Comparison of treatment modalities for non-tuberculous mycobacterial cervicofacial lymphadenitis in children.

PURPOSE: We aim to compare the different treatment modalities of non-tuberculous cervicofacial lymphadenitis in children, by means of a retrospective study conducted in the University Hospitals of Leuven of patients treated between 2012 and 2022. METHODS: For this retrospective cohort study, data were collected and pseudonimised from 52 patients with non-tuberculous cervicofacial lymphadenitis, who were treated in our hospital between January 2012 and December 2022, either conservatively, antibiotically, surgically, or with a combination of these options. We only included patients who were considered immunocompetent. All of the included patients were below 10 years at time of treatment. We collected data regarding time to resolution and adverse effects, i.e., skin discoloration, excessive scar formation, fistula formation, persistence of adenopathies after treatment, need for additional treatment, facial nerve paresis/paralysis, or systemic side-effects due to antibiotic treatment. RESULTS: The mean time to resolution (in days) when looking at primary treatments, was shortest in partial excisions (16), followed by complete excisions (19), antibiotic therapy (129), incision and drainage (153), curettage (240), and finally conservative management (280). Taking into account isolated treatments (i.e., both primary and adjuvant), we also observed consistently faster time to resolution in surgical and antibiotic treatments when compared to conservative treatment. Antibiotic therapy (p = 0.003), incision and drainage (p = 0,004) were associated with a significantly higher need for adjuvant treatment. Curettage was associated with a higher incidence of fistula formation (p = 0,006) and higher number of adjuvant treatments (p = 0,002). CONCLUSIONS: This study shows a faster resolution of nontuberculous mycobacterial cervicofacial lymphadenitis in children when treated surgically, more specifically when treated with partial or complete lymph node excision. Antibiotic treatment also leads to faster resolution than conservative management. There was a low rate of complications, and no permanent facial nerve damage was reported.

[How I treat : airway obstruction in children with sequence of Pierre Robin]. / Comment je traite l'obstruction respiratoire chez l'enfant atteint d'une séquence de Pierre Robin.

Pierre Robin sequence (PRS) is described as a triad of micrognathia, glossoptosis and cleft palate. This sequence may be isolated or associated with a genetic syndrome in half of the cases. Main complications affect respiratory function and the upper digestive tract. Respiratory obstruction can arise as soon as in the first hours of life and may be life-threatening if no early appropriate management is implemented. PRS is phenotypically variable and the required treatment varies accordingly: some patients will be relieved with prone positioning alone while others will benefit from nasopharyngeal tube, CPAP ("Continuous Positive Airway Pressure") or rarely surgery. In this article, we describe a clinical case and then discuss the available therapeutic strategies.

La séquence de Pierre Robin associe un rétrognatisme, une glossoptose et une fente palatine. Elle est isolée ou liée à un syndrome génétique dans la moitié des cas. Les complications sont principalement respiratoires et digestives. L'obstruction respiratoire peut se manifester dès les premières heures de vie et altérer la vie de l'enfant en l'absence d'une prise en charge précoce. Le degré de sévérité peut varier d'un enfant à l'autre et, alors que certains patients seront soulagés avec une position ventrale, d'autres nécessiteront un tube naso-pharyngé, une ventilation en pression positive continue (CPAP) ou, plus rarement, une intervention chirurgicale. Dans cet article, nous décrivons un cas clinique, puis nous rediscutons de l'ensemble des possibilités thérapeutiques.

A Comprehensive Craniofacial Study of 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) is one of the most frequent microdeletion syndromes and presents with a highly variable phenotype. In most affected individuals, specific but subtle facial features can be seen. In this observational study, we aim to investigate the craniofacial and dental features of 20 children with a confirmed diagnosis of 22q11.2DS by analyzing 3-dimensional (3D) facial surface scans, 2-dimensional (2D) clinical photographs, panoramic and cephalometric radiographs, and dental casts. The 3D facial scans were compared to scans of a healthy control group and analyzed using a spatially dense geometric morphometric approach. Cephalometric radiographs were digitally traced, and measurements were compared to existing standards. Occlusal and dental features were studied on dental casts and panoramic radiographs. Interestingly, a general trend of facial hypoplasia in the lower part of the face could be evidenced with the 3D facial analysis in children with 22q11.2DS compared to controls. Cephalometric analysis confirmed a dorsal position of the mandible to the maxilla in 2D and showed an enlarged cranial base angle. Measurements for occlusion did not differ significantly from standards. Despite individual variability, we observed a retruded lower part of the face as a common feature, and we also found a significantly higher prevalence of tooth agenesis in our cohort of 20 children with 22q11.2DS (20%). Furthermore, 3D facial surface scanning proved to be an important noninvasive, diagnostic tool to investigate external features and the underlying skeletal pattern.

