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What's new in allergy and immunology

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2014. | This topic last updated: Jul 24, 2014.

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.


Interplay between allergen and bacterial exposures in the development of asthma (June 2014)

Data have been conflicting about the role of allergen exposure in the development of asthma and recurrent wheeze in children. The Urban Environment and Childhood Asthma (URECA) study assessed allergen exposure in a large birth cohort at high risk for asthma, and also bacterial content of house dust in a nested study of 104 children [1]. Accumulated allergen exposure over the first three years of life was associated with increased allergic sensitization and with recurrent wheeze at age three, but exposure in the first year was negatively associated with recurrent wheeze. Moreover, the combination of early-life exposure to these allergens with high-level exposure to bacteria in house dust was associated with a further reduction in risk of recurrent wheeze by age three. These observations suggest that the effects of early life allergen exposure may differ from those of cumulative exposure and that the combination of high-level allergen and bacterial exposure in early-life may be protective against allergen sensitization and recurrent wheeze. (See "Risk factors for asthma", section on 'Influence of bacterial exposure'.)

An anti-thymic stromal lymphopoietin monoclonal antibody shows promise in allergic asthma (June 2014)

Thymic stromal lymphopoietin (TSLP) is an epithelial-cell-derived cytokine that may play a role in allergic inflammation. In a proof-of-concept study, 31 patients with allergic asthma were randomly assigned to receive the anti-TSLP monoclonal antibody (AMG 157) or placebo intravenously, once a month for three doses [2]. On day 84, patients who received AMG 157 demonstrated significant blunting in their response to inhaled allergen, when compared with those who received placebo. This study provides support for anti-TSLP as a novel therapy for allergic asthma; further studies are planned. (See "Alternative and experimental agents for the treatment of asthma", section on 'Anti-thymic stromal lymphopoietin'.)

Pediatric health effects of public smoking bans (June 2014)

Policies that ban indoor smoking in workplaces and public places have been associated with long-term health benefits in adults. Smoking bans also appear to be associated with immediate health benefits in children. In a meta-analysis of quasi-experimental observational studies, public smoking bans were associated with reductions of approximately 10 percent in preterm births and hospital admissions for asthma [3]. Some of the effects may be mediated through home smoking bans, which often are prompted by public smoking bans. Additional studies are necessary to determine the effects of smoking bans on respiratory tract infections and other child-health outcomes. (See "Control of secondhand smoke exposure", section on 'Public smoking bans'.)

Statin therapy does not reduce COPD exacerbations (June 2014)

In observational studies of chronic obstructive pulmonary disease (COPD), statins have been associated with a reduced rate and severity of exacerbations, rate of hospitalizations, and mortality. However, these beneficial effects were not supported in a trial that randomly assigned 885 participants with COPD, but without other indications or contraindications for statin therapy, to simvastatin or placebo for up to 36 months [4]. Simvastatin did not reduce the rate of exacerbations or the time to first exacerbation. (See "Management of exacerbations of chronic obstructive pulmonary disease", section on 'Ineffective interventions'.)

Breastfeeding and development of asthma (May 2014)

Studies of breastfeeding are invariably subject to confounding, and data regarding the effects of breastfeeding on the prevention of asthma have been conflicting. In a systematic review and meta-analysis, the strongest protective effect of breastfeeding was seen in the birth to two years age group, in which rates for both "recent asthma" and "asthma ever" were consistently reduced, regardless of duration or exclusivity of breastfeeding [5]. This protective effect decreased with age, which is consistent with findings from individual studies that followed children until adolescence and found that breastfeeding was ultimately not protective against asthma in the highest risk children. The early reduction in asthma-type symptoms is probably due in part to the decreased number of clinically significant respiratory tract infections seen in breastfed infants. (See "The impact of breastfeeding on the development of allergic disease", section on 'Breastfeeding and asthma'.)

Dexamethasone for acute asthma exacerbations in children (March 2014)

Oral, rather than intravenous or intramuscular, administration of glucocorticoids for acute asthma exacerbations in children is preferred because it is less invasive, equally effective, and can be more easily discontinued in the setting of intolerance. However, vomiting of orally administered prednisone/prednisolone has been an issue. A meta-analysis comparing a five-day course of oral prednisolone or prednisone to one to two doses of oral or intramuscular dexamethasone for asthma exacerbations managed in the emergency department (ED) found that the treatments were similarly effective, but dexamethasone by either route caused less vomiting [6]. However, most of the trials included in the meta-analysis used older prednisone formulations and more palatable formulations have since been developed. Thus, either the newer formulations of oral prednisone/prednisolone or oral dexamethasone are good options for ED therapy. (See "Acute asthma exacerbations in children: Emergency department management", section on 'Systemic glucocorticoids'.)


