Severe food allergy reactions are associated with α-tryptase.

BACKGROUND: Increased TPSAB1 copy numbers encoding ⍺-tryptase are associated with severe reactions in adults with Hymenoptera venom allergy, systemic mastocytosis, and idiopathic anaphylaxis. OBJECTIVE: The primary objective was to assess the association between ⍺-tryptase and severity of food allergy. METHODS: A total of 119 subjects underwent tryptase genotyping; 82 of them were from an observational food allergy cohort at the National Institute of Allergy and Infectious Disease (NIAID), and 37 were from a cohort of children who reacted to peanut oral food challenge (OFC) at Lurie Children's Hospital of Chicago. The primary predictor was presence or absence of ⍺-tryptase. The primary outcomes for both cohorts were measures of severity of food allergy reaction. Secondary outcomes included OFC symptom scores (Bock/Practical Allergy [PRACTALL] and Severity Grading Score for Acute Reactions [SGSAR]). Correlation between total α-tryptase isoforms and OFC scores was also assessed to account for gene dosage effects. RESULTS: Among the subjects in the NIAID cohort, the presence of ⍺-tryptase was associated with a higher prevalence of food-triggered anaphylaxis than in those with only ß-tryptase (P = .026). Similarly, only 1 of 6 subjects in the OFC cohort with only ß-tryptase (17%) had a severe reaction, whereas 20 of 31 of subjects with α-tryptase (65%) had a severe reaction (P = .066). Subjects with ⍺-tryptase also had higher total SGSAR scores than did the subjects with no ⍺-tryptase (P = .003). In addition, there were also significant positive correlations between ⍺-tryptase isoform copy numbers and both higher total SGSAR and Bock/PRACTALL OFC scores (P = .008 and P = .003, respectively). CONCLUSION: The presence of α-tryptase in subjects is correlated with a higher prevalence of anaphylaxis or severe reaction to food than in subjects without any α-tryptase.

Natural history of infants with non-SCID T cell lymphopenia identified on newborn screen.

Newborn screening (NBS) for severe combined immunodeficiency (SCID) can identify infants with non-SCID T cell lymphopenia (TCL). The purpose of this study was to characterize the natural history and genetic findings of infants with non-SCID TCL identified on NBS. We analyzed data from 80 infants with non-SCID TCL in the mid-Atlantic region between 2012 and 2019. 66 patients underwent genetic testing and 41 (51%) had identified genetic variant(s). The most common genetic variants were thymic defects (33%), defects with unknown mechanisms (12%) and bone marrow production defects (5%). The genetic cohort had significantly lower median initial CD3+, CD4+, CD8+ and CD4/CD45RA+ T cell counts compared to the non-genetic cohort. Thirty-six (45%) had either viral, bacterial, or fungal infection; only one patient had an opportunistic infection (vaccine strain VZV infection). Twenty-six (31%) of patients had resolution of TCL during the study period.

Risk Factors and Comorbidities in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a heterogeneous disorder that creates a significant burden on the healthcare system. It is caused by a combination of inflammatory, environmental, and host factors; however, the precise mechanism of how each factor leads to CRS continues to be a source of debate. Previous data regarding this topic is often inconsistent or of lower quality. In this article, we review the recent literature on the risk factors and comorbidities in CRS. Large population-based studies have helped establish smoking as a significant risk factor for CRS. The focus has now shifted towards smoking and its effect on long-term outcomes after endoscopic sinus surgery (ESS). Ciliary dyskinesia, both primary and secondary, can affect both the sinonasal cavity and lower airways simultaneously by decreasing the beat frequency of cilia and inducing mucostasis. The effects of secondary dyskinesia may be reversible and there is some evidence to suggest the use of topical mucolytics in patients with CRS. Allergy and variants of sinonasal anatomy have been hypothesized to increase the risk of developing CRS by inducing chronic inflammation and obstructing the sinus ostia. Nevertheless, emerging data regarding these topics continue to produce inconclusive results. Inflammation of the upper and lower airways can occur simultaneously as seen in patients with asthma and aspirin sensitivity. The connection between these pro-inflammatory disease states has been known for many years. Newer evidence include large population-based studies and studies that correlate objective tests, such as computer tomography scans to pulmonary function tests. However, the treatment of CRS and its effects on obstructive airway disease continues to be a topic of debate. More large prospective studies are needed in order to continue refining our knowledge of the disease processes in CRS.

