Disclosures: Anna M Feldweg, MD Nothing to disclose. Elizabeth TePas, MD, MS Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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
New biologic therapy approved for severe eosinophilic asthma (November 2015)
Mepolizumab, a monoclonal antibody to interleukin (IL)-5, has been approved by the US Food and Drug Administration for add-on, maintenance treatment of severe asthma in patients who are age 12 or older, have frequent asthma exacerbations, and have an eosinophilic phenotype . One marker of an eosinophilic phenotype is an absolute eosinophil count in peripheral blood of ≥150/microL. Studies in patients with severe eosinophilic asthma have shown that mepolizumab reduces the rate of exacerbations  and enables a reduction in the oral glucocorticoid dose. Mepolizumab is administered subcutaneously at four-week intervals. Based on a small increase in herpes zoster in treated adults, we suggest that patients who meet criteria for the varicella-zoster vaccine be immunized at least four weeks prior to initiation of mepolizumab. Mepolizumab will likely be commercially available in early 2016. (See "Treatment of severe asthma in adolescents and adults", section on 'Anti-IL-5 therapy'.)
Soy isoflavone supplementation does not improve asthma control (June 2015)
Patients with asthma often request guidance on dietary alterations that might improve asthma control. Preliminary studies suggested that soy isoflavone supplementation might fill this role, possibly by a reduction in eosinophil leukotriene synthesis. However, in a 24-week multicenter trial that included 386 adults and children age 12 or older with poorly controlled asthma, isoflavone supplementation did not significantly improve pulmonary function, symptom scores, episodes of poor asthma control, or exhaled nitric oxide . High-quality studies are essential to determining the efficacy of dietary adjustments; this study demonstrates that soy isoflavone supplements are not useful in poorly controlled asthma. (See "Complementary, alternative, and integrative therapies for asthma", section on 'Dietary changes and supplements'.)
Investigational agent shows promise in asthma (June 2015)
GATA3 is a transcription factor that is essential for Th2 lymphocyte differentiation and activation. An investigational synthetic DNA molecule (SB010) has been developed that uniquely binds to GATA3 messenger RNA and cleaves it. The effect of SB010 was assessed in 43 patients with mild allergic asthma who were randomly assigned to inhalation of SB010 or placebo once daily for 28 days . The early and late asthmatic responses to allergen bronchoprovocation were significantly attenuated by SB010. The degree of suppression of the late response was similar to that of inhaled glucocorticoids. This study supports a potential role for disruption of GATA3 (and thus Th2 cytokines) in asthma. (See "Investigational agents for asthma", section on 'GATA3-specific DNAzyme'.)
Eosinophilia during prolonged antibiotic therapy (June 2015)
Eosinophilia is not uncommon in patients receiving prolonged intravenous (IV) antibiotics, but the prevalence and significance has not been extensively studied. In a prospective cohort study of 824 patients receiving prolonged intravenous antibiotic therapy, eosinophilia developed in 25 percent, appearing at a median of 15 days of therapy and peaking at a median absolute count of 726/mL (500 to 8610/mL) . Although most patients with eosinophilia completed their courses without complications, one-third developed a hypersensitivity reaction involving rash or hepatic or renal involvement. Medication-associated eosinophilia does not mandate discontinuation of therapy but warrants close monitoring for evidence of hypersensitivity and consideration of alternative medications that could be substituted without compromising care. (See "Approach to the patient with unexplained eosinophilia", section on 'Medications and over the counter remedies'.)
Low allergic cross-reactivity between penicillins and carbapenems (May 2015)
Carbapenems (eg, imipenem, meropenem) share a common beta-lactam ring with penicillins and hence the potential for allergic cross-reactivity, and some drug information systems list penicillin allergy as a contraindication to the use of carbapenems (figure 1). In the largest study to date, 212 patients with allergy to penicillins, confirmed by skin testing, were then tested with carbapenems . All subjects were negative to carbapenem skin testing and tolerated graded challenges to three different carbapenems. Based on this and other series, the rate of reactivity to carbapenems in patients with confirmed penicillin allergy is estimated at <1 percent. This supports our current recommendations on administration of carbapenems to patients reporting immediate-type penicillin allergy: Perform penicillin skin testing when available. If negative, patients may safely receive penicillins and carbapenems. If penicillin skin testing is positive or not available, carbapenems may be administered via a graded challenge. (See "Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams", section on 'Carbapenems'.)
