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Purpose of Review: B cell disorders result in decreased levels or function of immunoglobulins in an individual. Genetic mutations have been reported in a variety of B cell disorders. This review, in follow-up to a previous review, describes some rare B cell disorders as well as their known underlying genetic etiologies., Recent Findings: Genetic studies identify and permit precise classification of an increasing number of B cell disorders, leading to a greater understanding of B cell development and function. The B cell disorders are rare diseases. While clinicians are most familiar with X-linked agammaglobulinemia and so-called common variable immunodeficiency (CVID), there are many causes of hypogammaglobulinemia. Genetic testing provides a specific diagnosis, offers useful information for genetic counseling, and can identify previously unrecognized B cell disorders.

Purpose of Review: The advent of enhanced genetic testing has allowed for the discovery of gene defects underlying two broad categories of antibody deficiency in children: agammaglobulinemia and common variable immunodeficiency (CVID). This review describes the underlying gene defects and the clinical manifestations., Recent Findings: Because novel monogenetic defects have been discovered in both categories, a strict dichotomous classification of B cell disorders as either X-linked agammaglobulinemia or common variable immunodeficiency is no longer appropriate. Advances in genetic testing technology and the decreasing cost of such testing permit more precise diagnosis of B cell disorders, more helpful information for genetic counselors, and a better understanding of the complex process of B cell development and function. More disorders await discovery.

Purpose: Allergic rhinitis (AR) is a highly prevalent disease, affecting the quality of life of millions of Americans. Intranasal corticosteroids (INCs) are widely recommended as first-line therapy for moderate to severe AR. Although these drugs exhibit similar safety and efficacy, a potentially differentiating factor within this class is the varying sensory attributes associated with each INC. The objective of this literature review was to evaluate product characteristics, sensory attributes, and patient preferences of fluticasone furoate intranasal spray (FFNS) compared with other INCs., Methods: A narrative literature search for studies evaluating FFNS was performed in MEDLINE and Google Scholar. Key terms included "allergic rhinitis," "anti-allergic agents," "intranasal administration," "fluticasone furoate," and "patient preference." Studies published from 2007 to present were included. Nine trials met the search criteria, each evaluating FFNS versus placebo or other INCs for efficacy, safety, and/or preference, and were included. Approximately 2400 patients with AR were enrolled across varying study protocols., Findings: In 4 placebo-controlled trials, FFNS showed significant efficacy in relieving symptoms of AR and a tolerable safety profile. Three trials evaluating FFNS and fluticasone propionate nasal spray (FPNS) found that FFNS was significantly preferred over FPNS regarding scent, aftertaste, and leakage down the throat/nose. The results of 2 trials found that FFNS was preferred overall over mometasone furoate nasal spray (MFNS)., Implications: INCs are effective first-line treatments for AR and show significant reduction in nasal and ocular symptoms. Patients preferred the scent, aftertaste, and mist gentleness of FFNS ∼2:1 over the same sensory attributes of FPNS. Patients experienced less negative sensory characteristics with FFNS compared with MFNS, preferring FFNS to MFNS overall. Selecting an INC with favorable attributes in accordance with patient preferences could potentially improve adherence, therapeutic outcomes, and health care costs., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Many genetic conditions predispose affected individuals to opportunistic infections. A number of immunodeficiency diseases, including genetic defects termed Mendelian susceptibility to mycobacterial disease (MSMD), permit infection from many different strains of mycobacteria that would otherwise not cause disease. These include tuberculous and nontuberculous mycobacteria, and bacille Calmette-Guérin vaccine (BCG). Patients may present with infections from other organisms that depend on macrophage function for containment. Defects in multiple genes in the IL-12 and NFKB signaling pathways can cause the MSMD phenotype, some of which include IL12RB1, IL12B, IKBKG, ISG15, IFNGR1, IFNGR2, CYBB, TYK2, IRF8, and STAT1., Recent Findings: Multiple autosomal recessive and dominant, and 2 X-linked recessive gene defects resulting in the MSMD phenotype have been reported, and others await discovery. This review presents the known gene defects and describes clinical findings that result from the mutations. If MSMD is suspected, a careful clinical history and examination and basic immunodeficiency screening tests will narrow the differential diagnosis. A specific diagnosis requires more sophisticated laboratory investigation. Genetic testing permits a definitive diagnosis, permitting genetic counseling. Mild cases respond well to appropriate antibiotic therapy, whereas severe disease may require hematopoietic stem cell transplantation.