Interventions for anxiety and depression in patients with atopic dermatitis: a systematic review and meta-analysis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with anxiety and depression. Few studies have addressed interventions for symptoms of anxiety and depression in this population. To determine the efficacy of interventions for anxiety and depression in patients with AD. PubMed, MEDLINE, EMBASE, and PsycINFO were searched from inception to November 2023. English-language studies published in peer-reviewed journals evaluating the effect of interventions on anxiety and/or depression using validated assessment tools on patients with AD were included. Titles, abstracts, and articles were screened by at least two independent reviewers. Of 1410 references that resulted in the initial search, 17 studies were included. Fourteen of these studies are randomized controlled trials, while the other 3 studies are prospective controlled trials with pre and post-test designs. Data were extracted using a standardized extraction form, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. To accommodate trials with multiple interventions (each compared to a control group), we conducted a mixed-effects meta-analysis with the trial as a random effect. Prespecified outcomes were changes in symptoms of anxiety and depression in patients with AD as evaluated using standardized assessment tools. Of the 17 studies included in this systematic review, 7 pharmacological intervention studies with 4723 participants examining 5 different medications were included in a meta-analysis. Of these studies, only 1 study evaluated medications prescribed to treat anxiety and/or depression; the rest evaluated medications prescribed to treat AD. Meta-analysis of all the pharmacological interventions resulted in significant improvement in anxiety, depression, and combined anxiety-depression scale scores (standardized mean difference [95% CI]: - 0.29 [- 0.49 to - 0.09], - 0.27 [- 0.45 to - 0.08], - 0.27 [- 0.45 to - 0.08]) respectively. The 10 non-pharmacological studies with 2058 participants showed general improvement in anxiety but not depression. A meta-analysis of the non-pharmacological interventions was not conducted due to variable approaches and limited data. Pharmacological interventions designed to improve AD were found to improve anxiety and depression in patients with moderate-severe disease. More comprehensive studies on non-pharmacological and pharmacological interventions that primarily target anxiety and depression are needed.

Challenge of food allergy testing and avoidance in children with atopic dermatitis.

Atopic dermatitis (AD) is a common presenting complaint by children and their caretakers to their primary care providers. On testing, children with AD frequently exhibit positive food-specific IgE levels in the absence of immediate allergic reactions. Misinterpretation of these false positive tests can lead to unnecessary food avoidance, which can have tremendous psychosocial, economic and nutritional consequences and, in some cases, facilitate the development of an immediate hypersensitivity to the food. We present a child with persistent AD who underwent broad testing that led to unnecessary food avoidance resulting in Vitamin D deficiency, growth failure and the development of an IgE-mediated food allergy. This case underscores the need for caution by primary care clinicians in using food avoidance diets as a treatment for AD and the importance of limiting allergy testing to foods only when the clinical history indicates an immediate hypersensitivity reaction.

Fatal autoimmune pneumonitis requiring bilobectomy and omental flap repair in a patient with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

We present a severe case of progressive autoimmune pneumonitis requiring surgical intervention in a patient with the monogenic syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). APECED is caused by loss-of-function mutations in the autoimmune regulator (AIRE) gene, which lead to impaired central immune tolerance and autoimmune organ destruction including pneumonitis, an underrecognized, life-threatening complication. When clinicians evaluate patients with pneumonitis, recurrent mucosal candidiasis, and autoimmunity, APECED should be considered in the differential. Additionally, in patients with established APECED, a chest computed tomography is preferred to identify pneumonitis early on and to promptly initiate lymphocyte-directed immunomodulatory treatment, which can prevent irreversible lung destruction.