FOOD ALLERGY AND INTOLERANCE
n-3 LCPUFA supplementation in pregnancy and allergies in offspring (November 2015)
It has been hypothesized that maternal intake of long chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy may prevent development of allergies in offspring. However, a recent systematic review of randomized trials assessing the effect of n-3 LCPUFA supplementation during pregnancy and/or breastfeeding on allergy outcomes in offspring found supplementation did not significantly reduce childhood allergic disease (food allergy, atopic dermatitis, allergic rhinitis, asthma) at 36 months of age compared with no treatment/placebo . (See "Fish consumption during pregnancy", section on 'Other outcomes'.)
Transient transfer of food allergies in a blood product (September 2015)
A recent case report highlights the possibility of acquiring food allergies following transfusion of a blood product such as platelets . This may also occur after solid organ or hematopoietic cell transplantation. In the former case, the allergy is transient and is due to food-specific immunoglobulin E (IgE) in the blood product. In the latter case, the potential mechanism depends upon the type of transplant and can range from temporary allergy due to transferred mast cells or allergen-specific IgE, to longer-lasting or permanent allergy due to transfer of food allergen-specific lymphocytes or hematopoietic stem cells from the donor. Finally, an allergic reaction to a food can occur in an allergic recipient after receiving a blood product that contains intact allergen consumed by the donor. (See "History and physical examination in the patient with possible food allergy", section on 'Questions related to contributory factors'.)
Updated guidelines for the diagnosis and management of primary immunodeficiency (November 2015)
A revised “Practice parameter for the diagnosis and management of primary immunodeficiency,” developed by the three national allergy and immunology societies in the United States, has been published to aid allergy/immunology specialists and other practitioners in the recognition, diagnosis, and general management of these disorders . Highlights include screening and advanced laboratory tests for the different components of immune function, characteristic clinical manifestations and laboratory findings for a number of disorders, internet resources, antibiotic prophylaxis, and indications for hematopoietic cell transplantation or gene therapy. There are now more than 200 genetically distinct disorders of immune function that are classified using the system devised by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS). Consultation with an immunology specialist with experience in diagnosing and managing primary immunodeficiencies is recommended. Our approach is consistent with that outlined in this practice parameter. (See "Approach to the child with recurrent infections" and "Laboratory evaluation of the immune system" and "Medical management of immunodeficiency".)
Pulmonary manifestations in adults with chronic granulomatous disease (June 2015)
Pulmonary complications remain the most common manifestation of chronic granulomatous disease (CGD) in adulthood. In a series of 67 adults with CGD, two-thirds had at least one infectious or noninfectious pulmonary event, and about half had manifestations involving the gastrointestinal tract or skin . Most patients with invasive pulmonary fungal infections were on itraconazole prophylaxis, although serum azole concentrations were low in the majority of the patients tested. One-third of patients with pulmonary complications, including invasive fungal infections, were asymptomatic. Serial screening for elevated inflammatory markers, such as C-reactive protein (CRP), followed by imaging of the suspected organ(s) involved if levels are elevated, are suggested to monitor for and diagnose infection. (See "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Sites of infection' and "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pulmonary' and "Chronic granulomatous disease: Treatment and prognosis", section on 'Antifungal prophylaxis' and "Pulmonary complications of primary immunodeficiencies", section on 'Chronic granulomatous disease' and "Chronic granulomatous disease: Treatment and prognosis", section on 'Monitoring and diagnosis'.)
Dedicator of cytokinesis 2 deficiency (June 2015)
Dedicator of cytokinesis 2 (DOCK2) deficiency is a newly recognized combined immunodeficiency (CID). Biallelic (homozygous or compound heterozygous) mutations in the DOCK2 gene were identified through whole-exome sequencing in a group of unrelated patients with early-onset invasive bacterial and viral infections, lymphopenia, and defective T, B, and NK cell responses . DOCK2 deficiency results in impaired activation of RAC1 that leads to defects in actin polymerization, lymphocyte proliferation and migration, natural killer cell degranulation, and response to viral infections in fibroblasts and peripheral blood mononuclear cells. Other CIDs that are the result of defects in actin regulation include Wiskott-Aldrich syndrome and DOCK8 deficiency. (See "Combined immunodeficiencies", section on 'Dedicator of cytokinesis 2 deficiency'.)