Novel IRF6 Mutations Detected in Orofacial Cleft Patients by Targeted Massively Parallel Sequencing.

Common variants in interferon regulatory factor 6 ( IRF6) have been associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) as well as with tooth agenesis (TA). These variants contribute a small risk towards the 2 congenital conditions and explain only a small percentage of heritability. On the other hand, many IRF6 mutations are known to be a monogenic cause of disease for syndromic orofacial clefting (OFC). We hypothesize that IRF6 mutations in some rare instances could also cause nonsyndromic OFC. To find novel rare variants in IRF6 responsible for nonsyndromic OFC and TA, we performed targeted multiplex sequencing using molecular inversion probes (MIPs) in 1,072 OFC patients, 67 TA patients, and 706 controls. We identified 3 potentially pathogenic de novo mutations in OFC patients. In addition, 3 rare missense variants were identified, for which pathogenicity could not unequivocally be shown, as all variants were either inherited from an unaffected parent or the parental DNA was not available. Retrospective investigation of the patients with these variants revealed the presence of lip pits in one of the patients with a de novo mutation suggesting a Van der Woude syndrome (VWS) phenotype, whereas, in other patients, no lip pits were identified.

Postoperative recovery in children after outpatient ENT surgery.

OBJECTIVE: To provide a comprehensive description of postoperative recovery after routine outpatient ENT procedures in children and to compare parental estimations to the child's self-reported ratings of postoperative pain. METHODS: For 14 days after surgery, we monitored pain, nausea or vomiting, problems with eating and fluid intake, sleep disturbances, behavioral changes, emotional impact, other types of discomfort, rehospitalization, and duration to full recovery, based on diary entries and telephone calls. RESULTS: 69 children and their parents participated. After inserting ventilation tubes, the average recovery time was 4.6 days. Symptoms were most intense during the first three days. Participants mainly reported pain, behavioral changes, and emotional impact. After more extensive ENT surgery (adenoidectomy and/or tonsillectomy, with or without insertion of ventilation tubes), the average recovery time was 6.2 days, and pain was more severe and longer-lasting. Apart from nausea or vomiting during the first three days, participants frequently reported behavioral changes, emotional impact, and sleep disturbances. Problems with eating and fluid intake were most prevalent. Pain scores reported by parents differed from the scores reported by their children; parents both underestimated and overestimated their child's pain. CONCLUSION: This study provided descriptions of postoperative recovery after outpatient ENT surgery in children. This information is indispensable for preparing the child and parents and for ensuring accurate follow-up. Recovery varied with the type of surgery. Mainly, postoperative discomfort was most severe after adenoidectomy and/or tonsillectomy. Parents tended to give inaccurate estimates of their child's pain. Self-reports from children should be considered the gold standard.

Review: Facial endophenotypes in non-syndromic orofacial clefting.

Cleft lip and/or palate (CL/P) is one of the most frequent congenital malformations, with a frequency of 1 in 700 live births. Non-syndromic orofacial clefting is a multifactorial condition, with both a genetic and an environmental component. Although numerous studies have been published addressing the genetic etiology of CL/P, this factor remains incompletely understood. A promising approach to find candidate gene regions for CL/P is the investigation of endophenotypes, which are characteristics associated with a certain condition and that can be an expression of underlying susceptibility genes. This review focuses on the known facial endophenotypes in CL/P (such as distortion of the orbicularis oris muscle and facial features in non-affected relatives of patients with CL/P) and genes that could be associated with these characteristics. Possibilities for further endophenotype-related studies in the field of non-syndromic CL/P are discussed.

Surgery for velopharyngeal insufficiency: The outcomes of the University Hospitals Leuven.

