Managing Diagnosis, Treatment, and Burden of Disease in Hereditary Angioedema Patients with Normal C1-Esterase Inhibitor.

Hereditary angioedema (HAE) is a rare, chronic, and debilitating genetic disorder characterized by recurrent and unpredictable swelling episodes that primarily affect the subcutaneous and/or submucosal tissues of the extremities, larynx, face, abdomen, and genitals. Most cases of HAE are caused by mutations in the serpin family G member 1 gene (SERPING1), which encodes C1-esterase inhibitor (C1-INH) protein. Mutations in SERPING1 lead to deficient (type I HAE-C1-INH) or dysfunctional (type II HAE-C1-INH) C1-INH protein and subsequent dysregulation of the kallikrein-bradykinin cascade. However, some patients present with a third type of HAE (HAE-nI-C1-INH), which was first described in the year 2000 and is characterized by an absence of mutations in SERPING1. Although mutations in the coagulation factor XII, angiopoietin-1, plasminogen, kininogen-1, myoferlin, and heparan sulfate-glucosamine 3-O-sulfotransferase-6 genes have been identified in some patients with HAE-nI-C1-INH, genetic cause is still unknown in many cases, hindering full elucidation of the pathology of this HAE subtype. Diagnosis of HAE-nI-C1-INH is also further complicated by the fact that patients typically demonstrate normal plasma levels of C1-INH and complement component 4 protein and normal C1-INH functionality during laboratory analysis. Therefore, we review the challenges associated with diagnosing, treating, and living with HAE-nI-C1-INH. We conclude that raising awareness of the presenting features of HAE-nI-C1-INH within the clinical setting and among the general public is critical to aid earlier suspicion and diagnosis of the disease. Furthermore, adopting an individualized approach to HAE-nI-C1-INH treatment is essential to help address the current and significant unmet needs in this patient population.

Hereditary Angioedema: A Review.

Hereditary angioedema (HAE) is a rare and disabling disorder wherein there is excessive bradykinin production, with subsequent increased vascular permeability in the superficial tissues and gastrointestinal and respiratory mucosa. This article serves as a review of the pathogenesis of the disease, as well as an update of the evidence-based new treatment recommendations to help clinicians with the diagnosis and management of HAE.

Vocal cord dysfunction: an update.

OBJECTIVES: To review the clinical manifestations of vocal cord dysfunction (VCD) and to discuss new developments in the diagnosis and treatment. DATA SOURCES: PubMed searches were performed for articles published regarding presentation, pathogenesis, diagnosis, and treatment options of VCD using the keywords vocal cord dysfunction, pathogenesis, clinical features, diagnosis, and management. STUDY SELECTION: Articles were selected based on their relevance to the topic of this review. The newest developments in VCD were defined by articles published in the past 8 years. RESULTS: The exact cause and pathogenesis remain unclear, although laryngeal hyperresponsiveness likely plays a role in a subset of patients. Certain findings on spirometry are often interpreted to suggest VCD, but recent studies have had varying results on how useful these are in the diagnosis of VCD. Diagnosis is made by direct visualization of the adduction of the vocal cords via rhinolaryngoscopy, but the method used to provoke symptoms and adduction varies. Other noninvasive tests have been evaluated as well. CONCLUSION: The early recognition and treatment of VCD are imperative to prevent the misdiagnosis and mismanagement of asthma. In addition, VCD and asthma can occur together. The origin and pathogenesis of VCD need to be better defined. More studies comparing the provocation methods during laryngoscopy may be helpful in further standardizing a diagnostic test. Further research is needed to determine whether other noninvasive tests are as effective in diagnosing VCD as laryngoscopy.

Egg baked in product open oral food challenges are safe in selected egg-allergic patients.

Egg allergy is one of the most common food allergies in children. Most egg-allergic children are able to tolerate egg baked in product (EBP) and will likely outgrow his/her egg allergy. By introducing EBP in the diet of an egg-allergic child, diet can be expanded and family stress can be reduced. Recent evidence suggests that children who tolerate EBP and continue to consume it will have quicker resolution of egg allergy than those who strictly avoid EBP; therefore, we aimed to evaluate the egg-allergic children who underwent EBP oral food challenge (OFC) in our allergy clinic to help define any specific predictors to be used in predicting the outcome of such challenges. We performed a retrospective chart review and 43 egg-allergic patients underwent EBP OFC in our outpatient allergy office from January 2011 to December 2012 were excluded. Nine patients who did not have a prior history of symptomatic egg ingestion. Clinical characteristics and laboratory findings of the remaining 34 patients were all recorded and analyzed. Of the remaining 34 patients, 22 (64.7%) were boys. Average age of first reaction to egg was 12.90 months, with average age at EBP OFC of 71.32 months. The average of the most recent skin-prick test wheal size was 10.10 mm and serum-specific IgE to egg white was 3.21 kU/L. Twenty-eight of the 34 patients (82.4%) passed the EBP OFC. Of the six patients who failed, none required epinephrine. After analysis of all of the clinical characteristics and laboratory findings, no risk factors, such as skin-prick test wheal size, were identified to be associated with an increased risk of failing EBP OFC. EBP OFC is a valuable tool to assess tolerance. As seen in our group of patients, the majority of egg-allergic patients pass EBP OFC. Thus, OFC should be considered as a clinical tool to expand a patient's diet and to improve quality of life as early as possible. Because we were unable to determine any clinical or laboratory predictors helpful to select egg-allergic patients who are likely to pass EBP OFC, additional prospective studies are necessary to determine the ideal egg-allergic patient who is likely to pass EBP OFC.

Systematic review of nutrient intake and growth in children with multiple IgE-mediated food allergies.

BACKGROUND: Food allergies affect up to 8% of American children. The current recommended treatment for food allergies is strict elimination of the allergens from the diet. Dietary elimination of nutrient-dense foods may result in inadequate nutrient intake and impaired growth. The purpose of this review was to critically analyze available research on the effect of an elimination diet on nutrient intake and growth in children with multiple food allergies. METHODS: A systematic review of the literature was conducted and a workgroup was established to critically analyze each relevant article. The findings were summarized and a conclusion was generated. RESULTS: Six studies were analyzed. One study found that children with food allergies are more likely to be malnourished than children without food allergies. Three studies found that children with multiple food allergies were shorter than children with 1 food allergy. Four studies assessed nutrient intake of children with multiple food allergies, but the inclusion and comparison criteria were different in each of the studies and the findings were conflicting. One study found that children with food allergies who did not receive nutrition counseling were more likely to have inadequate intake of calcium and vitamin D. CONCLUSION: Children with multiple food allergies have a higher risk of impaired growth and may have a higher risk of inadequate nutrient intake than children without food allergies. Until more research is available, we recommend monitoring of nutrition and growth of children with multiple food allergies to prevent possible nutrient deficiencies and to optimize growth.