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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
ASTHMA AND COPD
Global asthma mortality (October 2017)
Asthma ranks 32nd as a cause of death worldwide, but mortality varies among countries . Based on World Health Organization (WHO) data, age-standardized death rates per 100,000 individuals aged 5 to 34 years range from 17.16 in India and 1.65 in China to 0.88 in the United States and 0.24 in the Netherlands. In an analysis of the WHO database, asthma mortality was essentially unchanged from 2006 to 2012, after decreasing substantially from 1993 to 2006 . Lower mortality rates correlated with adoption of best practices and more widespread implementation of established asthma management strategies is needed. (See "Identifying patients at risk for fatal asthma", section on 'Mortality statistics'.)
Mepolizumab for eosinophilic granulomatosis with polyangiitis (August 2017)
Mepolizumab is a monoclonal anti-interleukin-5 antibody that is approved for use in severe eosinophilic asthma. In a multicenter trial, 136 patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) were randomly assigned to receive mepolizumab 300 mg (three times the US Food and Drug Administration-approved dose of 100 mg) or placebo subcutaneously every four weeks for 52 weeks . Mepolizumab led to significantly more accrued weeks of remission and a lower frequency of relapse than placebo. Among mepolizumab-treated subjects, 44 percent were able to taper prednisolone to ≤4 mg/day, compared with 7 percent on placebo. While not all patients respond, high-dose mepolizumab may be an additional option for selected patients with EGPA. (See "Treatment and prognosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Anti-IL-5 antibodies'.)
Benralizumab and glucocorticoid-sparing effect in severe asthma (June 2017)
Benralizumab, an investigational anti-IL-5 receptor alpha antibody, appears to have a glucocorticoid-sparing effect in patients requiring oral glucocorticoids to control severe asthma. In a multicenter trial, 220 patients who had ≥150 eosinophils/mL in peripheral blood AND required daily oral glucocorticoids for the previous six months were randomly assigned to one of two benralizumab treatment arms or placebo . The oral glucocorticoid dose was reduced according to a predetermined program (2.5 to 5 mg every four weeks). After 28 weeks, the oral glucocorticoid dose decreased by 75 percent from baseline in the two benralizumab groups, compared with 25 percent in the placebo group. Exacerbation rates were lower in the benralizumab groups despite glucocorticoid tapering, and pulmonary function remained stable. (See "Investigational agents for asthma", section on 'Anti-IL-5 receptor alpha antibodies'.)
Identification of children with low-risk past penicillin reactions (August 2017)
Many children who have mild adverse reactions to penicillins, such as maculopapular rash, hives, or gastrointestinal symptoms, are not allergic and can safely receive this class of antibiotics in the future. In a study of children presenting to an urban emergency department with histories of past penicillin reactions, nearly 600 parents/caregivers completed a questionnaire about the child’s past reaction . The questionnaire included hives as a low-risk feature (for true allergy), but considered facial angioedema as a high-risk feature. One hundred of 434 patients with low-risk reactions were referred to an allergist for evaluation. Ninety-seven had negative skin tests, while three initially had positive skin tests that were negative upon later repeat testing. Ultimately, all 100 children passed oral challenge to amoxicillin. Despite these results, we consider both hives and angioedema as high-risk features and would advocate that children with past reactions involving either of these symptoms be referred to an allergy specialist to determine if penicillins can be safely used again. (See "Penicillin allergy: Delayed hypersensitivity reactions", section on 'Studies in children'.)
Rapid aspirin desensitization in patients with acute coronary syndrome (April 2017)
There are well-established protocols for elective desensitization to aspirin, but fewer studies of approaches in patients needing urgent treatment. In a multicenter observational study of 330 consecutive patients with acute coronary syndrome and past hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs), 95 percent were successfully desensitized to low-dose aspirin using a protocol that could be completed within six hours . The procedure was aborted in 5 percent because symptoms developed during the protocol. While useful, we prefer our own approach because it does not exclude patients who react during the protocol. (See "Diagnostic challenge and desensitization protocols for NSAID reactions", section on 'Our approach'.)
