Undifferentiated recurrent fevers in pediatrics are clinically distinct from PFAPA syndrome but retain an IL-1 signature.

Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria. Here, we categorize these patients as syndrome of undifferentiated recurrent fever (SURF), and identify the unique features which distinguish them from the PFAPA syndrome. SURF patients were more likely to report gastrointestinal symptoms of nausea, vomiting and abdominal pain, and experienced inconsistent responses to on-demand steroid therapy compared to PFAPA patients. For this previously undefined cohort, an optimal course of therapy remains uncertain, with medical and surgical therapies largely driven by parental preference. A subset of patients with SURF underwent tonsillectomy with complete resolution. Flow cytometric evaluation demonstrates leukocytic populations distinct from PFAPA patients, with reduced CD3+ T cell numbers. SURF patient tonsils were predominantly characterized by an IL-1 signature compared to PFAPA, even during the afebrile period. Peripheral blood signatures were similar between groups suggesting that PFAPA and SURF patient tonsils have localized, persistent inflammation, without clinical symptoms. These data suggest that SURF is a heterogenous syndrome on the autoinflammatory disease spectrum.

Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood classically characterized by recurrent fevers, pharyngitis, stomatitis, cervical adenitis, and leukocytosis. While the mechanism is unclear, previous studies have shown that tonsillectomy can be a therapeutic option with improvement in quality of life in many patients with PFAPA, but the mechanisms behind surgical success remain unknown. In addition, long-term clinical follow-up is lacking. In our tertiary care center cohort, 62 patients with PFAPA syndrome had complete resolution of symptoms after surgery (95.3%). Flow cytometric evaluation demonstrates an inflammatory cell population, distinct from patients with infectious pharyngitis, with increased numbers of CD8+ T cells (5.9% vs. 3.8%, p < 0.01), CD19+ B cells (51% vs. 35%, p < 0.05), and CD19+CD20+CD27+CD38-memory B cells (14% vs. 7.7%, p < 0.01). Cells are primed at baseline with increased percentage of IL-1ß positive cells compared to control tonsil-derived cells, which require exogenous LPS stimulation. Gene expression analysis demonstrates a fivefold upregulation in IL1RN and TNF expression in whole tonsil compared to control tonsils, with persistent activation of the NF-κB signaling pathway, and differential microbial signatures, even in the afebrile period. Our data indicates that PFAPA patient tonsils have localized, persistent inflammation, in the absence of clinical symptoms, which may explain the success of tonsillectomy as an effective surgical treatment option. The differential expression of several genes and microbial signatures suggests the potential for a diagnostic biomarker for PFAPA syndrome.

Airway characteristics of infants with Pierre Robin sequence who undergo mandibular distraction osteogenesis.

Newborn upper airway obstruction secondary to micrognathia and Pierre Robin sequence can be managed with conservative and surgical interventions. Mandibular distraction osteogenesis has been used to relieve micrognathia associated with severe airway obstruction. We conducted a retrospective chart review to identify patients with Pierre Robin sequence who underwent mandibular distraction osteogenesis during a 2-year period. Our study group was made up of 16 infants-11 boys and 5 girls, aged 21 to 112 days (mean: 55.9). In addition to demographic data, we compiled data on their baseline characteristics, airway characteristics, pre- and perioperative findings, and postoperative airway outcomes. Although most patients experienced documented improvements in Cormack-Lehane laryngoscopy grades postoperatively, the severity of micrognathia and airway obstruction did not always correlate with the higher grades. As well, the degree of improvement on laryngoscopic findings was not always evident, even though patients experienced a clinical benefit. All patients who had undergone a preoperative tracheostomy were decannulated successfully. We found that mandibular distraction osteogenesis was a safe and effective intervention for newborns with severe micrognathia and airway obstruction in our study population. It is interesting that the degree of micrognathia was not always correlated with the degree of airway compromise and laryngoscopy grades.

The long-term effects of mandibular distraction osteogenesis on developing deciduous molar teeth.