OBJECTIVES: We reviewed the outcomes of patients who underwent a velopharyngoplasty and subsequent speech therapy for velopharyngeal insufficiency (VPI) to determine possible prognostic variables. METHODS: During the period 2002-2010, 91 patients with VPI underwent a velopharyngoplasty (either the Honig velopharyngoplasty, the modified Honig velopharyngoplasty or the Hynes pharyngoplasty). Of these, 62 had complete data for long-term evaluation of speech outcome and analysis of variables potentially influencing this outcome. Speech outcome was assessed using five criteria that were evaluated pre- and postoperatively: hypernasality, nasal emission, facial grimacing, retro-articulation and glottal stops. The former two variables were transformed into a semi-objective nasality index (NI), the latter three variables were assembled to form a subjective articulation index (AI). Prognostic variables for outcome that were studied included age at velopharyngoplasty, associated 22q11.2 deletion syndrome, intervention type, primary or secondary surgery and pre-intervention speech therapy. RESULTS: Before surgery, based on the NI, 15 patients had mild VPI and 44 patients had moderate to severe VPI. Postoperatively at 12 months, 46 patients had a good speech outcome (normal or mild VPI), 13 patients had moderate VPI and no more severe VPI was observed. The overall success rate of 78% after one year increased to 90% in the long-term (median 27 months) with further speech therapy. Patients without the diagnosis of 22q11.2 deletion syndrome had better speech outcomes than patients with the syndrome. No statistically significant effect of the age at velopharyngoplasty on speech outcome was found. No cases of sleep apnea syndrome were reported. CONCLUSIONS: Our protocol of patient tailored surgical interventions and further postoperative speech therapy results in good speech outcomes, with no or only mild remaining VPI for the majority of patients. The correction of VPI is more difficult for the subgroup of patients with 22q11.2 deletion syndrome.

Facial Characteristics and Olfactory Dysfunction: Two Endophenotypes Related to Nonsyndromic Cleft Lip and/or Palate.

Evidence exists for the presence of a specific facial phenotype in nonaffected first-degree relatives of persons with CL/P. An increased risk for olfactory dysfunction has also been reported in CL/P-relatives. These phenotypic features can probably be explained via the presence of CL/P-related susceptibility genes. We aimed at confirming the occurrence of these endophenotypic traits in first-degree CL/P-relatives, and we investigated the link between the facial phenotype and the smell capacity in this group. We studied the facial morphology of 88 nonaffected first-degree relatives of patients with CL/P and 33 control subjects without family history of facial clefting by 3D surface imaging and a spatially dense analysis of the images. Smell testing was performed in 30 relatives and compared with 23 control subjects. Nonaffected relatives showed midface retrusion, hypertelorism, and olfactory dysfunction, compared to controls. In addition, we show for the first time that olfactory dysfunction in relatives is correlated to a smaller upper nasal region. This might be explained by a smaller central olfactory system. The different facial morphology in the relatives with olfactory impairment as compared to the total group may be an illustration of the contribution of different genetic backgrounds to the occurrence of CL/P via different biological pathways.

Pierre Robin sequence: Management of respiratory and feeding complications during the first year of life in a tertiary referral centre.

OBJECTIVES: To review early clinical manifestations of Pierre Robin sequence (PRS) and their management during the first year of life in the University Hospitals Leuven. METHODS: Retrospective series of 48 patients with PRS born between 2001 and 2011 and treated at a tertiary referral hospital. Review of the current literature about management of respiratory and breathing difficulties in the early life of PRS patients. RESULTS: Of our cleft palate patients 15.3% presented with PRS. A syndrome was diagnosed in 14.6%, associated anomalies without a syndromic diagnosis in 56.3% and isolated PRS in 29.2% of the cases. Mortality rate directly related to PRS was 2.1%. Respiratory difficulties were observed in 83.3% and feeding difficulties in 95.6% of the patients. Respiratory problems were addressed in a conservative way in 75%, in a non-surgical invasive way in 42.5% and in a surgical way in 12.5%. A statistically significant relationship between the association of a syndrome or other anomalies, and a higher need for resuscitation and invasive treatment were found (chi-square test, p-values=0.019 and 0.034). Feeding difficulties were managed conservatively in 91.3%, invasively in 80.4% and surgically in 15.2%. CONCLUSIONS: PRS is frequently associated with other abnormalities or syndromes. Therefore routine screening for associated anomalies in neonates with PRS is recommendable. Respiratory and feeding complications are highly frequent and possibly severe, particularly in patients with associated anomalies or syndromes, and should be recognized and addressed appropriately in an early stage. There is a potential role for the nasopharyngeal airway in reducing the need for the more traditional surgical interventions for respiratory problems.

