A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation

B-cell lymphoma/leukemia 11B (BCL11B) is a C2H2 zinc finger transcription factor that is critically important for regulating the development and function of a variety of systems including the central nervous system, the skin, and the immune system. Germline heterozygous variants are associated with a spectrum of clinical disorders, including severe combined immunodeficiency as well as neurological, craniofacial, and dermal defects. Of these individuals, ~50% present with severe allergic disease. Here, we report the detailed clinical and laboratory workup of one of the most severe BCL11B-dependent atopic cases to date. Leveraging a zebrafish model, we were able to confirm a strong T-cell defect in the patient. Based on these data, we classify germline BCL11B-dependent atopic disease as a novel primary atopic disorder.

Risks for comorbidity in children with atopic disorders: an observational study in Dutch general practices

ObjectiveThis study aimed to investigate both atopic and non-atopic comorbid symptoms and diseases in children with physician-diagnosed atopic disorders (atopic eczema, asthma and allergic rhinitis).MethodsAll children aged 0–18 years listed in a nationwide primary care database (the Netherlands Institute for Health Services Research-Primary Care Database) with routinely collected healthcare data in 2014 were selected. Children with atopic disorders were matched on age and gender with non-atopic controls within the same general practice. A total of 404 International Classification of Primary Care codes were examined. Logistic regression analyses were performed to examine the associations between the presence of atopic disorders and (non-)atopic symptoms and diseases by calculating ORs.ResultsHaving one of the atopic disorders significantly increased the risk of having other atopic-related symptoms, even if the child was not registered as having the related atopic disorder. Regarding non-atopic comorbidity, children with atopic eczema (n=15 530) were at significantly increased risk for (infectious) skin diseases (OR: 1.2–3.4). Airway symptoms or (infectious) diseases (OR: 2.1–10.3) were observed significantly more frequently in children with asthma (n=7887). Children with allergic rhinitis (n=6835) had a significantly distinctive risk of ear-nose-throat-related symptoms and diseases (OR: 1.5–3.9). Neither age nor gender explained these increased risks.ConclusionGeneral practitioners are not always fully aware of relevant atopic and non-atopic comorbidity. In children known to have at least one atopic disorder, specific attention is required to avoid possible insufficient treatment and unnecessary loss of quality of life.

The Relationship Between Migraine and Atopic Disorders—the Contribution of Pulmonary Function Tests and Immunological Screening

This cross-sectional clinical study was conducted in order to explore the relationship between atopic disorders and migraine. We evaluated 186 consecutive patients with migraine. Patients with a history of atopic disorders were compared with the others during headache-free intervals, for their headache characteristics, pulmonary test (PFT) performances and immunological screenings, through appropriate statistical methods. Of the patients with migraine, 77 (41.4%) reported at least one atopic disorder. PFT screening showed a general decreased pulmonary capacity and an important correlation between a positive history of atopic disorders and both increased eosinophil and IgE levels in headache-free periods. It should be discussed whether screening with PFT or immunological tests helps in early detection of progressive lung disease which might develop in these patients.