Background. Many studies have demonstrated the effectiveness of mandibular distraction osteogenesis (MDO) in alleviating the micrognathia-associated upper airway obstruction but very few studies have focused on long-term dental outcomes. Objective. To report the effect of MDO on developing deciduous molars in the distraction area. Methods. A retrospective chart review was performed to identify patients with Pierre Robin sequence who underwent MDO with documented long-term dental assessments. Results. Ten children (mean age at surgery 69.8 days; 6 boys and 4 girls) were included for analysis. All patients underwent bilateral MDO with an inverted L-shaped osteotomy to avoid injuring tooth buds. The dental developmental stage was primary dentition in all children. Overall, 3 patients developed minor dental problems involving 4 molar teeth (2 root malformations and 2 shape anomalies) but they did not require any interventions. Conclusion. Significant primary molar developmental complications were not seen in our patients. The use of internal distractor device with an inverted L-shaped osteotomy seems to be a safe surgical approach in regards to dental outcomes.

Tracheostomy versus mandibular distraction osteogenesis in Canadian children with Pierre Robin sequence: a comparative cost analysis.

INTRODUCTION: Upper airway obstruction in newborns with Pierre Robin sequence (PRS) may be severe enough to require a surgical intervention. Tracheostomy has been the traditional gold standard, but mandibular distraction osteogenesis (MDO) has been proven to be an effective alternative procedure. OBJECTIVE: The objective of the present study was to conduct the first comparative cost analysis between tracheostomy and MDO in Canada. METHODS: All patients with PRS who underwent tracheostomy or MDO between January 2005 and December 2010 were included. Tracheostomy and MDO procedures were broken down into individual components, and the associated costs for these components were totaled. The average per-patient cost for each modality was then compared. RESULTS: During the study period, 52 children underwent either a tracheostomy (n  =  31) or MDO (n  =  21). The average age at surgery, gender, and presence of associated syndromes were similar in both groups. Taking into account the cost of the surgeries, health care professional fees, and hospital stay, the total per-patient treatment cost was determined to be $57,648.55 for MDO and $92,164.45 for tracheostomy. The majority of the cost for the tracheostomy group was associated with prolonged hospital stay after the operation ($72,827.85). Overall, the average per-patient cost was 1.6 times greater in the tracheostomy group compared to the MDO group (p  =  .039). CONCLUSION: The initial cost of MDO was less than the tracheostomy cost for newborns with PRS and severe upper airway obstruction at our health care centre. Further prospective analysis considering the long-term costs is required to possibly reduce long-term health care costs.

Mandibular distraction osteogenesis in children with Pierre Robin sequence: impact on health-related quality of life.

BACKGROUND: Upper airway obstruction in children with Pierre Robin sequence (PRS) may be severe enough to require surgical intervention. Although many studies have demonstrated the effectiveness of mandibular distraction osteogenesis (MDO) in relieving airway obstruction, no study has reported health-related quality of life (QOL) outcomes. The objective of the present study was to conduct the first health-related QOL assessment post-MDO. METHODS: The Glasgow Children's Benefit Inventory (GCBI) questionnaire was distributed in a retrospective manner to the caregivers of all children who had undergone MDO at the authors' institutions between January 2007 and December 2010. Patients who had other major surgical procedures were excluded. RESULTS: The response rate was 84% (21 of 25 questionnaires completed). The total mean GCBI score was +54 (SD, 19.5), which demonstrated a subjective overall benefit in health-related QOL post-MDO. All of the domains within the GCBI also scored in the positive range, indicating domain specific improvements in health-related QOL. There were no significant differences in the GCBI scores between syndromic-PRS patients and isolated PRS patients; similar results were observed between tracheostomy patients and no tracheostomy patients. SUMMARY: In treating children with PRS and severe upper airway obstruction, MDO resulted in a subjective overall benefit in health-related QOL in our study population.

Work environment discomfort and injury: an ergonomic survey study of the American Society of Pediatric Otolaryngology members.

