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What's new in allergy and immunology
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What's new in allergy and immunology

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.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2015. | This topic last updated: May 01, 2015.

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

Warning about use of non-prescription asthma treatments (April 2015)

The US Food and Drug Administration (FDA) released a consumer warning about the potential health risks of over-the-counter (OTC) homeopathic products for asthma [1]. The efficacy and safety of OTC products are not evaluated by the FDA. In addition, there is evidence that some non-prescription therapies, such as racemic epinephrine inhaler (sold as Asthmanefrin) and systemic ephedrine (sold as Bronkaid and Primatene tablets), are less effective than standard therapies for asthma and have a higher rate of side effects. Thus, OTC products are not recommended for the routine care of asthma, particularly acute asthma symptoms. These warnings are an important reminder for clinicians to ask their patients about use of OTC products. (See "Asthma in children younger than 12 years: Rescue treatment for acute symptoms", section on 'Nonstandard therapies' and "Alternative and experimental agents for the treatment of asthma", section on 'Risks associated with inhaled epinephrine' and "Alternative and experimental agents for the treatment of asthma", section on 'Homeopathic agents' and "Homeopathy", section on 'Specific diseases'.)

Safety of inhaled long-acting beta agonist/glucocorticoid for asthma during pregnancy (February 2015)

An important clinical question for pregnant women with asthma is whether using a combination long-acting beta-agonist (LABA) plus inhaled glucocorticoid confers an increased risk for adverse fetal outcomes, compared with monotherapy using a higher dose of the inhaled glucocorticoid. In a study of 1302 pregnant women with asthma, the risk for a major congenital malformation was not increased when a LABA plus low dose inhaled glucocorticoid was compared with a medium dose inhaled glucocorticoid, or when a LABA plus medium-dose inhaled glucocorticoid was compared with a high-dose inhaled glucocorticoid [2]. (See "Management of asthma during pregnancy", section on 'Long-acting beta-adrenergic agents'.)

Safety of omalizumab for asthma during pregnancy (February 2015)

The safety of omalizumab exposure during pregnancy in humans has not been formally evaluated, but outcomes from an omalizumab registry have been published [3]. There were 169 pregnancies with known outcomes: 156 live births (160 infants), 1 fetal death/stillborn, and 11 spontaneous abortions. The rate of preterm birth was 14 percent, and 11 percent of infants were small for gestational age. Congenital anomalies were present in 13 percent, and 4 percent had a major anomaly. While the sample size is small, these results are similar to findings from other studies of pregnant women with asthma. Further data are needed to more fully characterize outcomes of omalizumab use in pregnancy. (See "Management of asthma during pregnancy", section on 'Anti-immunoglobulin E'.)

Novel glucocorticoid receptor agonist for asthma (February 2015)

The investigational agent AZD5423 is a nonsteroidal compound that binds to the glucocorticoid receptor in a different manner from that of traditional glucocorticoids. It suppresses production of proinflammatory proteins (like traditional glucocorticoids), but with reduced adverse effects in animal models. An inhaled dry powder formulation of AZD5423 was assessed in a trial that randomly assigned 20 subjects with mild allergic asthma to pretreatment with AZD5423, budesonide, or placebo for seven days followed by allergen-bronchoprovocation [4]. AZD5423 attenuated the fall in forced expiratory volume in one second (FEV1) during the late phase asthmatic response compared with budesonide or placebo, but did not affect the early decrease in FEV1. AZD5423 also decreased allergen-induced sputum eosinophilia and allergen-induced airway hyperresponsiveness at 24 hours and was well-tolerated. Additional studies are needed to determine the safety and efficacy of AZD5423 compared with inhaled glucocorticoids. (See "Alternative and experimental agents for the treatment of asthma", section on 'Novel glucocorticoid receptor agonist'.)

DRUG HYPERSENSITIVITY

Immediate infusion reactions to leucovorin (April 2015)

Infusion reactions to leucovorin are rarely reported, but they may be under recognized because leucovorin is often administered simultaneously with other chemotherapy agents that are well known to cause reactions, such as oxaliplatin. In a series of 44 patients who had an immediate infusion reaction while receiving a leucovorin-containing regimen for metastatic colorectal cancer, five appeared related to leucovorin and not the coadministered drug (oxaliplatin, irinotecan) [5]. Leucovorin skin tests were negative, but challenge with leucovorin reproduced the symptoms in all five patients, while separate challenge with the co-administered agents produced no symptoms. All patients also reacted to subsequent challenge with LEVOleucovorin, suggesting that the L-isomer cannot necessarily be substituted for the more commonly used racemic leucovorin unless the patient has been specifically challenged and found to tolerate it. If continued leucovorin therapy is needed, it can be accomplished using a desensitization protocol. (See "Infusion reactions to systemic chemotherapy", section on 'Leucovorin'.)

