Infections represent an ongoing challenge for immunocompromised patients. Children are particularly vulnerable because of several age-related issues that relate in part to immune prematurity. This review addresses the challenges in managing infections among immunocompromised children and highlights several general principles that guide management.Statement of novelty: This work provides important guidance to clinicians who are involved in the management of pediatric patients with an ever-expanding spectrum of immunocompromising disorders.

Background: Primary immunodeficiency involving defective antibody formation requires antibody replacement therapy with immunoglobulin products to prevent and reduce infections. Immunoglobulin for intravenous use (IVIG) is a processed blood product with limited availability, and the various marketed IVIG products may have different tolerability among patients. New IVIG products are therefore necessary to offer options to patients and to reduce the risk of a product shortage.Methods: Forty-five adult and pediatric patients with primary immunodeficiency, documented agammaglobulinemia or hypogammaglobulinemia, and antibody deficiency were enrolled in a prospective, multi-centre, open-label, single-arm historically controlled Phase III study to evaluate the safety, efficacy, and pharmacokinetics of a new 10% IVIG produced by Kedrion.Results: Forty-four patients completed the study while one withdrew consent. Over the 12-month study period, only 2 episodes of acute serious bacterial infections (both bacterial pneumonias) were recorded, for a mean annual event rate of 0.04 per subject, with an upper one-sided 99% confidence limit of 0.11. Values for all secondary efficacy endpoints were comparable with those in similar studies. The primary safety endpoint was met as the rate of infusions temporally associated (i.e., within 72 hours) with ≥1 adverse event was 16% (upper 95% confidence limit 20.4%). Pharmacokinetics were assessed in 31 patients and found to be comparable with those published for other IVIG products.Conclusion: Kedrion IVIG 10% is safe, efficacious, and well tolerated by patients with primary immunodeficiency.Statement of novelty: This report describes the safety, efficacy, and pharmacokinetics of a new IVIG preparation.

Background: X-linked severe combined immunodeficiency (SCID) is caused by mutations in the IL2RG gene and classically presents with absent T cells and natural killer (NK) cells. Mutational analysis has contributed to the understanding of this gene.Methods: The primary immunodeficiency (PID) registry was reviewed for patients with SCID with novel IL2RG mutations. The clinical phenotype was assessed using a retrospective chart review.Results: We describe 3 novel mutations in the IL2RG. The first was a guanine to adenine substitution at position 215 (c.215 G > A) in exon 2 leading to a cysteine to tyrosine substitution at position 72 (p.Cys72Tyr), with a typical T⁻ B⁺ NK⁻ phenotype. The second was a deletion of thymine at position 618 and adenine at position 619 (c.618_619TA) in exon 5, leading to a frameshift at the 206 amino acid (p.His206fs). The phenotype was characterized by a classic SCID presentation and immunophenotyping revealed a low number of absolute lymphocytes with mostly B cells, low levels of immunoglobulins, as well as very low NK cells. Finally, the third mutation was a guanine to cytosine substitution at position 341 (c.341 G > C) in exon 3 leading to a glycine to alanine substitution at position 114 (p.Gly114Ala), presenting with a T⁺ B⁺ NK⁺ phenotype. The presence of T and NK cells in IL2RG are discussed in the context of other mutations allowing for T and NK cells in IL2RG mutations, as well as in the setting of maternal engraftment.Conclusion: To the best of our knowledge we describe 3 novel mutations in the IL2RG gene and the associated phenotypes. These mutations illustrate that these patients can have atypical immunological evaluations.Statement of novelty: To the best of our knowledge, this paper describes 3 novel mutations in the IL2RG gene.

Background: Hoyeraal–Hreidarsson syndrome (HHS), the severe clinical variant of X-linked dyskeratosis congenita, is caused by germline mutations in telomere associated genes. HHS usually manifests within the first years of life and is characterized by progressive bone marrow failure, immunodeficiency, neurological features including microcephaly and developmental delay, as well as intrauterine growth retardation. The typical mucocutaneous manifestations are nail dysplasia, lacy skin pigmentation, and oral leukoplakia. Importantly, gastrointestinal involvement is reported in most patients with HHS, and may be the presenting feature. Given the spectrum of gastrointestinal diseases with a similar presentation, recognizing the unique gastrointestinal histopathology of HHS may facilitate earlier diagnosis and treatment.Methods: This case series highlights the gastrointestinal pathology findings of 2 patients with HHS caused by DKC1 gene mutations.Results: Gastrointestinal biopsies reveal loss of mucosal glands, regenerative glandular alterations and increased colonic epithelial cell apoptosis. Immunostaining of biopsies for cleaved caspase 3, a marker of cellular apoptosis, demonstrates abnormal nonapical and random locations of enterocyte exit which was further exacerbated by enteritis.Conclusion: Gastrointestinal involvement is usually the presenting feature of patients with HHS. This case series highlights the important role on gastrointestinal histopathology in facilitating a diagnosis of HHS.Statement of novelty: Detailed gastrointestinal biopsy images associated with HHS involving DKC1 mutations.