Palate lengthening by buccinator myomucosal flaps for velopharyngeal insufficiency.

OBJECTIVE : To assess the outcome of palate lengthening by myomucosal buccinator flaps for velopharyngeal insufficiency both in terms of speech and changes in palate length. DESIGN : Thirty-two consecutive patients who underwent the buccinator flap procedure were reviewed retrospectively. Palate length and the presence or absence of a velopharyngeal gap were assessed on pre- and postoperative videofluoroscopic recordings using a calibrated image analysis system. Hypernasality, nasal emission, nasal turbulence, and passive cleft type articulation errors were evaluated blindly by a speech-language pathologist external to the team using pre- and postoperative speech recordings. SETTING : Multidisciplinary cleft team based in a tertiary referral center. Results : In 81% of patients, speech outcome was such that no further velopharyngeal surgery was considered necessary at the time of follow-up. The buccinator flap procedure resulted in a mean palate lengthening of 7.5 mm (±5.5 SD). After the operation, there was a complete elimination of the velopharyngeal gap on lateral videofluoroscopy in 77% of patients. There were significant decreases in hypernasality ratings and passive cleft type articulation errors postoperatively. CONCLUSION: Palatal lengthening with myomucosal buccinator flaps in patients with velopharyngeal insufficiency is effective and safe. It has become one of our routinely practiced procedures for velopharyngeal insufficiency.

Effect of adenotonsillectomy on the use of respiratory medication.

OBJECTIVE: Recurrent tonsillitis and upper respiratory tract obstruction due to adenotonsillar hypertrophy are the most common indications for (adeno)tonsillectomy ((A)TE). Symptoms of upper respiratory tract infection and obstruction can, however, be attributed to lower airway pathology and thus treated with respiratory medication - this is non-antimicrobial medication used for lower respiratory diseases like bronchitis, bronchiolitis, asthma and episodic wheezing. The aim of this study is to investigate the effect of the current (A)TE practice in Belgium on the use of respiratory medication in subjects aged 0-15. METHODS: Retrospective data on 11.114 subjects aged 0-15 years old who underwent (A)TE from January 1st 2002 until Sept 30th 2003 were retrieved from the database of the Christelijke Mutualiteit, the largest mutual health insurance society in Belgium. We compared the use of respiratory medication 12 months before and 12 months after (A)TE. RESULTS: Out of 11.114 subjects, 4.654 received at least one prescription for respiratory medication in the year before and/or after (A)TE. In this subgroup, the median respiratory medication use reduced with 32% in the year after surgery. CONCLUSION: Compared with the year before surgery, the median use of respiratory medication in subjects aged 0-15 drastically reduces in the year after (A)TE. A possible reason for this reduction is that children with upper airway obstruction and infections are often wrongly diagnosed as having lower airway problems.

Staphylococcus aureus enterotoxin B augments granulocyte migration and survival via airway epithelial cell activation.

BACKGROUND: Staphylococcus aureus enterotoxin B (SEB) has recently been postulated to be involved in the pathology of granulocyte-dominated disease. Studying the immunologic interaction between SEB and airway epithelial cells in immortalized cell lines or long-term epithelial cell cultures has obvious disadvantages. METHODS: We used a novel technique of freshly isolated and purified human nasal epithelial cells (HNEC) from healthy, nonallergic individuals, which were incubated for 24 h without/with SEB at different concentrations. Chemokine production was evaluated in the supernatant using Cytometric Bead Array. The chemotactic activity of the supernatant was studied in vitro using a Boyden chamber. Survival was evaluated with flow cytometry, using propidium iodide to identify dead cells. RESULTS: Staphylococcus aureus enterotoxin B showed a dose-dependent induction of interferon-inducible protein-10, monokine induced by interferon-gamma, regulated upon activation normal T cell expressed and secreted, monocyte chemoattractant protein 1 (MCP-1) and granulocyte colony stimulating factor production by epithelial cells in vitro. The supernatant of epithelial cells had chemotactic activity for granulocytes in vitro, which was enhanced in the supernatant of SEB-stimulated epithelial cells. Reduced number of propidium iodide positive granulocytes was found in the conditions where supernatant of SEB-stimulated epithelial cells was applied. CONCLUSION: Staphylococcus aureus enterotoxin B exerts a direct pro-inflammatory effect on HNEC, with induction of chemokine and growth factor release, resulting in the migration and prolonged survival of granulocytes in vitro.

