Kyla J. Hildebrand

Human primary immunodeficiencies causing defects in innate immunity.

Purpose of reviewThere have been exciting recent advances in identifying new mutations that cause human primary immunodeficiencies which impact innate immune defences. In this review, we will highlight the most important and influential advances published in the last 18 months related to the defects of the innate immune system. We will also provide clinical context to facilitate the incorporation of these discoveries into clinical practice. Recent findingsWe will specifically focus on three areas that have seen recent significant advances: defects in Toll-like receptor signalling that enhance susceptibility to viral infection, particularly herpes simplex encephalitis; defects in innate immunity that impact phagocyte function predisposing to mycobacterial infection; and the discovery of genes responsible for isolated congenital asplenia. SummaryThe field of innate immunodeficiency has benefited greatly from the recent improvements in genome sequencing technology and has advanced dramatically in the last 18 months. For clinicians confronted with patients with suspected innate immunodeficiency, these new discoveries not only increase the likelihood that a patient will receive a specific molecular diagnosis and tailored therapy, but also add significant complexity to the diagnostic workup. Future challenges will include identifying accurate, cost-effective diagnostic approaches to these novel immunodeficiencies, so these impressive advances in our understanding of innate immunity can be translated into improved health outcomes for our affected patients and their families.

Primum non nocere—first do no harm. And then feed peanut

The Addendum Guidelines for the Prevention of Peanut Allergy in the United States—Report of the NIAID-Sponsored Expert Panel were developed to build on previous food allergy guidelines after several key studies demonstrated the benefit of early introduction of allergenic foods. These landmark studies including the Learning Early about Peanut (LEAP), LEAP-On and Enquiring about Tolerance trials created a paradigm shift in food allergy prevention. The “take home” messages of this guideline include that peanut should be introduced early in the first year of life, and for the majority of infants, peanut can be introduced at home. The only group of infants for which medical assessment is recommended is those with severe eczema, egg allergy or both. Here we summarize the Guideline recommendations, endorsed by the Canadian Society of Allergy and Clinical Immunology, and highlight important aspects relevant to Canadian practitioners.

Impact of supervised epinephrine autoinjector administration during food challenges on parent confidence

the background of numerous plasma cells and foamy histiocytes. Lipid laden vacuoles were also seen (Fig 1F). Thus, a diagnosis of xanthogranulomatous lesion was made. Immunohistochemistry revealed positivity for CD3, CD20, CD68 (histiocyte specific), CD138, and CD134 (blood vessel specific). CD1a, CD30, CD15, and Latent Membrane Protein were negative. Liver and renal function tests results were within normal limits. Enzyme-linked immunosorbent assay results for human immunodeficiency virus, hepatitis B surface antigen, hepatitis C antigen were negative. A diagnostic endoscopy of the nasal cavity was normal. Positron emission tomography confirmed the absence of any systemic involvement. The patient was diagnosed as having adult-onset asthma and periocular xanthogranuloma (AAPOX). He was prescribed oral prednisolone, 1 mg/kg per day, and advised slow taper for a 3month period. He was also prescribed prism glasses to alleviate his double vision. A telephone conversation 45 months later revealed that he is continuing to take low-dose oral steroids (10 mg/d) under the care of a local physician and is symptom free (Fig 1G). The patient has been advised to undergo regular systemic evaluation. Xanthogranulomatous diseases are a group of noneLangerhans cell histiocytosis characterized histopathologically by the presence of Touton giant cells, lymphocytes, plasma cells, and histiocytes. Areas of fibrosis or necrosis may also be seen.1 It may involve the orbit and the adnexa in the following forms: (1) adult-onset xanthogranuloma, (2) AAPOX, (3) necrobiotic xanthogranuloma, or (4) Erdheim-Chester disease. Diseases with predominantly xanthomatized histiocytes form a major part of the non-Langerhan histiocytosis and are of unknown origina.2 Histopathologic and immunohistochemical analysis along with systemic investigations are imperative for accurate diagnosis.1 AAPOX is associated with late-onset asthma with bilateral anterior orbital or preseptal lesions (the overlying skin typically displaying a yellowish tint). Simultaneous involvement of conjunctiva along with the skin and orbit has also been reported.3 Associated lymphadenopathy and paraproteinemia indicate an underlying disorder of B-cell proliferation. Our patient did not have any systemic involvement. Because of the rarity of this disease, the management guidelines are not yet well defined. It is mandatory to perform a thorough search for systemic involvement and to rule out Erdheim-Chester disease, which involves multiple organs and has a devastating course and response to treatment. Fluorodeoxyglucose positron emission tomography and computed tomography are useful as an initial investigation and as a follow-up tool.4 Treatment options for AAPOX comprise systemic steroids, immunosuppressants, and surgery. When the lesions are confined to the anterior orbit, surgery or debulking alone has been successful in a few cases.1,2,5e8 Intralesional steroid injections may be useful in isolated preseptal or anterior orbital involvement but come with the inherent risk of central retinal artery occlusion, ophthalmic artery occlusion, glaucoma, eyelid necrosis, and subcutaneous fat atrophy.9 Systemic steroids are