Purpose: Allergic rhinitis is a highly prevalent disease affecting the quality of life of millions of North Americans. The management of allergic rhinitis includes allergen avoidance, pharmacotherapy, and immunotherapy. Current pharmacologic options include oral and intranasal antihistamines, intranasal corticosteroids, oral and intranasal decongestants, oral and intranasal anticholinergics, and leukotriene receptor antagonists. Second-generation oral antihistamines and intranasal corticosteroids are the mainstays of treatment, with practice guidelines recommending intranasal corticosteroids as first-line treatment for moderate to severe allergic rhinitis., Methods: Clinical trials studying a widely used intranasal corticosteroid, fluticasone propionate, in comparison with second-generation oral antihistamines, cetirizine, loratadine, or montelukast, were selected to support the comparative review of the efficacy and tolerability of these 2 classes of medications. Studies evaluating the combination of fluticasone propionate with an oral antihistamine were also included to review the efficacy and tolerability of combination therapy to treat allergic rhinitis., Findings: Studies comparing fluticasone propionate with cetirizine had mixed findings; fluticasone propionate was found to have equal or greater efficacy in reducing nasal symptom scores. Combination therapy of fluticasone propionate and the oral antihistamine, loratadine, was found to have efficacy comparable with that of intranasal corticosteroid alone., Implications: Many of these medications are available over the counter in the pharmacy, and the community pharmacist plays an important role as part of the patient's health care team in managing this disease. Pharmacotherapy is patient-specific, based on type, duration, and severity of symptoms, comorbidities, prior treatment, and patient preference. This article aims to provide an overview of the pathophysiology, available treatment options, guideline recommendations, and role of the pharmacist for this disease., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Healthy children may develop candidal infections as the result of exposure to antibiotics or corticosteroids, but chronic candidiasis in children after the newborn period is unusual. Chronic mucocutaneous candidiasis (CMC) refers to a group of conditions characterized by recurrent or persistent infections with Candida species, particularly Candida albicans. CMC is a phenotype observed in a spectrum of immunologic disorders, some with endocrinologic and autoimmune features., Recent Findings: CMC can arise secondary to inherited or acquired T cell deficiencies, but in children is largely due to inborn errors impairing the dectin pathway and IL-17 immunity. We review the current understanding of the pathogenesis of chronic mucocutaneous candidiasis and discuss the immunologic pathways by which the immune system handles Candida. We highlight the historical and recent knowledge of CMC in children, emphasizing recent insights into basic science aspects of the dectin pathway, IL-17 signaling, consequences of AIRE gene defects, and clinical aspects of inheritance, and features that distinguish the different syndromes. The clinical phenotype of CMC has many underlying genetic causes. Genetic testing is required for definitive diagnosis.

A recreational scuba diver wore a second scuba regulator against his face during a scuba dive, attached by an elastic rubber cord necklace. After surfacing, the diver's left face became swollen. Through a process of elimination all other items of scuba equipment were excluded as potential causes. A dive with the same equipment minus the necklace confirmed the involvement of the necklace in the pathogenesis of the hypersensitive reaction. In vitro ImmunoCap IgE assay was positive to latex (1.30 kUa/L), subsequent patch testing for contact dermatitis provoked a reaction for benzophenone-4, (a UV stabalizer) and Fourier Transform Infra Red spectroscopy identified the elastic as ethylene propylene rubber, containing additional unidentified compounds. Allergy to natural rubber latex occurs in as many as 6% of Americans and Australians. Around three million American residents are thought to scuba dive each year. Recreational divers are, therefore, advised to check such necklaces, which are typically worn around the throat, for frayed ends and exposed rubber filaments., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The ability to perceive the onset and severity of symptoms of worsening asthma is important, not only for initial diagnosis but also for early identification of an asthma exacerbation and prompt management. There are subjective and objective methods for identifying symptoms. Symptom perception is affected by multiple mechanisms, and not all patients can accurately perceive symptoms of airflow limitation. Hyperperceivers will report substantial discomfort in the face of minimal bronchoconstriction, and poor perceivers will report no symptoms even in the presence of severe obstruction. The use of objective measures of airflow limitation is essential for such patients. Regimens for training perception in children and adults have been studied and are available.

Background: Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells., Methods: We used whole-exome sequencing and array-based comparative genomic hybridization to evaluate a subset of patients with CVID and low B-cell numbers. Mutant proteins were analyzed for DNA binding with the use of an electrophoretic mobility-shift assay (EMSA) and confocal microscopy. Flow cytometry was used to analyze peripheral-blood lymphocytes and bone marrow aspirates., Results: Six different heterozygous mutations in IKZF1, the gene encoding the transcription factor IKAROS, were identified in 29 persons from six families. In two families, the mutation was a de novo event in the proband. All the mutations, four amino acid substitutions, an intragenic deletion, and a 4.7-Mb multigene deletion involved the DNA-binding domain of IKAROS. The proteins bearing missense mutations failed to bind target DNA sequences on EMSA and confocal microscopy; however, they did not inhibit the binding of wild-type IKAROS. Studies in family members showed progressive loss of B cells and serum immunoglobulins. Bone marrow aspirates in two patients had markedly decreased early B-cell precursors, but plasma cells were present. Acute lymphoblastic leukemia developed in 2 of the 29 patients., Conclusions: Heterozygous mutations in the transcription factor IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-cell numbers. (Funded by the National Institutes of Health and others.).