Unique approach to secondary cleft-lip rhinoplasty in facial plastic surgery.

Rhinoplasty occupies a unique position in facial plastic surgery due to the central position of the nose in the face and the vital functions of the nose. Among facial plastic surgeons, secondary rhinoplasty in adult cleft-lip patients is considered to be one of the most challenging surgical interventions due to the congenital distortion of the cartilaginous and bony nasal pyramid, with consequences for both nasal aesthetics and breathing. In spite of the challenging nature of the procedure, post-operative satisfaction is high, matching that of non-cleft-lip patients, as long as appropriate surgical techniques are applied. Specific rhinoplasty methods are used in unilateral or bilateral cleft-lip patients with extensive grafting, combined efforts for aligning the nasal dorsum and the creation of symmetry in the nasal tip, medialisation of the anterior nasal spine with augmentation of the premaxilla, correction of nasal vestibulum stenosis and specific post-operative care with a nasal vestibulum device. This review aims to address some specific surgical issues relating to cleft-lip rhinoplasty, resulting in the high subjective satisfaction rate reported by cleft patients operated upon in the University Hospitals Leuven.

Sinonasal pathology in nonallergic asthma and COPD: 'united airway disease' beyond the scope of allergy.

BACKGROUND: In contrast to the epidemiological and clinical association between allergic rhinitis and asthma, upper airway inflammation is less characterized in patients with nonatopic asthma and virtually unexplored in chronic obstructive pulmonary disease (COPD). Here, sinonasal pathology is studied in patients with allergic asthma, nonallergic asthma and COPD. METHODS: Ninety patients with stable bronchial disease were included in the study, of which 35 were diagnosed with allergic asthma, 24 with nonallergic asthma and 31 with COPD. Concurrently, 61 control subjects without pulmonary disease were included and matched for age and smoking habits respectively with the asthma and the COPD group. Sinonasal symptoms were evaluated on a visual analogue scale and rhinosinusitis-related impairment of quality of life was assessed with the sino-nasal outcome test-22 (SNOT-22) questionnaire. Nasal mucosal abnormalities were quantified with nasal endoscopy and nasal secretions collected for measuring inflammatory mediators. RESULTS: Allergic asthmatics, nonallergic asthmatics and COPD patients reported more nasal symptoms than their respective control subjects, had a higher SNOT-22 score and presented more mucosal abnormalities in the nose. Nasal secretions of both allergic and nonallergic asthmatics contained higher levels of eotaxin, G-CSF, IFN-gamma and MCP-1 than controls. Allergic asthmatics had higher nasal IP-10 levels as well. COPD-patients had higher nasal levels of eotaxin, G-CSF and IFN-gamma than controls. CONCLUSION: Patients with allergic and nonallergic asthma and COPD show increased nasal symptoms and more nasal inflammation. Hence, our data confirm the 'united airways' concept to be beyond the scope of allergic asthma.

The nose: gatekeeper and trigger of bronchial disease.

