Short-term symptom improvement in infants with suspected cow’s milk protein allergy using amino acid formula: a prospective cohort analysis

BackgroundCow’s milk protein allergy (CMPA) occurs commonly in infants. While the long-term efficacy of amino acid formulas for managing CMPA is well-established, there is limited data on the short-term symptom improvement of using amino acid formula (AAF).ObjectiveThis study aimed to determine the short-term effects of managing suspected CMPA in infants aged 6 months and under using a commercial AAF.MethodsHealthcare providers who treated infants with suspected CMPA aged 6 months or younger (n = 104) provided de-identified survey data in this prospective study. Healthcare providers scored symptoms for severity from 0 to 3 (none, low, moderate, severe) before using a commercial AAF at Visit 1 and at Visit 2 (3–6 weeks later).ResultsGastrointestinal (94%), skin (87%), respiratory (86%), and uncategorized symptoms (89%) improved from AAF initiation, and these findings were consistent across different follow-up visit durations.ConclusionThis study is the most extensive prospective analysis conducted in the United States examining the short-term change in suspected CMPA symptoms using an AAF. These findings suggest that AAF may decrease the severity of suspected CMPA symptoms in infants 6 months or younger, often by the next follow-up visit. Further randomized controlled trials are required to confirm these initial findings

Familial Immune Thrombocytopenia Associated With a Novel Variant in IKZF1

We report a novel variant in IKZF1 associated with IKAROS haploinsufficiency in a patient with familial immune thrombocytopenia (ITP). IKAROS, encoded by the IKZF1 gene, is a hematopoietic zinc-finger transcription factor that can directly bind to DNA. We show that the identified IKZF1 variant (p.His195Arg) alters a completely conserved histidine residue required for the folding of the third zinc-finger of IKAROS protein, leading to a loss of characteristic immunofluorescence nuclear staining pattern. In our case, genetic testing was essential for the diagnosis of IKAROS haploinsufficiency, of which known presentations include infections, aberrant hematopoiesis, leukemia, and age-related decrease in humoral immunity. Our family study underscores that, after infections, ITP is the second most common clinical manifestation of IKAROS haploinsufficiency

Two Unique Cases of X-linked SCID: A Diagnostic Challenge in the Era of Newborn Screening

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

Case Report: ASCENIV use in three young children with immune abnormalities and acute respiratory failure secondary to RSV infection

Respiratory syncytial virus (RSV) is the most common etiology of bronchiolitis in young children. While most children clinically improve with care at home, RSV is the leading cause of hospitalization among infants aged 12 months or less. Common modalities of treatment for children with immune dysregulation include respiratory support and best supportive care, which may include immunoglobulin therapy. All immunoglobulin therapies adhere to Food and Drug Administration (FDA) - established standards for antibodies against measles, polio, and diphtheria, but there are no required standards for problematic respiratory viral pathogens, including RSV and others. ASCENIV is an approved IVIG that is manufactured from blending normal source plasma with plasma from donors that possess high antibody titers against RSV and other respiratory pathogens of concern. ASCENIV was developed, in part, to the unmet need that exists in immunocompromised patients who lack sufficient antibodies against problematic viral pathogens. ASCENIV is not a currently approved treatment for severe RSV and other viral infections. There is a lack of research regarding its potential benefits in the acute treatment period for RSV and in the pediatric population. Therefore, this case series was developed to describe real-world experiences of ASCENIV use in this less well studied clinical scenario. This case series reviews three pediatric patients ≤ 5 years of age with immune dysregulation and who were severely ill with RSV. Despite receiving best supportive care, and standard immunoglobulin therapy for some, the patients’ clinical status continued to decline. All patients received ASCENIV in an intensive care setting. Each patient had ultimately recovered due to the various medical interventions done. This case series demonstrated that ASCENIV (500mg/kg) administration may have contributed to the treatment outcomes of a less well studied age-cohort of patients. In addition, no adverse side effects were observed after ASCENIV administration. Further analysis of the benefits of ASCENIV for the acute and preventative treatment in patients younger than 12 years of age with immune dysregulation should continue to be explored

Associations of Microbial Diversity with Age and Other Clinical Variables among Pediatric Chronic Rhinosinusitis (CRS) Patients

