and -4 A>G, and the exonic SNP c.772G>T were determined by light SNP assay after realtime PCR analysis using genomic DNA samples obtained from peripheral blood samples of all participants. RESULTS: Of the 101 chronic tonsillitis patients, 38 were girls and 63 were boys; the mean age was 5.2 ± 2.3 years. The c.772G>T SNP frequency was significantly higher in chronic adenotonsillitis cases compared to the control group (p = 0.00); however, no significant difference was determined at positions -602 G>A or -4 A>G (p > 0.05). CONCLUSIONS: The FCN2 c.772G>T genotype appears to be associated with predisposition to chronic adenotonsillitis in the pediatric age group. This nucleotide change is likely to influence the level of gene expression and contribute to the development of disease.

Different Patterns of Acetylation and Dimethylation of Histone H3 between Young and Aged Cases with Chronic Tonsillitis: Influences of Inflammation and Aging.

INTRODUCTION: Epigenetics is now considered to be crucially involved in normal genetics and differentiation and in pathological conditions, such as cancer, aging, and inflammation. Epigenetic mechanisms involve DNA methylation and histone modifications. The purpose of this study was to investigate the effects of inflammation on epigenetics in young subjects and the effect of aging. MATERIALS AND METHODS: The palatine tonsils were extracted from child and adult patients with chronic tonsillitis. Hematoxylin-eosin staining was performed to examine the morphology of the palatine tonsils. A fluorescence immunological examination was also performed to detect acetyl-histone H3 or dimethyl-histone H3. Confocal scanning microscopy was used for observations. RESULTS: Acetylated histone H3 was detected in tonsils from child patients but not from adult patients. Dimethylated histone H3 was not detected in tonsils from either group of patients. Degeneration of the tonsillar structures was apparent in tonsils from adult patients. DISCUSSION: The differential expression of acetylated histone H3 Lys9 may reflect immunological differences between young and aged tonsils. The decrease observed in the activity of histone methyltransferase induced the down-regulated expression of methylated histone H3. CONCLUSION: Our results suggest that epigenetic changes participate in chronic inflammation and aging in the palatine tonsils. Although the results do not lead to a direct treatment, the epigenetic pathogenesis of chronic inflammation, such as immunoglobulin A nephropathy, by focal infections will be described in greater detail in future studies, which will lead to new treatments being developed.

Expression and Localization of Human Defensins in Palatine Tonsils.

Defensins are small antimicrobial peptides and effector components of innate immune responses. Recent studies have shed light on their beneficial functions for the prevention of infection and potential for development of new drugs. Here, we showed the expression profiles of human defensins in palatine tonsils with 3 different diseases: tonsillar hypertrophy, recurrent tonsillitis and focal infection of the tonsil. RT-PCR analysis and immunofluorescence revealed that the expression of human α-defensin 4 and ß-defensin 3 (ß3) in palatine tonsils with tonsillar hypertrophy was lower than that in recurrent tonsillitis and focal infection of the tonsil, suggesting that chronic inflammation induces defensin expression. Interestingly, ß2 and ß3 mRNAs were specifically expressed by palatine tonsil tissues but not in human peripheral blood mononuclear cells and mucosa of the small intestine. Additionally, we observed that exposure to a Toll-like receptor 4 ligand, lipopolysaccharide, which is used as a bacterial infection model, increases the production of ß2 in culture supernatants from tonsillar epithelial cells in a dose-dependent manner. Taken together, these results indicate that ß2 produced by tonsillar epithelial cells plays an important role in the innate immune response for bacterial infections.

DEFB1 polymorphisms and susceptibility to recurrent tonsillitis in Italian children.

INTRODUCTION: The tonsils are secondary lymphoid organs fundamental for immune system response against pathogens within the oral cavity. Tonsillitis refers to inflammation of the pharyngeal tonsils that may include the adenoids and the lingual tonsils and that can be acute, recurrent, and chronic. Viral or bacterial infections, as well as immunologic factors are the main trigger to tonsillitis and disease's chronicity: the host immune responses, especially the innate one, could play an important role in susceptibility to the disease. OBJECTIVES: The current study aims at investigating the role of functional polymorphisms in the 5'UTR (c.-52G>A, c.-44G>C and c.-20G>A) of DEFB1 gene, encoding for the antimicrobial peptide human beta-defensin 1, in the predisposition to recurrent tonsillitis in children from North Eastern Italy. RESULTS: No significant correlation was found between DEFB1 allele, genotype and haplotype frequencies and recurrent tonsillitis susceptibility with the exception of an increased risk to disease development in patients carrying DEFB1 rare haplotypes. CONCLUSION: Our results may suggest that DEFB1 polymorphisms alone may not influence pathology susceptibility, however they could possibly concur, together with other factors involved in the genetic control of innate immune system, in the predisposition towards recurrent tonsillitis.

Proteolytic processing of the streptococcal IgG endopeptidase IdeS modulates the functional properties of the enzyme and results in reduced immunorecognition.