FOOD ALLERGY AND INTOLERANCE

Early introduction of peanuts in high-risk infants (March 2015)

Previous guidelines recommended delayed introduction of highly allergenic solid foods (eg, eggs, peanuts, tree nuts, dairy products other than cow's milk, fish, and shellfish) for the purpose of preventing allergic disease in high-risk infants. However, evidence from observational studies suggested this practice was not effective and may lead to an increased incidence of food allergies. The Learning Early about Peanut Allergy (LEAP) trial is the first randomized trial to show benefit of early introduction of a major food allergen [6]. In this study, introduction of peanut at 4 to 11 months of age rather than avoidance until 60 months of age in children at high risk for peanut allergy due to severe eczema and/or egg allergy decreased the risk of developing peanut allergy. The rate of peanut allergy in the consumption group compared with the avoidance group was 1.9 versus 13.7 percent in children who were skin prick test-negative, and 10.6 versus 35.3 percent in children who were skin prick test-positive (wheal 1 to 4 mm). Exclusion criteria included a skin prick test wheal >4 mm or a positive baseline oral food challenge to peanut. These findings indicate that past recommendations to delay introduction of highly allergenic foods were appropriately rescinded. (See "Introducing formula and solid foods to infants at risk for allergic disease", section on 'Introduction of solid foods to high-risk infants'.)

Oat cereal for thickening infant bottle feeds (February 2015)

For healthy infants with problematic gastroesophageal reflux who are bottle-fed, thickening feeds with infant cereal slightly improves symptoms. Although rice cereal has traditionally been used for this purpose, oat cereal is now preferred because of concerns about possible contamination of rice cereal with arsenic [7-9]. The US Food and Drug Administration (FDA) is investigating to determine if there are clinically significant traces of arsenic in rice cereal. (See "Gastroesophageal reflux in infants", section on 'Thickening feeds'.)

2014 Food allergy practice parameter update (December 2014)

The American Academy of Allergy, Asthma & Immunology, the American College of Allergy, Asthma & Immunology, and the Joint Council of Allergy, Asthma & Immunology have updated their practice parameter for food allergy that covers multiple aspects of patient care [10]. Recommendations are largely consistent with those presented in UpToDate. One area highlighted was the utility of component-resolved diagnostic testing for peanut allergy. (See "Component testing for pollen-related, plant-derived food allergies", section on 'Peanut testing approach' and "Component testing for pollen-related, plant-derived food allergies", section on 'Overview'.)

Role of exercise in food-dependent exercise-induced anaphylaxis (November 2014)

Food-dependent exercise-induced anaphylaxis (FDEIAn) is a disorder in which patients have a food allergy that is believed to cause symptoms only when food ingestion is followed by physical exercise in the ensuing few hours. Although exercise has been viewed as an essential trigger, a new study has raised the question of whether various factors, other than exercise, could also trigger symptoms when combined with food. In this study, 16 patients with wheat-dependent FDEIAn were challenged with increasing amounts of the causative allergen, alone or combined with aspirin and/or alcohol (both associated with more severe reactions in this disorder) [11]. Fourteen of the 16 patients developed symptoms with various combinations of these factors, with only two requiring exercise. These findings suggest that FDEIAn may be more accurately viewed as a food allergy that requires one or more augmenting factors, of which one may be exercise, to cause a clinically-significant reaction. (See "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis", section on 'Wheat-dependent FDEIAn'.)

IMMUNODEFICIENCY

Hypogammaglobulinemia following rituximab therapy (November 2014)

Rituximab, a monoclonal antibody used in the treatment of hematologic malignancies and several autoimmune and rheumatologic disorders, depletes B cells and may cause hypogammaglobulinemia in some patients. Early clinical trials suggested that hypogammaglobulinemia following rituximab administration was transient and not associated with serious infections. However, subsequent reports have described persistent hypogammaglobulinemia associated with significant infections in a small subset of patients. A retrospective review of 19 patients with persistent, symptomatic hypogammaglobulinemia included patients who had received rituximab for periods ranging from one month to four years for hematologic malignancies or autoimmune or rheumatologic disorders [12]. Most patients experienced sinopulmonary infections, but three had enteroviral meningoencephalitis (with one fatality). All but one required immune globulin replacement to prevent infections. Clinicians should be aware of this complication, particularly in patients receiving multiple courses of rituximab, although risk factors for and incidence of hypogammaglobulinemia remain poorly defined. (See "Secondary immunodeficiency induced by drugs and biologic therapies", section on 'Hypogammaglobulinemia'.)