BACKGROUND: Workplace-related musculoskeletal pain has been studied in various occupations, but it is rarely reported in the surgical literature. OBJECTIVE: The aim of this study was to examine work-related discomfort and injury among pediatric otolaryngologists and to assess their knowledge of workplace ergonomic principles. METHODS: We surveyed current North American members of the American Society of Pediatric Otolaryngology. Our main outcomes were whether the physician had ever experienced discomfort or physical symptoms that they attributed to their surgical practice. RESULTS: Response rate of 43.7% was attained, and 62.0% of respondents reported experiencing pain or discomfort that they attributed to their surgical practice. Women were significantly more likely to report experiencing pain or discomfort that they associated with their surgical practice (P = .033). There were no significant differences found among length of time in practice, academic vs community setting, or number of surgeries completed by the surgeon. Some of the surgeons (31.0%) were aware of ergonomic principles, and of those who were aware, 83.9% had implemented ergonomic principles into their surgical practice. CONCLUSION: Almost two thirds of surgeons who responded to the survey reported experiencing pain or discomfort that they attributed to their surgical practice. Only a minority of respondents were aware of ergonomic principles. These findings may confirm that most physicians believe that their physical health is affected by their operative environment. Increased knowledge of surgical ergonomics may lead to strategies that improve workplace health and safety.

Chronic esophageal foreign bodies and secondary mediastinitis in children.

OBJECTIVES: The purpose of this study was to review the clinical presentation, diagnosis, and management of chronic esophageal foreign bodies complicated by mediastinitis in children. METHODS: A retrospective study of children with a chronic esophageal foreign body and secondary mediastinal complications diagnosed at Rady Children's Hospital in San Diego over a 12-month period is reported. RESULTS: Three patients received a diagnosis of an esophageal foreign body, retained from 1 to 12 months, and mediastinitis. Each patient presented primarily with respiratory signs and had been treated previously for alternate diagnoses (ie, asthma, reflux, and upper respiratory tract infection) by emergency or pediatric providers. The diagnosis of a foreign body was made after a chest radiograph was examined. Operative airway evaluation confirmed tracheal narrowing in all patients, and a computed tomographic scan of the chest was performed after removal of the foreign body to confirm mediastinal involvement. After medical and/or surgical treatment, the patients were released from the hospital tolerating soft diets. There were no reports of long-term complications in our series of patients. CONCLUSIONS: It is critical to rule out esophageal and airway foreign bodies in pediatric patients with respiratory symptoms that do not respond to medical treatment. Timely recognition of an esophageal foreign body generally allows for removal with minimal morbidity, whereas the incidence of serious complications increases significantly when the diagnosis is delayed. Our series provides support for conservative management of mediastinal complications after removal of chronically retained esophageal foreign bodies in children.

Nasal dermoids.

PURPOSE OF REVIEW: Midline congenital nasal lesions are rare, occurring in one out of every 20,000-40,000 births. Of these midline lesions, nasal dermoids are the most common. This review centers on diagnosis of nasal dermoids, the role of imaging in diagnosis and surgical planning and the various approaches to surgical management of these lesions. RECENT FINDINGS: Multiplanar, high-resolution thin section magnetic resonance imaging allows for excellent soft tissue detail, particularly when intracranial extension is expected. Open rhinoplasty is favored by many authors for excision of dermoids. Transnasal endoscopic excision of nasal dermoids has been reported but is not recommended for dermoids extending into or beyond the falx cerebri. SUMMARY: Imaging of the midface and brain is essential for accurate diagnosis, assessment for any intracranial extension and appropriate surgical planning. Any surgical approach for removal of nasal dermoid cysts should permit adequate access, allow repair of the skull base and cerebrospinal fluid leak, facilitate nasal reconstruction and result in acceptable cosmesis. The head and neck surgeon should be able to consider various surgical approaches to manage these lesions.

Professional diversity and personal commitments of pediatric otolaryngologists.