The important human gram positive bacterial pathogen Streptococcus pyogenes employs various virulence factors to promote inflammation and to facilitate invasive disease progression. In this study we explored the relation of the secreted streptococcal cysteine proteases IdeS and SpeB, and neutrophil (PMN) proteases. We found that SpeB is resistant to proteolytic attack in an inflammatory environment, emphasizing the importance of SpeB for streptococcal pathogenicity, while PMN enzymes and SpeB itself process the IgG degrading endopeptidase IdeS. Processing occurs as NH2-terminal cleavage of IdeS resulting in reduced immunorecognition of the protease by specific antibodies. While the endopeptidase retains IgG cleaving activity, its ability to suppress the generation of reactive oxygen species is abolished. We suggest that the cleavage of NH2-terminal peptides by SpeB and/or neutrophil proteases is a mechanism evolved to prevent early inactivation of this important streptococcal virulence factor, albeit at the cost of impaired functionality.

Actualización del sistema de codificación diagnóstica de la Sociedad Española de Urgencias de Pediatría / An update of the diagnostic coding system by the Spanish Society of Pediatric Emergencies

Se presenta la actualización del listado de codificación diagnóstica de la Sociedad Española de Urgencias de Pediatría (SEUP) que ha realizado el Grupo de Trabajo de Calidad de dicha Sociedad. El listado original fue elaborado y publicado en ANALES DE PEDIATRÍA el año 2000, basándose en la edición existente en aquel momento del sistema de codificación internacional CIE-9-MC. Siguiendo la misma metodología utilizada en aquel momento, y basándose en la edición del año 2014 del CIE-9-MC, se han añadido el listado 35 nuevos códigos, se han actualizado 15 y se ha añadido un listado de referencia con los diagnósticos traumatológicos más frecuentes en pediatría. El listado de diagnósticos SEUP actual refleja los importantes cambios experimentados por los Servicios de Urgencia Pediátricos en el último decenio (AU)

The Quality Working Group of the Spanish Society of Pediatric Emergencies (SEUP) presents an update of the diagnostic coding list. The original list was prepared and published in ANALES DE PEDIATRÍA in 2000, being based on the International Coding system ICD-9-CM current at that time. Following the same methodology used at that time and based on the 2014 edition of the ICD-9-CM, 35 new codes have been added to the list, 15 have been updated, and a list of the most frequent references to trauma diagnoses in pediatrics have been provided. In the current list of diagnoses, SEUP reflects the significant changes that have taken place in Pediatric Emergency Services in the last decade (AU)

DNA damage and oxidative status in PFAPA syndrome.

OBJECTIVE: PFAPA syndrome is a clinical entity of unknown etiology which presents with periodic episodes of fever, aphthous stomatitis, tonsillitis or pharyngitis, and cervical adenitis. In this study we investigated DNA damage and the oxidative stress parameters in patients diagnosed with PFAPA, to elucidate the underlying pathophysiological mechanism of this syndrome. METHODS: Thirty-one patients diagnosed with PFAPA (Group 1), 22 patients diagnosed with normal tonsillitis or pharyngitis (Group 2), and 20 healthy volunteers (Group 3) were included in our study. Heparinized peripheral blood samples were drawn from all patients and volunteers. DNA damage was assessed by single cell alkaline electrophoresis assay in peripheral mononuclear leukocytes. Plasma levels of total antioxidant status (TAS) and total oxidative status (TOS) were determined by using a novel automated measurement method, and oxidative stress index (OSI) was calculated. RESULTS: DNA damage in the mononuclear leukocytes of Group 1 was significantly higher than that of Group 2 and Group 3. The oxidative stress parameters revealed that the TOS and OSI values of Group 1 were significantly higher than those of Group 2 and Group 3. TAS values of Group 1 were significantly lower than those of Group 2 and Group 3. Correlation analysis of Group 1 demonstrated a significant correlation between TOS, one of the oxidative stress parameters, and DNA damage. Correlations between DNA damage and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were also significant. CONCLUSION: Our study indicated that both the inflammatory and the oxidative stress parameters were significantly increased in patients with PFAPA syndrome, accompanied by a significant positive correlation between DNA damage and oxidative stress.

Chronic tonsillitis is not associated with beta defensin 1 gene polymorphisms in Turkish population.

BACKGROUND: Defensins are antimicrobial peptides expressed on mucosal surfaces. They function as part of the innate immune system. Palatine tonsils play important roles in innate immune system. However, our knowledge on the pathophysiology of chronic tonsils is limited. OBJECTIVE: The aim of this study was to investigate the association between beta defensin 1 gene single nucleotide polymorphisms and chronic tonsillitis. STUDY DESIGN: Prospective, non-randomized, controlled clinical study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Eighty six patients with chronic tonsillitis and eighty controls without history of chronic tonsillitis were enrolled in this study. Genotypes were determined by restriction fragment length polymorphism analyses after polymerase chain reaction. RESULTS: Genotype and allele frequencies of the -20G/A (rs11362), -44C/G (rs1800972) and -52G/A (rs1799946) single nucleotide polymorphisms were not statistically different between patients and control groups (p>0.05). CONCLUSION: In this study, we found that DEFB1 gene -20G/A, -44C/G and -52G/A single nucleotide polymorphisms were not associated with chronic tonsillitis. Studies, which analyse other polymorphism of the beta defensin 1 gene in large case series, should be conducted to understand the role of DEFB1 gene on chronic tonsillitis.