Chronic rhinosinusitis (CRS) is a heterogenous disease that causes persistent paranasal sinus inflammation in children. Microorganisms are thought to contribute to the etiology and progression of CRS. Culture-independent microbiome analysis offers deeper insights into sinonasal microbial diversity and microbe–disease associations than culture-based methods. To date, CRS-related microbiome studies have mostly focused on the adult population, and only one study has characterized the pediatric CRS microbiome. In this study, we analyzed the bacterial diversity of adenoid tissue, adenoid swab, maxillary sinus, and sinus wash samples from 45 pediatric CRS patients recruited from the Johns Hopkins All Children’s Hospital (JHACH) in St. Petersburg, FL, USA. The alpha diversity in these samples was associated with baseline nasal steroid use, leukotriene receptor antagonist (LTRA) use, and total serum immunoglobulin (Ig) E (IgE) level. Streptococcus, Moraxella, and Haemophilus spp. were most frequently identified from sinus cultures and the sequenced 16S rRNA gene content. Comparative analyses combining our samples with the samples from the previous microbiome study revealed differentially abundant genera between patients with pediatric CRS and healthy controls, including Cutibacterium and Moraxella. Additionally, the abundances of Streptobacillus and Staphylococcus were consistently correlated with age in both adenoid- and sinus-derived samples. Our study uncovers new associations of alpha diversity with clinical parameters, as well as associations of specific genera with disease status and age, that can be further investigated

Extensively Hydrolyzed Formula Improves Allergic Symptoms in the Short Term in Infants with Suspected Cow’s Milk Protein Allergy

Although extensively hydrolyzed formula is widely accepted for managing cow’s milk protein allergy (CMPA) long-term, there is a lack of evidence on its short-term efficacy. This study’s objective was to investigate the short-term symptom changes (within 3–6 weeks) of infants diagnosed with CMPA and managed with extensively hydrolyzed formula containing Lactobacillus rhamnosus at their subsequent physician visit. Healthcare providers treating 202 patients diagnosed with CMPA under six months old completed de-identified surveys, which were then analyzed in this prospective study. After their first visit, the patients were started on extensively hydrolyzed formula, and their baseline symptoms were scored on a severity scale of 0–3. Patients were then reevaluated at their next follow-up visit to assess changes in symptom severity. The study found statistically significant improvements in gastrointestinal (93%), skin (83%), respiratory (73%), and uncategorized symptoms (90%). These symptom improvements were consistent across different follow-up visit durations. This study is the largest prospective analysis conducted in the United States evaluating short-term change in CMPA symptoms severity in infants under six months old using extensively hydrolyzed formula. These findings suggest that extensively hydrolyzed formula is associated with clinical symptom relief, which is often noticeable by the next follow-up visit. However, additional randomized control trials are needed to validate these results

Hyaluronidase-Facilitated High-Dose Subcutaneous IgG Effectively Controls Parvovirus B19 Infection in a Pediatric Cardiac Transplant Patient With Severe T-Cell Lymphopenia

We treated three pediatric cardiac transplant patients with chronic parvovirus viremia with high-dose intravenous immunoglobulin (HD-IVIG). One patient with severe T-cell lymphopenia suffered recurrent viremia and aseptic meningitis, which resolved remarkably when he was switched to high-dose hyaluronidase-facilitated subcutaneous immunoglobulin (HD-SCIG-Hy). We discuss the advantages of HD-SCIG-Hy vs HD-IVIG treatment for similar cases

Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study

Purpose: To evaluate the safety and tolerability of subcutaneous IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) administered at high infusion parameters (\u3e 25 mL and \u3e 25 mL/h per injection site) in patients with primary immunodeficiency. Methods: The Hizentra® Label Optimization (HILO) study was an open-label, parallel-arm, non-randomized study (NCT03033745) of IgPro20 using a forced upward titration design for infusion parameters. Patients experienced with pump-assisted IgPro20 infusions received weekly IgPro20 infusions at a stable dose in the Pump-Assisted Volume Cohort (N = 15; 25-50 mL per injection site) and in the Pump-Assisted Flow Rate Cohort (N = 18; 25-100 mL/h per injection site). Responder rates (percentage of patients who successfully completed ≥ 75% of planned infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated. Results: Responder rates were 86.7% (13/15, 25 mL) and 73.3% (11/15, 40 and 50 mL) in the Volume Cohort, and 77.8% (14/18, 25 and 50 mL/h), 66.7% (12/18, 75 mL/h), and 61.1% (11/18, 100 mL/h) in the Flow Rate Cohort. Infusion compliance was ≥ 90% in all patients in the Volume Cohort and in 83.3% of patients in the Flow Rate Cohort. The number of injection sites (Volume Cohort) and the infusion duration (Flow Rate Cohort) decreased with increasing infusion parameters. The rate of treatment-emergent adverse events per infusion was low (0.138 [Volume Cohort] and 0.216 [Flow Rate Cohort]). Serum IgG levels remained stable during the study. Conclusion: Pump-assisted IgPro20 infusions are feasible at 50 mL and 100 mL/h per injection site in treatment-experienced patients, which may result in fewer injection sites and shorter infusion times