RHINITIS AND RHINOSINUSITIS
Systematic review of medical therapies for adults with chronic rhinosinusitis (September 2015)
A new systematic review of medical therapies for adults with chronic rhinosinusitis (CRS, both with and without nasal polyposis) concluded that topical glucocorticoids and high-volume nasal saline irrigations were the two therapies best supported by evidence . Evidence for the effectiveness of other therapies was conflicting, but the review supports the use of short courses (one to three weeks) of oral glucocorticoids, doxycycline, and leukotriene receptor antagonists for CRS with nasal polyposis, with which UpToDate largely agrees. The review also suggests a trial of long-term macrolide therapy for CRS without polyposis, although evidence for this is weak and UpToDate authors do not agree that benefits outweigh risks (drug resistance, costs, adverse effects) for most patients. More high-quality studies are needed for the optimal treatment of CRS. (See "Chronic rhinosinusitis: Management", section on 'Oral glucocorticoids'.)
URTICARIA AND ANGIOEDEMA
Mechanism proposed for hereditary angioedema with normal C1 inhibitor and FXII mutations (August 2015)
Hereditary angioedema with normal C1 inhibitor is a rare disorder; normal complement studies distinguish this from other forms of hereditary angioedema. Defects in the gene for coagulation factor XII (FXII) are seen in some patients with hereditary angioedema with normal C1 inhibitor but a mechanism linking FXII defects and angioedema has been lacking. A new study proposes that one FXII mutation found in these patients affects a glycosylation site, resulting in increased autoactivation of FXII . Increased FXII autoactivation could lead to enhanced activation of the kallikrein-kinin pathway and excessive bradykinin formation. Thus, a potential mechanism has been identified for the pathogenesis of the hereditary angioedema in patients with normal complement studies and a FXII mutation. (See "Hereditary angioedema with normal C1 inhibitor (type III HAE)", section on 'Mutations in the FXII gene'.)
VACCINES AND VACCINE HYPERSENSITIVITY
Revised schedule for pneumococcal vaccination in older adults (September 2015)
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many years in the United States for all adults ≥65 years of age. In 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending the 13-valent pneumococcal conjugate vaccine (PCV13) for adults ≥65 years of age . In September 2015, the ACIP changed the recommended interval between administration of PCV13 and PPSV23 for immunocompetent adults ≥65 years of age from 6-12 months to ≥1 year to simplify the administration schedule (algorithm 1) . In patients who have already received PPSV23, at least 1 year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Schedule for dual vaccination'.)
US ACIP recommendations for serogroup B meningococcal vaccination (June 2015)
In late 2014 and early 2015, the US Food and Drug Administration approved two serogroup B meningococcal vaccines (Trumenba, MenB-FHbp and Bexsero, MenB-4C). In June 2015, the Advisory Committee on Immunization Practices (ACIP) issued recommendations for serogroup B meningococcal vaccine for high-risk individuals aged 10 years or older; these include individuals with persistent complement component deficiencies, individuals with anatomic or functional asplenia, microbiologists routinely exposed to N. meningitidis isolates, and individuals at increased risk because of a serogroup B meningococcal disease outbreak . These indications overlap with those for the quadrivalent meningococcal conjugate vaccine and are summarized in the table (table 1). Among patients with none of the above risk factors, the ACIP advises discussion between doctors and patients regarding vaccination against serogroup B meningococcus; routine vaccination has not been recommended . (See "Meningococcal vaccines", section on 'Use in United States'.)
OTHER GENERAL ALLERGY AND IMMUNOLOGY
Auvi-Q and Allerject epinephrine autoinjectors recalled by manufacturer (October 2015)
A manufacturer's recall was issued in October 2015 of all Auvi-Q epinephrine autoinjectors in the United States, as well as all Allerject devices in Canada, including both the 0.15 and 0.3 mg strengths, due to potentially inaccurate dose delivery [18,19]. Patients should be provided with a prescription for an alternate epinephrine device and return Auvi-Q and Allerject autoinjectors to their pharmacy for replacement and instruction on how to use the new device. Patients should only use Auvi-Q or Allerject if no other device is available in a severe allergic reaction and then immediately contact 9-1-1 or emergency medical services. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Types of autoinjectors'.)