FOOD ALLERGY AND INTOLERANCE
Data limited for probiotic plus oral immunotherapy for peanut allergy (August 2017)
Oral immunotherapy (OIT) for foods is an investigational treatment for food allergies that can lead to temporary desensitization to a food, but the ability of OIT to induce permanent tolerance to the food is less clear. Adding an immunostimulatory adjuvant, such as a probiotic, to OIT may improve sustained unresponsiveness (SU) to the food allergen. In a follow-up study four years after completion of a randomized trial and cessation of treatment, patients treated with peanut OIT plus probiotic were more likely to still be eating peanut and to have SU after eight weeks of avoidance compared with patients treated with placebo only . However, there were significant flaws in the study design, and we await further data before recommending routine use of OIT (with or without an adjuvant). (See "Investigational therapies for food allergy: Oral immunotherapy", section on 'OIT plus adjuvant'.)
National Academies consensus report on food allergies (August 2017)
The National Academies of Sciences, Engineering, and Medicine consensus report on food allergies highlights a number of critical issues related to food allergy .
●Judicious use of food allergy testing, performed and interpreted in the context of the patient's clinical history
●Prompt treatment of anaphylaxis with epinephrine
●Primary prevention of peanut allergy through early dietary introduction
Our approach to the diagnosis and management of food allergies is consistent with the recommendations in this report. (See "Diagnostic evaluation of food allergy", section on 'Role of allergy tests in diagnosis' and "Food-induced anaphylaxis", section on 'Epinephrine' and "Introducing highly allergenic foods to infants and children", section on 'Suggested approach'.)
Four-food elimination diet for eosinophilic esophagitis (July 2017)
The traditional six-food (cow's milk, hen's egg, soy, wheat, peanut/tree nuts, and fish/shellfish) elimination diet for eosinophilic esophagitis (EoE) results in resolution of EoE in approximately three-quarters of children but is challenging and can have negative nutritional consequences. In a prospective study of four-food elimination (milk, soy, egg, wheat) in 78 children with EoE, histologic remission was achieved in 64 percent, with decreased symptoms in 91 percent . Thus, we now suggest either the four-food or six-food empiric elimination diet for most patients who opt for dietary management of EoE. (See "Dietary management of eosinophilic esophagitis", section on 'Elimination diets'.)
Introducing solids in infants with milk or soy FPIES (June 2017)
Food protein-induced enterocolitis syndrome (FPIES) is a nonimmunoglobulin E (IgE)-mediated gastrointestinal food hypersensitivity most commonly caused by cow's milk (CM) or soy protein. Recent international consensus guidelines from the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group provide guidance on the introduction of solid foods in infants with CM or soy FPIES (table 1) . In accordance with these guidelines, for infants with CM or soy FPIES, we suggest introduction of vegetables and then fruits, rather than cereals, at four to six months of age, to reduce the risk of reactions to rice and other grains that may occur among infants with CM or soy FPIES. (See "Food protein-induced enterocolitis syndrome (FPIES)", section on 'Introduction of new foods'.)
New guidelines for management of peanut and tree nut allergies (June 2017)
The most straightforward approach in managing any food allergy is complete avoidance of the culprit food and all similar foods, particularly for peanut and tree nuts. However, some patients may find this approach too burdensome. Reflecting a shift in clinical practice, the recent British Society of Allergy and Clinical Immunology guidelines permit, with certain restrictions, consumption of similar foods after confirming that they are safe, if the patient and family prefer this approach . This guideline for the management of peanut and tree nut allergy is consistent with our approach. (See "Peanut, tree nut, and seed allergy: Management", section on 'Clinical scenarios'.)
Consensus statement on granulomatous and lymphocytic interstitial lung disease (August 2017)
Granulomatous and lymphocytic interstitial lung disease (GLILD) is the most common cause of diffuse parenchymal lung disease in patients with common variable immunodeficiency, but the literature to date has been limited to case reports and small series. The British Lung Foundation and UK Primary Immunodeficiency Network published a consensus statement summarizing the experience of approximately 30 physicians caring for over 100 patients with GLILD . It includes a proposed definition for the disorder, as well as several statements about diagnosis and first-line therapy, and is intended to provide preliminary guidance for care and future research. (See "Pulmonary complications of primary immunodeficiencies", section on 'Granulomatous and lymphocytic interstitial lung disease'.)