HLA-B*1502 testing prior to oxcarbazepine therapy (June 2014)

The HLA-B*1502 allele is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis due to carbamazepine, and screening for this allele is recommended prior to initiating therapy in patients with Asian ancestry, who are more likely to carry the allele. Although data are weaker for the relationship between oxcarbazepine-induced hypersensitivity reactions and the HLA-B*1502 allele, the two drugs have similar chemical structures, and preclinical data have shown a direct interaction between oxcarbazepine and the HLA-B*1502 protein. For these reasons, the US Food and Drug Administration has revised the oxcarbazepine label to suggest testing for the HLA-B*1502 allele in genetically at-risk populations (ie, those with Asian ancestry) before initiating treatment with oxcarbazepine [7]. (See "Pharmacology of antiepileptic drugs", section on 'Oxcarbazepine'.)

Recurrence of Stevens-Johnson syndrome/toxic epidermal necrolysis (June 2014)

Although there are reports of recurrence of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the overall risk of recurrence is unknown. In a 10-year population-based cohort of 708 patients hospitalized for a first episode of SJS or TEN, 7.2 percent of 581 survivors were hospitalized for a second episode and 1.4 percent had multiple recurrences; lack of direct access to medical records precluded information about medication exposures [8]. The median time to first recurrence was 315 days. The high risk of recurrence after a first episode of SJS/TEN may reflect a long-lasting vulnerability or a genetic predisposition to severe drug reactions. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae", section on 'Recurrence'.)

Highly selective COX-2 inhibitors in aspirin-exacerbated respiratory disease (January 2014)

Patients with aspirin-exacerbated respiratory disease (AERD) often have severe hypersensitivity reactions to nonsteroidal antiinflammatory drugs (NSAIDs), which are directly related to inhibition of the enzyme COX-1. Although highly selective COX-2 inhibitors are theoretically safe, observational studies described patients who appeared to react to these agents. In a new meta-analysis of placebo-controlled blinded trials, over 400 patients with AERD were challenged with highly selective (celecoxib, rofecoxib) or relatively selective (ie, meloxicam, nabumetone, nimesulide) COX-2 inhibitors [9]. Whereas 1 in 13 patients had reactions to the relatively selective agents, there were no reactions to the highly selective agents. This analysis supports the safety of highly selective COX-2 inhibitors in patients with AERD. (See "NSAIDs (including aspirin): Allergic and pseudoallergic reactions", section on 'Highly selective COX-2 inhibitors'.)


Oral immunotherapy for food allergy (March 2014)

Data continue to accumulate regarding the efficacy and limitations of oral immunotherapy (OIT) for childhood food allergies. Important developments of several phase 1/pilot studies include safe administration of OIT with multiple foods simultaneously [10], ability to perform OIT in high-risk patients and reach maintenance more quickly with concomitant anti-immunoglobulin E therapy [11], and unresponsiveness to the allergenic food in some patients for one to six months after discontinuing successful OIT [12,13]. OIT is associated with a greater risk of anaphylaxis compared with avoidance [14,15], although despite this, parents assess their children’s quality of life as higher with OIT [16]. Additional studies, particularly randomized trials, are still needed to determine if the benefits outweigh the risks for most food-allergic children. (See "Future therapies for food allergy", section on 'Oral immunotherapy' and "Future therapies for food allergy", section on 'OIT combined with anti-IgE'.)

Maternal intake of highly allergenic foods during pregnancy (March 2014)

To date, most studies have found that maternal avoidance of highly allergenic foods during pregnancy does not reduce the incidence of allergic disease in infants and children at risk for these disorders. However, participants in such studies are often from "high risk" atopic families and thus may not be representative of the general population. A new cohort study in over 1200 unselected mother-child pairs examined the association between maternal intake of common allergenic foods during pregnancy and the development of allergic disorders in the offspring [17]. Data from mid-childhood visits found that diets lower in allergenic foods were not associated with reduction in the incidence of food allergy, asthma, allergic rhinitis, or atopic dermatitis, and in some situations, higher intake in early pregnancy appeared to have a protective effect. These findings support our current suggestion that women not restrict their diets during pregnancy for the purpose of reducing allergic disease in their children. (See "Primary prevention of allergic disease: Maternal avoidance diets in pregnancy and lactation", section on 'Definitions'.)


Plerixafor in WHIM syndrome (February 2014)

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) is a rare primary immunodeficiency syndrome in which mutations in the gene encoding a chemokine receptor (CXCR4) cause abnormal retention of blood cells in the bone marrow. Patients can have severe neutropenia, bacterial infections, and warts due to unchecked human papilloma virus. The efficacy of the CXCR4 antagonist plerixafor was tested in three individuals with WHIM syndrome for six months [18]. Self-injection of low-dose plerixafor, in combination with imiquimod, led to improved white blood cell counts, fewer bacterial infections, and regression of warts; no major adverse events were noted. Low-dose plerixafor is a potential long-term strategy for patients with WHIM syndrome. (See "Combined immunodeficiencies", section on 'Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome'.)

