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Allergen-specific immunotherapy for the treatment of immunoglobulin E mediated food allergies, specifically oral, epicutaneous, and sublingual immunotherapies, are promising options that may provide an alternative to strict avoidance of the dietary allergen. Of these potential therapies, oral immunotherapy is the furthest along in development, with strong evidence of efficacy in clinical trials, and has achieved regulatory approval. Nevertheless, oral immunotherapy may not be a suitable therapy for some patients due to the risk of adverse effects. In contrast to oral immunotherapy, epicutaneous and sublingual immunotherapies have demonstrated modest efficacy in clinical trials, with a favorable adverse effect profile, which suggests that these therapies may be possible contenders to oral immunotherapy in certain clinical situations. Familiarity with the various treatment approaches is vital for guiding patients and families as more therapeutic modalities become available for use outside of the research setting.
RESUMO
BACKGROUND: Exposure to adverse childhood experiences (ACEs) is associated with many childhood diseases and poor health outcomes in adulthood. However, the association with childhood obesity is inconsistent. We investigated the association between reported cumulative ACE score and body mass index (BMI) in a large sample of patients at a single institution. METHODS: This cross-sectional study included children aged 2-20 years that were screened in a general pediatrics clinic for ACEs utilizing the Center for Youth Wellness ACEs questionnaire between July 2017 and July 2018. Overall ACE score was categorized as 'no exposure' (score = 0), 'low exposure' (score = 1), and 'high exposure' (score≥ 2). BMI was categorized as overweight/obese (BMI percentile ≥ 85) or non-obese (BMI percentile < 85). The association between ACEs score and obesity was determined using univariate and multivariable logistic regression. RESULTS: Of the 948 patients included in the study, 30% (n = 314) were overweight/obese and 53% (n = 504) had no ACE exposure, 19% (n = 179) had low ACE exposure, and 28% (n = 265) had high ACE exposure. High ACE exposure was associated with increased odds of obesity (OR = 1.47, 95%CI = 1.07-2.03, p = 0.026). However, after adjusting for age, race/ethnicity, insurance type, and birth weight, the association attenuated and was null (OR = 1.01, 95%CI = 0.70-1.46, p = 0.97). CONCLUSION: The study findings may suggest an association between ACE and childhood obesity. However, the association attenuated after adjusting for age, race/ethnicity, insurance type, and birth weight. Larger prospective studies are warranted to better understand the association.
Assuntos
Experiências Adversas da Infância/estatística & dados numéricos , Obesidade Infantil/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Obesidade Infantil/psicologia , Fatores Socioeconômicos , Adulto JovemRESUMO
Autoimmunity is becoming an increasingly recognized complication in patients with primary immunodeficiencies (PIDs), including a variety of combined immune deficiencies such as Recombination Activating Gene (RAG) defects. The approach to treating autoimmunity in PID patients is complex, requiring a balance between immunosuppression and susceptibility to infection. Inflammatory arthritis is a feature of immune dysregulation in many PIDs, and the optimal treatment may differ from first line therapies that usually consist of disease-modifying anti rheumatic drugs (DMARDs). An example of mechanism-based therapy of arthritis in PID uses blockade of IL-6 signaling with tocilizumab for patients with STAT 3 gain-of-function (GOF) mutation and augmented IL-6 pathway. Herein, we describe two PID cases with arthritis who were found to have defects in RAG. One patient with refractory inflammatory arthritis experienced remarkable improvement in symptoms with tocilizumab therapy. Arthritis can be a clinical feature of immune dysregulation in RAG deficiency, and tocilizumab therapy has been suggested to have utility in treatment of arthritis in RAG deficiency.
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In the era of newborn screening (NBS) for severe combined immunodeficiency (SCID) and the possibility of gene therapy (GT), it is important to link SCID phenotype to the underlying genetic disease. In western countries, X-linked interleukin 2 receptor gamma chain (IL2RG) and adenosine deaminase (ADA) deficiency SCID are two of the most common types of SCID and can be treated by GT. As a challenge, both IL2RG and ADA genes are highly polymorphic and a gene-based diagnosis may be difficult if the variant is of unknown significance or if it is located in non-coding areas of the genes that are not routinely evaluated with exon-based genetic testing (e.g., introns, promoters, and the 5'and 3' untranslated regions). Therefore, it is important to extend evaluation to non-coding areas of a SCID gene if the exon-based sequencing is inconclusive and there is strong suspicion that a variant in that gene is the cause for disease. Functional studies are often required in these cases to confirm a pathogenic variant. We present here two unique examples of X-linked SCID with variable immune phenotypes, where IL2R gamma chain expression was detected and no pathogenic variant was identified on initial genetic testing. Pathogenic IL2RG variants were subsequently confirmed by functional assay of gamma chain signaling and maternal X-inactivation studies. We propose that such tests can facilitate confirmation of suspected cases of X-linked SCID in newborns when initial genetic testing is inconclusive. Early identification of pathogenic IL2RG variants is especially important to ensure eligibility for gene therapy.