A 14-Year-Old Girl with Shortness of Breath and Chest Pain.

A 14-Year-Old Girl with Dyspnea and Chest PainA 14-year-old girl presented for evaluation of shortness of breath and chest pain after recent travel to the Caribbean. How do you approach the evaluation, and what is the diagnosis?

Ureasplasma and Its Role in Adverse Perinatal Outcomes: A Review.

Human Ureaplasma species are the most common microbes found in amniotic fluid and in the placenta after preterm birth, and have previously been correlated with chorioamnionitis, preterm labor, and bronchopulmonary dysplasia, among other adverse birth and neonatal outcomes. Although these correlations exist, there still remains little explanation as to whether Ureaplasma plays a pathogenic role in the development of neonatal disease. In addition, Ureaplasma species are not usually identified on routine culture as they require special culture methods because of their fastidious growth requirements. Treatment of Ureaplasma with macrolides has been shown to effectively eradicate the bacteria in pregnant women and infants. However, it is unclear whether this leads to improved neonatal morbidity and mortality, or whether these generally represent commensal organisms. This review will synthesize the current perspectives about the proposed mechanisms of pathogenicity of Ureaplasma bacteria, its links to poor neonatal outcomes, and the role of screening and treatment in current clinical practice.

Maternal IgG immune complexes induce food allergen-specific tolerance in offspring.

The role of maternal immune responses in tolerance induction is poorly understood. To study whether maternal allergen sensitization affects offspring susceptibility to food allergy, we epicutaneously sensitized female mice with ovalbumin (OVA) followed by epicutaneous sensitization and oral challenge of their offspring with OVA. Maternal OVA sensitization prevented food anaphylaxis, OVA-specific IgE production, and intestinal mast cell expansion in offspring. This protection was mediated by neonatal crystallizable fragment receptor (FcRn)-dependent transfer of maternal IgG and OVA immune complexes (IgG-IC) via breast milk and induction of allergen-specific regulatory T (T reg) cells in offspring. Breastfeeding by OVA-sensitized mothers or maternal supplementation with IgG-IC was sufficient to induce neonatal tolerance. FcRn-dependent antigen presentation by CD11c+ dendritic cells (DCs) in offspring was required for oral tolerance. Human breast milk containing OVA-IgG-IC induced tolerance in humanized FcRn mice. Collectively, we demonstrate that interactions of maternal IgG-IC and offspring FcRn are critical for induction of T reg cell responses and control of food-specific tolerance in neonates.

Allergic skin sensitization promotes eosinophilic esophagitis through the IL-33-basophil axis in mice.

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder characterized by accumulation of eosinophils in the esophagus. EoE often coexists with atopic dermatitis, a chronic inflammatory skin disease. The impaired skin barrier in patients with atopic dermatitis has been suggested as an entry point for allergic sensitization that triggers development of EoE. OBJECTIVE: We sought to define the mechanisms whereby epicutaneous sensitization through a disrupted skin barrier induces development of EoE. METHODS: To elicit experimental EoE, mice were epicutaneously sensitized with ovalbumin (OVA), followed by intranasal OVA challenge. Levels of esophageal mRNA for TH2 cytokines and the IL-33 receptor Il1rl1 (St2) were measured by using quantitative PCR. Esophageal eosinophil accumulation was assessed by using flow cytometry and hematoxylin and eosin staining. In vivo basophil depletion was achieved with diphtheria toxin treatment of Mcpt8DTR mice, and animals were repopulated with bone marrow basophils. mRNA analysis of esophageal biopsy specimens from patients with EoE was used to validate our findings in human subjects. RESULTS: Epicutaneous sensitization and intranasal challenge of wild-type mice resulted in accumulation of eosinophils and upregulation of TH2 cytokines and St2 in the esophagus. Disruption of the IL-33-ST2 axis or depletion of basophils reduced these features. Expression of ST2 on basophils was required to accumulate in the esophagus and transfer experimental EoE. Expression of IL1RL1/ST2 mRNA was increased in esophageal biopsy specimens from patients with EoE. Topical OVA application on unstripped skin induced experimental EoE in filaggrin-deficient flaky tail (ft/ft) mice but not in wild-type control or ft/ft.St2-/- mice. CONCLUSION: Epicutaneous allergic sensitization promotes EoE, and this is critically mediated through the IL-33-ST2-basophil axis.

Filaggrin deficiency promotes the dissemination of cutaneously inoculated vaccinia virus.

BACKGROUND: Eczema vaccinatum is a life-threatening complication of smallpox vaccination in patients with atopic dermatitis (AD) characterized by dissemination of vaccinia virus (VV) in the skin and internal organs. Mutations in the filaggrin (FLG) gene, the most common genetic risk factor for AD, confer a greater risk for eczema herpeticum in patients with AD, suggesting that it impairs the response to cutaneous viral infections. OBJECTIVE: We sought to determine the effects of FLG deficiency on the response of mice to cutaneous VV inoculation. METHODS: VV was inoculated by means of scarification of unsensitized skin or skin topically sensitized with ovalbumin in FLG-deficient flaky tail (ft/ft) mice or wild-type (WT) control mice. The sizes of primary and satellite skin lesions were measured, and hematoxylin and eosin staining was performed. VV genome copy numbers and cytokine mRNA levels were measured by using quantitative PCR. RESULTS: VV inoculation in unsensitized skin of ft/ft mice, independent of the matted hair mutation, resulted in larger primary lesions, more abundant satellite lesions, heavier viral loads in internal organs, greater epidermal thickness, dermal cellular infiltration, and higher local Il17a, Il4, Il13, and Ifng mRNA levels than in WT control mice. VV inoculation at sites of topical ovalbumin application amplified all of these features in ft/ft mice but had no detectable effect in WT control mice. The number of satellite lesions and the viral loads in internal organs after cutaneous VV inoculation were significantly reduced in both unsensitized and topically sensitized ft/ftxIl17a(-/-) mice. CONCLUSION: FLG deficiency predisposes to eczema vaccinatum. This is mediated primarily through production of IL-17A.