The nose is strategically placed at the entrance of the airway. Nose breathing takes place under physiologic circumstances and protects the lower airways from exposure to unconditioned air and exogenous particles. Alternatively, nasal disease may have a negative impact on lower airway biology, being involved in aggravation of bronchial disease. The interaction between upper and lower airway disease has been recognized for centuries. Due to the increase in prevalence of allergic diseases during the last decades, new interest has been gained in understanding the mechanisms underlying the interaction between rhinitis and asthma. Nowadays, allergic rhinitis and asthma are considered part of a global airway disease, with both diagnostic and therapeutic consequences for every day clinical practice. Besides allergy, other inflammatory conditions of the upper airways are associated with lower airway disease via unknown mechanisms. Viral rhinitis often coincides with exacerbations of bronchial disease, chronic sinus disease with or without nasal polyps frequently relates to bronchial dysfunction and occupational rhinitis and asthma are often present in the same individuals. In spite of the clinical relevance of considering the airway as one organ with major involvement of disease in upper, lower or both parts, many clues to understand the pathology still remain to be explored. This manuscript aims at providing a comprehensive overview of the current knowledge on the interaction between nasal disease and lower airway biology and stresses the importance of further research on this important matter.

Aggravation of bronchial eosinophilia in mice by nasal and bronchial exposure to Staphylococcus aureus enterotoxin B.

BACKGROUND: The role of bacterial enterotoxins like Staphylococcus aureus enterotoxin B (SEB) in allergic asthma remains unknown. We used a mouse model of airway allergy to study the effects of nasal or bronchial contact with SEB on bronchial allergic inflammation. METHODS: The features of allergic asthma were induced in ovalbumin (OVA)-sensitized mice (days 1-13) by repeated exposures to nebulized OVA (days 33-37). Nasal or bronchial application of SEB was performed on three occasions (days 33-35-37), and the effects on bronchial inflammation, IgE titres and expression levels of mRNA for T helper type 2 cytokines and other inflammatory mediators were evaluated. RESULTS: Both nasal and bronchial SEB enhanced the allergen-induced bronchial inflammation, as reflected by more eosinophilic inflammation in the airway lumen and in bronchial tissue. Aggravation of experimental asthma correlated with higher expression of mRNA for IL-5, IL-4, IFN-gamma, IL-12 p40, eotaxin-1 and TGF-beta in bronchi. In addition, nasal SEB elevated concentrations of IL-4, IL-5 and IFN-gamma in serum and bronchial SEB increased titres of OVA-specific and total IgE in serum. CONCLUSION: Our data illustrate the potential of both nasal as well as bronchial SEB to aggravate several features of allergic asthma in a mouse model.

Chronic maxillary atelectasis.

Chronic maxillary atelectasis (CMA) is characterized by a reduced maxillary sinus volume due to an inward bowing of one or more of the sinus walls. The disorder is probably caused by an obstruction of the maxillary ostium, leading to a persistent negative pressure within the sinus lumen. To provide insight into the epidemiology, pathogenesis and treatment of this disorder, a retrospective study of twelve cases that met radiographic criteria of CMA was carried out. The patients were equally divided between both sexes and were on average 25 years old. Five of the twelve patients were under eighteen years of age. The patients had chronic sinonasal complaints except two, who had a "silent sinus syndrome", characterized by enophthalmos associated with a marked sinus deformation. This is the first report of CMA associated with a benign nasal tumour and also of CMA following cicatrisation due to nasal packing for bleeding after endoscopic sinus surgery. All patients were treated surgically by creating a middle meatal antrostomy, thus restoring sinus ventilation. To conclude, CMA is rare and probably underestimated, especially in the paediatric population. Different entities causing a complete ostial occlusion can lead to CMA. Endoscopically restoring maxillary sinus ventilation is the recommended treatment.

Progeroid syndrome with facial teleangiectatic erythema, posterior subcapsular cataracts, calcification of basal ganglia and atrium septum defect type 2.

In this report we present the long-term follow-up findings in a young female born to consanguineous parents with the unique association of (1) a progeroid syndrome, (2) facial dysmorphism with relative microcephaly, triangular face, retrognathism and skin erythema, (3) bilateral posterior cataracts, (4) basal ganglia calcifications and (5) atrium septum defect type 2. Intelligence is borderline. Clinical evolution after normal puberty was positive with regression of the facial erythematous changes. Over the years differential diagnosis included progeria, hypohidrotic ectodermal dysplasia, Rothmund-Thompson syndrome, Cockayne syndrome, Bloom syndrome, but the clinical spectrum of abnormalities and the evolution with age were not compatible with one of these diagnoses. Parental consanguinity is in favour of autosomal recessive inheritance.