RHINITIS AND RHINOSINUSITIS
Sublingual immunotherapy tablet for house dust mite allergy (April 2017)
A house dust mite (HDM) sublingual immunotherapy tablet was approved in the United States by the US Food and Drug Administration (FDA) for treatment of HDM-induced allergic rhinitis with or without conjunctivitis (AR/C) in adults (ages 18 to 65) . HDM tablet immunotherapy is available in Europe, Australia, and Asia. Approval was based on several studies, including a recent randomized trial of over 1400 subjects with HDM-induced AR/C with or without asthma, who received HDM tablets or placebo daily for 52 weeks . The total combined rhinitis score improved by 17 percent compared with placebo, with no serious treatment-related adverse events. Treatment is given daily for at least one year. Further study is needed to define the optimal duration of therapy and to what extent the effect persists after therapy is stopped. (See "Sublingual immunotherapy for allergic rhinoconjunctivitis and asthma", section on 'Availability'.)
URTICARIA AND ANGIOEDEMA
Subcutaneous C1 inhibitor for hereditary angioedema (April 2017, Modified September 2017)
Patients with hereditary angioedema (C1 inhibitor deficiency) develop attacks of angioedema affecting the skin, gastrointestinal tract, and airway, which can be prevented with intravenous infusions of C1 inhibitor, typically given twice weekly. Subcutaneous administration should significantly facilitate self-treatment. In a randomized multicenter trial of 90 children and adults, participants injected a subcutaneous formulation of C1 inhibitor or placebo twice weekly for 16 weeks . Therapy was well tolerated and participants receiving active drug had fewer attacks per month (mean 0.5 versus 4.0 attacks). This formulation was approved for prophylaxis by the US Food and Drug Administration (FDA) in June 2017 and is an appropriate option for patients who prefer this form of administration. Approval in Europe is anticipated in the near future. (See "Hereditary angioedema: General care and long-term prophylaxis", section on 'Subcutaneous C1 inhibitor'.)
Mixed data regarding icatibant in ACE inhibitor-induced angioedema (August 2017)
Although the bradykinin receptor antagonist icatibant has proven efficacy in hereditary angioedema, particularly when given soon after onset of symptoms, evidence is mixed regarding its utility in angiotensin-converting enzyme inhibitor-associated angioedema (AceIA). In a randomized trial of 121 patients with AceIA of the head or neck, icatibant did not decrease the time to discharge relative to placebo . Therefore, careful airway management, rather than icatibant, remains the primary intervention for most cases of AceIA, although icatibant may have a role in rare instances when patients present very early. (See "ACE inhibitor-induced angioedema", section on 'Icatibant'.)
New mutation in hereditary angioedema with normal C1 inhibitor (July 2017)
Most patients with hereditary angioedema have deficiency or dysfunction of C1 inhibitor, but a subset have no identifiable complement abnormalities. Within this subgroup, mutations in the gene for factor XII account for the disease in some families, while pathogenesis in the remainder has been unexplained. Now, a mutation has been identified in the gene encoding angiopoietin-1 (ANGPT1), a glycoprotein that inhibits bradykinin-induced plasma leakage, in one Italian family . The mutation was present in four symptomatic women and absent in seven asymptomatic relatives. Understanding of the genetic basis of this disease is gradually expanding, and other mutations potentially leading to the hereditary angioedema phenotype will likely be found over time. (See "Hereditary angioedema with normal C1 inhibitor", section on 'Other mutations'.)
Systemic symptoms in patients with chronic idiopathic urticaria (June 2017)
Patients with chronic idiopathic urticaria (CIU) sometimes report accompanying systemic symptoms, although the prevalence of such symptoms has not been specifically examined. In a study of 155 CIU patients presenting to a referral allergy clinic, 66 percent reported systemic symptoms, including headache, fatigue, joint pain or swelling, wheezing, flushing, gastrointestinal symptoms, and palpitations . Patients with systemic symptoms had a greater disease burden compared with those without symptoms. Although this study population was probably skewed towards more severe disease, it is helpful to recognize that systemic symptoms are not uncommon in CIU. (See "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history", section on 'Systemic symptoms'.)