Mobile health applications in clinical practice: pearls, pitfalls, and key considerations

INSTRUCTIONS Credit can now be obtained, free for a limited time, by reading the review article and completing all activity components. Please note the instructions listed below: Review the target audience, learning objectives and all disclosures. Complete the pre-test. Read the article and reflect on all content as to how it may be applicable to your practice. Complete the post-test/evaluation and claim credit earned. At this time, physicians will have earned up to 1.0 AMA PRA Category 1 CreditTM. Minimum passing score on the post-test is 70%. Overall Purpose Participants will be able to demonstrate increased knowledge of the clinical treatment of allergy/asthma/immunology and how new information can be applied to their own practices. Learning Objectives At the conclusion of this activity, participants should be able to: Describe mobile health applications and the potential benefits associated with use Evaluate a mobile health application in regards to accessibility, content, and privacy Release Date: August 1, 2016 Expiration Date: July 31, 2018 Target Audience Physicians involved in providing patient care in the field of allergy/asthma/immunology Accreditation The American College of Allergy, Asthma & Immunology (ACAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Designation The American College of Allergy, Asthma & Immunology (ACAAI) designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Planning Committee Members Victoria E. Cook, MD (Author) Anne K. Ellis, MD (Author) Kyla J. Hildebrand, MD, FRCPC, MScCH, (HPTE), (Author) Jonathan A. Bernstein, MD (CME Subcommittee) Guha Krishnaswamy, MD (CME Subcommittee) John J. Oppenheimer, MD (CME Subcommittee, Associate Editor) Mitchell H. Grayson, MD (CME Series Editor, Deputy Editor)

Epinephrine auto injector administration by parents or patients for anaphylaxis during supervised oral food challenges and assessment of confidence

Background Barriers to administering epinephrine auto injectors include failure to recognize signs and symptoms of anaphylaxis, administering oral antihistamines or asthma inhalers due to lack of education, failing to administer epinephrine correctly, fear of giving a needle, auto injector misplaced, and past experiences with spontaneous recovery. The aim of this study is to assess the impact of supervised auto injector administration by parents/patients on confidence, knowledge and skill for future treatment of severe allergic reactions. Methods

Early introduction of foods to prevent food allergy

Food allergy is a growing public health problem, and in many affected individuals, the food allergy begins early in life and persists as a lifelong condition (e.g., peanut allergy). Although early clinical practice guidelines recommended delaying the introduction of peanut and other allergenic foods in children, this may have in fact contributed to the dramatic increase in the prevalence of food allergy in recent decades. In January 2017, new guidelines on peanut allergy prevention were released which represented a significant paradigm shift in early food introduction. Development of these guidelines was prompted by findings from the Learning Early About Peanut Allergy study—the first randomized trial to investigate early allergen introduction as a strategy to prevent peanut allergy. This article will review and compare the new guidelines with previous guidelines on food introduction, and will also review recent evidence that has led to the paradigm shift in early food introduction.

Case 3: Persistent Fever in an 8-month-old Boy

1. Megan Kilvert, MD* 2. Ashley Roberts, MD, MEd† 3. Kyla J. Hildebrand, MD, MScCH‡ 1. *Department of Pediatrics, 2. †Department of Infectious Diseases, and 3. ‡Department of Clinical Allergy and Immunology, BC Children’s Hospital, Vancouver, British Columbia, Canada An 8-month-old unimmunized fraternal-twin boy, born at term, presents to the hospital with fever, cough, rhinorrhea, and right-sided neck swelling with drainage. On history, the fever and neck swelling began 7 weeks earlier, at which time he presented to a rural hospital where ultrasonography confirmed a cervical lymph node abscess. The abscess spontaneously drained and was positive for Staphylococcus aureus. He was treated with intravenous (IV) cefotaxime for 6 days, followed by 14 days of oral cefuroxime. The fever resolved completely after 4 days of treatment, but the neck lesion continued to drain during the next 7 weeks. One week before his presentation to our hospital, he had recurrence of daily fever (to 104°F [40°C]) associated with neck drainage, cough, and rhinorrhea. Further history reveals an otherwise healthy infant boy with normal energy, appetite, and appropriate development. There is no history of weight loss, night sweats, or risk factors for tuberculosis. The boy is febrile (to 103.1°F [39.5°C]), with otherwise normal vital signs. Growth plots on the 25th percentile for weight and length. The site of …