OBJECTIVE: To characterize the time demands and practice patterns of pediatric otolaryngologists. DESIGN: Prospective survey of members from the American Society of Pediatric Otolaryngology. RESULTS: The survey response rate was 54% (n = 136) of practicing members of the American Society of Pediatric Otolaryngology. Respondents described being actively engaged in clinical otolaryngology (99%), hospital or practice administration (71%), private enterprise (17%), research (71%), and teaching (89%) on a weekly basis. Sixty percent considered their time demands to be "too busy"; however, few anticipated changing their activities in 5 years. Among the responding physicians, 90% believed that nonotolaryngology peers within their institutions viewed pediatric otolaryngology favorably whereas only 50% thought that other otolaryngologists held the same opinion. CONCLUSIONS: Pediatric otolaryngologists participate in many activities beyond clinical medicine. While most considered their time demands to be too busy, few anticipated a change in their activities. This may be reflective of a high level of job satisfaction, financial constraints, or the relative youth of the subspecialty.

The otolaryngological manifestations of mitochondrial disease and the risk of neurodegeneration with infection.

OBJECTIVE: To report the nature and extent of hearing loss and other otolaryngological problems in patients with mitochondrial disease, and to document the risk of neurodegeneration with infection. DESIGN: Medical chart review and telephone interview of 40 patients with documented mitochondrial disease. SETTING: An international referral center for the diagnosis and management of mitochondrial disorders. PATIENTS: We describe 40 patients with a definitive diagnosis of mitochondrial disease. Thirty-three (82%) were younger than 15 years. RESULTS: Hearing loss was the most common clinical finding associated with mitochondrial disease. Twenty-eight (80%) of the 35 patients undergoing testing had hearing loss or significant auditory dysfunction. In 20 (57%) of these, brainstem conduction abnormalities were identified. Eight (30%) of the 27 patients had an abnormal number of recurrent upper respiratory tract infections, and 4 (50%) of these had life-threatening or neurodegenerative sequelae. Mitochondrial disease followed an episodic course, with periods of stasis or slow developmental progress, punctuated by neurodegenerative events in 18 (60%) of 30 patients. Intercurrent infection was recognized as a precipitant of neurodegenerative events in 13 (72%) of 18 patients with a history of episodic degeneration. CONCLUSIONS: Children and adults with mitochondrial disorders are at high risk for hearing loss and life-threatening complications of intercurrent infections. A constellation of audiologic abnormalities, multiorgan system involvement, and history of neuromuscular setbacks with infection strongly suggests mitochondrial disease. Knowledge of these features can lead to more rapid diagnosis and improved medical and surgical management for this special group of patients with fundamental defects in bioenergy metabolism.

Imaging and surgical approach of nasal dermoids.

OBJECTIVE: Determine the most accurate and cost effective radiographic evaluation for nasal dermoids. Determine the best surgical approach for excision of nasal dermoids. DESIGN: Retrospective chart review. SETTING: Division of Pediatric Otolaryngology, Children's Hospital and Health Center, San Diego, California. PARTICIPANTS: All patients with nasal dermoids evaluated and treated from 1990 to 2000. INTERVENTION: Preoperative radiographic evaluation and surgical excision. OUTCOME MEASURES: Accuracy of CT and MRI correlated with surgical findings and results. RESULTS: Ten patients were identified with the diagnosis of nasal dermoid. The age at diagnosis ranged from 0 to 24 months, with a mean of 3 months. Six children presented with masses located at the glabella, three patients presented with masses located at the nasal dorsum and one presented with a mass at the nasal tip. Six children underwent a computed tomogram with contrast of the head. Seven children underwent a MRI study of the head. Three children underwent an initial CT followed by MRI. Twenty percent of children were found to have intracranial extension. CT scan accurately diagnosed intracranial extension in one case, was indeterminate in a second case and falsely positive in a third case. MRI correctly diagnosed intracranial extension in two cases and had no false positive or false negative results. No children were found to have associated intracranial anomalies. In the early years of the review, a simple excision was made over the mass with blunt and sharp dissection for removal. (An external rhinoplasty incision is now used with better exposure and improved cosmetic results.) In cases with intracranial communication, a combined approach of external rhinoplasty and craniotomy was used. CONCLUSIONS: MRI alone is the most cost effective and accurate means of evaluating nasal dermoids and is essential for preoperative planning. The surgical approach of choice is external rhinoplasty for both cosmetic reasons and exposure of nasal dermoids with and without intracranial extension.