Hyaluronidase-facilitated subcutaneous immune globulin (November 2014)

Subcutaneous immune globulin is usually given in weekly doses, because the amount of solution that can be comfortably infused in the subcutaneous space is limited. To circumvent this, a solution of hyaluronidase can be administered immediately before the immune globulin, to increase dispersion. HyQvia is a 10 percent immune globulin preparation (Gammagard) packaged together with a fixed dose of recombinant human hyaluronidase in a separate vial. It was introduced in Europe in 2013, and was recently approved by the US Food and Drug Administration (FDA) for adults but not pregnant women or children under 18 years of age [13]. It can be given in doses similar to intravenous immune globulin (IVIG) every three to four weeks, and may be particularly useful for patients with difficult venous access. A seven-week "ramping up" protocol is recommended when initiating therapy with HyQvia (table 1). (See "Subcutaneous and intramuscular immune globulin therapy", section on 'Hyaluronidase-facilitated SCIG'.)

URTICARIA AND ANGIOEDEMA

Effective long-term management of Schnitzler's syndrome with anakinra (March 2015)

Schnitzler's syndrome is a form of urticarial vasculitis associated with monoclonal gammopathy, primarily IgM, and other systemic manifestations including bone pain, skeletal hyperostosis, arthralgias, lymphadenopathy, and intermittent fevers. In the past, this condition has been shown to respond to therapy with interleukin-1 inhibition. The largest study to demonstrate the long-term effectiveness of interleukin-1 inhibition included 29 patients with Schnitzler's syndrome treated with anakinra, all of whom demonstrated sustained improvement in disease activity [14]. After a median follow-up of 36 months, 24 patients were in complete remission and 5 patients were in partial remission. Severe infections were observed in six patients, although no lymphoproliferative diseases occurred during the treatment. Thus, anakinra appears to be a effective long-term therapy for Schnitzler's syndrome, although the risk of infectious complications with long-term use requires further study. (See "Urticarial vasculitis", section on 'Differential diagnosis'.)

Sensitivity to nonsteroidal antiinflammatory drugs in children with chronic urticaria (February 2015)

In many patients with chronic spontaneous urticaria (CSU), nonsteroidal antiinflammatory drugs (NSAIDs) exacerbate symptoms. NSAID sensitivity has been demonstrated in 20 to 40 percent of adults with CSU and typically presents as an increase in urticaria lesions appearing one to four hours after ingestion. However, data in children have been limited. In a new study of 68 children with CSU and no history of previous reactions to NSAIDs, subjects underwent single-blind challenge with aspirin, and 10 to 24 percent developed increased symptoms, with the majority experiencing isolated lip angioedema [15]. Clinicians should inform patients with CSU (and their caretakers) about potential sensitivity to NSAIDs. (See "Chronic urticaria: Standard management and patient education", section on 'Avoidance of exacerbating factors'.)

Icatibant for ACE-inhibitor associated angioedema (February 2015)

Angiotensin-converting enzyme (ACE) inhibitors cause episodic, bradykinin-mediated angioedema in less than 1 percent of recipients, but this accounts for approximately one-third of angioedema cases presenting to emergency departments in countries where these medicines are widely used. The most common approach to management of severe episodes affecting the airway has been discontinuation of the ACE inhibitors and supportive care, which may involve intubation and even tracheotomy. Icatibant, a bradykinin receptor antagonist approved for use in hereditary angioedema, has now been shown to be effective for ACE inhibitor-associated angioedema [16]. In a randomized trial of 27 adults presenting to the emergency department with angioedema of the upper aerodigestive tract while taking an ACE inhibitor, patients received one dose of icatibant or standard therapy (an intravenous glucocorticoid plus an antihistamine). Symptoms in the icatibant group resolved in a median of 8 hours, compared with 27 hours in the glucocorticoid/antihistamine group, and icatibant was well tolerated. Icatibant is most likely to be effective if given in the first few hours of an angioedema attack when the swelling is still increasing. (See "ACE inhibitor-induced angioedema", section on 'Icatibant'.)