Distinguishing DOCK8 deficiency from severe atopic dermatitis (January 2014)

Distinguishing a serious primary immunodeficiency from a more benign pediatric disease can be difficult without specialized testing. A child with severe eczema, recurrent skin infections, and food allergy, for example, may have atopic dermatitis or dedicator of cytokinesis 8 (DOCK8) deficiency, a combined immunodeficiency seen primarily in children of Middle Eastern descent. Certain findings on standard lymphocyte flow cytometry can help determine which of these children should have more extensive diagnostic testing for DOCK8 deficiency [19]. (See "Combined immunodeficiencies", section on 'Dedicator of cytokinesis 8 (DOCK8) deficiency'.)

A new combined immunodeficiency with normal T and B cell counts (January 2014)

A new defect in nuclear factor-kappa-B (NF-kappa-B) regulation has been identified that causes a combined immunodeficiency [20]. Patients with homozygous null mutations in I-kappa-B kinase beta chain (IKBKB), the kinase that inactivates the inhibitor of NF-kappa-B, have defective responses to various activating stimuli, leading to impairments in both adaptive and innate immune responses. The patients described so far presented with oral candidiasis in early infancy and then developed more severe fungal, viral, and bacterial infections. Unlike many other forms of combined immunodeficiency, patients have normal T and B cell counts. (See "Combined immunodeficiencies", section on 'Defects of NF-kappa-B regulation'.)

A new genetic cause of recurrent respiratory infections and bronchiectasis (January 2014)

A new genetic defect has been identified that causes a primary immunodeficiency (PID) associated with recurrent respiratory tract infections and bronchiectasis. This dominant gain-of-function point mutation in the catalytic subunit (p110δ) of phosphoinositide 3-kinase delta (PI3Kδ) causes increased production of phosphatidylinositol 3,4,5-trisphosphate (PIP3), leading to defective T and B cell function [21]. Activated PI3K-delta syndrome (APDS) was found in 17 patients from 7 unrelated families, suggesting that it is a relatively common PID in patients with this clinical presentation. Patient are treated with immune globulin replacement therapy and antibiotics. Selective p110δ inhibitors are a possible alternative therapeutic approach. (See "Combined immunodeficiencies", section on 'Activated PI3K-delta syndrome (APDS)'.)

IDSA guidelines for vaccination of immunocompromised hosts (January 2014)

The Infectious Diseases Society of America has published new guidelines for vaccination of immunocompromised hosts, including hematopoietic cell transplant recipients, solid organ transplant recipients, as well as patients with cancer, asplenia, primary immunodeficiency disorders, chronic inflammatory conditions, HIV infection, and chronic inflammatory diseases receiving immunosuppressive agents [22]. The document includes recommendations about the appropriate use (and avoidance) of specific vaccines in immunocompromised hosts. (See "Immunizations in hematopoietic cell transplant candidates and recipients" and "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in patients with cancer" and "Prevention of sepsis in the asplenic patient".)


Diagnostic criteria for mucous recirculation syndrome (July 2014)

Mucous recirculation syndrome is an acquired disorder of impaired mucous clearance in which mucus draining through a sinus ostium re-enters the sinus through a different ostium and recirculates, rather than draining out through the nasopharynx. It is a cause of refractory chronic rhinosinusitis (CRS). Based upon a cohort of 12 patients and review of the literature including an additional 44 cases, researchers have proposed diagnostic criteria for mucous recirculation syndrome and described various recirculation patterns [23]. Proposed diagnostic criteria are: CRS not responding to oral or topical therapies, visualization of mucous recirculation between two or more ostia by rhinoscopy, and resolution of symptoms with surgical treatment. (See "Management of chronic rhinosinusitis", section on 'Mucous recirculation syndrome'.)

Sublingual tablet immunotherapy for pollen-induced rhinitis (April 2014)

Sublingual immunotherapy has been used for decades in Europe to treat allergic rhinoconjunctivitis, although products specifically designed for oral use and proven effective in high-quality studies had not been available in the United States. Two products, a five-grass sublingual tablet (Oralair), and a single-grass tablet (Grastek) were approved by the US Food and Drug Administration in early April 2014 [24,25] based on earlier randomized trials demonstrating efficacy. A third product (Ragwitek) for allergic rhinitis (with or without conjunctivitis) due to short ragweed pollen was approved in late April [26]. Sublingual tablet immunotherapy expands the available treatment options for patients with seasonal nasal and ocular allergies. The first dose should be administered under medical supervision. The most common adverse effects are oral or pharyngeal pruritus, but systemic allergic reactions are rare. (See "Sublingual immunotherapy for allergic rhinitis", section on 'Availability'.)