Prediction model for eosinophilic esophagitis (September 2015)
The distinction between eosinophilic esophagitis and gastroesophageal reflux disease is often difficult to make. A prediction model that incorporated eight clinical and endoscopic features (younger age; male sex; presence of dysphagia and food allergies; presence of esophageal rings, furrows, and plaques; and lack of a hiatal hernia) predicted eosinophilic esophagitis with an accuracy, sensitivity, and specificity of 84, 97, and 92 percent, respectively . However, additional studies are needed to validate this model. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis", section on 'Distinction from GERD'.)
Stevens-Johnson syndrome outbreak associated with M. pneumoniae (August 2015)
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe blistering mucocutaneous reaction, most commonly triggered by medications, characterized by extensive necrosis and detachment of the epidermis and mucosa. Mycoplasma pneumoniae and cytomegalovirus infections are the next most common trigger of SJS/TEN, particularly in children. Between September and November 2013, an outbreak of eight pediatric cases of M. pneumoniae-associated SJS/TEN was reported in Colorado, likely related to high levels of M. pneumoniae infection in the region . All children had severe oropharyngeal mucositis; the conjunctiva was involved in seven children and the genital mucosa in five. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Infection'.)
Influenza vaccine recommendations for 2015-2016 influenza season (August 2015)
In August 2015, the Advisory Committee on Immunization Practices released recommendations for the prevention and control of influenza during the 2015-2016 influenza season in the United States. As in previous seasons, seasonal influenza vaccination is recommended for everyone ≥6 months of age . Changes for the 2015-2016 season include:
●Different influenza A H3N2 and influenza B (Yamagata lineage) antigens than were in the 2014-2015 vaccines
●A simplified dosing algorithm for children six months through eight years (algorithm 2)
●Availability of a quadrivalent intradermal vaccine for adults 18 through 64 years of age (table 2)
Predictors of the need for repeat epinephrine doses in anaphylaxis (August 2015)
Epinephrine is the first-line therapy for anaphylaxis, and retrospective studies suggest that up to one-third of patients may require a second dose. However, predictive factors for requiring more than one dose are not well defined. In a prospective cohort study of over 500 patients (all ages) treated for anaphylaxis in a tertiary care emergency department, 14 percent of those requiring any epinephrine required more than one dose . Patients with a history of previous anaphylaxis, and those presenting with flushing, diaphoresis, or dyspnea, were more likely to require multiple doses of epinephrine to control symptoms. Anaphylaxis is an inherently unpredictable disorder, but this study provides some insight into predictors of a more complicated treatment course and may help clinicians managing such patients. (See "Anaphylaxis: Rapid recognition and treatment", section on 'Dosing and administration'.)
Ease of use of different epinephrine autoinjectors for anaphylaxis (July 2015)
Epinephrine autoinjectors can be life saving for patients with serious allergies, but even with specific training, many people have trouble using the various devices properly. A randomized trial of mothers of food-allergic children, tested in simulated anaphylaxis scenarios, suggested that the Auvi-Q device, a rectangular cassette that has audible instructions to guide the user through the injection process, was easier to use than non-audible pen devices . When prescribing an epinephrine autoinjector, ease of use, cost, the need for multiple injectors, and patient facility with self-injection should all be considered. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Ease of use'.)
Acute worsening of atopic dermatitis due to aeroallergen exposure (July 2015)
Environmental allergens are a trigger of atopic dermatitis (AD) in a small subset of children and adults. Patients who have environmental allergies as a trigger of AD have persistent disease with chronic exposure to an allergen in the environment. A small study of adults with AD demonstrated that exposure to grass pollen in an environmental challenge chamber for two consecutive days resulted in a significant worsening of AD on exposed skin for the five days after challenge compared with exposure to clean air (placebo) . This study shows that an isolated exposure to an aeroallergen can cause an acute flare of AD in sensitized individuals. (See "Role of allergy in atopic dermatitis (eczema)", section on 'Aeroallergens'.)
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