VACCINES AND VACCINE HYPERSENSITIVITY

Choice of influenza vaccine formulation in patients with egg allergy (March 2015)

Most influenza vaccines are produced in an egg-based system, which has been a concern in patients with egg allergy. A number of observational studies have shown that administration of injectable inactivated influenza vaccine (IIV) containing up to 0.7 mcg ovalbumin per 0.5 mL dose is safe in patients with egg allergy. Two new observational studies have demonstrated safe administration of the intranasal live attenuated influenza vaccine (LAIV) containing <0.24 mcg ovalbumin per 0.2 mL dose in patients with egg allergy [17,18]. Influenza vaccine ovalbumin content is shown in the table (table 2). About 40 percent of patients in these studies had a history of anaphylaxis to egg and around 60 to 70 percent had asthma.

Based upon these findings and accumulating unpublished clinical experience, we recommend that all patients with egg allergy ≥6 months of age, including those with a history of anaphylaxis, receive annual immunization with an influenza vaccine according to the indications for all other patients without egg allergy. We would administer any age-appropriate, approved influenza vaccine (table 2), including the LAIV, in these patients according to the indications and contraindications outlined in the tables (table 3 and table 4). The vaccine is administered in a single dose rather than in two or more doses as a graded challenge. A 30 minute observation period is still suggested for patients with egg allergy who receive an egg-based influenza vaccine. This observation period is not necessary for those receiving an egg-free influenza vaccine. (See "Influenza vaccination in individuals with egg allergy", section on 'Safety of vaccines in patients with egg allergy' and "Influenza vaccination in individuals with egg allergy", section on 'Our approach'.)

Pneumococcal conjugate vaccine in adults ≥65 years of age (September 2014, MODIFIED March 2015)

The CAPiTA trial, which is the largest trial to assess the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13) in adults, compared PCV13 to placebo in approximately 85,000 immunocompetent adults ≥65 years of age in the Netherlands who had not received a pneumococcal vaccine previously [19]. The trial demonstrated 46 percent efficacy of PCV13 against vaccine-type pneumococcal pneumonia, 45 percent efficacy against vaccine-type nonbacteremic pneumococcal pneumonia, and 75 percent efficacy against vaccine-type invasive pneumococcal disease. Efficacy persisted for the duration of the trial (mean follow-up four years). However, some concern has been raised that since this trial began before PCV13 was used routinely in infants in the Netherlands, it might not answer the question of whether its use in adults is efficacious in countries that routinely vaccinate infants. (See "Pneumococcal vaccination in adults", section on 'Efficacy'.)

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 September 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending PCV13 for all adults ≥65 years of age [20]. The ACIP revision was prompted by results from the CAPiTA trial. Current recommendations for individuals ≥65 years of age who have not previously received either PCV13 or PPSV23 are to administer PCV13 followed 6 to 12 months later by PPSV23 (algorithm 1). In patients who have already received PPSV23, at least one year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Indications'.)

OTHER GENERAL ALLERGY AND IMMUNOLOGY

Depression and anxiety disorders in patients with atopic dermatitis (April 2015)

Several lines of evidence suggest that the incidence of psychiatric comorbidities, including major depression and anxiety disorders, is increased among patients with atopic dermatitis and may be influenced by factors such as perceived disease severity and quality of life. A longitudinal cohort study evaluated the risk of developing major depression or anxiety disorders later in life among more than 8000 adolescents and adults with atopic dermatitis and age- and sex-matched controls [21]. Patients with atopic dermatitis had a six- and fourfold increased risk of developing major depression or anxiety disorders, respectively. These findings suggest that the identification and treatment of psychiatric comorbidities are important aspects of the management of patients with atopic dermatitis. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Depression and anxiety disorder'.)

Circulating influenza A H3N2 viruses and influenza vaccine effectiveness in the United States (December 2014, MODIFIED March 2015)

In December 2014, the United States Centers for Disease Control and Prevention (CDC) released a health advisory stating that more than half of influenza A H3N2 viruses collected and analyzed in the United States in October and November 2014 were antigenically different (drifted) from the H3N2 antigen included in this season's influenza vaccines [22]. Most isolated influenza viruses to date have been H3N2 strains. During previous seasons in which influenza A H3N2 viruses have predominated, higher hospitalization and mortality rates have been reported among older people, very young children, and individuals with certain medical conditions. In seasons where predominant circulating influenza viruses have antigenically drifted, decreased vaccine effectiveness has been observed. Nevertheless, vaccination typically provides some cross-protection against drifted viruses and should still reduce hospitalization and death. As of late February 2015, overall vaccine effectiveness was only 19 percent and vaccine effectiveness against influenza A H3N2 was only 18 percent [23]. Influenza vaccination is still highly recommended [22]. The CDC health advisory was issued to reemphasize the importance of the use of neuraminidase inhibitors (eg, oseltamivir, zanamivir) when indicated for the treatment and prevention of influenza infection as an adjunct to vaccination. (See "Seasonal influenza vaccination in adults", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season' and "Seasonal influenza in children: Prevention with vaccines", section on 'Drifted H3N2 viruses during the 2014 to 2015 influenza season'.)