Glucocorticoids not necessary for simple acute urticaria (May 2017)
Although patients with urticaria and symptoms involving other organ systems are treated with epinephrine given the likelihood of anaphylaxis, H1 antihistamines are the initial treatment for those with isolated urticaria. For such patients, the additive benefit of glucocorticoids is not well defined. In a randomized trial of 100 adults presenting to the emergency department with isolated urticaria (without angioedema, anaphylaxis, or fever) of ≤24 hours duration, patients received the H1 antihistamine levocetirizine plus either prednisone or placebo for four days . There was no significant difference in the rate of symptom resolution, and most patients were symptom-free within two days. This study supports our suggestion to reserve glucocorticoids for those patients with new urticaria who have prominent angioedema or whose symptoms persist despite antihistamines. (See "New-onset urticaria", section on 'Glucocorticoids'.)
VACCINES AND VACCINE HYPERSENSITIVITY
2017-2018 influenza immunization recommendations for the United States (September 2017)
The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) have released recommendations for influenza immunization for the 2017-2018 season in the United States [20,21]. Routine influenza immunization with a licensed, age-appropriate vaccine (table 2) is recommended for all persons ≥6 months of age. Live attenuated influenza vaccine is not recommended for the 2017-2018 season. Pregnant women and persons with egg allergy of any severity can receive any licensed, age-appropriate inactivated influenza vaccine with standard immunization precautions. Although neither the ACIP nor the AAP provide a preference for a particular formulation, we favor a quadrivalent vaccine when available for adults <65 years and we recommend the high-dose vaccine for those ≥65 years. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Types of vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Influenza and pregnancy", section on 'Vaccination' and "Influenza vaccination in individuals with egg allergy", section on 'Safety of vaccines in patients with egg allergy'.)
OTHER GENERAL ALLERGY AND IMMUNOLOGY
Midostaurin for advanced systemic mastocytosis (August 2017)
Cytoreductive treatment of advanced systemic mastocytosis (SM) can mitigate organ dysfunction, improve quality of life, and limit disease progression until a suitable donor for allogeneic hematopoietic cell transplant is identified. Midostaurin is a multikinase inhibitor that is effective against SM with wild type or mutant KIT (eg, KIT D816V). A recent phase II study found that midostaurin was associated with improved measures of organ damage (eg, cytopenias, liver function studies) in two-thirds of patients with advanced SM, with median overall survival >3 years , confirming similar findings from an earlier trial . The drug was well tolerated, with primarily grade 1 to 2 nausea/vomiting or modest cytopenias. The US Food and Drug Administration approved midostaurin for treatment of advanced SM earlier this year. We now suggest midostaurin for initial systemic therapy of advanced SM. (See "Systemic mastocytosis: Management and prognosis", section on 'Choice of therapy'.)
Countering the high cost of epinephrine autoinjectors (June 2017)
Physicians and patients in the United States have been struggling with the high cost of epinephrine autoinjectors, and alternatives, as well as ways to maximize the utility of expensive devices, have begun to appear:
●A prefilled syringe (Symjepi) containing 0.3 mg epinephrine per dose was approved by the US Food and Drug Administration (FDA) in June 2017 and should offer a more affordable alternative to autoinjectors . It will be available in upcoming months in just one dose, labeled for use in patients weighing ≥30 kg (66 lbs). (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Prefilled syringes'.)
●A study of 31 expired autoinjectors (EpiPens) found that devices as much as four years past the expiration date still contained 84 to 88 percent of the intended epinephrine dose . Thus, patients should understand that expired devices retain most of their potency and that if anaphylaxis develops, using an outdated device is preferable to not injecting epinephrine at all. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Use of expired autoinjectors'.)
Dupilumab for moderate to severe atopic dermatitis (April 2017)
Dupilumab is an interleukin-4 receptor alpha antagonist being evaluated in atopic dermatitis. In two 16-week clinical trials (SOLO1 and SOLO2), dupilumab was more effective than placebo in improving the signs and symptoms of atopic dermatitis . Based on these results, the US Food and Drug Administration has approved dupilumab for the treatment of adult patients with moderate to severe atopic dermatitis not adequately controlled with topical prescription therapies . While the role for dupilumab is still evolving, it appears to be a reasonable option for adult patients with severe disease who have failed other systemic therapies. (See "Treatment of atopic dermatitis (eczema)", section on 'Dupilumab'.)
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