- Eosinophilic annular erythema treated with dupilumab. [Journal Article]
- PDPediatr Dermatol 2018 May 23
- Eosinophilic annular erythema is a rare, benign, recurrent condition characterized by annular skin lesions, tissue eosinophilia, and resistance to a variety of treatments. There are fewer than 30 cas...
Eosinophilic annular erythema is a rare, benign, recurrent condition characterized by annular skin lesions, tissue eosinophilia, and resistance to a variety of treatments. There are fewer than 30 cases reported in the English literature, 7 of which are in children. We present a case of recurrent eosinophilic annular erythema in an adolescent that was successfully treated with dupilumab, an interleukin-4 receptor alpha antagonist.
- A Very Rare Case of Hypereosinophilic Syndrome Secondary to Natural Killer/T-Cell Lymphoma. [Journal Article]
- CRCase Rep Otolaryngol 2018; 2018:5965029
- Hypereosinophilic syndrome (HES) is a systemic disease characterized by an increased peripheral blood eosinophil count accompanied by systemic organ dysfunction. HES is classified into idiopathic HES...
Hypereosinophilic syndrome (HES) is a systemic disease characterized by an increased peripheral blood eosinophil count accompanied by systemic organ dysfunction. HES is classified into idiopathic HES, primary (neoplastic) HES (HESN), and secondary (reactive) HES (HESR). In this case report, a patient who developed peripheral blood eosinophilia and granulation tissue in the pharynx and paranasal sinus, which was initially diagnosed as chronic eosinophilic leukemia (CEL), categorized as HESN, but was eventually identified after the patient had died as natural killer/T-cell (NK/T) lymphoma, nasal type (ENKL), categorized as HESR, is presented. ENKL-induced HES is very rare but must be considered.
- Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. [Journal Article]
- NEJMN Engl J Med 2018 May 21
- Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid ...
Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown. Methods We randomly assigned 210 patients with oral glucocorticoid-treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expiratory volume in 1 second (FEV1) before bronchodilator use were also assessed. Results The percentage change in the glucocorticoid dose was -70.1% in the dupilumab group, as compared with -41.9% in the placebo group (P<0.001); 80% versus 50% of the patients had a dose reduction of at least 50%, 69% versus 33% had a dose reduction to less than 5 mg per day, and 48% versus 25% completely discontinued oral glucocorticoid use. Despite reductions in the glucocorticoid dose, in the overall population, dupilumab treatment resulted in a severe exacerbation rate that was 59% (95% confidence interval [CI], 37 to 74) lower than that in the placebo group and resulted in an FEV1 that was 0.22 liters (95% CI, 0.09 to 0.34) higher. Injection-site reactions were more common with dupilumab than with placebo (9% vs. 4%). Transient blood eosinophilia was observed in more patients in the dupilumab group than in the placebo group (14% vs. 1%). Conclusions In patients with glucocorticoid-dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1. Transient eosinophilia was observed in approximately 1 in 7 dupilumab-treated patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA VENTURE ClinicalTrials.gov number, NCT02528214 .).
- Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. [Journal Article]
- NEJMN Engl J Med 2018 May 21
- Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients wi...
Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. Methods We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. Results The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. Conclusions In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .).
- Controlled Human Hookworm Infection: Accelerating Human Hookworm Vaccine Development. [Journal Article]
- OFOpen Forum Infect Dis 2018; 5(5):ofy083
- CONCLUSIONS: The inoculum of 50 NaL3 was well tolerated and consistently induced patent N. americanus infection suitable for future HVCM trials.
- Eosinophilic Esophagitis Is an Underlying Cause for Gastrointestinal Concerns in Children. [Review]
- FPFront Pediatr 2018; 6:113
- Eosinophilic esophagitis (EoE) is a chronic immune antigen-mediated disorder characterized by symptoms of esophageal dysfunction in combination with dense esophageal eosinophilia. The clinical presen...
Eosinophilic esophagitis (EoE) is a chronic immune antigen-mediated disorder characterized by symptoms of esophageal dysfunction in combination with dense esophageal eosinophilia. The clinical presentation of EoE can vary depending on children's age and their ability to report symptoms, therefore a high index of suspicion for EoE is required because children and teenagers may develop coping strategies around eating. The development of symptoms measurement tools in EoE assists in not only assessing symptoms, but also coping strategies children may have developed. While the diagnosis of EoE requires endoscopic evaluation with histologic assessment of esophageal mucosal biopsy samples, several emerging methods to assess and survey the esophageal mucosa have been developed. Advances in the field to better understand the natural history, clinical and molecular features of phenotypes in EoE will be important in considering novel therapeutic options and assessing outcomes.
- Update on new biologics for intractable eosinophilic asthma: impact of reslizumab. [Review]
- DDDrug Des Devel Ther 2018; 12:1173-1181
- A small percentage of patients with asthma have uncontrolled symptoms and frequent exacerbations, despite treatment with inhaled corticosteroids and other agents. It has become clear that different s...