Safety of calcineurin inhibitors for treatment of atopic dermatitis in children (February 2015)

Topical calcineurin inhibitors can be used as an alternative to topical corticosteroids for the treatment of mild to moderate atopic dermatitis. In 2005, based upon case reports, animal studies, and the known risks with systemic calcineurin inhibitors, the US Food and Drug Administration (FDA) issued boxed warnings about a possible link between the topical calcineurin inhibitors and cancer. An analysis of data from 7500 children enrolled between 2004 and 2014 in the Pediatric Eczema Elective Registry (PEER), an ongoing post-marketing cohort study, found a trend toward increased risk for lymphoma and leukemia that was not statistically significant compared with incidence in the general population based on the SEER database [24]. The small sample size and wide confidence intervals for these data may not exclude all risk. While awaiting data from a larger study, it seems prudent to use topical calcineurin inhibitors only as second-line therapy for the management of atopic dermatitis in areas at high risk for skin atrophy when treated with topical corticosteroids. (See "Treatment of atopic dermatitis (eczema)", section on 'Long-term safety concerns'.)

Caustic ingestions mimicking anaphylaxis in young children (February 2015)

Accidental ingestion of caustic liquids by young children may be mistaken for anaphylaxis because both may present with nausea, vomiting, difficulty swallowing, and swelling of the lips, tongue, or pharynx. In a report of two cases and review of the literature, clinical clues to the diagnosis of caustic ingestion include the lack of a history of food allergy or other allergic disease and failure to respond to treatment for anaphylaxis [25]. Caretakers may not have witnessed the ingestion, or may not report it for fear of reprisal. Careful visualization of the affected areas with endoscopy or microlaryngoscopy can distinguish caustic ingestion from anaphylaxis by identifying ulceration and mucosal damage to the upper airway and esophagus. Preparations should be in place to intubate, if necessary, when manipulating a compromised airway. (See "Differential diagnosis of anaphylaxis in children and adults", section on 'Caustic ingestion (young children)' and "Caustic esophageal injury in children".)

Adjunctive glucocorticoids for hospitalized patients with community-acquired pneumonia (January 2015)

There has been interest in using glucocorticoids as adjunctive therapy to antibiotics in hospitalized patients with community-acquired pneumonia (CAP) in an attempt to reduce the inflammatory response, which is likely to contribute to the morbidity of the disease. There are conflicting data on this approach, but the largest randomized trial suggests a modest benefit. In the trial, which included 785 hospitalized adults with CAP, prednisone 50 mg daily for seven days shortened the time to clinical stability by approximately one day compared with placebo, without an increase in complications [26]. In another randomized trial that included 120 patients in Spain with severe CAP and a high inflammatory response, there was less treatment failure among patients who received methylprednisolone 0.5 mg/kg every 12 hours for five days than in those who received placebo, but no difference in the rate of in-hospital mortality [27]. Pending the results of a larger trial evaluating mortality rates in severe CAP, we do not favor the routine use of adjunctive glucocorticoids in adults with CAP. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Glucocorticoids'.)

Emollient therapy from birth and incidence of atopic dermatitis (October 2014)

Epidermal barrier dysfunction is a key factor in the initiation and progression of atopic dermatitis. Two randomized trials, one performed in Japan and the other in the United States and United Kingdom, found that enhancement of the skin barrier with daily application of emollient reduced the incidence of atopic dermatitis at six to eight months of age in infants at increased risk (ie, those with a parent or sibling with atopic dermatitis) [28,29]. Although the long-term efficacy of this treatment needs to be evaluated in larger studies with extended follow-up, emollient therapy from birth is a simple, inexpensive, and safe intervention that may prevent the onset of atopic dermatitis in the first year of life. (See "Treatment of atopic dermatitis (eczema)", section on 'Prevention'.)

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REFERENCES

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