Subject(s)
Cooperative Behavior , Patient Care Team , Patient-Centered Care , Pediatric Dentistry , Pediatrics , Advisory Committees , Brain Abscess/diagnosis , Cariostatic Agents/therapeutic use , Child, Preschool , Clinical Competence , Cost-Benefit Analysis , Dental Care for Children , Dental Caries/diagnosis , Dental Caries/prevention & control , Ectodermal Dysplasia/diagnosis , Genetic Diseases, X-Linked/diagnosis , Health Education, Dental , Health Services Accessibility , Humans , Immunologic Deficiency Syndromes/diagnosis , Infant , Male , Medically Underserved Area , Patient-Centered Care/economics , Patient-Centered Care/standards , Pediatric Dentistry/economics , Pediatric Dentistry/standards , Pediatrics/economics , Pediatrics/standards , Pennsylvania , Primary Immunodeficiency Diseases , Quality of Health Care , Referral and Consultation , Risk Assessment , United States , Vulnerable PopulationsABSTRACT
BACKGROUND: Hypomorphic mutations in the nuclear factor-κB (NF-κB) essential modulator (NEMO) gene result in a variable syndrome of somatic and immunologic abnormalities. Clinically relevant genotype-phenotype associations are essential to understanding this complex disease. OBJECTIVE: To study 2 unrelated boys with novel NEMO mutations altering codon 223 for similarity in phenotype in consideration of potential genotype-phenotype associations. METHODS: Clinical and laboratory features, including cell counts, immunoglobulin quantity and quality, natural killer cell cytotoxicity, and Toll-like and tumor necrosis factor receptor signaling, were evaluated. Because both mutations affected NEMO codon 223 and were novel, consideration was given to new potential genotype-phenotype associations. RESULTS: Both patients were diagnosed as having hypohidrotic ectodermal dysplasia and had severe or recurrent infections. One had recurrent sinopulmonary infections and the other necrotizing soft tissue methicillin-resistant Staphylococcus aureus infection and Streptococcus anginosus subdural empyema with bacteremia. NEMO gene sequence demonstrated a 3-nucleotide deletion (c.667_669delGAG) in one patient and a substitution (667G>A) in the other. These findings predict either the deletion of NEMO glutamic acid 223 or it being replaced with lysine, respectively. Both patients had normal serum IgG levels but poor specific antibodies. Natural killer cell cytotoxicity and Toll-like and tumor necrosis factor receptor signaling were also impaired. Serious bacterial infection did not occur in both patients after immunoglobulin replacement therapy. CONCLUSIONS: Two different novel mutations affecting NEMO glutamic acid 223 resulted in clinically relevant similar phenotypes, providing further evidence to support genotype-phenotype correlations in this disease. They suggest NEMO residue 223 is required for ectodermal development and immunity and is apparently dispensable for quantitative IgG production but may be required for specific antibody production.
Subject(s)
I-kappa B Kinase/genetics , Immunoglobulin G/blood , Immunologic Deficiency Syndromes/genetics , Antibody Specificity/immunology , Child, Preschool , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/immunology , Ectodermal Dysplasia 1, Anhidrotic , Humans , I-kappa B Kinase/immunology , Immunoglobulins, Intravenous/therapeutic use , Immunologic Deficiency Syndromes/immunology , Infant , Killer Cells, Natural/immunology , Male , Mutation , Receptors, Tumor Necrosis Factor/immunology , Signal Transduction/immunology , Toll-Like Receptors/immunologyABSTRACT
OBJECTIVE: This guideline provides evidence-based recommendations on managing hoarseness (dysphonia), defined as a disorder characterized by altered vocal quality, pitch, loudness, or vocal effort that impairs communication or reduces voice-related quality of life (QOL). Hoarseness affects nearly one-third of the population at some point in their lives. This guideline applies to all age groups evaluated in a setting where hoarseness would be identified or managed. It is intended for all clinicians who are likely to diagnose and manage patients with hoarseness. PURPOSE: The primary purpose of this guideline is to improve diagnostic accuracy for hoarseness (dysphonia), reduce inappropriate antibiotic use, reduce inappropriate steroid use, reduce inappropriate use of anti-reflux medications, reduce inappropriate use of radiographic imaging, and promote appropriate use of laryngoscopy, voice therapy, and surgery. In creating this guideline the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of neurology, speech-language pathology, professional voice teaching, family medicine, pulmonology, geriatric medicine, nursing, internal medicine, otolaryngology-head and neck surgery, pediatrics, and consumers. RESULTS: The panel made strong recommendations that 1) the clinician should not routinely prescribe antibiotics to treat hoarseness and 2) the clinician should advocate voice therapy for patients diagnosed with hoarseness that reduces voice-related QOL. The panel made recommendations that 1) the clinician should diagnose hoarseness (dysphonia) in a patient with altered voice quality, pitch, loudness, or vocal effort that impairs communication or reduces voice-related QOL; 2) the clinician should assess the patient with hoarseness by history and/or physical examination for factors that modify management, such as one or more of the following: recent surgical procedures involving the neck or affecting the recurrent laryngeal nerve, recent endotracheal intubation, radiation treatment to the neck, a history of tobacco abuse, and occupation as a singer or vocal performer; 3) the clinician should visualize the patient's larynx, or refer the patient to a clinician who can visualize the larynx, when hoarseness fails to resolve by a maximum of three months after onset, or irrespective of duration if a serious underlying cause is suspected; 4) the clinician should not obtain computed tomography or magnetic resonance imaging of the patient with a primary complaint of hoarseness prior to visualizing the larynx; 5) the clinician should not prescribe anti-reflux medications for patients with hoarseness without signs or symptoms of gastroesophageal reflux disease; 6) the clinician should not routinely prescribe oral corticosteroids to treat hoarseness; 7) the clinician should visualize the larynx before prescribing voice therapy and document/communicate the results to the speech-language pathologist; and 8) the clinician should prescribe, or refer the patient to a clinician who can prescribe, botulinum toxin injections for the treatment of hoarseness caused by adductor spasmodic dysphonia. The panel offered as options that 1) the clinician may perform laryngoscopy at any time in a patient with hoarseness, or may refer the patient to a clinician who can visualize the larynx; 2) the clinician may prescribe anti-reflux medication for patients with hoarseness and signs of chronic laryngitis; and 3) the clinician may educate/counsel patients with hoarseness about control/preventive measures. DISCLAIMER: This clinical practice guideline is not intended as a sole source of guidance in managing hoarseness (dysphonia). Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. The guideline is not intended to replace clinical judgment or establish a protocol for all individuals with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem.