A small percentage of patients with asthma have uncontrolled symptoms and frequent exacerbations, despite treatment with inhaled corticosteroids and other agents. It has become clear that different subtypes of this severe, treatment-resistant group exist due to different mechanisms of the disease. All such patients require detailed assessment in specialist centers to characterize the disease and assess treatment adherence. Recently, monoclonal antibodies have become available, which target specific pathways that may contribute to persistent inflammation and asthma exacerbations. These antibodies include those targeting interleukin (IL)-5, which drives eosinophilic inflammation. Reslizumab is a newly licensed antibody that blocks binding of IL-5 to its receptor. Here, we discuss the significance of clinical data of this drug, which show up to 50% reduction in exacerbation rates, together with modest but significant improvements in lung function and quality of life, in those with persistent eosinophilia. The combination of reslizumab with mepolizumab and benralizumab, which also target IL-5, may be a useful addition to the therapeutic armamentarium in a selected group of patients with severe asthma.
- A viral-vectored RSV vaccine induces long-lived humoral immunity in cotton rats. [Journal Article]
- VVaccine 2018 May 17
- Human respiratory syncytial virus (RSV) is the leading cause of lower airway disease in infants worldwide and repeatedly infects immunocompetent individuals throughout life. Severe lower airway RSV i...
Human respiratory syncytial virus (RSV) is the leading cause of lower airway disease in infants worldwide and repeatedly infects immunocompetent individuals throughout life. Severe lower airway RSV infection during infancy can be life-threatening, but is also associated with important sequelae including development of asthma and recurrent wheezing in later childhood. The basis for the inadequate, short-lived adaptive immune response to RSV infection is poorly understood, but it is widely recognized that RSV actively antagonizes Type I interferon (IFN) production. In addition to the induction of the anti-viral state, IFN production during viral infection is critical for downstream development of robust, long-lived immunity. Based on the hypothesis that a vaccine that induced robust IFN production would be protective, we previously constructed a Newcastle disease virus-vectored vaccine that expresses the F glycoprotein of RSV (NDV-F) and demonstrated that vaccinated mice had reduced lung viral loads and an enhanced IFN-γ response after RSV challenge. Here we show that vaccination also protected cotton rats from RSV challenge and induced long-lived neutralizing antibody production, even in RSV immune animals. Finally, pulmonary eosinophilia induced by RSV infection of unvaccinated cotton rats was prevented by vaccination. Overall, these data demonstrate enhanced protective immunity to RSV F when this protein is presented in the context of an abortive NDV infection.
- Hypersensitivity Pneumonitis and Acute Respiratory Distress Syndrome From E-Cigarette Use. [Journal Article]
- PedPediatrics 2018 May 17
- Electronic cigarette (e-cigarette) use, or "vaping," is gaining widespread popularity as an alternative to conventional cigarettes among adolescents. Little is known of the health risks of e-cigarett...
Electronic cigarette (e-cigarette) use, or "vaping," is gaining widespread popularity as an alternative to conventional cigarettes among adolescents. Little is known of the health risks of e-cigarette use, especially in children and adolescents. We present a Case Report of a previously healthy 18-year-old woman who presented with dyspnea, cough, and pleuritic chest pain after e-cigarette use. She developed respiratory failure with hypoxia and was intubated, and ultimately met diagnostic criteria for acute respiratory distress syndrome. Chest tubes were placed to drain worsening pleural effusions. Computed tomography of the chest revealed dependent opacities in both lung bases, superimposed smooth interlobular septal thickening, and pleural effusions. Bronchoalveolar lavage revealed cellular debris and reactive mononuclear cells, and cell counts were remarkable for elevated mononuclear cells and eosinophilia. After the results of a workup for an infectious etiology came back negative, the patient was diagnosed with hypersensitivity pneumonitis and intravenous methylprednisolone therapy was initiated. After this the patient rapidly improved, was weaned off vasopressor support, and was extubated. This is the first reported case of hypersensitivity pneumonitis and acute respiratory distress syndrome as a risk of e-cigarette use in an adolescent, and it should prompt pediatricians to discuss the potential harms of vaping with their patients. Hypersensitivity pneumonitis, lipid pneumonia, and eosinophilic pneumonia should be included in the differential diagnosis of patients who exhibit respiratory symptoms after the use of an e-cigarette.
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- Concordance between Aspergillus-specific precipitating antibody and IgG in allergic bronchopulmonary aspergillosis. [Journal Article]
- AIAllergol Int 2018 May 15
- CONCLUSIONS: Positive rate of A. fumigatus-specific precipitin or IgG (ImmunoCAP) was superior to IgG (CF), but relatively poor concordance was noted between precipitin and IgG (ImmunoCAP). Positive precipitin for A. fumigatus suggests more active diseases. Cross-reactivity may exist between antibodies to different Aspergillus spp. Therefore, the type III hypersensitivity results in ABPA diagnosis should be carefully evaluated.