Triamcinolone nasal spray available without a prescription in US (February 2014)

Intranasal glucocorticoid (INGC) sprays alleviate nasal blockage, discharge, sneezing, and other nasal allergy symptoms and are considered first-line treatment for allergic rhinitis in most patients (table 1). Triamcinolone is the first INGC to be available in the United States without a prescription for once-daily treatment of nasal allergy symptoms in adults and children two years of age or older [27].  INGC sprays have been available without prescription outside the US for some time. (See "Pharmacotherapy of allergic rhinitis", section on 'Intranasal glucocorticoids'.)


Omalizumab for refractory chronic urticaria (April 2014)

Omalizumab, a recombinant humanized monoclonal antibody that binds immunoglobulin E (IgE), was approved by the US Food and Drug Administration in March 2014 for the treatment of chronic urticaria (CU) that is not controlled with H1 antihistamine therapy in patients 12 years of age and older [28]. Approval was based on several randomized trials published in recent years, in which most patients responded within the first few weeks of therapy. Two doses were approved: 150 mg or 300 mg injected subcutaneously every four weeks. Omalizumab has a superior safety profile to many of the other agents used in the treatment of refractory CU, although it is the most expensive and does not appear to have a long-term disease modifying effect. Studies directly comparing omalizumab to other treatments for refractory CU are needed to determine the optimal use for omalizumab in the management of this disorder. (See "Chronic urticaria: Treatment of refractory symptoms", section on 'Omalizumab'.)

Chronic idiopathic urticaria and food/drug additives (March 2014)

Although food and drug additives are felt to cause chronic urticaria only rarely, if at all, many patients with chronic urticaria believe that additives are partly or entirely to blame. In a referral center study of 100 patients with chronic urticaria, including 43 who suspected they were sensitive to one or more additives, subjects were systematically challenged with common food and drug additives [29]. In an initial challenge with a combination of 11 additives, two patients had significant worsening of symptoms. Neither patient reacted to a series of subsequent double-blind placebo-controlled challenges with each additive. Thus, none of the 100 patients was sensitive to any of the additives tested. This study should prove helpful in communicating with patients who suffer from this vexing disorder, while research into its true etiology(ies) continues. (See "Allergic and asthmatic reactions to food additives", section on 'Patients with chronic urticaria'.)

Sulfasalazine in recalcitrant chronic urticaria (January 2014)

Sulfasalazine, an antiinflammatory agent, is used to treat chronic urticaria (CU) that is refractory to antihistamines, although data on efficacy are lacking. The impact of sulfasalazine as add-on therapy in recalcitrant CU was examined in a retrospective review of 31 patients, representing the largest study to date [30]. Sulfasalazine was added to the patients' existing therapies, and if symptoms were controlled, therapies other than antihistamines were reduced/discontinued. Symptoms improved in 84 percent within three months and were completely controlled in 51 percent by six months. Nine of 10 steroid-dependent patients discontinued glucocorticoids. Although randomized trials are needed, this study suggests that sulfasalazine has utility in recalcitrant CU and may reduce dependence on more toxic agents, such as glucocorticoids. (See "Chronic urticaria: Treatment of refractory symptoms", section on 'Sulfasalazine'.)


Influenza vaccine administration by needle-free jet injector (June 2014)

Needle-free vaccine technology could be useful for immunizing needle-phobic patients and reducing the risk of needlestick injuries. An example of needle-free technology is the jet injector, an investigational device that uses a high-pressure narrow jet of liquid vaccine to penetrate tissue [31]. In a randomized trial in healthy adults, the immune response to influenza vaccine was comparable when administered by jet injector device or needle and syringe. The jet injector device was associated with a higher frequency of local injection site reactions. (See "Seasonal influenza vaccination in adults", section on 'Needle-free jet injector'.)


Dupilumab for atopic dermatitis (July 2014)

Dupilumab is a fully human monoclonal antibody that inhibits downstream signaling of IL-4 and IL-13, cytokines of type 2 helper T lymphocytes (Th2) that are believed to play a key role in atopic diseases, including asthma and atopic dermatitis. Dupilumab was evaluated in four small, industry-sponsored randomized trials in adult patients with moderate to severe atopic dermatitis [32]. In the largest study, 109 patients received weekly subcutaneous injections of dupilumab 300 mg or placebo. At 12 weeks, patients in the dupilumab group had a greater reduction in the Eczema Area and Severity Index score, body surface area affected, and pruritus than patients in the placebo group. Nasopharyngitis and headache were the most frequent adverse events. Although the results suggest that dupilumab may be a promising treatment for atopic dermatitis, additional studies are needed to evaluate its long-term efficacy and safety. (See "Treatment of atopic dermatitis (eczema)", section on 'Experimental agents'.)

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